tag:theconversation.com,2011:/id/topics/hiv-vaccine-11449/articlesHIV vaccine – The Conversation2021-03-24T02:57:55Ztag:theconversation.com,2011:article/1563732021-03-24T02:57:55Z2021-03-24T02:57:55ZA single vaccine to beat all coronaviruses sounds impossible. But scientists are already working on one<figure><img src="https://images.theconversation.com/files/391301/original/file-20210324-24-wvgakd.jpg?ixlib=rb-1.1.0&rect=0%2C2%2C998%2C562&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/coronavirus-deadly-outbreak-coronaviruses-influenza-background-1624413559">from www.shutterstock.com</a></span></figcaption></figure><p><a href="https://theconversation.com/what-you-need-to-know-about-the-new-covid-19-variants-153366">Variants of the virus</a> that causes COVID-19 are emerging and becoming dominant around the world. So some vaccines <a href="https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-first-participants-dosed-study-evaluating">are being updated</a> to allow our immune system to learn how to deal with them.</p>
<p>But this process of identifying and characterising variants that can escape our immune system, then tweaking a vaccine to deal with them, can take time.</p>
<p>So researchers are designing a <a href="https://futurehuman.medium.com/the-search-for-one-vaccine-to-rule-them-all-d44bae3d634a">universal coronavirus vaccine</a>. This could mean one vaccine to protect against different variants of SARS-CoV-2, the coronavirus that causes COVID-19. Alternatively, a universal vaccine would target many different coronaviruses, perhaps one waiting in the wings to cause the next pandemic.</p>
<p>Here’s where the science is up to and the challenges ahead.</p>
<h2>Why would we need a universal coronavirus vaccine?</h2>
<p><a href="https://www.frontiersin.org/articles/10.3389/fvets.2020.00578/full">Coronaviruses</a>, such as SARS-CoV-2, belong to a large and diverse family of viruses that infect humans and animals. And a <a href="https://www.nature.com/articles/s41541-020-0198-1">universal coronavirus vaccine</a> might be particularly important under two scenarios.</p>
<p>The first is the emergence of new variants of SARS-CoV-2. The second is the emergence of new coronaviruses that <a href="https://www.nature.com/articles/d41586-021-00340-4">may cause a pandemic in the future</a>. Indeed, SARS-CoV-2 is <a href="https://www.bmj.com/content/368/bmj.m634">not the first</a> of the coronaviruses that has “crossed” from animals and can cause severe disease in humans and it is unlikely to be the last.</p>
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<a href="https://theconversation.com/un-report-says-up-to-850-000-animal-viruses-could-be-caught-by-humans-unless-we-protect-nature-148911">UN report says up to 850,000 animal viruses could be caught by humans, unless we protect nature</a>
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<h2>How do we even start?</h2>
<p>Researchers are already designing and testing a universal vaccine against <a href="https://asm.org/Articles/2019/August/A-Universal-Influenza-Vaccine-How-Close-Are-We">influenza</a>. If successful, this would avoid needing to <a href="https://theconversation.com/flu-vaccines-are-updated-every-year-we-can-learn-from-this-process-as-we-respond-to-covid-variants-156580">tweak the vaccine</a> every year to guard against new variants. So we can apply what we’ve learnt to designing a universal coronavirus vaccine.</p>
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<a href="https://theconversation.com/a-universal-influenza-vaccine-may-be-one-step-closer-bringing-long-lasting-protection-against-flu-152274">A universal influenza vaccine may be one step closer, bringing long-lasting protection against flu</a>
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<p><strong>We could look for common features</strong></p>
<p>We could identify parts of the virus common to the entire family of coronaviruses or variants. So we could analyse and compare the genetic sequences of the viruses to find some common ground.</p>
<p>Alternatively, we could isolate immune cells that can react with all coronaviruses or a number of variants. These could be antibodies or T cells (a type of immune cell that specialises in identifying and killing virus-infected cells). Then we could map where on the viruses these target. In other words, we’re looking for a common antigen or group of antigens.</p>
<p>We can then use that knowledge to design a vaccine to teach the immune system how to specifically recognise those parts of the virus.</p>
<p><a href="https://www.theguardian.com/world/2020/nov/13/the-mutation-game-the-race-for-a-vaccine-against-all-coronaviruses">Several pharmaceutical companies</a> around the world are investigating such approaches against COVID-19, although all are at very early stages of development, and have yet to start clinical trials.</p>
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<a href="https://theconversation.com/explainer-what-is-the-immune-system-19240">Explainer: what is the immune system?</a>
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<p><strong>We could make a ‘mosaic’ vaccine</strong></p>
<p>An alternative approach is to make a “<a href="https://www.nature.com/articles/d41586-019-02319-8">mosaic</a>” vaccine. This is a vaccine that contains antigens from a few different variants or coronaviruses. </p>
<p>These are arranged on a nanoparticle — an extremely small biological structure made from proteins that serves as a platform for delivering antigens. Using this approach, our immune system figures out the commonalities itself. It then learns how to generate antibodies that react broadly to all the different viruses. </p>
<p>Scientists from the US <a href="https://science.sciencemag.org/content/371/6530/735">have tested</a> this approach in mice. After being vaccinated with the mosaic vaccine, the mice had an immune response against SARS-CoV-2 and a range of other coronaviruses from bats. The results are interesting for two reasons.</p>
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<p>The first is the type of immune response. The mice raised a broad range of neutralising antibodies, the types of antibodies that can stop a virus from infecting our cells and therefore provide the strongest protection. These neutralising antibodies are the main goal of vaccines.</p>
<p>The mice also raised an immune response to bat coronaviruses. This strategy could be useful for providing protection against future pandemics, should a bat coronavirus cross over to infect humans.</p>
<p>But “mosaic” vaccines against coronaviruses have yet to be tested in humans.</p>
<h2>So what are the challenges ahead?</h2>
<p>The design of a universal vaccine against any group of viruses <a href="https://science.sciencemag.org/content/371/6531/759.full">is no small task</a>. Indeed, universal vaccines <a href="https://www.nature.com/articles/d41586-019-02319-8">against HIV</a> or <a href="https://asm.org/Articles/2019/August/A-Universal-Influenza-Vaccine-How-Close-Are-We">influenza</a> have been the focus of intense research for years. </p>
<p>Some candidate universal vaccines against HIV or influenza have been assessed in human clinical trials and shown to be safe. However, the efficacy results have generally been modest.</p>
<p>One big challenge is these vaccines need to able to protect against an incredibly large number of possible variants. The good news is that SARS-CoV-2 <a href="https://www.nature.com/articles/d41586-020-02544-6">mutates slower</a> than HIV or influenza viruses, so variants may take longer to arise.</p>
<p>The second challenge is establishing long-lasting immunity, which both <a href="https://www.nature.com/news/2009/090924/full/news.2009.947.html">HIV</a> and <a href="https://www.fiercebiotech.com/biotech/gsk-dumps-universal-flu-vaccine-after-interim-data-readout">influenza</a> universal vaccines have yet to show.</p>
<p>A third barrier to overcome is learning <a href="https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(21)00089-5">how to anticipate</a> the virus’ next mutation or which animal coronavirus may cause the next pandemic. </p>
<p>So it is likely a universal coronavirus vaccine, whether it aims to cover multiple variants of SARS-CoV-2 or animal coronaviruses with pandemic potential, may take years to develop.</p>
<p>For now, we have to rely on <a href="https://theconversation.com/why-well-get-covid-booster-vaccines-quickly-and-how-we-know-theyre-safe-156120">reformulating currently available vaccines</a> against SARS-CoV-2 to accommodate the emergence of new variants.</p>
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<a href="https://theconversation.com/why-well-get-covid-booster-vaccines-quickly-and-how-we-know-theyre-safe-156120">Why we'll get COVID booster vaccines quickly and how we know they're safe</a>
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<p class="fine-print"><em><span>Marios Koutsakos receives funding from the NHMRC and the University of Melbourne. </span></em></p>Scientists around the world are trying to come up with universal coronavirus vaccines to combat the emergence of variants. But what are these vaccines and are they even possible?Marios Koutsakos, Research Fellow, The Peter Doherty Institute for Infection and ImmunityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1314872020-02-13T08:59:34Z2020-02-13T08:59:34ZThe search for an effective HIV vaccine continues<figure><img src="https://images.theconversation.com/files/314696/original/file-20200211-146708-2ci32u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">New HIV infections remain high.</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p><em>An HIV vaccine trial that started in 2016 in South Africa was <a href="https://www.niaid.nih.gov/news-events/experimental-hiv-vaccine-regimen-ineffective-preventing-hiv">halted</a> in February 2020. The study sponsors made the call after interim results showed that the vaccine, known as HVTN 702, did not prevent HIV. This result was disappointing, but the search for an effective HIV vaccine continues. Anatoli Kamali speaks to The Conversation Africa’s Ina Skosana about other developments in the field.</em></p>
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<p><strong>Why do we need an HIV vaccine?</strong></p>
<p>HIV remains a dangerous pandemic. The number of new infections remains high – about <a href="https://www.unaids.org/en/resources/fact-sheet">1.7 million</a> new cases every year. Young people, particularly <a href="https://www.unaids.org/en/resources/fact-sheet">young women</a>, account for a large portion of the new infections. Scientists have made progress in developing <a href="https://theconversation.com/one-year-in-lessons-on-rolling-out-an-hiv-prevention-pill-in-south-africa-88255">HIV prevention tools</a> in recent years. But marginalised groups – such as adolescent girls and young women, and men who have sex with men – can’t always access these tools easily. </p>
<p>A vaccine that prevents HIV infection will provide long-lasting protection and alleviate the need for prevention methods. It is critical to stopping the spread of HIV in areas where the use of current prevention tools is complicated by social, economic and political concerns. Simply put, we won’t be able to end the AIDS epidemic without a vaccine.</p>
<p>And there is progress. For example, the <a href="https://www.iavi.org/">International AIDS Vaccine Initiative</a>, a nonprofit scientific research organisation, leads a <a href="https://www.iavi.org/our-work/clinical-epidemiology-research/advance">programme</a> that’s been advancing the global search for a safe, effective preventive vaccine while building scientific capacity in Africa. This programme has supported 11 <a href="https://www.iavi.org/our-work/clinical-epidemiology-research/clinical-research-centers">clinical research centres</a> and over 50 scientists working in this field in African countries. </p>
<p><strong>How many HIV vaccine trials are there in the world?</strong></p>
<p>There are more HIV vaccine trials happening around the world right now than there have been in years. About 40 vaccine candidates are in or near clinical trials. </p>
<p>But there are numerous scientific challenges to developing an HIV vaccine. The virus is complex and the methods that produced vaccines for other diseases haven’t been applicable to HIV. </p>
<p>The International AIDS Vaccine Initiative and its partners have, over the past 20 years, tested 33 HIV vaccine candidates. These advanced to clinical trials in 11 countries including Kenya, Rwanda, Uganda, Zambia, India and Germany. </p>
<p><strong>What are the main things that are tested in trials, and how?</strong></p>
<p>Because HIV mutates rapidly and evades the immune system, HIV vaccine clinical trials focus on a variety of promising scientific approaches and theories. </p>
<p>The first trials of a new vaccine performed in humans are known as Phase 1 studies and test the safety of the treatment. These studies may also look for early signs of effectiveness, such as viral load reductions a week or two after the vaccine is taken. Once Phase 1 studies are completed, the vaccine moves into Phase 2 testing. These studies collect safety and dosing information and begin to show how effective the treatment is when taken for several months. </p>
