I´ve been in Boston this week attending the annual Conference on Retroviruses and Opportunistic Infections (CROI). While here mixing it with my colleagues, I´ve been reflecting on where we´ve come scientifically on the path towards an HIV Cure.
The field has certainly come a long way in the four years since the first Global Scientific Strategy: Towards an HIV Cure, was launched by the International AIDS Society (IAS) at the XIX International AIDS Conference in Washington D.C. in 2012. Many new strategies are being tested, often inspired from other disciplines - including the vaccine and cancer fields now playing very important roles in the search for a cure.
Threes studies in particular have caught my eye this week.
The combination of a vaccine developed by a Norwegian company, Bionor, together with a histone deacetylase inhibitor (HDACi) Romedepsin in HIV-infected individuals on antiretroviral therapy led to a modest decrease in the number of infected cells. They used three ways to measure the number of infected cells and 2 of those measures were certainly heading in the right direction! This is the only study of a latency reversing agent to show such an effect. A larger study of over 100 individuals using this same strategy will be starting in Europe, the US and Australia later this year. This will be the first large placebo controlled randomised study testing a cure intervention which is an exciting advance.
Fascinating too has been a follow up study led by the Beth Israel Deaconess Medical Center using a drug that stimulates TLR 7 to activate latent HIV in monkeys. This drug, being developed by Gilead, is currently in clinical trials in HIV-infected individuals on antiretroviral therapy. A similar drug was shown last year to potently activate latent HIV in monkeys. This new study not only confirmed the effect but also demonstrated that the modified form of the drug worked too.
Lastly, the American Clinical Trials Group study led by Joseph Eron from the University of North Carolina at Chapel Hill presented preliminary results of a PD-L1 antibody, developed as a cancer treatment, in people living with HIV on ART. Unfortunately only 8 patients were enrolled, as the trial was stopped early due to retinal toxicity in infected monkeys. However, in the 6 patients who received the drug, there was quite a dramatic improvement in CD8+T cell exhaustion in two participants providing supportive evidence that similar drugs, commonly referred to as immune checkpoint blockers, may play a key role in future strategies in finding a cure for HIV.
We are still learning that the virus can persist in multiple forms in different T-cell subsets and in different tissues but with improved technologies and improved collaboration amongst different investigators, the mysteries of how to best measure virus persistence are slowly being unravelled - although there is still a way to go. It seems that the majority of viruses we detect in our current assays are defective, even when treatment is started early. The real challenge will be knowing how to measure the virus that actually matters.
This week has certainly been a reminder of where the field in HIV Cure research has shifted in just five years. It`s with a great deal of anticipation that I and my colleagues look forward to the IAS Towards an HIV Cure Symposium taking place prior to the 21st International AIDS Conference (AIDS2016) in Durban, South Africa, this coming July.