Dolutegravir with tenofovir disoproxil fumarate–emtricitabine as HIV postexposure prophylaxis in gay and bisexual men

Objectives: Completion rates for HIV postexposure prophylaxis (PEP) are often low. We investigated the adherence and safety of dolutegravir (DTG; 50 mg daily) with tenofovir disoproxil fumarate–emtricitabine (TDF–FTC; 300/200 mg, respectively) as three-drug PEP in gay and bisexual men. Design: Open-label, single-arm study at three sexual health clinics and two emergency departments in Australia. Methods: In total, 100 HIV-uninfected gay and bisexual men requiring PEP received DTG and TDF–FTC for 28 days. The primary end point was PEP failure (premature PEP cessation or primary HIV infection through week 12). Additional end points were adherence by self-report (n = 98) and pill count (n = 55), safety, and plasma drug levels at day 28. Results: PEP completion was 90% (95% confidence interval 84–96%). Failures (occurring at a median 9 days, interquartile range 3–16) comprised loss to follow-up (9%) and adverse event resulting in study drug discontinuation (headache, 1%). No participant was found to acquire HIV through week 12. Adherence to PEP was 98% by self-report and in the 55 participants with corresponding pill count data. The most common clinical adverse events were fatigue (26%), nausea (25%), diarrhoea (21%), and headache (10%). There were only four grade 3–4 subjective adverse events. The most common laboratory adverse event was raised alanine aminotransferase (22%), but there was no case of clinical hepatitis. At day 28, the mean estimated glomerular filtration rate decrease was 14 ml/min/1.73m2 (SD 17, P = 0.001); an estimated glomerular filtration rate of less than 60 ml/min/1.73m2 occurred in 3%. Conclusions: DTG with TDF–FTC is a well tolerated option for once-daily PEP.