The important legacy of the ‘man who couldn’t get AIDS’

Fighter in the war against AIDS. Photograph supplied

All scientists have that moment when an idea is initiated or when things come together and a project flourishes. One such moment for me came at a Keystone scientific meeting in South Carolina in 1994.

It was here that I first met Gregg Consalves, an AIDS activist with Treatment Action Group (TAG) based in New York. I explained I was setting up a study of individuals who had been heavily exposed to HIV for many years but who hadn’t been infected. Gregg got involved and within a week I had my first recruit: Steve Crohn. Steve became the focal point of our research over the following years.

We found that Steve had CD4 cells that were resistant to HIV infection and he carried a genetic alteration that was responsible. Even though we exposed his blood to 3,000 times the amount of HIV normally needed to infect a cell, he never became infected. It was a revelation – soon we realised what we had found.

CD4 cells are the lymphocytes of the immune system that HIV usually infects and destroys. Steve helped us to identify a key molecule called CCR5 that the virus requires to enter lymphocytes. Sadly Steve passed away in August this year when he committed suicide at the age of 66.

He had described his own exposure to the AIDS epidemic in war terminology. I certainly would not like to conclude that Steve’s death stemmed from post-traumatic stress disorder or what’s otherwise known as “survivor’s guilt”, but it certainly shouldn’t be ignored within the HIV/AIDS community. He was always heartened to have contributed to the “fight” against AIDS and in helping provide a pivotal piece of the jigsaw that saw Maraviroc, a CCR5 blocking antiretroviral drug, being brought quickly to the market.

The AIDS fallout

Steve wasn’t the only one for whom the impact of AIDS had unexpectedly taken its toll. One of the prominent activists in the early days in New York was Spencer Cox. He devised the first trial protocols for the testing of protease inhibitors, which proved to be the drugs that changed the face of HIV treatment and the pandemic in general.

For the first time, the people “on the front line” – the subject of a new film, How to Survive a Plague – were at the table influencing the decisions. I was shocked to learn through the New York Times in December 2012 that Spencer himself had died after he stopped taking his life-saving medications and had succumbed to pneumonia brought about by HIV. Why would the person who fought for these drugs cause his own death?

Another reported case has been that of Gabe Torres, the first director of the St Vincent’s Hospital AIDS programme in New York’s West Village, one of the death centres in the city which at the peak of the epidemic was losing a third of its patients each day. After years of fighting, the introduction of HIV drugs meant he had less to fight. In order to (in his own words) “celebrate living”, Gabe turned to recreational drugs, became infected with HIV and lost his license to practice medicine.

Of course, these may be isolated incidents. But what these individuals went through can’t be ignored. And we owe it to them to figure out what the fallout has been from a world where AIDS was a likely death sentence and many lost friends and loved ones. And to keep on with their early fight for treatment and prevention.

HIV still has the power to surprise

Although HIV research and the virus’ impact on the immune system has come a long way, not all HIV vaccine trials have been successful. One was prematurely halted because the vaccine was actually associated with a higher risk of infection when compared to the placebo.

The mechanism resulting in higher transmissions is not known, but given that HIV infects immune cells, it’s likely due to the immune activation that the vaccine stimulated. This is exactly what a vaccine is meant to do, but rather than induce a protective response, the activated immune cells were rendered more prone to infection with HIV. Not all HIV vaccines tested to date have demonstrated this enhancing effect but clearly, individuals in such trials need to be carefully monitored.

We recently published a study that suggested that neutralising antibodies against HIV are a magnitude higher in mothers who transmit the virus to their infants while in the womb than those who don’t.

But these are the same antibody responses that we all want to see induced in HIV-1 vaccine recipients. So this might mean that a vaccinated mother is actually at higher risk of transmitting the virus to her unborn child than if she wasn’t vaccinated. Getting this wrong could have immense psychological implications.

Similarly there has been much talk concerning “HIV functional cures” where therapy intensification or early treatment may mean that an individual can come off of their drugs. Here great care has to be taken not to provide false hope for HIV-infected individuals. Eradication is an extremely active and exciting area of HIV research and needs testing.

One recent study suggested that HIV reservoirs, the pool of inactive HIV virus that lay dormant in the body, may be much larger than believed, further highlighting the big challenges ahead.