A pilot, randomized controlled trial of Dual Daily HIV and sexually transmitted infection pre-exposure prophylaxis using tenofovir disoproxil fumarate/emtricitabine and doxycycline in gay, bisexual and other men who have sex with men and transgender women: The DuDHS Study.

Abstract

BACKGROUND Men who have sex with men (MSM) and transgender women experience high sexually transmitted infection (STI) rates. This study evaluated the feasibility of doxycycline pre-exposure prophylaxis (doxyPrEP) for STI prevention in these key populations. METHODS Sexually-active MSM and transgender women without HIV with prior syphilis were recruited. Participants initiated HIV PrEP with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) daily for 48 weeks, and were randomized 1:1 to daily doxyPrEP for 48 weeks (immediate arm), or doxyPrEP initiated at 24 weeks (deferred arm). Primary outcomes included adherence, measured using questionnaires, along with tolerability; STI incidence (chlamydia, gonorrhea, syphilis) was a secondary outcome. Nasal carriage of S. aureus was assessed serially for doxycycline resistance. RESULTS Fifty-two participants were enrolled into the immediate (n=26) and deferred (n=26) arms. At 48 weeks, self-reported adherence (≥95%) was 75.0% vs. 66.7% (p=0.538) for TDF/FTC, and 70.8% vs. 61.9% (p=0.526) for doxycycline in the immediate vs. deferred arms, respectively. No doxyPrEP-related serious adverse events occurred. Incidence of any STI at 24 weeks was reduced in the immediate vs. deferred arms, and over 48 weeks, being on doxycycline (vs. being off; i.e. first 24 weeks of deferred arm) was associated with STI reduction (adjusted odds ratio [aOR] 0.36; 95 % confidence interval [CI] 0.15-0.89). Emergent doxycycline-resistant S. aureus was identified in six individuals, with five in the immediate arm (p=0.077). CONCLUSIONS Dual HIV/doxyPrEP is feasible and associated with a significant reduction in incident STI. Further evaluation of dosing strategies, efficacy and impact on antimicrobial resistance is warranted.