The past year has been wrought with disappointment on the HIV cure front. Most notably was the return of virus in both of the “Boston patients” and the “Mississippi Baby” that many had hoped would be sustained HIV remissions/cures: The Boston patients through stem cell transplants and the Mississippi Baby through very early administration of antiretroviral therapy. However, this past year has also been a learning experience that allowed researchers a better understanding of what basic questions need to be answered to set us on a course to eradicating HIV or achieving sustained HIV remissions.
NIH Director Tony Fauci told AIDS 2014 conference delegates that the definition of an HIV cure is the “permanent remission of disease following cessation of treatment.” He also explained that a cure from HIV can be two things: total eradication of HIV from the body or driving HIV so far underground that, even if HIV still exists in the body, treatment is not needed to sustain health.
There are many basic science questions that researchers are now asking in the search to “cure” HIV. For instance, it is still unclear exactly what eradication would look like. There are many things we would need to know in order to eradicate HIV. In what cells and compartments does HIV hide? What new assays do we need to look for “hidden” HIV? How big are reservoirs? How do we “wake up” cells with latent virus? How long would it take after no sign of HIV is found to dub a person cured?
More questions: For a sustained remission how long would a person need to be off treatment and undetectable to be considered in remission? What makes the virus rebound after a remission is induced such in the cases of the Mississippi baby and the Boston patients? Where is low level viral replication occurring when HIV is undetectable in the blood?
The NIH has made a bigger commitment over the past year to HIV cure research than ever before through grants and the AIDS Clinical Trials Group studies. Numerous studies are ongoing and accruing to help answer many important questions. Not all clinical trials require a person to take medications that are not FDA-approved, though some do. Whether or not to participate in a clinical trial that will help to answer critical questions needed to find a cure is a decision that all HIV-positive people must weigh carefully with their physician. Below are some interesting cure trials whose results will greatly help to advance our field of knowledge.
P1115 (DAIDS ID 11954): Very Early Intensive Treatment of HIV-Infected Infants to Achieve HIV Remission: A Phase I/II Proof of Concept Study: This study is based on the temporary remission of the Mississippi baby and aims to see if very early initiation of ARVs in infants leads to remission and a reduction in the latent reservoir. This is an important study as it not only could help to keep babies off of ARVs for an extended period but if successful may also be replicatable in adults treated immediately following HIV transmission.
A5326: Anti-PD-L1 Antibody in HIV-1: Safety, Pharmacokinetics and Immunotherapeutic Activity of an Anti-PD-L1 Antibody (BMS-936559) in HIV-1 Infected Participants on Suppressive cART: A Phase I, Double-Blind, Placebo-Controlled, Ascending Single Dose Study: Virus-specific T cells are critical to control of chronic viral infections. PD-1 is a key inhibitory receptor affecting T-cell response. In chronic HIV infection, persistent antigen expression leads to T-cell exhaustion and functionality of T-cell declines. ARVs don’t fully reverse this process. Treatment with anti-PD-L1 (BMS-936559) leads to transient effects on viremia, restored immune cell function and number, and prolonged survival in macaques. Anti-PD-L1 antibody also reduced post-treatment rebound viremia in macaques. This study aims to measure the best dosage and safety and efficacy of BMS-936559 as well as its effects on immune response and circulating virus.
A5321: Reservoirs in Long-Term ART: Decay of HIV-1 Reservoirs in Subjects on Long-Term Antiretroviral Therapy: The ACTG HIV Reservoirs Cohort (AHRC) Study: This study is currently recruiting participants from two prior studies (A5276s or A5001). A5321 measures the HIV reservoirs and their decline over seven years in people on long-term HIV antiretrovirals. No experimental medication is given.
This study is important as it measures the effect different factors have on reservoir size and decay such as viral load, CD4 count, when a person started ARVs and ARV concentration.
If you are interested in participating in a “cure” study please check for studies on the following sites:
Jeannie Wraight is the editor-in-chief and co-founder of HIV and HCV Haven (www.hivhaven.com) and a blogger and writer for TheBody. com. She is a member of the Board of Directors of Health People, a community-based organization in the South Bronx and an advisor to TRW (Teach me to Read and Write), a community-based organization in Kampala, Uganda. She lives with her husband in the Bronx, New York.