Setting the Bar High or Setting Up to Fail? Interpretations and Implications of The EXPLORE Study (HPTN 015)

Abstract

Controlled studies show that HIV risk reduction counseling significantly increases condom use, reduces unprotected sex and prevents sexually transmitted infections. Nevertheless, without evidence of reducing HIV incidence, these interventions are generally discarded. One trial, the EXPLORE study, was designed to test whether 10 sessions of risk reduction counseling could impact HIV incidence among men who have sex with men in six US cities. Based on epidemiologic models to define effective HIV vaccines, a 35% reduction in HIV incidence was set a priori as the benchmark of success in this behavioral intervention trial. Results demonstrated a significant effect of the intervention, with more than a 35% reduction in HIV incidence observed during the initial 12 to 18 months following counseling. Over an unprecedented 48-month follow-up, however, the effect of counseling on HIV incidence declined to 18%. The current review examined how the scientific literature has thus far judged the outcomes of the EXPLORE study as well as the policy implications of these judgments. We identified 127 articles that cited The EXPLORE Study since its publication. Among articles that discuss the HIV incidence outcomes, 20% judged the intervention effective and 80% judged the intervention ineffective. The overwhelmingly negative interpretation of the EXPLORE study outcomes is reflected in public policies and prevention planning. We conclude that using a vaccine standard to define success led to a broad discrediting of the benefits of behavioral counseling and, ultimately, adversely impacted policies critical to the field of HIV prevention.

Critical Review: When the Party is Over: A Systematic Review of Behavioral Interventions for Substance-Using Men Who Have Sex with Men

“…EXPLORE was a multi-site RCT of a 10-session, individually delivered intervention for HIV-negative MSM that achieved significant reductions in CAI and serodiscordant CAI. 43 Although men randomized to the sexual risk reduction intervention also displayed an 18% decrease in HIV incidence at two years, 44 behavioral interventions targeting pre-exposure prophylaxis (PrEP) uptake and adherence are needed to achieve greater reductions HIV incidence among MSM. 45,46 The NIMH Healthy Living Project was a multi-site RCT of a 15-session, individually delivered intervention for HIV-positive persons to reduce serodiscordant, condomless sexual intercourse and optimize HIV disease management.…”

Feasibility of a Combination HIV Prevention Program for Men Who Have Sex With Men in Blantyre, Malawi

“…While we collected data on HIV infection at each study visit, this was not an efficacy study that aimed to reduce HIV incidence nor was it hypothesized the HIV acquisition would be prevented given the high force of HIV infection among MSM and expert opinion that behavioral interventions may result in limited reduction of incidence in high incidence settings, relative to biomedical approaches. 1,33 Seven participants seroconverted in the study and all seroconverted during the first study period. Though this is consistent with other incidence studies among MSM in African settings, 34 it could also be reflective of early, undetectable infection at enrollment or acquisition during the period when the study was temporarily closed.…”

Moving the Bar to the Right Place: Positioning Interventions in HIV Prevention

“…: Interpretations and Implications of the EXPLORE Study”, Kalichman and colleagues (1) discuss the positive and negative interpretations in the research literature about the effectiveness of the EXPLORE behavioral intervention in reducing HIV incidence. They conclude that the preponderance of negative interpretations has had a consequential negative impact on policy decisions about the role of behavioral counseling in HIV prevention in the United States (US).…”

“…They conclude that the preponderance of negative interpretations has had a consequential negative impact on policy decisions about the role of behavioral counseling in HIV prevention in the United States (US). Kalichman et al go on to discuss that the 35% benchmark for a reduction in HIV incidence in the EXPLORE Study was “setting the bar too high.” (1) We believe that while the role of behavioral counseling is critical for HIV prevention, the HIV prevention intervention “bar” needs to move to a different location altogether.…”

“…Many, if not most, commentators on the EXPLORE Study have failed to recognize the subtleties of the results and, as Kalichman et al point out, positive and negative interpretations of the trial have proliferated and have not done the study justice. (1) The EXPLORE Study was the first, and only behavioral counseling intervention for men who have sex with men (MSM) tested against an HIV infection outcome. The EXPLORE Study was designed as a Phase IIb screening proof-of-concept trial (as opposed to a Phase III definitive efficacy trial), a prudent approach given the resources and time needed to conduct a trial with an incident HIV endpoint.…”