<p>One approach used in the halted <a href="https://www.unaids.org/en/resources/presscentre/pressreleaseandstatementarchive/2020/february/20200204_vaccine">HVTN 702 trial</a> built on the promise of modest results seen in the US Army-led HIV vaccine trial in Thailand in 2009. The 2009 trial was the first and only one to date to demonstrate that an HIV vaccine can protect against infection. But this vaccine candidate decreased the infection rate by only 31% and had no effect on viral load.</p>
<p>Another large efficacy trial called <a href="https://www.hvtn.org/en/community/community-compass/current-issue/cc-current-article3.html">HVTN 705/HPX2008</a> or Imbokodo launched in 2017 and currently has 2,600 women volunteers in South Africa. It’s evaluating a vaccine regimen designed to induce immune responses against a variety of HIV strains.</p>
<p>The main theoretical approach to developing an HIV vaccine aims to prevent HIV infection by getting the body to produce <a href="https://retrovirology.biomedcentral.com/articles/10.1186/s12977-018-0433-2">antibodies</a> that fight most HIV strains. </p>
<p>Two vaccines have been designed to produce antibodies in reaction to the outer coat of the HIV virus. One of these is in a Phase 1 trial with men and women in Nairobi, Boston and Seattle. </p>
<p>Additional approaches use viral vectors, tools commonly used to deliver a gene from a target pathogen and elicit an immune response in the recipient. These are in early development and are approaching clinical trials.</p>
<p>In addition, two multinational clinical trials are testing whether it is possible to prevent HIV by directly infusing people with antibodies several times a year. Known as the <a href="https://ampstudy.org.za/">AMP studies</a>, for antibody-mediated prevention, these trials have completed enrolment of 4,600 men and women across four continents, including Africa. </p>
<p>It’s important to note that the preventive HIV vaccines being studied in clinical trials do not contain HIV. Approximately 30,000 people have participated in HIV vaccine studies around the world in the past 25 years. None have been infected with HIV from any of the vaccines tested.</p>
<p><strong>What is the impact of the decision to halt the HVTN 702 trial in South Africa?</strong></p>
<p>It’s obviously very disappointing, but there are many other vaccine candidates. We commend the trial volunteers, trial workers, scientists, and all the partners who collaborated to evaluate the vaccination regimen in this trial. Their efforts have led us to a greater understanding of what it will take to stop the global HIV/AIDS crisis. </p>
<p>Several promising HIV vaccines are in various stages of clinical development. We are optimistic that one or more of them may lead us to a vaccine that will reliably prevent infection from the wide variety of HIV strains.</p><img src="https://counter.theconversation.com/content/131487/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Anatoli Kamali does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The key to ending the HIV epidemic is a vaccine that will provide long-lasting protection and alleviate the need for prevention methods.Anatoli Kamali, Regional Director for Africa, IAVI, and Honorary Professor in the Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical MedicineLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1297132020-02-06T11:45:38Z2020-02-06T11:45:38ZWhat the discovery of a new HIV strain means for the pandemic<figure><img src="https://images.theconversation.com/files/309642/original/file-20200113-103987-1fkdus0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">It's important for scientists to have the most thorough understanding of HIV. </span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>The discovery of a rare new strain of HIV for the first time in nearly 20 years recently made <a href="https://edition.cnn.com/2019/11/06/health/hiv-new-strain-discovered/index.html">headlines</a> around the world. </p>
<p>The big question is what the discovery means for the overall response to the HIV epidemic.</p>
<p>A team of US researchers from Abbott, an American medical devices and health care company, led by Mary Rodgers and co-authors at the University of Missouri, announced the discovery in a <a href="https://journals.lww.com/jaids/Abstract/publishahead/Complete_genome_sequence_of_CG_0018a_01.96307.aspx">study</a> published in the Journal of Acquired Immune Deficiency Syndrome. The new subtype is the first strain to be identified since <a href="https://www.avert.org/professionals/hiv-science/types-strains">guidelines</a> for classifying new HIV strains were first established in 2000.</p>
<p>HIV has a multitude of different subtypes and, like other viruses, it changes (mutates) over time. This new strain is an important discovery, but it does not signify a new public health threat. It occurs rarely and can be effectively treated with existing antiretrovirals. Because antiretrovirals target characteristics of HIV that are common across all different subtypes, this new finding will not affect treatment and antiretroviral agents will still be effective as long as drug resistant mutations have not occurred. </p>
<p>The essence of the discovery is that it enhances scientists’ understanding of the complexity of the human immunodeficiency virus and its evolution and adds detail to the already comprehensive viral picture. </p>
<p>Having a thorough understanding of HIV is crucial in ensuring that HIV tests are effectively detecting the virus. Deeper insights could also have a bearing on vaccine development. </p>
<h2>Viral strains</h2>
<p>There are two main types of HIV. HIV-1 is the most common. HIV-2 is less common and accounts for fewer infections. The strains of HIV-1 can be classified into four groups – M, N, O and P. While N, O and P are quite uncommon, group M is responsible for most of the global HIV epidemic, accounting for roughly <a href="https://www.avert.org/professionals/hiv-science/types-strains">95%</a> of all infections worldwide. The newly discovered strain (also known as a clade) is part of group M and has been labelled as “subtype L”. </p>
<p>The prevalent strain found in South Africa is <a href="https://www.avert.org/professionals/hiv-science/types-strains">known</a> as a subtype of clade C.</p>
<p>One of the candidate HIV vaccine regimens <a href="http://www.samj.org.za/index.php/samj/article/view/5668/4223">currently</a> under investigation in South Africa is designed to be effective against subtype C. It is not yet known whether, if found to be effective in this region, it will be as effective in a region with a different prevalent strain. For example, in the US the predominant strain is subtype B.</p>
<p>The process of confirming a new strain of any virus can be long. Three separate cases need to be identified before a new subtype can be announced. The first two cases of this new strain were found in the Democratic Republic of Congo in 1983 and 1990 and the third case in 2001. So while the strain has been known to scientists for 18 years, the entire genome needed to be tested for confirmation. The technology to do this did not exist at the time.</p>
<p>The genome sequencing technology available today allows scientists and researchers to build entire genomes at a faster rate and lower cost than ever before. To use this next-generation technology successfully, the responsible scientists had to apply new techniques that focus on the virus portion of the collected sample in order to fully sequence the genome. </p>
<p>From a scientific point of view, the discovery helps us stay one step ahead of a virus. Furthermore, the role that new technology played in identifying the strain serves as an important reminder of how far we have come. The innovation and advancements in technology and molecular virology should be celebrated.</p>
<p>The fight against HIV has made some formidable gains in treatment and treatment outcomes with remarkable gains in longevity. </p>
<p>UNAIDS <a href="https://www.unaids.org/en/resources/fact-sheet">estimates</a> that new infections have decreased by 16% from 2,1 million in 2010 to 1,7 million in 2017. Undoubtedly one of the most promising achievements is the reduction in mother-to-child transmissions around the world. But the HIV response does not favour complacency. </p>
<h2>Emergency persists</h2>
<p>The notion that HIV is no longer an emergent threat is one that jeopardises the work of scientists and communities who continue to drive prevention of HIV and fight against the pervading stigma. The HIV emergency is not over. The epidemic still needs vigilant attention, especially as reduction rates stall. </p>
<p>The ultimate solution is a working cure and preventative vaccine. Trials were being held in South Africa – the <a href="https://desmondtutuhivfoundation.org.za/hiv-vaccine-trial-is-underway/">HVTN 702 studies</a> – into a HIV preventative vaccine in the hope that there would be an effective vaccine to prevent HIV. But they <a href="https://www.fredhutch.org/en/news/center-news/2020/02/hiv-vaccine-trial-africa.html">were halted</a> in early February 2020. This points to the need to refocus our energy on scaling up the effective treatment and prevention tools we have in hand to all those who need them.</p>
<p><em>This story was updated to reflect the fact that the HVTN 702 trials in South Africa were halted in February 2020.</em></p><img src="https://counter.theconversation.com/content/129713/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Linda-Gail Bekker does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The discovery of a new strain of HIV gives scientists a better understanding of the virus.Linda-Gail Bekker, Professor of medicine and deputy director of the Desmond Tutu HIV Centre at the Institute of Infectious Disease and Molecular Medicine, University of Cape TownLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1187342019-06-13T11:54:32Z2019-06-13T11:54:32ZThe three big studies pushing at the frontiers of HIV prevention<figure><img src="https://images.theconversation.com/files/279332/original/file-20190613-32356-10vjrgd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>There are an estimated 5000 new HIV transmissions every day. Around 70% of the 37 million people living with HIV globally are in sub-Saharan Africa. Of the 1.8 million new HIV transmissions worldwide in 2017, <a href="https://www.afro.who.int/health-topics/hivaids">800 000</a> occurred in eastern and southern Africa. New, effective prevention strategies are essential to reducing HIV transmission.</p>
<p>So what will it take to reduce HIV transmission? Prevention. </p>
<p>This is why researchers around the world are working hard to find a vaccine that is safe and effective. This requires extensive testing, starting in laboratories and then moving to animal trials. Then comes the crucial human clinical trials. A number of these are underway at the moment, running at different sites in 12 countries across four continents.</p>
<p>These trials are being conducted under the auspices of the <a href="http://www.hvtn.org/en.html">HIV Vaccine Trials Network</a>. The network currently runs 49 clinical trial sites in nine countries with 18 ongoing <a href="http://www.hvtn.org/en/science/HVTN-studies.html">trials</a>, four of which are efficacy trials. Three trials are of particular interest as they have already been running since 2016 and are expected to close in late 2021.</p>
<p>The first is known as the <a href="https://ampstudy.org.za/">Antibody Mediated Prevention studies</a>. It’s testing whether a broadly neutralising antibody can prevent HIV acquisition in people. The second, called <a href="http://uhambo.org.za/">Uhambo</a>, is testing an experimental vaccine regimen against HIV. And the third, <a href="https://www.imbokodo.org.za/">Imbokodo</a>, is testing an experimental vaccine regimen that’s designed to offer protection against a variety of global HIV strains.</p>
<p>These studies involve thousands of people all over the world, including countries hardest hit by HIV. If any of them are successful – that is, if the drugs being tested prove to be safe and effective for human use – the 30-year fight to end the HIV/AIDS epidemic will take a huge step towards victory.</p>
<p>It has been incredibly hard to make a vaccine against HIV. Some of the hurdles to overcome include the genetic diversity of HIV, which is greater than any other pathogen, the lack of a good animal model, no natural human cure and the complexity of the virus’s outer structure or envelope.</p>
<h2>The antibody search</h2>
<p>The Antibody Mediated Prevention studies have 4625 participants from the US, Brazil, Peru, Switzerland, Tanzania, Zimbabwe, Botswana, South Africa, Kenya, Malawi and Mozambique.</p>
<p>These trials started in May 2016 and are expected to close in late 2021. The clinical trials are designed to test if a broadly neutralising antibody (VRC01), given intravenously, can prevent HIV acquisition. </p>
<p>A broadly neutralising antibody is an antibody that has been found to neutralise or inactivate HIV in non-clinical experiments. Study participants are receiving intravenous infusions of the VRC01 broadly neutralising antibody every eight weeks.</p>
<p>This is the furthest that a clinical trial testing the effectiveness of a broadly neutralising antibody in preventing HIV acquisition in people has progressed. These studies can potentially clarify what level of neutralisation a vaccine or antibody-based method of HIV prevention needs to achieve and maintain to provide sustained protection.</p>
<h2>Vaccine</h2>
