Seattle HIV conference showcases latest research

Timothy Ray Brown’s HIV cure passed its 10^th anniversary in mid-February. At the same time, leading HIV researchers met in Seattle to share the latest developments in HIV science. The Conference on Retroviruses and Opportunistic Infections (CROI) is a major platform for cutting-edge HIV research of all types.

This year, CROI included a pre-conference workshop on good participatory practice in honour of pioneering HIV advocate, Martin Delaney. There were also inspiring talks on progress towards an HIV cure from renown Thai researcher Jintanat Ananworanich and from eminent cancer scientist Carl June on advances in cellular therapy in cancer and HIV, including the potential of CAR-T cells to fight HIV, which we wrote about recently .

What’s new in HIV vaccines?

The biggest news on HIV vaccines came out of a vaccine trial in Spain. Beatriz Mothe from the IrsiCaixa AIDS Research Institute in Barcelona presented early results from the BCN02-Romi trial.

This trial involves 15 HIV positive people who are all on ART. The participants were all previously involved in the BCN01 trial. This time, participants were given the HIV Conserv vaccine (more details here). Participants then got three doses of the latency reversing drug romidepsin and another dose of vaccine. Four months after the first vaccine, the 13 participants who showed good vaccine-induced immune responses stopped ART. In eight of the 13 participants (61%), the virus rebounded within 4 weeks and the participants had to start ART again. But for five participants (38%), the delay in rebound was even longer. Some participants are still being monitored off therapy after seven months.

This study is exciting because it is the first vaccine trial to demonstrate post-treatment control – that is, the virus is present but doesn’t rebound after stopping antiretroviral therapy.

Sharon Lewin, Doherty Institute Director

The viral control following vaccination seems to be due to two factors. The first factor is low HIV DNA levels (a small HIV reservoir). The other factor an effective vaccine-induced immune response. Read here for a more detailed account of the trial.

It is still too early to know exactly why the five participants were able to stay off therapy for so long. It is also unclear whether it will be possible to do the same thing in a larger group of participants. For starters, there was no control group (no group which didn’t get the vaccine and/or romidepsin). It is also not clear if the effect was due to early treatment, the first doses of vaccine (from the BCN01 trial), the additional doses of vaccine or the romidepsin. It is, however, a very clear call for more detailed research.

What more do we know about reservoir development?

Understanding how HIV sets up a permanent camp in the body is a critical step towards either blocking it or getting rid of it. Dr Louis Picker from the Oregon Health and Science University summarised vaccine studies in a non-human primate model of HIV infection. The group led by Dr Picker have been studying a therapeutic vaccine for SIV, the primate version of HIV. Dr Picker described a study where SIV was given to animals, followed by early ART. A therapeutic vaccine to boost immunity was given (or not to the control group) and ART stopped almost two years later. This produced two main results. The first was that the vaccine did boost immune responses. The second was that despite these boosted responses, the vaccine did not change how quickly the virus came back when ART was stopped. This was obviously disappointing, but there were some interesting results.

There were individuals in BOTH groups (that either did or did not get the vaccine) that controlled virus even when ART was stopped. These individuals had started ART extremely early after infection (4-5 days). Picker’s group concluded that the virus reservoir in the first few days after infection is unstable. This unstable reservoir is gradually removed from the body during treatment. After that time, the virus is ‘fixed’, and even long-term ART can’t get rid of it. This means that for people with HIV, even treating in the first weeks of infection may not stop a latent HIV reservoir from forming. Strategies to reactivate latent virus will be needed to get rid of the reservoir.

Supporting this idea, studies in HIV+ people in Thailand who were treated very early were also presented. These people were given ART in the first weeks after infection, even before the development of an immune response. When these people stopped ART, the virus still came back within a month. This is only slightly longer than the 2-3 weeks for people starting treatment during chronic HIV infection. Two studies presented on children in South Africa suggest that HIV DNA levels drop much faster in children than in adults when ART starts. This means that the early development of an HIV reservoir might be different in children and adults.

What else?

A large conference like CROI covers a very wide range of research. The conference website has a wealth of information, including webcasts of presentations and all the abstracts and posters presented. Check out studies extending our understanding of how broadly neutralising antibodies work and early results from the development of an immune-stimulating compound that could help clear latent HIV. Great commentaries on the research presented can be found here and here.