Tenofovir-based preexposure prophylaxis for HIV infection among African women.

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.).

• Authors: 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
• Journal: The New England journal of medicine (N Engl J Med) Vol. 372 Issue 6 Pg. 509-18 (Feb 05 2015) ISSN: 1533-4406 [Electronic] United States
• PMID: 25651245 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Anti-Retroviral Agents
• Organophosphonates
• Deoxycytidine
• Tenofovir
• Emtricitabine
• Adenine

Topics

• Adenine (administration & dosage, adverse effects, analogs & derivatives, blood)
• Administration, Intravaginal
• Administration, Oral
• Adolescent
• Adult
• Africa South of the Sahara
• Anti-Retroviral Agents (administration & dosage, adverse effects, blood)
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives, blood)
• Drug Resistance, Viral
• Drug Therapy, Combination
• Emtricitabine
• Female
• HIV Infections (complications, prevention & control)
• HIV Seropositivity
• HIV-1 (drug effects)
• Humans
• Medication Adherence
• Middle Aged
• Organophosphonates (administration & dosage, adverse effects, blood)
• Pre-Exposure Prophylaxis
• Surveys and Questionnaires
• Tenofovir
• Young Adult