Preexposure prophylaxis for HIV infection among African women.
BACKGROUND
Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus (HIV) infection in some trials but not in others.


METHODS
In this randomized, double-blind, placebo-controlled trial, we assigned 2120 HIV-negative women in Kenya, South Africa, and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or placebo once daily. The primary objective was to assess the effectiveness of TDF-FTC in preventing HIV acquisition and to evaluate safety.


RESULTS
HIV infections occurred in 33 women in the TDF-FTC group (incidence rate, 4.7 per 100 person-years) and in 35 in the placebo group (incidence rate, 5.0 per 100 person-years), for an estimated hazard ratio in the TDF-FTC group of 0.94 (95% confidence interval, 0.59 to 1.52; P=0.81). The proportions of women with nausea, vomiting, or elevated alanine aminotransferase levels were significantly higher in the TDF-FTC group (P=0.04, P<0.001, and P=0.03, respectively). Rates of drug discontinuation because of hepatic or renal abnormalities were higher in the TDF-FTC group (4.7%) than in the placebo group (3.0%, P=0.051). Less than 40% of the HIV-uninfected women in the TDF-FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion. The study was stopped early, on April 18, 2011, because of lack of efficacy.


CONCLUSIONS
Prophylaxis with TDF-FTC did not significantly reduce the rate of HIV infection and was associated with increased rates of side effects, as compared with placebo. