TY - JOUR
T1 - Tenofovir-based preexposure prophylaxis for HIV infection among African women
AU - VOICE Study Team
AU - Marrazzo, Jeanne M.
AU - Ramjee, Gita
AU - Richardson, Barbra A.
AU - Gomez, Kailazarid
AU - Mgodi, Nyaradzo
AU - Nair, Gonasagrie
AU - Palanee, Thesla
AU - Nakabiito, Clemensia
AU - Van Der Straten, Ariane
AU - Noguchi, Lisa
AU - Hendrix, Craig W.
AU - Dai, James Y.
AU - Ganesh, Shayhana
AU - Mkhize, Baningi
AU - Taljaard, Marthinette
AU - Parikh, Urvi M.
AU - Piper, Jeanna
AU - Mâsse, Benoît
AU - Grossman, Cynthia
AU - Rooney, James
AU - Schwartz, Jill L.
AU - Watts, Heather
AU - Marzinke, Mark A.
AU - Hillier, Sharon L.
AU - McGowan, Ian M.
AU - Chirenje, Z. Mike
N1 - Publisher Copyright:
Copyright © 2015 Massachusetts Medical Society.
PY - 2015/2/5
Y1 - 2015/2/5
N2 - BACKGROUND: Reproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection. METHODS: We conducted a randomized, placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate (TDF), oral tenofovir-emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel as preexposure prophylaxis against HIV-1 infection in women in South Africa, Uganda, and Zimbabwe. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly. RESULTS: Of 12,320 women who were screened, 5029 were enrolled in the study. The rate of retention in the study was 91% during 5509 person-years of follow-up. A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 personyears. In the modified intention-to-treat analysis, the effectiveness was-49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29),-4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49), and 14.5% with TFV gel (hazard ratio, 0.85; 95% CI, 0.61 to 1.21). In a random sample, TFV was detected in 30%, 29%, and 25% of available plasma samples from participants randomly assigned to receive TDF, TDF-FTC, and TFV gel, respectively. Independent predictors of TFV detection included being married, being older than 25 years of age, and being multiparous. Detection of TFV in plasma was negatively associated with characteristics predictive of HIV-1 acquisition. Elevations of serum creatinine levels were seen more frequently among participants randomly assigned to receive oral TDF-FTC than among those assigned to receive oral placebo (1.3% vs. 0.2%, P = 0.004). We observed no significant differences in the frequencies of other adverse events. CONCLUSIONS: None of the drug regimens we evaluated reduced the rates of HIV-1 acquisition in an intention-to-treat analysis. Adherence to study drugs was low.
AB - BACKGROUND: Reproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection. METHODS: We conducted a randomized, placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate (TDF), oral tenofovir-emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel as preexposure prophylaxis against HIV-1 infection in women in South Africa, Uganda, and Zimbabwe. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly. RESULTS: Of 12,320 women who were screened, 5029 were enrolled in the study. The rate of retention in the study was 91% during 5509 person-years of follow-up. A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 personyears. In the modified intention-to-treat analysis, the effectiveness was-49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29),-4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49), and 14.5% with TFV gel (hazard ratio, 0.85; 95% CI, 0.61 to 1.21). In a random sample, TFV was detected in 30%, 29%, and 25% of available plasma samples from participants randomly assigned to receive TDF, TDF-FTC, and TFV gel, respectively. Independent predictors of TFV detection included being married, being older than 25 years of age, and being multiparous. Detection of TFV in plasma was negatively associated with characteristics predictive of HIV-1 acquisition. Elevations of serum creatinine levels were seen more frequently among participants randomly assigned to receive oral TDF-FTC than among those assigned to receive oral placebo (1.3% vs. 0.2%, P = 0.004). We observed no significant differences in the frequencies of other adverse events. CONCLUSIONS: None of the drug regimens we evaluated reduced the rates of HIV-1 acquisition in an intention-to-treat analysis. Adherence to study drugs was low.
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U2 - 10.1056/NEJMoa1402269
DO - 10.1056/NEJMoa1402269
M3 - Article
C2 - 25651245
AN - SCOPUS:84922287392
VL - 372
SP - 509
EP - 518
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 6
ER -