Forty-three percent took the pills correctly. The participants were followed for a median of 9.3 months. Overall, 72% of the participants took the study drugs (TDF-FTC or placebo), although 29% took a suboptimal dose. There was no change in the sexual behavior of the participants during the study. The study was unblinded after 20 months and is continuing as an open-label study because of the discontinuation of another preexposure prophylaxis study in the United Kingdom, which showed an NNT of 13 to prevent one new HIV infection per year.3
An independent data and safety monitoring board recommended the unblinding because the placebo group was considered to be at significantly increased risk of contracting HIV without PrEP. The open-label part of the study, iPrex-OLE, completed enrollment and data gathering in November 2013, and the data analysis and results are presently pending.9
Eighty-six percent relative reduction in HIV. The primary end-point was the diagnosis of HIV-1 infection, and the results were based on an intention-to-treat analysis. HIV-1 infection was diagnosed in 19 study participants, with 3 of those new cases occurring between the time of randomization and enrollment. Fourteen of the cases were in the placebo group (6.6 infections per 100 person-years) and 2 of the new cases were in the TDF-FTC group (incidence 0.91 per 100 person-years). This translated to a relative reduction in the incidence of new HIV-1 seroconversion in the TDF-FTC group of 86% (95% confidence interval, 40%-98%; P=.002; NNT=17 over 9.3 months).
The 2 study participants in the TDF-FTC group diagnosed with new HIV-1 were found to be non-adherent to the prescribed prophylaxis, as they returned 58 and 60 of the 60 pills administered to them, and no study drugs were found in their plasma samples.
Adverse events included gastrointestinal symptoms of nausea, vomiting, diarrhea, and abdominal pain and were seen at a greater rate (14% vs 5%, P=.002; number needed to harm=11) in the treatment group than in the placebo group. There were also mild increases in serum creatinine level (seen in 18% of the TDF-FTC group), but only 2 participants had a transient decrease in creatinine clearance to <60 mL/min. None of the participants discontinued medications due to renal issues.
WHAT’S NEW
Risk reduction with on-demand use is nearly double that of daily use
This is the first study to look at on-demand preexposure prophylaxis with TDF-FTC to decrease the incidence of HIV-1 infection in high-risk MSM. The risk reduction in this study (86%) was much better than the 44% seen in the prior study that used daily PrEP in this population.6 We suspect the higher benefit of on-demand PrEP is likely due to increased compliance with medication use.
CAVEATS
Is fewer pills enough to maintain adherence over time?
The median length of follow-up in the study was 9.3 months. One concern is that adherence may wane over time, decreasing the efficacy of the prophylaxis. Continued efforts to improve compliance with this type of PrEP may be needed to ensure efficacy. Since the study was shortened and reported early, we will need to wait for the results of the open-label study to fully assess the risks of adverse events.
CHALLENGES TO IMPLEMENTATION
Efficacy and convenience come at a cost
The main challenge to implementation could be the cost of TDF-FTC, the retail price of which is about $50 per dose.10 Insurance coverage for the medication varies.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
