Tenofovir-based preexposure prophylaxis for HIV infection among African women
Jeanne M Marrazzo, Gita Ramjee, Barbra A Richardson, Kailazarid Gomez, Nyaradzo Mgodi, Gonasagrie Nair, Thesla Palanee, Clemensia Nakabiito, Ariane van der Straten, Lisa Noguchi, Craig W Hendrix, James Y Dai, Shayhana Ganesh, Baningi Mkhize, Marthinette Taljaard, Urvi M Parikh, Jeanna Piper, Benoît Mâsse, Cynthia Grossman, James Rooney, Jill L Schwartz, Heather Watts, Mark A Marzinke, Sharon L Hillier, Ian M McGowan, Z Mike Chirenje, VOICE Study Team, Zvavahera Mike Chirenje, Jeanne Marrazzo, Vivian Bragg, Kailazarid Gomez, Stephanie Horn, Lisa Levy, Ashley Mayo, Ayana T Moore, Katherine Richards, Katie Schwartz, Rhonda White, Kristine Torjesen, Joleen Borgerding, Sharavi Gandham, Cliff Kelly, Benoît Mâsse, Karen Patterson, Barbra Richardson, Molly Swenson, James Dai, Craig Hendrix, Edward Livant, John Mellors, Urvi Parikh, Mark Marzinke, Krista Eskay, Russell Hardesty, Kelley Gordon, Kristen Cummings, Katherine Bunge, Connie L Celum, Ross D Cranston, Beth Galaska Burzuk, Betsy Herold, Devika Singh, Sharon Hillier, Cindy Jacobson, Ian McGowan, Patrick Ndase, Lisa Noguchi, Sharon A Riddler, Ariane van der Straten, Roberta Black, Scharla Estep, Andrew D Forsyth, Jeanna Piper, Usha Sharma, Lydia E Soto-Torres, Cyndi Grossman, Heather Watts, Tsitsi Magure, Nyaradzo Mgodi, Petina Musara, Margaret Mlingo, Clemensia Nakabiito, Flavia Matovu, Samuel Kabwigu, Shayhana Ganesh, Sharika Gappoo, Marwah Jenneker, Shahnaaz Kadwa, Vimla Naicker, Sarita Naidoo, Gita Ramjee, Yuki Sookrajh, Linda Zako, Sharika Gappoo, Nicola Coumi, Arendevi Pather, Vijayanand Guddera, Gonasagrie Nair, Kalendri Naidoo, Baningi Mkhize, Wilma Pelser, Kathy Mngadi, Marthinette Taljaard, Pearl Selepe, Ronel Brown, Thesla Palanee, Pranitha Ramchuran, Godspower Akpomiemie, Henry L Gabelnick, Jill Schwartz, James Rooney, Jeanne M Marrazzo, Gita Ramjee, Barbra A Richardson, Kailazarid Gomez, Nyaradzo Mgodi, Gonasagrie Nair, Thesla Palanee, Clemensia Nakabiito, Ariane van der Straten, Lisa Noguchi, Craig W Hendrix, James Y Dai, Shayhana Ganesh, Baningi Mkhize, Marthinette Taljaard, Urvi M Parikh, Jeanna Piper, Benoît Mâsse, Cynthia Grossman, James Rooney, Jill L Schwartz, Heather Watts, Mark A Marzinke, Sharon L Hillier, Ian M McGowan, Z Mike Chirenje, VOICE Study Team, Zvavahera Mike Chirenje, Jeanne Marrazzo, Vivian Bragg, Kailazarid Gomez, Stephanie Horn, Lisa Levy, Ashley Mayo, Ayana T Moore, Katherine Richards, Katie Schwartz, Rhonda White, Kristine Torjesen, Joleen Borgerding, Sharavi Gandham, Cliff Kelly, Benoît Mâsse, Karen Patterson, Barbra Richardson, Molly Swenson, James Dai, Craig Hendrix, Edward Livant, John Mellors, Urvi Parikh, Mark Marzinke, Krista Eskay, Russell Hardesty, Kelley Gordon, Kristen Cummings, Katherine Bunge, Connie L Celum, Ross D Cranston, Beth Galaska Burzuk, Betsy Herold, Devika Singh, Sharon Hillier, Cindy Jacobson, Ian McGowan, Patrick Ndase, Lisa Noguchi, Sharon A Riddler, Ariane van der Straten, Roberta Black, Scharla Estep, Andrew D Forsyth, Jeanna Piper, Usha Sharma, Lydia E Soto-Torres, Cyndi Grossman, Heather Watts, Tsitsi Magure, Nyaradzo Mgodi, Petina Musara, Margaret Mlingo, Clemensia Nakabiito, Flavia Matovu, Samuel Kabwigu, Shayhana Ganesh, Sharika Gappoo, Marwah Jenneker, Shahnaaz Kadwa, Vimla Naicker, Sarita Naidoo, Gita Ramjee, Yuki Sookrajh, Linda Zako, Sharika Gappoo, Nicola Coumi, Arendevi Pather, Vijayanand Guddera, Gonasagrie Nair, Kalendri Naidoo, Baningi Mkhize, Wilma Pelser, Kathy Mngadi, Marthinette Taljaard, Pearl Selepe, Ronel Brown, Thesla Palanee, Pranitha Ramchuran, Godspower Akpomiemie, Henry L Gabelnick, Jill Schwartz, James Rooney
Abstract
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 person-years. 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. (Funded by the National Institutes of Health; VOICE ClinicalTrials.gov number, NCT00705679.).
Conflict of interest statement
No other potential conflict of interest relevant to this article was reported.
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Source: PubMed