Whither HIV Clinical Research?

Twenty-seven years ago, the National Institutes of Health (NIH)-funded AIDS Clinical Trials Group (ACTG) was formed. Arguably, clinical and basic science research performed by investigators funded by the ACTG has been one of the best uses of US government tax dollars. We speak today, as we have for at least several years, of having achieved, at a minimum, a “functional cure” of HIV, at least in North America and Western Europe. An individual living in the US, infected today with HIV at the age of 26, is likely to live into her 70s, or about 80% to 85% of the life expectancy of a similar individual not infected with HIV.

Some of the most important advances along the path from a death sentence to functional cure have come as a result of clinical trials funded by the ACTG, or another NIH-funded clinical trials group, the Community Programs for Clinical Research on AIDS, which was formed in 1989 and folded into the ACTG in 2006. At its peak, several years ago, the ACTG consisted of more than 70 domestic sites spread throughout more than 20 states, as well as dozens of additional international sites in Africa, South America, and Asia.

These days, however, success does not guarantee continued funding, especially when the US Congress, which must approve all funding, is gridlocked and mired in partisan bickering. Nevertheless it came as a shock to investigators at approximately one-third of the domestic sites and many international sites several months ago to learn that they had been “defunded.”

The reason: not quality, not performance, but funding cuts due to the Sequester.

The defunded sites included, among other locations, Stanford University, Duke University, Drexel University, and Wayne State University, which has been funded to do clinical trials research for 25 years. A quick glance at the numbers tells most of the story: in 2012, total NIH funding dropped $4.5 billion to $30.6 billion, about the same as it received in 2005. For 2013, the NIH budget dropped another $4.2 billion (14 percent). For 2014, the NIH is anticipating another drop of $2.0 billion (8 percent). Of course, the ACTG budget is substantially less (approximately $275 million for 2014, or 1.1% of the total NIH budget for 2014).

Losing grant funding, or failure to obtain new grant funding, is a fact of life for basic scientists and clinical researchers in academia. And, of course, $275 million can still buy a lot of progress, even if it seems, for HIV research anyway, that it is the “one percent solution.” In addition, multiple questions come to mind: 

1. Will the pharmaceutical industry, with their shareholders’ interests front and center, pick up the slack? 

2. Will the commendable diversity of participants enrolled in ACTG trials be equaled in pharmaceutical-sponsored trials? 

3. What, exactly, will the ACTG accomplish in this new era of reduced NIH funding? After all, even ACTG sites that were not defunded were told to expect approximately 30% cuts in funding.

The answers to the first two questions are unknown. However, from comments made by Carl Dieffenbach, PhD, Director of the National Institute of Allergy and Infectious Diseases (NIAID), Division of AIDS (DAIDS), we can get a glimpse of the future, or at least the next 7 years of US taxpayer-funded future. Specifically, when asked if the ACTG will continue to be involved in antiretroviral clinical trials, he replied, “If by that you mean will the ACTG be involved in looking for the next ‘best’ PI or the next ‘best’ integrase strand transfer inhibitor in combination with Truvada, the answer is decidedly ‘no.’”And, as to the ACTG’s exemplary enrollment of a diverse population in clinical trials, it is absolutely true that the ACTG has done its best with diversity when enrolling into trials of antiretroviral comparisons. In other words, the face, sex, and color of participation in ACTG-sponsored trials is about to change.

Where will the dollars go?

On what exactly will the ACTG focus in the next 7 years?  Director Dieffenbach laid out the plans at a meeting in Washington, DC, last November. Substantial resources will be invested in finding the elusive “cure” (ie, HIV eradication). Additional resources will be invested in finding effective HIV prevention interventions, treating HIV comorbidities, including hepatitis C infection and tuberculosis, and “assisting in taking interventions to scale” (in other words, partnering with other funders). All of Dr Dieffenbach’s stated goals are important and admirable, but many of us who were there had the sense, as we left the meeting, that the ACTG might no longer be the premier HIV research organization in the world. Budget cuts, talk of looking for “partners,” and the plan to emphasize smaller, “pilot, proof-of-concept” trials reinforced that perception.

Whither HIV clinical research? My predictions: (1) HIV clinical trials will be increasingly more likely to be funded by the pharmaceutical industry; (2) HIV-related clinical trials will be increasingly less diverse (race/ethnicity and sex); and (3) advances are more likely to be made in HCV eradication efforts, funded by the pharmaceutical industry, than in new HIV-specific advances.

Concur? Disagree? Other thoughts?  Please let us know, below.