<p>The Uhambo trial is currently underway in South Africa and aims to enrol 5400 healthy, HIV-negative men and women aged between 18 and 35 years. This clinical trial involves a new version of the only HIV vaccine candidate ever shown to provide some protection against the virus. That vaccine candidate was investigated in the RV144 clinical trial from <a href="http://www.aidsmap.com/The-RV144-trial/page/2028003/">2003 to 2006</a> in Thailand led by the U.S Military HIV Research Program and the Thai Ministry of Health.</p>
<p>The Thai trial delivered landmark results in 2009 when it found, for the first time, that a vaccine could confer – albeit modest – protection against HIV.</p>
<p>The Uhambo regimen aims to provide greater and more sustained protection than the RV144 regimen and has been adapted to the HIV subtype that predominates in southern Africa.</p>
<h2>Immune responses</h2>
<p>The <a href="https://www.imbokodo.org.za/">Imbokodo</a> study (Imbokodo means “rock” in isiZulu) is formally known as the HVTN 705/HPX2008 trial. It’s being conducted in more than 2600 healthy, HIV-negative women in South Africa, Malawi, Mozambique, Zambia, and Zimbabwe aged between 18 and 35.</p>
<p>The vaccine regimen being tested in this trial is based on “mosaic” immunogens. These are vaccine components derived from strains of HIV from different regions of the world. This approach has been designed to induce immune responses against a wide variety of global HIV strains.</p>
<h2>Way forward</h2>
<p>Our scientific journey is remarkable. </p>
<p>But there is some way to go before we know the full impact of these trials. All three trials are building on important breakthroughs over the past two decades. We hope that out of these three areas of exploration clarity will emerge that brings the world closer to solving what is required to protect against HIV.</p>
<p>If any of the vaccines or antibodies are effective, it will unleash an enormous explosion in scientific enquiry to improve, adapt and, most importantly, bring a new form of HIV prevention to people.</p><img src="https://counter.theconversation.com/content/118734/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Glenda Gray is the deputy chairperson of the Orange Babies Charity in South Africa, director of HCRISA, president and CEO of the South African Medical Research Council and a board member at the NRF. She is the Co-PI of the HIV Vaccine Trials Network and Director of HVTN International Programs.</span></em></p>Researchers around the world are working hard to find a vaccine that is safe and effective.Glenda Gray, Research Professor, Perinatal HIV Research Unit and President, South African Medical Research CouncilLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1135922019-03-28T13:53:37Z2019-03-28T13:53:37ZWhy ending HIV still rests on a working cure – as well as prevention<figure><img src="https://images.theconversation.com/files/266131/original/file-20190327-139361-yx3de3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">New HIV infections continue to drive the epidemic.</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>The global AIDS response has made significant progress in reducing HIV infections and AIDS-related deaths. New HIV infections dropped by <a href="http://www.unaids.org/en/resources/fact-sheet">16%</a> from 1.9 million 2010 to 1.6 million in 2017. And the number of AIDS-related deaths decreased from 1.4 million to 940 000 in the same period.</p>
<p>But HIV/AIDS has not been brought under control and new infections continue to drive the epidemic. AIDS remains a leading <a href="http://www.aho.afro.who.int/sites/default/files/Atlas%202018-eng_1.pdf">cause of death</a> in Africa.</p>
<p>Even if new infections are prevented, <a href="http://www.unaids.org/en/resources/fact-sheet">36.9 million</a> people with HIV around the world must take antiretroviral treatment to live a healthy life. While treatment is now as simple as taking a single pill a day, there are still many challenges to daily adherence, including ongoing stigma. </p>
<p>An ultimate solution would be a workable cure. At the recent Conference on Retroviruses and Opportunistic Infections researchers <a href="http://www.aidsmap.com/page/3463421/">confirmed</a> the second ever case of HIV remission or “cure”. Known as the “London patient”, the person went into remission after a stem cell transplant as part of his treatment for cancer. He emerged from the procedure free of both his life-threatening Lymphoma and need for anti-HIV therapy.</p>
<p>The <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287108/">“Berlin patient”</a>, Timothy Brown, made global headlines in 2008 when scientists announced that he had been cured of HIV. It’s been 12 years since Brown was cured, after undergoing chemotherapy, total body irradiation and two stem cell transplants. Brown has been off treatment since the transplant and, after multiple tissue sampling procedures, has no remaining evidence of HIV reservoirs. The London patient is now the longest adult HIV remission after stem cell transplantation since the “Berlin patient”.</p>
<p>This development is a triumph for medical science as well as for the London patient. But, as exciting as it is, stem cell transplant is a gruelling and dangerous procedure and isn’t the magic bullet that will end HIV/AIDS. This is because it’s unfortunately not a scalable, feasible cure for the 39 million people currently living with HIV.</p>
<h2>Stem cell transplants</h2>
<p>The “London patient” was HIV positive, but it was his Hodgkin’s lymphoma that led to the need for a stem cell transplant. </p>
<p>The HI virus must link to a human host T cell in the blood or lymph nodes to replicate and infect the body. The virus attaches itself to a set of special links on the human T cell. If one of those links isn’t available due to genetic mutations, the virus may find it harder to get an infection foothold.</p>
<p>One such genetic mutation occurs in a link called the “CCR5 receptor”. Some people have this mutation naturally. The “London patient”, while on antiretroviral therapy and virally suppressed, had a bone marrow transplant as part of his lymphoma treatment. The bone marrow donor had the genetic mutation and passed it on to the “London patient” through the procedure, making it more difficult for HIV to replicate. </p>
<p>The “London patient” stopped taking antiretroviral therapy 16 months after the transplant. And 18 months later the virus remains undetectable. Usually, when a person with HIV stops treatment, the virus rebounds within the first month. </p>
<p>The achievement of remission in a second patient has provided further critical information to inform our understanding of how HIV infection occurs and the interaction between human cells and the virus. </p>
<p>As important as this work is, there’s no scalable cure yet and it’s also vital that researchers – and countries – keep putting effort into prevention. Important work continues to be done in this area.</p>
<h2>Prevention</h2>
<p>As HIV cure research goes on, so does research into HIV prevention tools, such as <a href="https://www.cdc.gov/hiv/basics/prep.html">Pre-exposure prophylaxis</a> (a daily pill that protects you from HIV infection) and the development of a <a href="http://data.unaids.org/publications/irc-pub01/jc072-ethicalcons_en.pdf">preventative vaccine</a>.</p>
<p>Two late stage vaccine <a href="http://www.mrc.ac.za/media-release/public-private-partnership-begins-hiv-vaccine-clinical-trial-sub-saharan-africa">trials</a> are underway in sub-Saharan Africa. Results will be available in 2022. A preventative vaccine would also greatly enhance efforts to being the HIV epidemic under control. </p>
<p>A working cure, together with a preventative vaccine would be the ingredients for HIV eradication. Until then we need to get effective, accessible treatment for all who need it, while deploying the many prevention tools at our disposal.</p><img src="https://counter.theconversation.com/content/113592/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Linda-Gail Bekker is Professor of Medicine and Deputy Director of the Desmond Tutu HIV Centre at the Institute of Infectious Disease and Molecular Medicine, University of Cape Town</span></em></p>Until then we need to get effective, accessible treatment for all who need it, while deploying the many prevention tools at our disposal.Linda-Gail Bekker, Professor of medicine and deputy director of the Desmond Tutu HIV Centre at the Institute of Infectious Disease and Molecular Medicine, University of Cape TownLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1077652018-11-30T11:41:51Z2018-11-30T11:41:51ZAIDS treatment has progressed, but without a vaccine, suffering still abounds<p>I mentioned to a friend, a gay man nearing 60, that <a href="https://www.worldaidsday.org">World AIDS Day</a>, which has been observed on Dec. 1 since 1988, was almost upon us. He had no idea that World AIDS Day still exists. </p>
<p>This lack of knowledge is a testament to the great accomplishments that have occurred since World AIDS Day was created 30 years ago. It is also due to an accident in the timing of his birth that my friend escaped the devastation wreaked by AIDS among gay men in the U.S., before there was antiretroviral therapy. </p>
<p>Many people have forgotten AIDS, but there are consequences to forgetting. The fight against AIDS is at a tipping point. Increasingly, there are signs that we may be heading in the wrong direction.</p>
<h2>Many successes, yet the grand prize is elusive</h2>
<p>I am a social epidemiologist with more than 20 years of research experience in HIV and STD prevention. I am also the founder of <a href="https://www.youtube.com/c/TheBasicswithDrMo">The Basics with Dr. Mo</a>, a sex health communications project that translates prevention science directly for people who need it most.</p>
<p>It is true that global HIV/AIDS success stories abound: Mother-to-child transmission can be reduced to <a href="http://www.who.int/hiv/topics/mtct/en/">below 5 percent</a>, 75 percent of people living with HIV know their status and <a href="http://www.unaids.org/en/resources/fact-sheet">59 percent receive antiretroviral therapy</a>. </p>
<p>Most recently, Pre-Exposure Prophylaxis (PrEP) – the use of antiretrovial drugs to prevent HIV infection among those exposed – has proved to be a <a href="https://www.cdc.gov/hiv/risk/prep/index.html">successful prevention approach</a>.</p>
<p>Yet the prize – a vaccine that can prevent HIV infection – remains elusive, and makes impossible the use of the only known strategy to have ever eradicated an infectious disease: widespread vaccination. That disease was smallpox, in 1980.</p>
<h2>The seeds of unease</h2>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/247810/original/file-20181128-32197-1302x3v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/247810/original/file-20181128-32197-1302x3v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=404&fit=crop&dpr=1 600w, https://images.theconversation.com/files/247810/original/file-20181128-32197-1302x3v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=404&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/247810/original/file-20181128-32197-1302x3v.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=404&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/247810/original/file-20181128-32197-1302x3v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=508&fit=crop&dpr=1 754w, https://images.theconversation.com/files/247810/original/file-20181128-32197-1302x3v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=508&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/247810/original/file-20181128-32197-1302x3v.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=508&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A demonstration for AIDS advances in July 2018 in The Netherlands, with Princess Margaret Van Orange pictured at the center.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/amsterdamnetherlands-july-232018-princess-mabel-van-1140466079?src=dBNVXnXsHdBScshgvjTuTA-1-19">Paolo Amorim/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>Despite the lack of a vaccine, in 2016 United Nations member states adopted a <a href="http://www.unaids.org/en/resources/presscentre/pressreleaseandstatementarchive/2016/june/20160608_PS_HLM_PoliticalDeclaration">political declaration</a> on ending the AIDS epidemic by 2030. </p>
<p>As part of the accountability framework, interim 2020 goals set a target of 500,000 new HIV infections for that year. A review of the most recent data estimated <a href="http://www.unaids.org/en/resources/documents/2018/unaids-data-2018">1.8 million new HIV infections</a> in 2017, exactly the <a href="http://www.unaids.org/en/resources/documents/2017/20170720_Core_epidemiology_slides">same number as in 2016</a>.</p>
<p><a href="https://www.bbc.com/news/health-44884593">Prominent scientists</a> have already begun to question the ability to eradicate AIDS by the 2030 deadline, and concede that the situation has stagnated. The attainment of eradication looks bleak, without the aid of either an effective vaccine or the immediate large-scale promotion and utilization of existing prevention tools (i.e., condoms, voluntary circumcision and potentially PrEP). Given that the vast majority of new HIV infections are sexually transmitted and that <a href="http://www.unaids.org/en/resources/presscentre/featurestories/2015/july/20150702_condoms_prevention">condoms have played a decisive role</a> in the global control of HIV transmission, ongoing condom availability and use will be essential to future eradication.</p>
<p>Condoms – both male and female – remain a <a href="https://www.cdc.gov/std/hiv/stds-and-hiv-fact-sheet-press.pdf">highly effective mechanism</a> of HIV/AIDS prevention, as well as of other sexually transmitted infections that greatly enhance the risk of HIV transmission. </p>
<p>Condom use is also strongly advised by global public health institutions, including the <a href="http://www.who.int/hiv/mediacentre/news/condoms-joint-positionpaper/en/">World Health Organization</a> and the <a href="https://www.cdc.gov/hiv/basics/prevention.html">U.S. Centers for Disease Control and Prevention</a>, in conjunction will all other HIV prevention tools including PrEP, because of their lower levels of effectiveness in preventing transmission. </p>
<p>Condom availability is a different matter and varies greatly from country to country. Countries with the highest levels of HIV often rely heavily on donor support. According to the most recent data, in sub-Saharan Africa in 2013, only <a href="http://www.who.int/hiv/mediacentre/news/condoms-joint-positionpaper/en/">10 condoms were available</a> annually for every man aged 15 to 64 (as compared with the recommended 50 to 60), and, on average, there was one female condom available for every eight women. Funding required to maintain – let alone scale up – HIV commitments, particularly those dedicated to prevention, are <a href="https://www.avert.org/professionals/hiv-around-world/global-response/funding">increasingly uncertain.</a></p>
<h2>The hydra, sprouting new heads</h2>
<p>Even though condoms are an extremely effective barrier method, it is usage that makes condoms efficacious in preventing HIV transmission. Reported condom use varies considerably around the world, and ranges from 80 percent use by men in Namibia and Cambodia to less than 40 percent usage by men and women in other countries, including some highly affected by HIV such as Sierra Leone and Mozambique. </p>
<p>Age plays a role, too. Among young people aged 15 to 24, <a href="http://www.who.int/hiv/mediacentre/news/condoms-joint-positionpaper/en/">condom use at last sex varies</a> from more than 80 percent in some Latin American and European countries to less than <a href="http://www.who.int/hiv/mediacentre/news/condoms-joint-positionpaper/en/">30 percent in some West African countries</a>. In the U.S., condom use is at the lower end of the spectrum: Only one-third of the population uses condoms, a number that has not changed significantly over the past two decades.</p>
<p>The majority – 66 percent – of the <a href="https://www.avert.org/global-hiv-and-aids-statistics">world’s HIV/AIDS cases</a> are in sub-Saharan Africa, where there has been much progress, particularly with the provision of antiretroviral therapy.</p>
<p>However, there are worrying signs in other parts of the world. There has been <a href="http://www.unaids.org/en/resources/documents/2018/unaids-data-2018">little change in new HIV infections</a> in countries outside of sub-Saharan Africa between 1990 and 2017. </p>
<p>In fact, six of the 10 most populous countries in the world have experienced <a href="http://www.unaids.org/en/regionscountries/countries">10 percent to 45 percent increases in new HIV infections since 2010</a>: Russia, China, Brazil, Pakistan, Mexico and Bangladesh. Even in countries such as the U.S., where new HIV infections have decreased by 8 percent overall, the rates of change are unevenly distributed. For example, <a href="https://www.cdc.gov/hiv/statistics/overview/ataglance.html">young African-American men</a> who have sex with men show no decrease in new infections; African-American gay and bisexual men represent the largest percentage of new HIV infections: more than one-quarter. </p>
<p>The increased provision of antiretroviral therapy to people living with AIDS has had a huge impact on extending life and in preventing new HIV infections. However, there remains 25 percent of the population who live with HIV, about 9 million people, who do not know their status. </p>
<p>While we have been necessarily focused on the head of the hydra in sub-Saharan Africa, other hydra heads are beginning to make their presence known, many in countries ill-prepared to deal with increases in the number of new HIV infections. </p>
<p>In the absence of a vaccine, behavior change in the form of condom use promotion, acceptance and adoption, at a scale that many gay men utilized during the peak of the AIDS epidemic in the industrialized world, will need to occur. There are many challenges: continued stigma and gender inequality, not to mention issues of availability, distribution and proactive, nonjudgmental promotion. </p>
<p>We must not forget. Progress on reducing the rate of new HIV infection has been done before. It can be done again, but only if we take forceful, funded action now.</p><img src="https://counter.theconversation.com/content/107765/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Maureen Miller does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>World AIDS Day is Dec. 1. With many advances in preventing and treating the disease, the disease has fallen from top of mind for many. An epidemiologist explains why that could be dangerous.Maureen Miller, Adjunct Associate Professor of Epidemiology, Columbia UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/888502017-12-28T04:28:32Z2017-12-28T04:28:32ZKenya’s HIV progress report: good progress, but also big gaps<figure><img src="https://images.theconversation.com/files/198304/original/file-20171208-27698-1si7940.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Antiretroviral treatment prevents the virus from multiplying and prolongs the lives of HIV positive people.</span> <span class="attribution"><span class="source">Thomas Mukoya/Reuters</span></span></figcaption></figure><p>The World Health Organisation (WHO) has clear markers on the road to controlling the global HIV/AIDS pandemic. By 2020, about nine out of every ten people should <a href="http://www.who.int/mediacentre/factsheets/fs360/en/">know their HIV status</a>. Nine out of ten HIV positive people should be on <a href="http://www.who.int/mediacentre/factsheets/fs360/en/">antiretroviral treatment</a> (ARVs) and the virus should not be detectable in their blood.</p>
<p>And by 2030, the WHO says, there should be no new infections, no AIDS-related deaths and no stigma or discrimination related to the virus. </p>
<p>These are all good goals and important ways to measure how countries are progressing. In Kenya, where I live and conduct <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=manguro+g">my research</a>, there has been some progress, but more must be done. We see progress in reducing new infections among adults, providing preventive medication and providing oral self-testing for HIV. </p>
<p>But more must be done to reduce new infections among adolescent girls and young women, female sex workers and men who have sex with men.</p>
<h2>Fewer new infections, more people on treatment</h2>
<p>Kenya’s latest <a href="http://nacc.or.ke/wp-content/uploads/2016/11/Kenya-AIDS-Progress-Report_web.pdf">HIV progress report</a> shows that new infections are dropping.</p>
<p>There were <a href="http://nacc.or.ke/wp-content/uploads/2016/11/Kenya-AIDS-Progress-Report_web.pdf">40% more</a> people on antiretroviral treatment in 2017 than there were four years ago. Antiretroviral treatment prevents the virus from multiplying and prolongs the lives of HIV positive people. It also lowers the risk of transmission from HIV positive to HIV negative people.</p>
<p>Currently, 66% of the <a href="https://www.standardmedia.co.ke/health/article/2001255406/good-news-for-kenyans-living-with-hiv-aids">1.5 million people</a> living with HIV in Kenya are on antiretroviral treatment. The goal is to have at least <a href="http://nascop.or.ke/hivforum/">90% on treatment by 2020</a>. </p>
<p>This strategy is based on <a href="http://www.who.int/mediacentre/news/releases/2015/hiv-treat-all-recommendation/en/">WHO recommendations</a>, which call for a person to start treatment immediately after testing positive. Previously it was recommended that people start ARVs only after their CD4 cells (blood cells which fight infection) dropped below 500 cells per cubic millimetre of blood. </p>
<h2>HIV self-testing strategy</h2>
<p>One of the biggest changes in Kenya’s strategy this year was the introduction of guidelines for <a href="https://www.standardmedia.co.ke/health/article/2001238625/hiv-home-test-kits-now-in-kenya">oral HIV self-testing</a>. </p>
<p>People can test themselves for HIV using their saliva. In most African countries, self-testing is mostly used for research. Kenya is the first country to introduce a plan to make it available nationally. The aim is to increase the number of people getting tested and link those who are HIV positive to care and treatment. </p>
<p>The self-testing kits became available in public and private health facilities and in some pharmacies countrywide from July and could be bought at subsidised prices. They will help fill a gap in HIV testing. The number of Kenyan adults who have ever tested for HIV has <a href="http://nacc.or.ke/wp-content/uploads/2016/11/Kenya-AIDS-Progress-Report_web.pdf">grown</a> between 2008 and 2016, from roughly a quarter of adults to more than half.</p>
<p>But certain populations, such as <a href="https://www.avert.org/professionals/hiv-social-issues/key-affected-populations">men who have sex with men, sex workers and adolescents</a>, have low testing rates. This is mostly because they may experience stigma and discrimination when seeking routine HIV services. </p>
<p>Self-testing is a way to <a href="https://www.avert.org/professionals/hiv-social-issues/stigma-discrimination">avoid stigma and discrimination</a> and boost people’s links to care.</p>
<p>But the process has some problems, including the <a href="http://www.who.int/hiv/pub/hiv_self-testing_kpp_2015.pdf">absence of counselling</a> before and after testing. Without good counselling, people who test positive may not seek treatment and care. This can be solved by community health volunteers following up at people’s homes. They already support family planning, maternal health and child health and can help people who use the kit and test positive.</p>
<h2>Preventive medicine</h2>
<p>Kenya also launched <a href="http://www.health.go.ke/2017/05/govt-launches-a-new-arv-drug-for-hiv-negative-people-and-innovative-hiv-self-testing-to-revitalize-hiv-prevention/">guidelines</a> on the use of pre-exposure prophylaxis (PrEP). This comes in several forms, including vaginal rings and gels. The most common is a tablet taken daily.</p>
<p>PrEP is given to people in high-risk groups who are HIV negative to prevent them from contracting the virus. They may be <a href="http://www.nation.co.ke/lifestyle/saturday/When-positive-and-negative-come-together/1216-2974118-wltx9r/index.html">in relationships</a> where one partner is infected with HIV and the other is not. Others at high risk are male and female sex workers. </p>
<p>Kenya and <a href="https://www.avert.org/professionals/hiv-around-world/sub-saharan-africa/south-africa">South Africa</a> are the only countries in Africa that offer this type of treatment as part of a <a href="https://www.nap.edu/read/5177/chapter/8">national HIV prevention strategy</a>. </p>
<h2>On alert for infections among youth</h2>
<p>Kenya also started paying more attention to young people. More than half of the world’s new HIV infections are in the group aged between <a href="http://www.unaids.org/sites/default/files/media_asset/youngpeoplehivaids_en_0.pdf">15 and 24</a>.</p>
<p>In Kenya, too, 51% of <a href="http://nacc.or.ke/wp-content/uploads/2016/11/Kenya-AIDS-Progress-Report_web.pdf">new adult HIV infections</a> were in this age group by 2016 – a steep increase from 29% in 2013. It is also the only age group in Kenya that has recorded an increase in new infections. This is because young people tend to have little knowledge about the virus and the behaviours that increase their chances of infection. </p>
<p>People in this age group often have sex while under the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728293/">influence of alcohol</a>, which can result in poor decisions. Girls in this age group also have transactional sex with older men.</p>
<h2>Looking ahead</h2>
<p>Kenya has made great strides against HIV and in providing care to all HIV infected people. But more work is needed.</p>
<p>The country must step up its efforts to get more men tested. It will also be important to get more adolescents and young girls to adopt HIV prevention methods, and to reduce stigma and discrimination among sex workers and men who have sex with men.</p><img src="https://counter.theconversation.com/content/88850/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Griffins Manguro does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>HIV self-testing is a potential strategy to overcome access to testing. However, there are emerging concerns on the lack of counselling, possible user error and accuracy of the kits.Griffins Manguro, PhD candidate, Ghent UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/867362017-11-23T14:24:02Z2017-11-23T14:24:02ZFour big insights into HIV/AIDS that provide hope of finding a vaccine<figure><img src="https://images.theconversation.com/files/195865/original/file-20171122-6027-1oe0fkn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>HIV remains one of the continent’s most intractable health challenges.
Tremendous progress is being made to understand the virus, the immune mechanisms that contribute to its control and for new antiretroviral drugs and vaccines to be developed to treat and prevent HIV. </p>
<p>But much remains to be done to overcome the health and economic devastation of the epidemic. African researchers have been performing cutting-edge research to contribute to addressing these problems. The sub-Saharan African Network for TB/HIV Research Excellence has been at the forefront of this research and has provided some important insights into how the virus spreads as well as the immune mechanisms that enable some people to control the virus without antiretroviral drugs. </p>
<p>This knowledge could be translated into effective vaccines or other novel interventions to prevent the spread of the virus or achieve a functional cure where people are able to live without antiretroviral drugs at least for a while. </p>
<p>Although the goals of a vaccine or cure remain elusive, the research being done makes these goals appear increasingly likely.</p>
<hr>
<h2>Immune systems are critical</h2>
<p>A major plank of <a href="http://jvi.asm.org/content/early/2016/05/12/JVI.00276-16.abstract">our research</a>, in collaboration with others, has been around understanding what mechanisms the body uses to control HIV – particularly in the early phase of infection. </p>
<p>Our research shows that within a few weeks of becoming HIV infected, almost all people have a very robust immune response through cells known as<a href="https://www.ncbi.nlm.nih.gov/pubmed/26362266"> cytotoxic T lymphocytes, or killer CD8 T cells</a>. These cells are able to partially suppress HIV. </p>
<p>But when most people are exposed to the virus, their immune systems are mostly skewed to respond to regions of HIV that are highly variable. This allows the virus to easily change to escape immune recognition. </p>
<p>The killer CD8 T cells produced during the acute phase are also<a href="http://journals.lww.com/aidsonline/Citation/2015/01020/Broad_and_persistent_Gag_specific_CD8__T_cell.4.aspx"> highly defective</a>. They become exhausted and die off easily, which enables the virus to persist. </p>
<p>But we’ve discovered an interesting twist. Some people have a genetic makeup that facilitates development of very good CD8 killer T cell immune responses. These rare individuals can control the virus without antiretroviral drugs. These are also a few people who appear to control the virus without using CD8 killer T cells, and we are in hot pursuit of the mechanisms that control the virus in such individuals. </p>
<p>This ground-breaking research is vital because understanding how the immune system is able to control the virus – either by killer T cells or other mechanisms – could lead to effective HIV vaccines or cures.</p>
<h2>HIV evades or adapts to immune pressure</h2>
<p>Our work has shown that HIV is very adept at evading the body’s immune responses to the virus. The main way it does this is by <a href="http://jvi.asm.org/content/86/6/3193.abstract">developing mutations</a> that enable the virus not to be recognised by a person’s immune system. At the same time it continues to replicate and reproduce itself. </p>
<p>Our work shows that although this immune escape is common, in some cases the virus develops mutations that cripple it, making it unable to continue <a href="http://jvi.asm.org/content/85/8/3996.abstract">replicating efficiently</a>. </p>
<p>We have identified some of the regions of virus that are vulnerable that cripple the virus if it is targeted by the immune system. These regions of viral vulnerability could be included in HIV vaccines so that the body makes an immune response against these regions of the virus ensuring that the immune system cripples the virus. This may be an effective way to make an HIV vaccine or achieve natural control of the virus in those already infected. </p>
<p>But that’s not the end of the story. There’s a further complication because we’ve also discovered that the virus can acquire new mutations that <a href="http://jvi.asm.org/content/84/20/10820.abstract">restore its ability to replicate</a> efficiently. But we think that there may be ways to block or limit escape. The viral regions of vulnerability that we have identified could be good candidates for vaccines designed to disable virus replication.</p>
<h2>Genetic and viral factors matter</h2>
<p>There is a lot of variability in HIV disease progression. </p>
<p>Without antiretroviral therapy, most HIV infected people develop full blown AIDS within 10 years. But some people succumb more rapidly, within two years. There is also a rare group of individuals known as elite controllers who have been shown to live with HIV for more than 20 years with almost undetectable viral load and without developing AIDS. </p>
<p>Our group and others have shown that <a href="https://www.ncbi.nlm.nih.gov/pubmed/19996938">variability in disease progression</a> can be explained by differences in genetic factors that govern the immune response. </p>
<p>Some people are naturally equipped with better genetic makeup that enables them to develop a very good immune response that can fight off the virus and control it. But in almost all cases, a robust and good immune response eventually leads to immune escape in the virus, which means that the virus acquires changes that enable it to hide from the immune system. </p>
<p>But some of these mutations can <a href="https://www.nature.com/articles/nature07746">cripple the virus</a>. </p>
<p>People infected with HIV but with superior immune responses – or with a virus that has been crippled by the immune system end up living long healthy lives without antiretroviral drugs. </p>
<p>This kind of knowledge is very useful for the potential development of vaccines.</p>
<h2>The influence of viral genetic factors</h2>
<p>One of the defining characteristics of the HIV/AIDS epidemic is that there are multiple genetic strains (known as subtypes or clades) that are unevenly spread throughout the world. </p>
<p>We have demonstrated that some regions of HIV differ in biological activity according to HIV subtypes, and these differences are consistent with reported differences in rates of disease progression. </p>
<p>For example, our work shows that there are <a href="http://jvi.asm.org/content/early/2017/06/15/JVI.00518-17.abstract">characteristics in the Gag region</a> (a specific part of the HIV virus) that make subtypes B and D able to replicate more efficiently than subtypes A and C, which may explain why subtypes B and D are associated with <a href="http://jvi.asm.org/content/early/2017/04/13/JVI.00253-17.short">faster disease progression</a> compared to A and D in some population-based studies. </p>
<p>Paradoxically, it appears that the subtypes that <a href="https://www.ncbi.nlm.nih.gov/pubmed/25013080">replicate less efficiently</a> such as A and C are more successful in infecting more people, perhaps because infected people live longer with these viruses. </p>
<p>The work helps to explain how HIV affects the rate of disease progression in individuals and how in general epidemics spread and change over time. This kind of knowledge is important for predicting the spread of epidemics and how to combat outbreaks so that they do not cause massive suffering as has been the case with HIV and viruses such as Ebola.</p><img src="https://counter.theconversation.com/content/86736/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Thumbi Ndung'u receives funding from the Gates Foundation, Gilead Sciences, the South Africa National Research Foundation, The National Institutes of Health, the Victor Daitz Foundation and the Wellcome Trust. He is affiliated with the University of KwaZulu-Natal, the Africa Health Research Institute and the Ragon Institute of MGH, MIT and Harvard University. </span></em></p>To get an effective vaccine for HIV/AIDS, scientists need to understand exactly how the virus works and immune system responds to it. African scientists have come one step closer.Thumbi Ndung'u, Programme Director for the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), University of KwaZulu-NatalLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/867872017-11-08T11:04:24Z2017-11-08T11:04:24ZHIV remission: the quest to turn lessons from exceptional cases into solutions<figure><img src="https://images.theconversation.com/files/193738/original/file-20171108-2025-113phwk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A 3D depiction of HIV which attacks T-cells in the body.</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>The case of an <a href="https://www.wits.ac.za/news/latest-news/research-news/2017/2017-07/sa-child-living-with-hiv-maintains-remission-without-antiretroviral-drugs-since-2008.html">HIV-infected child</a> in South Africa who has been in remission for nearly nine years without taking any antiretroviral drugs has provided further proof that HIV remission is possible. </p>
<p>Remission (also known as functional cure) is a term that describes the body’s ability to <a href="https://www.viivhealthcare.com/inside-viiv-healthcare/part-1-what-does-cure-and-remission-mean-in-hiv.aspx">control HIV to undetectable levels</a> without the use of antiretroviral therapy. Remission refers to a state following treatment that is then stopped. Less than 1% of people who are infected with HIV are <a href="https://www.ajol.info/index.php/cme/article/viewFile/80842/71076">naturally able to do this</a> without any treatment.</p>
<p>The South African case – the first reported instance of HIV remission in an African child, and only the third case in the world – has raised many questions: what makes this child so unique? Is it the virus? Is it the host? Were the drugs essential to this outcome? </p>
<p>I am part of a team of researchers that’s investigating this unusual case, an endeavour that’s intensified this year. What we found were signs that HIV can be suppressed naturally for a long time after someone has been on a short spell of treatment. We presented <a href="http://programme.ias2017.org/Abstract/Abstract/5836">our findings</a> at the 9th International Aids Society conference on HIV science in Paris in July. </p>
<p>The discovery is only the first bit of a puzzle we are piecing together – on an ongoing basis – into what exactly causes suppression. It opens the door for researchers to establish how to make long-term remission possible for other people. This is a critical part of making HIV a manageable disease.</p>
<h2>A remarkable outcome</h2>
<p>The child – whose gender has not been disclosed – was born in 2007 to an HIV-infected mother. The child was diagnosed as HIV-positive at one month of age and then enrolled in a clinical trial called CHER (Children with HIV Early Antiretroviral Therapy). The trial ran from 2005 to 2011. </p>
<p>The child – randomly selected in the trial to receive early treatment – started anti-retrovirals just after turning two months old. The child was one of 143 babies who received early treatment for 40 weeks.</p>
<p>The virus rebounds within weeks in most people who stop taking the drugs. HIV attacks the T-cells, forcing the person’s CD4 count to drop significantly. But in this instance the child’s CD4 count remained at the level of a healthy child’s after the drugs were stopped. And has remained so ever since. </p>
<p>More than eight and half years later the child has no symptoms of infection. The virus has not rebounded and it cannot be detected with standard methods. </p>
<p>To establish what led to this outcome the child’s blood samples have been subjected to detailed virological, immunological and genetic studies to understand the state of the virus in the body. </p>
<p>The child had high levels of the virus in the blood before starting treatment at two and a half months. This suggested that the child had an actively replicating virus at the time. </p>
<p>But by the time the child was nine and a half years old, there were only small traces of virus in the cells and the virus was no longer actively replicating.</p>
<p>In addition, we saw signs that the child’s immune system had identified the virus before. At this stage we don’t know which parts of the immune system were active close to the time of infection and treatment. Understanding both the response now – and which immune responses were initially involved – is critical to help us develop a vaccine, or other strategies, that could solicit a similar immune response in other people. </p>
<h2>What the three rare finds tell us</h2>
<p>The three remission cases have provided researchers with different lessons. The first case was a baby born in <a href="https://theconversation.com/sad-tale-of-hiv-return-in-cured-baby-comes-as-new-study-suggests-virus-seeds-early-29433">Mississippi in 2010</a> who was HIV infected at birth. The baby started treatment 30 hours after she was diagnosed and continued treatment until she was 18-months-old. The virus remained under control – that is below detectable levels – for the next 27 months. But then it rebounded. </p>
<p>This case highlighted that remission was possible for a period of time.</p>
<p>The second case involved <a href="http://www.nature.com/news/french-teenager-healthy-12-years-after-ceasing-hiv-treatment-1.17951">a child born in France in 1996</a>. Treatment was started at three-months-old but then stopped when the child was about six years old. The virus remains under control. This case showed that long-term remission is possible.</p>
<p>Our case further confirms that long term remission is possible, even with a short period of treatment. </p>
<p>Since the first remission case, <a href="http://impaactnetwork.org/studies/P1115.asp">several trials</a> are trying to establish whether starting babies identified with HIV at birth with treatment within 48 hours of the discovery could help. </p>
<p>The thinking is that intercepting HIV as close to the time of infection as possible can result in a smaller reservoir of virus in the cells. This in turn could increase the chances of remission for sustained periods of time or maybe even permanently. </p>
<h2>Take home messages</h2>
<p>There is no doubt that early treatment is desirable. It reduces chances of transmission, protects the immune system from damage caused by the virus, keeps virus reservoirs small and improves general health and the chances of survival.</p>
<p>But we know that, if treatment is stopped, early treatment isn’t enough for most people to achieve remission. Other interventions need to be sought. </p>
<p>For most infected patients, treatment starts long after they are infected. This presents an even greater challenge to achieve remission. </p>
<p>The South African child tells us that other factors, unique to an individual or to very rare groups of individuals, are important. The clues are there. We need to find what these factors are from the few and turn them into solutions for the many.</p>
<p>And, more important than anything, is that patients don’t stop their treatment until we have all the pieces of the puzzle in place.</p><img src="https://counter.theconversation.com/content/86787/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Caroline T. Tiemessen receives research funding from the South African Medical Research Council (MRC) Strategic Health Innovation Partnerships (SHIP) programme, Department of Science and Technology/National Research Foundation (DST/NRF) South Africans Chair Initiative (SARChI) programme, Poliomyelitis Research Foundation (PRF), and the US National Institutes of Health (NIH). </span></em></p>A South African child, who has been in HIV remission for nearly nine years, could help researchers understand how to make remission possible for millions of other HIV positive people.Caroline T. Tiemessen, Head: Cell Biology, Centre for HIV and STIs, National Institute for Communicable DiseasesLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/692782016-12-11T19:07:32Z2016-12-11T19:07:32ZHow HIV’s evasion tactics could help fight the flu<figure><img src="https://images.theconversation.com/files/149003/original/image-20161207-25721-3burj8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">HIV plays hide and seek with the body's immune system to evade detection. But we can learn from its tactics to make a range of vaccines against infectious diseases.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/175902236?src=Bafv5GAoP-GQP_1jSjMBtg-1-61&id=175902236&size=medium_jpg">from www.shutterstock.com</a></span></figcaption></figure><p>One vaccine. Lifetime immunity. This is the goal for thousands of researchers tackling one of the world’s most evasive pathogens – human immunodeficiency virus (<a href="https://theconversation.com/au/topics/hiv-677">HIV</a>).</p>
<p>HIV has foiled both the immune system and vaccines. However, the success of HIV at evading the immune system is leading to vaccine research that may help tackle other illnesses, like influenza, hepatitis C, and mosquito-borne malaria, dengue and West Nile virus.</p>
<p>So how can the way HIV shields itself from the immune system lead us to make new vaccines for other infectious pathogens?</p>
<h2>HIV hides from the immune system</h2>
<p>HIV has a number of different tricks to evade the immune system. During an immune response to infection, antibodies normally lock onto a target on the surface of the virus to disable the infectious threat. To avoid this, HIV changes its shape so a known target for antibodies is hidden within the virus. Antibodies scan the surface, but can’t lock onto their target.</p>
<p>HIV can also adapt to mimic other proteins in our bodies. It is critical the immune system identifies and attacks foreign pathogens, but not target and damage normal cells. So when HIV changes its structure to imitate a normal part of our body, the immune system is tricked into leaving it alone.</p>
<p>By using these methods HIV escapes elimination. So, HIV is still responsible for a significant global burden of disease, with <a href="http://www.who.int/hiv/en/">1.8 million</a> children living with HIV and <a href="http://www.who.int/hiv/en/">1.1 million people</a> who died of HIV-related causes in 2015.</p>
<h2>New generation vaccines to outsmart HIV</h2>
<p>“Elite controllers” are HIV patients whose immune systems are unusually good at controlling the virus. When researchers looked at their immune systems, they found <a href="http://science.sciencemag.org/content/341/6151/1168">rare antibodies</a> that bind many different versions of the virus. These antibodies are also stickier and more potent than normal antibodies, latching onto many different parts of the virus to get a good firm grip. So, these patients’ immune system can better prevent the virus multiplying rapidly and overwhelming the body. </p>
<p>The focus is now on developing a new generation of vaccines against HIV that teach the immune system how to make these rare antibodies.</p>
<p>Standard vaccines involve injecting someone with an inactive whole or part of the pathogen to form immunity. For HIV, researchers first need to identify the antibody best able to disarm multiple variations of the virus. Then, researchers will <a href="https://www.ncbi.nlm.nih.gov/pubmed/27617678">design</a> a vaccination strategy to prompt the immune response to make that unique antibody. This may involve multiple injections with slightly different versions of the vaccine to <a href="https://www.ncbi.nlm.nih.gov/pubmed/27610569">guide</a> the immune response.</p>
<p>Although this strategy will likely be tricky to implement globally, the benefit of being able to defeat viral evasion techniques will be a giant step in tackling this disease.</p>
<h2>The good news for tackling other crafty pathogens</h2>
<p>Vaccines that prompt the body to make these special antibodies may have broader implications for other difficult-to-fight infections.</p>
<p>The influenza virus can reemerge in a different structure to evade immunity formed during a previous infection; the malarial parasite produces hundreds of targets during an infection, which confuses the immune system, making it difficult to focus antibody production on the best target to clear infection; and dengue virus can <a href="https://theconversation.com/explainer-how-viruses-can-fool-the-immune-system-43707">manipulate the immune system</a> to produce antibodies for the wrong target, with potentially lethal consequences.</p>
<p>There is now an intense effort to find unique antibodies that can overcome the evasion techniques of influenza, malaria, dengue and hepatitis C. To do this, researchers screen thousands of individual immune cells to find the most potent antibody that simultaneously disables multiple variations of each pathogen. There has been some progress; researchers have recently identified an antibody that can protect against all <a href="https://www.ncbi.nlm.nih.gov/pubmed/25581790">four versions of the dengue virus</a>.</p>
<h2>What are the barriers?</h2>
<p>There are two main options for using these antibodies – giving them directly to <a href="https://theconversation.com/antibody-injections-could-be-stepping-stone-to-hiv-vaccine-58858">patients already infected with a pathogen</a> or using vaccines to prevent infection in the first place and perhaps one day eradicating the disease. </p>
<p>A number of hurdles remain for vaccine development. During HIV infection, the best antibodies can take as long as a year after infection to develop their power. Acquired immunity to malaria takes multiple infections and many years to develop, leaving young children in particular at risk of dying. It is not yet known whether we can design vaccines to speed up the process.</p>
<p>Immunity also works because immune memory cells are faster and better at fighting an infection before it can damage the body. </p>
<p>Unfortunately, HIV, malaria and hepatitis C can all exhaust immune memory cells; they fight for so long they effectively retire. It’s unclear whether a vaccine for HIV will make effective immune memory cells, or whether exhausted memory cells may stop vaccines working effectively. </p>
<p>Despite these barriers, the knowledge gained in the past decade has made the once impossible task of generating vaccines for evasive pathogens appear to be in reach.</p><img src="https://counter.theconversation.com/content/69278/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kim Jacobson receives funding from the National Health and Medical Research Council and is the current treasurer of the Australasian Society for Immunology.</span></em></p>Researchers are learning how HIV hides from the immune system to develop a new generation of vaccines for seemingly unrelated diseases, like the flu.Kim Jacobson, Senior Research Fellow, Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/679872016-11-01T13:32:51Z2016-11-01T13:32:51ZExplainer: the how, what and why of the latest HIV vaccine trial<figure><img src="https://images.theconversation.com/files/144042/original/image-20161101-8691-1jgg4qi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p><em>As the global quest for an HIV vaccine continues, Linda-Gail Bekker explains the significance of the <a href="http://m.news24.com/news24/SouthAfrica/News/hiv-vaccine-historic-trial-begins-20161029">latest large-scale trial</a> underway in South Africa.</em> </p>
<p><strong>What’s the significance of the trial for the global fight against HIV?</strong></p>
<p>The world needs an HIV vaccine. Our prevention toolbox is better than it has ever been. But there is increasing recognition that the world needs to scale up primary HIV prevention.</p>
<p>Effective vaccination is the poster child for prevention – it is the thing we are missing. If we can get that we can talk about eliminating HIV across the world. </p>
<p>It is fantastic that once again a vaccine is being put into the field. The only way scientists can really learn and understand human immunity is through human clinical trials. I think everyone agrees that laboratory and animal research can only take us so far. </p>
<p>There has been a decrease in the incidence of HIV in some parts of the world. The best news is the impressive downturn in mother-to-child-transmission. </p>
<p>But this is an epidemic that needs constant surveillance because it is still on the rise in many parts of the world. We cannot be complacent. Reduction rates in adult infections are stalling. We are not on course to meet the targets set for 2030 to get the epidemic under control. </p>
<p>But we shouldn’t hang everything on getting a vaccine, as important as that is. The world also needs a primary prevention revolution. If we are really intent on getting the epidemic under control by 2030, we need a call to prevention action while working hard on a definitive vaccine. </p>
<p><strong>What does the trial entail? How will it be done?</strong></p>
<p>This trial – HVTN 702 – is based on a trial from <a href="http://www.aidsmap.com/The-RV144-trial/page/2028003/">Thailand in 2009</a> which showed a 31% reduction in HIV after three years. It is important to note that after 12 months the vaccines showed 60% efficacy. </p>
<p>In the South African study we are hoping to increase the potency and durability of its effect to reach at least a 50% reduction in HIV infection after three years. </p>
<p>There will be 5400 participants aged between 18 and 35 (the most at risk age group) at 15 sites across South Africa. And there are two vaccine products in the regime. The participants will get five shots over the first year. Some of the shots include just one product and some involve both products. The shots are given into the muscle of the upper arm by injection, much like a tetanus or measles vaccine.</p>
<p>This is an efficacy trial. The main question it will answer is: does the vaccine work? To get to this question, the trial is designed so that half of the cohort will get a sham vaccine and half will get a real vaccine, with neither research site staff nor participant knowing which. The cohort will then be followed up after three years when the number of infections in each cohort will be counted.</p>
<p>At that point we will ask whether more infections occurred in the one cohort compared to the other. We will then be able to conclude whether and by what margin the vaccine has been able to prevent HIV infections. That will give us an indication of the vaccine’s efficacy.</p>
<p>This trial also follows an initial “lead in” safety and immunogenicity trial (<a href="http://www.aids2016.org/Media-Centre/The-Latest/Press-Releases/ArticleID/62/New-vigour-in-HIV-vaccine-research-evident-at-AIDS-2016">HVTN100</a>) of the vaccine regimen conducted last year with 252 people in six sites in South Africa. This gave the green light for the HVTN 702 trial. </p>
<p><strong>How is this trial different from the one in Thailand?</strong></p>
<p>The vaccine being used in South Africa is very similar to the one used in an earlier trial in Thailand <a href="http://www.aidsmap.com/The-RV144-trial/page/2028003/">(RV144)</a>. The virus products in that vaccine – RV144 – were designed to reflect the HIV that is circulating in Thailand (subtype BE). In the last five years scientists have modified the inserts in the vaccine to be compatible to the subtype of the virus circulating in southern Africa (subtype C).</p>
<p>Apart from the different inserts, scientists have also changed the adjuvant, which is an agent often used with vaccines to give the immune system an additional boost. In Thailand the adjuvant alum was used. In South Africa we are using a well known adjuvant called MF59, which is also widely used in the flu vaccine. </p>
<p>The last thing we are doing differently in this trial is that the South African participants will receive an additional vaccine boost at 12 months. In Thailand everyone got all their boosts within the first six months. </p>
<p><strong>When will first results be known? And then what happens?</strong></p>
<p>It will take us 12 to 18 months to accrue participants. The study will end when all participants have completed three years of the vaccination regime. </p>
<p>During the three years there will be opportunities for a special safety committee to look at the data in an “unblinded” fashion to check whether we have a winner early on, whether the trial is not going to yield any meaningful results or if there are important safety concerns. </p>
<p>This is important because if the vaccine is shown to be working we will be able to move towards licensing the vaccine for HIV.</p>
<p>In addition, the minute we know it works we would want to do bridge studies in other parts of Africa and then in other parts of the world. </p>
<p><strong>Why is this trial being done in South Africa?</strong></p>
<p>The trial is a partnership between a number of entities, vaccine developers and funders, including the South African Medical Research Council. Southern Africa was chosen as the trial site because of the very high burden of infection in the region.</p>
<p>It is important to see if we can get a vaccine that works in the world’s toughest region. </p>
<p>Up to 300 young women get infected with HIV in South Africa every day. The overall prevalence in South Africa is 19.2% but we know there is a wide range across areas and some populations are more affected than others.</p>
<p>South Africa has <a href="http://www.unaids.org/en/regionscountries/countries/southafrica">7 million people with HIV</a>, almost <a href="http://www.avert.org/professionals/hiv-around-world/sub-saharan-africa/overview">one-fifth</a> of the global HIV positive population. It treats more people than any other country with anti-retrovirals, consuming one-quarter of global generics.</p><img src="https://counter.theconversation.com/content/67987/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Linda-Gail Bekker receives funding from a number of academic funding agencies including the NIH (USA). She is currently the President of the International AIDS Society.</span></em></p>For the next five years South Africa will be leading one of the latest large-scale trials for a vaccine for HIV.Linda-Gail Bekker, Professor of medicine and deputy director of the Desmond Tutu HIV Centre at the Institute of Infectious Disease and Molecular Medicine, University of Cape TownLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/511622015-11-29T13:54:53Z2015-11-29T13:54:53ZTwo trials signal pivotal point in fight against the AIDS epidemic<figure><img src="https://images.theconversation.com/files/103444/original/image-20151127-11640-t9nnyb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A women gets an HIV test. Sub-Saharan Africa accounts for the majority of the HIV deaths annually. </span> <span class="attribution"><span class="source">World Bank Collection/flickr</span></span></figcaption></figure><p><em>Foundation essay: This article is part of a series marking World Aids Day. Our foundation essays are longer than usual and take a wider look at key issues affecting society.</em></p>
<p>There is no doubt that the crisis caused by the HIV pandemic requires urgent and bold steps. While the roll-out of anti-retroviral therapy has had a significant impact on the epidemic, there are still 1.5 million deaths and two million new <a href="http://www.unaids.org/en/resources/campaigns/HowAIDSchangedeverything/factsheet">HIV infections</a> globally every year. In South Africa alone, there are <a href="http://www.unaids.org/en/regionscountries/countries/southafrica">more than six million</a> people living with HIV. Only 42% of these people are being treated with anti-retrovirals. </p>
<p>In the long-term, the use of anti-retrovirals to control the HIV epidemic is unrealistic. Our best hope for an AIDS-free future is the development of a vaccine. Two major clinical trials are set to begin in South Africa in 2016. Both seek to test whether antibodies, which circulate in blood and are part of our natural defence to infection, can prevent new HIV infections. </p>
<p>The first trial, called HVTN 702, relies on the classical approach of active immunisation. Here a vaccine designed to mimic an infection causes the body to make antibodies to HIV. </p>
<p>The second trial, called AMP or antibody-mediated protection, will run in parallel to the first trial. It will use manufactured antibodies that are infused into the body. This approach, called passive immunisation, has been employed for over a 100 years to treat a variety of infectious diseases. This has only recently become an option for HIV. This trial is unprecedented in HIV prevention research.</p>
<p>We are at a pivotal stage in HIV vaccine development. Conducting two large scale efficacy trials in the region of the world with the highest HIV prevalence heralds a new more aggressive approach to tackle what is our most serious public health threat. </p>
<h2>Active vaccination</h2>
<p>The HVTN 702 vaccine trial was inspired by the results of an earlier trial – <a href="http://www.aidsmap.com/The-RV144-trial/page/2028003/">RV144</a> – conducted in Thailand. This trial showed a modest 31% efficacy and provided the first ever indication that a vaccine against HIV may be possible. </p>
<p>This vaccine is now being tested in southern Africa, but it has been tailored to match the viruses circulating in this region. There are also other modifications that are intended to improve on the efficacy of the vaccine which will hopefully facilitate its licensure. </p>
<p>The vaccine comprises two components that stimulate the body’s disease fighting immune helper cells as well as antibodies. </p>
<p>The first, a cellular response, uses a harmless canarypox virus that has been engineered to carry small pieces of HIV. This tricks the body into thinking it is under attack so that it mounts an immune response to HIV. </p>
<p>For the other component – the antibody response – soluble protein derived from the outer envelope coat of the virus are recreated in the laboratory, and used to elicit antibodies to HIV. In RV144, individuals who developed antibodies to a small fragment of envelope called the variable region 1 and 2 (V1V2) had a reduced risk of HIV infection. As such, these immune responses are used to benchmark future trials. </p>
<p>Since the trial in South Africa is using a newly configured vaccine, it first needs to undergo safety and immunogenicity testing. As such, a small trial involving 252 healthy people at low risk of HIV infection is currently taking place.</p>
<p>If the results look promising then HVTN 702, the large efficacy trial that will be done in high-risk individuals, will proceed. For this, more than half the participants in the small safety trial must have V1V2 binding antibodies and HIV-specific helper cell responses. </p>
<p>The decision to go ahead with HVTN 702 will be made in the first quarter of 2016. If this happens, 5400 people will be enrolled at various clinical sites across South Africa. Half the participants in the trial will receive the vaccine, while the other half will receive a placebo, which contains no HIV components. Neither the participants nor the study co-ordinators will know who received the vaccine or placebo. This is known as a double-blinded randomized clinical trial, or RCT and is the “gold standard” for assessing whether a product actually works. </p>
<p>The participants will be followed for up to three years for evidence of HIV infection. If there are significantly fewer infections in those who received the vaccine, it will be considered efficacious and may be licensed. If the vaccine is able to reduce the number of infection by at least 50% it will be considered suitable for general use. It will also be expected to have a major impact on the HIV epidemic.</p>
<h2>Gaining new ground</h2>
<p>While HVTN 702 takes place, the antibody-mediated protection (AMP) trial will be conducted concurrently in the region. This trial will test a related but different concept: whether a pre-formed antibody (called VRC01), which was cloned from an antibody-producing cell isolated from an HIV-infected individual, can prevent HIV infection after it has been transferred into the body. </p>
<p>To participate in this trial, 1500 healthy HIV negative women who are at high risk of HIV infection will receive intravenous infusions every two months for 20 months. </p>
<p>This is also a randomized controlled trial and women will be split into three groups. The first 500 women will receive VRC01 at the higher dose while 500 will receive a lower dose of the antibody. The remaining 500 women will receive a placebo. The volunteers will be studied for over two years with HIV infection as an end-point. During the trial, they will be counselled on safe sexual practises.</p>
<p>Unlike the binding antibodies which are induced by vaccination, VRC01 is a broadly neutralizing antibody. This antibody targets the part of the viral envelope that is needed to bind and infect human cells (similar to a lock and key). Since it targets an essential part of the viral life cycle, this antibody shows excellent coverage and is able to block infection of the majority of global viruses, including those circulating in South Africa. VRC01 has already been shown to be safe in humans and to prevent infection in monkeys. </p>
<p>The purpose of this trial is to provide important proof-of-concept that broadly neutralizing antibodies can prevent HIV infection in humans. Although no vaccine has yet been able to stimulate these types of antibodies, many believe that a highly efficacious vaccine will depend on this. </p>
<p>In addition, this trial will provide an important benchmark for HIV vaccines by revealing the dose of antibody needed to protect an individual from HIV infection. If the trial is shown to work, it will open options to use antibodies as drugs to prevent HIV infection, which is similar to <a href="http://www.cdc.gov/hiv/basics/prep.html">pre-exposure prophylaxis</a> or PreP. </p>
<p>There is also the possibility in future of using more potent antibodies or combinations of antibodies or those engineered for improved efficacy and longevity. The use of gene therapy is also being explored. In this case antibody genes are inserted into a vector which then becomes a local antibody-producing factory inside the body.</p><img src="https://counter.theconversation.com/content/51162/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Lynn Morris receives funding from the South African Medical Research Council, the National Research Foundation, the US National Institutes of Health and the Bill and Melinda Gates Foundation. She is a member of the Board of the Global HIV Vaccine Enterprise. </span></em></p><p class="fine-print"><em><span>Penny Moore receives funding from the National Research Foundation, the South African Medical Research Council, the Poliomyelitis Research Foundation and the US National Institutes of Health. </span></em></p><p class="fine-print"><em><span>Nono Mkhize and Zanele Ditse do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Two major clinical trials will be conducted in South Africa in 2016 to test ways of preventing new HIV infections.Lynn Morris, Medical Scientist at the National Institute for Communicable Diseases; Research Associate at CAPRISA; Research Professor in the School of Pathology, University of the WitwatersrandNono Mkhize, Medical Scientist, National Institute for Communicable DiseasesPenny Moore, Reader and DST/NRF SARChI Chair of Virus-Host Dynamics, National Institute for Communicable Diseases, CAPRISA Research Associate, University of the WitwatersrandZanele Ditse, Medical Scientist, National Institute for Communicable DiseasesLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/354592014-12-16T10:37:56Z2014-12-16T10:37:56ZDon’t believe the hype – we are a long way from an HIV cure<p>HIV has infected <a href="http://www.who.int/gho/hiv/en/">over seventy million people</a> but only one of them has been cured: Timothy Ray Brown.</p>
