HIV Prevention: PrEP With TAF/FTC Is More Protective Than Placebo

The risk for HIV infection is substantially lower with tenofovir alafenamide plus emtricitabine (TAF/FTC) compared with placebo, according to results of a study published in The Journal of Infectious Diseases.

Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) has been shown to be an effective HIV prevention strategy, demonstrating noninferiority when compared against TAF/FTC.

To estimate the efficacy of TAF/FTC relative to placebo for the prevention of HIV infection among men who have sex with men, researchers sourced data from a phase 3 noninferiority trial (ClinicalTrials.gov Identifier: NCT02842086) and a phase 3 placebo-controlled trial (NCT00458393) trial. The trials were conducted from 2016 to 2017 and 2017 to 2009, respectively. Adult high-risk patients were randomly assigned 1:1 to treatment groups in both the nonferiority (TAF/FTC or TDF/FTC) and placebo-controlled (TDF/FTC or placebo) trials. The primary outcome of both trials was incident HIV infection. To standardize patient data captured in each trial, an inverse probability weighting approach was used. Contextual differences between the trials were addressed via bridged treatment comparison.

There were 2488 patients assigned to TDF/FTC and 2464 assigned to TAF/FTC in the noninferiority trial, of whom 11% and 12% were aged 18 to 24 years, 15% and 14% were non-White, 15% and 16% reported consuming at least 5 alcoholic beverages daily, and 24% and 23% reported no history of unprotected receptive anal intercourse, respectively.

Of TDF/FTC (n=1059) and placebo (n=1049) recipients enrolled in the placebo-controlled trial, 47% and 52% were aged 18 to 24 years, 81% and 82% were non-White, 54% and 55% reported consuming at least 5 alcoholic beverages daily, and 46% and 44% reported no history of unprotected receptive anal intercourse, respectively.

At 96 weeks, 1% of TDF/FTC and 0% of TAF/FTC recipients in the noninferiority trial, and 3% of TDF/FTC and 6% of placebo recipients in the placebo-controlled trial, tested positive for HIV infection.

Prior to standardization, the risk for HIV infection was significantly higher among TDF/FTC recipients in the placebo-controlled trial compared with TDF/FTC recipients in the noninferiority trial (P <.01). However, the risk was not significantly different between these groups after standardization (P =.87).

In a simple transitive comparison, the risk for HIV infection was 7.8% lower among patients who received TAF/FTC compared with those who received placebo (risk ratio [RR], 0.04).

In the bridged comparison, the risk for HIV infection at 96 weeks was 5.8% (95% CI, -2.0 to -9.6) lower among TAF/FTC vs placebo recipients (RR, 0.08; 95% CI, 0.02-0.31).

The researchers observed similar findings in 2 sensitivity analyses.

Limitations of this study include significant differences between the 2 trials. These include the enrollment of patients from middle- and high-income countries, the use of different HIV testing methods, and the separation of nearly a decade in time between the trials.

“We found a meaningful reduction in HIV risk with TAF/FTC versus placebo, but the estimated reduction was smaller than anticipated based on a simple comparison across trials,” the researchers noted. “The over-estimate from the simple comparison stemmed from underlying differences in the trial populations in terms of demographics, HIV risk factors, and other contextual factors,” they concluded.

This article originally appeared on Infectious Disease Advisor