Table 2.

Summary of randomised, placebo-controlled clinical trials of daily oral PrEP

Trial	Population	Proportion of women	Intervention	Overall efficacy	Efficacy among women	Adherence	Efficacy based on adherence
iPrEX [10,27,42]	2499 men and transgender women who have sex with men Followed for median 1.2 years	339 (14%) classified as transgender women	Daily oral TDF/FTC vs placebo	44% (95% CI: 15–63%) 36 HIV infections in TDF/FTC group vs 64 in placebo group	Among transgender women, 11 infections in TDF/FTC group vs 10 in placebo group (HR: 1.1, 95% CI: 0.5–2.7)	Detectable study drug level in 51% of seronegative subjects vs 9% of HIV-infected subjects No detectable drug among transgender women who acquired HIV	95% risk reduction with detectable study drug; 90% reduction with 16 fmol tenofovir-diphosphate/ million PBMCs; 96% reduction estimated by taking 4 doses/ week
Partners PrEP [11,17]	4758 HIV-mutually disclosed serodiscordant couples in Uganda and Kenya where seropositive partner was not eligible for ART enrolment Followed for median 23 months	1785 (52%) women	Daily oral TDF vs TDF/FTC vs placebo	67% (95% CI: 44–81%) for TDF; 75% (95% CI: 55–87%) for TDF/FTC 17 HIV infections in TDF group (0.65/100 person-years) vs 13 in TDF/FTC group (0.50/100 person-years) vs 52 in placebo group (1.99/100 person-years)	No difference in efficacy between men and women Efficacy among women 71% for TDF and 66% for TDF/FTC Efficacy consistently demonstrated (64–84%) among higher-risk subgroups of women	Detectable plasma tenofovir levels in 83% who did not acquire HIV vs 31% who acquired HIV	86% risk reduction for TDF and 90% for TDF/FTC with detectable tenofovir level
TDF2 [12]	1219 heterosexual men and women in Botswana Followed for median 1.1 years	557 (45.7%) women	Daily oral TDF/FTC vs placebo	62.2% (95% CI: 21.5–83.4%) 9 HIV infections in TDF/FTC group (1.2/100 person-years) vs 24 in placebo group (3.1/100 person-years)	Efficacy among women 49%	Detectable plasma tenofovir levels in 80% who did not acquire HIV vs 50% who acquired HIV	HIV acquisition associated with lower plasma concentrations of tenofovir and emtricitabine
BTS [13]	2413 men and women who use injection drugs in Thailand Followed for average 4 years	489 (20%) women	Daily oral TDF vs placebo	48.9% (95% CI: 9.6–72.2%) 17 HIV infections in TDF group (0.35/100 person-years) vs 33 in placebo group (0.68/100 person-years)	Efficacy among women 78.6%	Detectable plasma tenofovir levels in 66% overall	70% risk reduction with detectable tenofovir level
FEM-PrEP [16]	2120 heterosexual women in South Africa, Kenya, Tanzania Followed for 1407 person-years Study terminated early due to lack of efficacy	100% women	Daily oral TDF/FTC vs placebo	No reduction in HIV acquisition risk (HR: 0.94, 95% CI: 0.59–1.52) 33 HIV infections in TDF/FTC group (4.7/100 person-years) vs 35 in placebo group (5.0/100 person-years)	N/A	Adherence 95% by self-report, 88% by pill count, but <40% by plasma tenofovir levels (≥10 ng/mL)	No statistically significant association between HIV seroconversion and plasma tenofovir levels
VOICE [15]	5029 heterosexual women in South Africa, Uganda and Zimbabwe 5509 person-years follow-up	100% women	Daily oral TDF vs TDF/FTC vs oral placebo vs daily vaginal 1% tenofovir gel vs vaginal placebo gel	No difference in HIV acquisition risk by study group; 312 HIV infections (5.7/100 person-years) TDF: HR:1.49 (95% CI: 0.97–2.29) TDF/FTC: HR: 1.04 (95% CI: 0.73–1.49)	N/A	Adherence 90% by self-report, 86% by returned pills; plasma tenofovir detected in 30% of group on TDF and 29% of those on TDF/FTC Factors negatively associated with detectable plasma tenofovir also associated with increased HIV acquisition risk	No statistically significant association between plasma tenofovir detection and HIV incidence in oral TDF or TDF/FTC groups

Abbreviations: TDF, tenofovir disoproxil fumarate; FTC, emtricitabine; HR, hazard ratio; CI, confidence interval; PBMC, peripheral blood mononuclear cells; ART, antiretroviral therapy.