<p>An HIV-positive resident of Berlin, Germany, Brown developed relapsed leukemia in 2006. To treat the leukemia, he underwent special bone marrow transplants that also rendered him genetically resistant to HIV. Brown’s HIV medications were stopped in 2007 and several years later he remains free of HIV.</p>
<p>Brown is historically unique but in recent years scientific journals and the popular press alike have published multiple claims of HIV cures.</p>
<p>In 2012, French scientists announced a “<a href="http://www.theguardian.com/society/2012/jul/26/french-study-scientists-hiv">functional cure</a>” of HIV when 14 patients who were treated within months of initial HIV infection remained clinically stable after treatment stopped. Similarly mild cases of HIV disease had been reported even in untreated patients, and unlike Brown the French patients still have detectable HIV in their bodies. Thus the French researchers likened a fairly common piece of good clinical fortune to a historically important cure, and added little more than confusion in the process.</p>
<p>The same year Boston researchers <a href="http://www.npr.org/blogs/health/2012/07/26/157444649/two-more-nearing-aids-cure-after-bone-marrow-transplants-doctors-say">announced</a> that two HIV patients with cancer had undergone standard bone marrow transplants on HIV therapy, and afterward had unusually low levels of HIV in their blood. Preeminent scientists said it was “<a href="http://www.nytimes.com/2013/07/04/health/post-transplant-and-off-drugs-hiv-patients-are-apparently-virus-free.html?_r=0">conceivable and maybe even likely</a>” the Boston patients’ HIV was gone, HIV medications were stopped, the virus <a href="http://www.independent.co.uk/life-style/health-and-families/health-news/hiv-patients-cured-of-aids-suffer-relapse-9000785.html">rebounded</a>, and several months after it started the Boston celebration came to an end. </p>
<p>In March 2013, doctors <a href="http://www.wsj.com/articles/SB10001424127887324539404578338300521959748">announced</a> that an HIV-exposed baby from Mississippi who was treated within hours of exposure was considered cured as once-detectable HIV could no longer be found off of therapy. Scientists speculated HIV never gained a foothold in vulnerable immune cells. In July 2014 it was reported that the Mississippi baby <a href="http://www.nytimes.com/2014/07/11/health/signs-of-infection-seen-in-child-believed-to-have-been-cured-of-hiv.html">relapsed</a>, most likely because the virus had been lurking all along in those self-same cells.</p>
<p>Echoing the Boston experience, this year two Australian patients were called “HIV-free” and <a href="http://www.nature.com/news/cancer-treatment-clears-two-australian-patients-of-hiv-1.15587?WT.mc_id=TWT_NatureNews">“cleared” of HIV</a> after very low levels of the virus were detected in the blood after stem cell treatments. Both men remain on HIV therapy “as a precaution” so there is no definitive proof of anything more than highly effective therapy and an intense hunger to claim something approximating a cure.</p>
<p>None of these patients, with the exception of Brown, was cured of HIV. Yet in each case a cure has been claimed or the words used to describe the story were so similar to “cure” as to be indistinguishable to the untrained reader. </p>
<p>Why?</p>
<p>Desperation, for starters. HIV has killed over <a href="http://www.unaids.org/en/resources/campaigns/2014/2014gapreport/factsheet">39 million people</a> so far and every year more than a million more are infected. There is no more urgent public health priority than the discovery of an HIV cure. As a result, when new and exciting HIV findings emerge scientists and journalists can abandon their usual caution and succumb to the temptation to use words like “cure” loosely. </p>
<p>Even coolheaded researchers are keenly aware that generating buzz can be the difference between generous funding or the closure of their labs. Salesmanship can devolve into exaggeration as the press conference begins. Journalists and editors, too, are tempted to generate more clicks and sell more papers by freeing the results they report from the scientists’ humdrum caveats.</p>
<p>Desperation and salesmanship aside, even the brightest and most cautious scientists and journalists can get fooled. Many honestly believed, for instance, that the Mississippi baby was free of HIV.</p>
<p>Whatever their motivations, premature intimations of a cure can be dangerous. </p>
<p>The credibility of the HIV research effort is undermined when retractions follow each exciting new announcement of a cure (or whichever phrase like “cleared” is that day’s facsimile). The confusion and skepticism created by repeated retractions can dampen research subjects’ enthusiasm to enroll in studies and even weaken research funding.</p>
<p>The intimations of a cure can also lead to complacency about HIV. Reducing HIV risk behaviors is always challenging, and it is harder when the potency of HIV treatments or the near-availability of an HIV cure make HIV infection seem like, as one newly-diagnosed man told me, “no big deal.” Modern treatments for HIV do keep millions alive for decades and we are closer to a cure than ever before but nonetheless HIV is most definitely a very big deal.</p>
<p>To preserve our scientific credibility, and support our prevention efforts, we should put the word “cure” on a shelf and let it gather a little dust. Someday, when we finally find a cure, a real-life, honest to goodness, checked and double-checked cure, then we can dust off the “C” word and let Timothy Ray Brown know at long last he can have some company in the world’s most elite club.</p>
<p>Until then, we should remember Margaret Heckler. As the Secretary of Health and Human Services, she helped announce Robert Gallo’s discovery of the HIV virus in 1984. Famously she concluded by <a href="http://ota-cdn.fas.org/reports/8523.pdf">predicting</a> that we would develop an HIV vaccine within two years. Thirty years later our patients still don’t have an HIV vaccine, or a <a href="http://www.newyorker.com/magazine/2014/12/22/can-aids-cured">cure</a>. The next time the lights go up and the microphones click on, let us remember that the way we celebrate progress today cannot forget the unfinished work we take up first thing tomorrow.</p><img src="https://counter.theconversation.com/content/35459/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Timothy P Lahey does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>HIV has infected over seventy million people but only one of them has been cured: Timothy Ray Brown. An HIV-positive resident of Berlin, Germany, Brown developed relapsed leukemia in 2006. To treat the…Timothy P Lahey, Associate professor of medicine, Dartmouth CollegeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/290662014-07-11T05:08:05Z2014-07-11T05:08:05ZResearch may be beating HIV, but vaccine remains a way off<figure><img src="https://images.theconversation.com/files/53550/original/c825bjmd-1405002441.jpg?ixlib=rb-1.1.0&rect=0%2C70%2C1024%2C619&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">This would be the ideal way to fight HIV.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/europedistrict/4092914530/">europedistrict</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>Three decades since the onset of the infection in a global population, HIV care and treatment is looking very different. Given the difficulties involved, it is remarkable that having developed good treatments, the global community is racing towards finding a vaccine cure.</p>
<p>The first clinical observation of AIDS was recorded in the US in 1981. The focus then was to identify what caused the new disease and to help people to a dignified death. Once HIV was identified, understanding the behaviour of the virus became vital. </p>
<p>Soon antiretroviral therapies were developed that attempted to disrupt the replication of the virus in the body. In the late 1990s, a combination of these therapies showed better results and had a huge impact on the future of HIV-infected individuals. In the UK the healthcare discourse changed from the person dying from AIDS to the person living with HIV. Today, those individuals diagnosed with HIV infection have a <a href="http://www.lef.org/protocols/infections/hiv_aids_01.htm">similar life expectancy</a> to those without.</p>
<p>Now research is gathering pace to search for a cure. A <a href="https://www.youtube.com/watch?v=OL-gWUHWkR0">recent advert</a> from Cancer Research UK claims “research is beating HIV”. However, it is not that simple.</p>
<p>There have been claims of a cure for a few individuals: the now famous <a href="http://www.stern.de/gesundheit/the-berlin-patient-der-mann-der-hiv-besiegte-1631908.html">Timothy Ray Brown</a>, known as the “Berlin patient”, became clear of his HIV while receiving bone marrow transplantation for his leukaemia. In Mississippi in the US, a baby was treated with antiretroviral therapies for the <a href="http://www.theguardian.com/society/2013/mar/03/us-doctors-cure-child-born-hiv">first 18 months of her life</a> and appears to be infection-free. The “<a href="http://www.economist.com/blogs/babbage/2013/03/aids-treatment">Visconti group</a>” consisting of 14 patients with HIV who have had their antiretroviral therapies stopped with no sign of further infection. </p>
<p>However, bone marrow transplantation would not be the most appropriate way forward as the procedure carries risks in itself. Also two men undergoing treatment for lymphoma in Boston, US <a href="http://www.aidsmap.com/The-Boston-patients-experience-HIV-rebound-after-stem-cell-transplants/page/2833963/">showed a return</a> to HIV infection some months after their transplants. Seeking a cure is still needed.</p>
<p>The development of a vaccine for HIV is complex and this is what leads to its elusiveness. The purpose of a vaccine is to provide a protective immune response to a particular microorganism. The body’s immune system produces antibodies that purge the microorganism with weapons tailored to specifically attack it.</p>
<p>But this is where the difficulties begin: HIV undergoes many mutations, as do most viruses and, therefore, we are not dealing with just one-size-fits-all weapon to fight a virus. The virus also has the ability to evolve resistance to immune control. Our understanding of <a href="https://theconversation.com/hiv-bolts-past-immune-defences-despite-humble-beginnings-5949">HIV’s adaptive evolution</a> must improve if vaccination development is going to be effective.</p>
<p>In creating an appropriate approach to vaccine development the response of the immune system to the virus is important as we want to encourage the development of antibodies to the proteins within the virus. According to a new review published in the journal <a href="http://dx.doi.org/10.1126/science.1256526">Science</a>, two approaches to elicit antibody protection in HIV are being pursued: a vaccine that is potent and produces broadly reactive neutralising antibodies (bnAbs) and vaccines that induce “conventional antibodies”.</p>
<p>Broadly reactive neutralising antibodies (bnAbs) are considered important as they are more likely to cope with mutations of viruses. When developed they ought to be potent and induce high levels of protection. But there are complexities with their structure and it may take months to years in order to evolve a response. </p>
<p>On the other hand, conventional antibodies are less potent but they are produced by the majority of infected individuals and are the only antibodies that have been seen in vaccine trials to date. Unlike bnAbs, conventional antibodies take only weeks to months to evolve a response.</p>
<p>While bnAbs are probably the desired approach to vaccine development, vaccines that support conventional antibodies should not be ignored as they have shown some success in clinical trials. It is not the time to put all our eggs in one basket and research into the development of a vaccine should concentrate on both approaches.</p>
<hr>
<p><em>Next, read this: <a href="https://theconversation.com/the-important-legacy-of-the-man-who-couldnt-get-aids-20505">The important legacy of the ‘man who couldn’t get AIDS’</a></em></p><img src="https://counter.theconversation.com/content/29066/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>John McLuskey does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Three decades since the onset of the infection in a global population, HIV care and treatment is looking very different. Given the difficulties involved, it is remarkable that having developed good treatments…John McLuskey, Associate Professor, University of NottinghamLicensed as Creative Commons – attribution, no derivatives.