CROI 2013: Learning from the PrEP Access “Gap” in the iPrEx Trial
Demonstration projects are launching across the country and around the world to evaluate how best to make PrEP available in the real world, but another important question is this: What happens when PrEP becomes unavailable to people who are already using it?
Today at the 20th Retrovirus Conference, Robert Grant, MD, MPH, of the University of California at San Francisco addressed this question with data from the iPrEx trial of PrEP in men who have sex with men and transgender women.
Grant recalled in his March 4 presentation that the randomized, double-blind, placebo-controlled iPrEx trial (for which he is the protocol chair) found an overall 44% reduction in HIV incidence (that is, the rate of new infections) associated with Truvada PrEP. Protective benefit strengthened as adherence increased—up to 99% among those with drug levels in their blood corresponding to daily use.
The randomization phase of the iPrEx study ended in November 2010, and from June 2011 to June 2012 the iPrEx OLE (open-label extension) study enrolled former trial participants to gather further data on the safety of PrEP and the behavior of PrEP users over a longer period. For a number of reasons (including safety and funding protocols), PrEP was not made available to former study participants during this period.
This seven-to-nineteen-month gap, explained Grant, offers important insights into how interruptions in PrEP access may contribute—or not—to HIV acquisitions.
“In particular we’re concerned about the concept of ‘prevention futility’ and its relationship to PrEP,” he stated, defining prevention futility as “the notion that interventions like PrEP will eventually fail if they do not durably alter the conditions that allow HIV transmission.” Will it prove that PrEP only delayed HIV infection among people who will continue to be at high risk after discontinuing PrEP?
The iPrEx OLE study enrolled 1,529 previously HIV-negative former iPrEx participants, representing 65% of the original study population. In the gap between trial phases, participants had access to services (such as HIV testing) offered at study sites but had no scheduled study visits and did not receive PrEP.
“We found that we preferentially retained persons who had slightly higher HIV risk factors, as indicated by condomless receptive anal intercourse,” noted Grant: 67% of iPrEx participants who reported having condomless receptive anal sex opted to join iPrEx OLE, compared with 63% who reported no condomless receptive anal sex.
Interestingly, those who had received Truvada rather than placebo pills during the blinded phase of iPrEx were neither more nor less likely to be interested in continuing to take PrEP in OLE. However, Grant added, “those in the active arm who had detectable drug during the randomized phase”—indicating their consistent adherence—“were much more likely to want to continue participating in the open-label extension.” Of those with detectable drug in blood plasma at any study visit, 72% opted into OLE, compared with 57% of participants with no detectable drug at any study visit.
During the gap in access to PrEP, 78 new HIV infections occurred. Among those who had taken placebo pills during iPrEx, HIV incidence during the gap was 4.1 infection events per person-year, or PY (that is, the number or people who received placebo multiplied by the number of years they took it) compared with 3.3 new infections per PY in those who had taken Truvada during iPrEx. (This difference did not reach statistical significance.)
“There was no excess incidence after stopping PrEP, even in the case of protective PrEP as observed in iPrEx,” Grant concluded.
In addition, HIV risk in the iPrEx trial was not constant; reports of engaging in condomless receptive anal sex fluctuated over time: “Despite high HIV incidence overall in this cohort, participants moved in and out of ‘seasons of risk.’”
Grant ended his presentation by thanking the iPrEx participants and highlighting their newly debuted video, “Voices of Choice.” In the video, PrEP users from Brazil, Peru, and the United States frankly share their experiences—why they wanted to take PrEP, how it affected their lives and relationships, and the challenges that came with it (including issues around paying for PrEP; a link to Gilead Sciences’ Truvada Medication Assistance Program appears near the end). Check out the new video here.
Reilly O’Neal is the editor of BETA.
Grant, R. and others. No excess in HIV incidence after stopping oral emtricitabine/tenofovir pre-exposure prophylaxis: the iPrEx trial. 20th Conference on Retroviruses and Opportunistic Infections. Atlanta. March 3–6, 2013. Abstract #27.Related