By Françoise Barré-Sinoussi, IAS Governing Council Member and President of the International Scientific Advisory Board of ANRS and Richard Jefferys, TAG, Coordinator, Michael Palm Basic Science, Vaccines & Prevention Project

From 16 to 17 July, immediately prior to the XVIII International AIDS Conference (AIDS 2010), the International AIDS Society held a workshop addressing the critically important subject of moving beyond antiretroviral therapy and addressing HIV persistence. Towards a Cure: HIV Reservoirs and Strategies to Control Them was co-sponsored by the French National Agency for Research on AIDS and Viral Hepatitis (ANRS), Bundesministirium fur Wissenschaft und Forschung (BMWFa), the National Institutes of Health (NIH), Sidaction and Treatment Action Group (TAG).

Françoise Barré-Sinoussi, Workshop Chair

As eloquently described by Sharon Lewin in an opening plenary (at 1hr 55 mins), the push to make curing HIV infection a research priority is motivated by several factors. The success of highly active antiretroviral therapy (HAART) has brought the life expectancy of HIV-positive people very close to that of their HIV-negative counterparts, but in most studies a slight difference is still observed. And while HAART has revolutionized HIV care, it remains imperfect, coming with a range of possible complications that can impair quality of life. Furthermore, the cost of delivering life-long HAART to all who need it will eventually consume a daunting proportion of aid budgets.

The Towards a Cure workshop sought to encourage young investigators to work on this priority topic, as well as expose a broad array of stakeholders – basic and clinical researchers, policymakers, community advocates and journalists – to new scientific results relevant to tackling HIV persistence, whether by eradicating the virus (sterilizing cure) or achieving long-term remission in the absence of ongoing therapy (functional cure). The categories of the workshop sessions spanned from identifying the locations of quiescent or “latent” HIV reservoirs in the body and the mechanisms of viral persistence, to potential therapeutic interventions and methods to evaluate their impact.

As examples of the science presented, Sandrina Da Fonseca from the Vaccine and Gene Therapy Institute, Port St. Lucie, United States, described the potential utility of a cellular marker named PD-1 in identifying memory CD4+ T cells harboring HIV. Da Fonseca also showed data indicating that inhibiting PD-1 may awaken the silent viral genomes in these cells, potentially offering a new method for depleting the persistent HIV reservoir. PD-1 inhibitors currently are in human trials for the treatment of cancer.

The possible roles of early HAART and treatment intensification also were described. Brigitte Autran outlined the design of two ORVAC (Objectif Recherche Vaccins SIDA) trials, Eramune 01 and Eramune 02, that will soon be enrolling participants. (The protocols are described in detail in the clinicaltrials.gov database. Click on the trial names for more information.)  Eramune 01 will explore HAART intensification plus modulation of the immune system with IL-7, a cytokine that may be able to deplete HIV from memory CD4+ T cells. Eramune 02 involves the addition of a therapeutic vaccine to intensified HAART, with the goal of bolstering the ability of the immune system to specifically recognize and eliminate HIV-infected cells.

In the closing session, Daria Hazuda from Merck & Co. reviewed some of the issues in conducting industrial-scale screening of compounds for anti-latency activity. As Hazuda noted, many research teams have identified compounds known as histone deacetylase (HDAC) inhibitors that can prod HIV out of hiding, and a number of the drugs (such as SAHA) already are approved for human use in cancer. Several additional pharmaceutical companies are known to be initiating programs to search for potentially curative drugs.

Detailed rapporteur summaries from the workshop will soon be available on the AIDS 2010 website, and a meeting summary will be published in the Journal of the IAS. The Thursday conference session “Persistence of HIV Reservoirs” (THAA01) will include some of the abstracts that were presented, and additional background materials and a press release about the workshop will be made available today. Slide presentations will be posted on the workshop website by the end of July.

A background review outlining the key scientific issues was published in Science on 9 July 2010. The authors are Didier Trono, Carine Van Lint, Christine Rouzioux, Eric Verdin, Françoise Barré-Sinoussi, Tae-Wook Chun and Nicolas Chomont. Free copies are available at the Science booth in the exhibition hall.