Paris highlights
The International AIDS Society Conference on HIV Science was held in Paris last week. HIV scientists, clinicians and community advocates gathered to hear about the latest in HIV research. From more support for treatment as prevention and the loud ‘undetectable = untransmissable’ message, to advances in treatment, pre-exposure prophylaxis (PrEP) and basic science, the conference covered a huge range of topics. Read on for a taster.
Broadly neutralising antibodies
Broadly neutralising antibodies (bNAbs) are powerful tools for HIV prevention and treatment. Most antibodies against HIV bind to parts of the virus that vary between strains, or that mutate during infection. Some rare antibodies are able to block (neutralise) many different strains, and these have enormous potential for prevention and treatment. Good bNAbs are hard to make, and take a long time to develop even in people with long term HIV infection. There are robust methods for isolating the bNAb-producing B cells and growing them in the lab, allowing bulk quantities to be made for use in clinical trials. Some of the bNAbs currently in development include VRC01, BNC117 and 10-1074. There was a great press conference outlining the huge potential of bNAbs.
The conference featured the results from the first randomised controlled trial of the bNAb VRC01. This trial, RV397, used VRC01 in people who were diagnosed and began treatment early after HIV infection. Trial participants received intravenous VRC01 (or a placebo) every 3 weeks for up to 6 months while their usual treatment was halted. Due to their early treatment, these people have a low HIV reservoir, preserved immunity and less resistance to interventions. Participants were closely monitored, and restarted on therapy if their virus rebounded. Most participants showed rapid rebound, whether they had been given the placebo or the bNAb infusions, although there was a slight delay in the time to rebound people given the VRC01. While obviously not a resounding success, the results of this trial will inform future bNAb studies.
HIV reservoirs
One of the major barriers to HIV cure is the persistence of hidden HIV reservoirs during treatment. The recent discovery of CD32a as a marker of CD4+ T cells harbouring latent HIV provides a window to study and possibly eliminate these cells. Genevieve Martin from John Frater’s group at Oxford presented results revealing a more detailed picture of CD32 expressing cells. They showed that CD32 is found on more mature immune cells, and that CD32+CD4 cells have greater than 100-times more HIV DNA than CD4 cells without CD32. They also showed that the CD32+CD4 cells have high levels of immune checkpoint markers including PD-1 on their surface. These results confirm the importance of CD32 as a marker of the HIV reservoir.
The latent reservoir was further described in studies from Australia looking at integration sites – the spot where HIV incorporates into the host genome. Using advanced sequencing techniques, Jori Symons from Sharon Lewin’s group at the Peter Doherty Institute for Infection and Immunity looked at integration sites in blood, lymph node and rectal tissue cells from HIV+ people with undetectable viral loads. Symons found that HIV prefers to integrate into genes (rather than non-coding DNA), and that it usually inserts itself backwards. The studies showed that HIV does not selectively integrate into oncogenes (genes that can lead to cancer). Evidence for clonal expansion was also found, suggesting that the reservoir on treatment develops from the multiplication of a few selected cells. Understanding HIV reservoirs at this level can inform strategies to eradicate HIV, and also help in the development of methods for measuring and detecting the reservoir in people on treatment.
Unicorns and other challenges in cure research
Micheal Louella from Defeat HIV, one of the NIH HIV Cure collaboratories, gave a fantastic rundown of the issues raised during the HIV Cure and Cancer Forum. A video of his presentation can be seen on our Facebook page. Louella likened the search for HIV cure trial participants to finding a unicorn – extremely rare creatures!
A further cautionary tale for small studies was raised by Anthony Fauci. Fauci presented details from a therapeutic vaccine trial that highlighted the importance of including a placebo control. In the study, the vaccine (or placebo) was administered to participants who started therapy early after infection. Treatment was then interrupted to see if the vaccine had any effect. While the vaccine did not delay viral rebound or reduce the HIV reservoir, there were two individuals with delayed rebound in the placebo group. If those two individuals had been placed in the vaccination group, it would have appeared that the vaccine caused the delay. These results mean that claims of efficacy in non-placebo controlled trials (such as the Spanish vaccine study presented earlier this year) need to be interpreted carefully.
Slide from Michael Louella’s presentation.
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