Over the last five or six years, scientific progress in the HIV prevention and treatment field has been tremendous. New technologies and better understanding are influencing policy and practice. The Conference on Retroviruses and Opportunistic Infections (CROI) is arguably the single most important research-focused HIV/AIDS conference held in North America each year. In March I was fortunate to attend my fifth as a community educator scholarship recipient.
Despite bold headlines that mainstream media use to capture readers’ attention, these developments occur in small steps rather than giant leaps. Some years at CROI feature reporting of major milestones and this can be exhilarating and inspiring. Others yield fewer headlines, but exemplify the amazing depth and breadth of the slow, steady work that is constantly ongoing and just as inspiring to me.
We’ve made big strides and we have an amazing number of interventions we can use to combat HIV/AIDS. The challenge is to create a truly comprehensive, science-based plan that is inclusive, accepting, and unencumbered by outdated understanding, preconceptions, or moral judgments.
Something we must recognize and work to overcome is that all of these interventions, both old and new, have a number of vulnerabilities that render them only partially effective. These can be very specific to one strategy, but a few stand out as common challenges to all: adherence, access and reach.
There’s no intervention that’s older or more dependent on adherence than the condom. One CROI presentation from the CDC estimated condom efficacy in men who have sex with men, generating heated discussion. It has always been difficult to wrap our minds around the difference between the theoretical efficacy of condoms as a device (somewhere in the high 90 percent range) vs. the impact they have as a prevention intervention in communities. Most information available to date has been based on heterosexual couples and focused on vaginal sex. A highly regarded meta-analysis (a compilation of multiple studies) has estimated that individuals who express commitment to consistent condom use realize an average reduction in risk of acquiring HIV of about 80%. The shortfall includes things like breakage and leakage, but also the difference between reported intentions and actual use. The new analysis looked at data from two large prevention studies in gay and bi men, and found that those who reported “always” use experienced a 70% lower risk of infection than those who reported “never” use. In addition, the analysis, which focused on men who had anal sex with at least one HIV-positive partner, did not find a significant difference in risk between those reporting “sometimes” and “never” use. This seems counterintuitive, but in our highly impacted community it makes sense that the accumulated risk with “sometimes” use can overcome its limited protection over time.
The ability of antiviral therapy to reduce transmission (known as treatment as prevention or TasP,) has been a hot topic for several years. While the large and highly regarded HPTN052 study found that being on treatment can reduce the risk of transmission by 96%, and many believe the reduction may be higher when viral loads are undetectable, TasP is dramatically vulnerable to the common barriers of adherence, access and reach.
United States estimates have previously indicated that only about 25% of HIV-positive persons in the U.S. have an undetectable viral load both because about one-fifth of them are unaware of their status and because efforts at linking those who are diagnosed to care and treatment are only partially successful. One CROI report showed that the proportion of HIV-positive individuals achieving an undetectable viral load in France is dramatically higher at roughly 50%. Interestingly, though, the percentage of undiagnosed cases there is no lower than that in the U.S. This may be TasP’s Achilles’ heel.
Assessments of the impact of treatment roll-out on new infections in studied communities have yielded mixed results to date, but there was promising news from a resource limited setting. When researchers analyzed data from rural KwaZulu-Natal, South Africa, they found that in areas with the highest treatment uptake, the number of folks living with HIV increased (because they were surviving and living longer) and the risk of contracting HIV was lower.
Two important new prevention technologies, pre-exposure prophylaxis (PrEP) and microbicides, may become key to preventing new infections. Last year the use of Truvada for PrEP (which involves prescribing this two-drug pill to HIV negative individuals who are at high risk) was approved by the FDA based on results from three major studies. One large vaginal microbicide trial has shown efficacy with insertion of a lubricant gel containing tenofovir (one of the two antiviral drugs in Truvada) before and after sex, but similar results from additional trials are needed for product approval.
Results from the “VOICE” trial reported at CROI reminded us that hurdles remain. Designed to compare three interventions used daily by women (Viread or Truvada for PrEP, or the tenofovir vaginal gel), the study was unable to show a difference between product and placebo in all three cases. While reported use was high for each option, drug level measurements indicate that actual use was so low it rendered them ineffective. This outcome was essentially the same as that reported for the “FemPrEP” trial last year. Young single women have been thought to be ideal beneficiaries for such products, but for whatever reasons in this population and in the respective settings of these trials, they were not motivated to use them.
Second generation products may help overcome these shortcomings. Hopeful reporting included a study in rhesus macaques using a long-acting injectable form of a new antiviral drug, GSK744. 16 macaques were exposed weekly to SHIV, a primate analog of HIV. The 8 who did not receive drug became infected within between 2 and 8 weeks, but none of the 8 who did receive it appeared to have seroconverted as far out as 16 weeks. It was said that this drug is “a promising next-generation PreP agent suitable for monthly to quarterly injections.” Another study similarly explored the potential of a polyurethane vaginal ring that delivers tenofovir to protect female macaques against repeated vaginal exposures, and yielded similar outcomes.
There was a lot of talk at CROI about possible “functional cures.” The presentation that made headlines, of course, described the Mississippi infant, believed to have acquired HIV from her mother. She received nearly immediate treatment with a full antiviral regimen which was continued for over a year, and after stopping treatment, little or no sign of virus has been detected.
Less reported, but very exciting, was data from a group of Thai patients diagnosed early (during “acute” infection) and treated beginning shortly thereafter. Using special blood tests to examine HIV in their bodies, scientists noted similarities to rare “elite controllers” who are able to maintain undetectable viral loads without medication. The Thai patients have not yet stopped therapy, but recent data on a group of French patients known as the Visconti cohort indicates that a relatively long period of treatment beginning early in infection may enable a minority of individuals to control the virus on their own after a time. The difficulty we currently have in getting HIV-positive persons tested and into care, however, seems magnified in the face of any objective to aggressively diagnose and treat so soon after infection.
For years, researchers and physicians invested great effort to combine what were less than ideal drugs into combinations customized for each patient, achieving surprising success. Perhaps we must now strive to combine similarly imperfect and partially effective prevention strategies into combinations tailored to reduce the risk of transmission for individuals and communities. To do this well, we must listen closely as those people tell us what they need, what works, and what doesn’t work for them.
My view is that because every available strategy has a number of vulnerabilities, we can neither afford to disproportionately rely on nor can we afford to dismiss or discard any one of them.
About the author: Mark Hubbard has been living with HIV for 26 years. He is a self-trained community educator, advocate, and activist who serves on the combined Community Advisory Board of the Vanderbilt University’s Therapeutics Clinical Research Site and HIV Vaccine Program. He is the educational liaison for the Tennessee Association of People With AIDS. Mark will explain what recent research findings mean to our communities in understandable language during an interactive HIV/AIDS presentation at OutCentral on Wednesday, May 22nd at 6 PM. Made possible with support from the Tennessee AIDS Education and Training Center, the Music City Sisters, and OutCentral, the event is free and open to the public. Light refreshments will be provided and door prizes awarded.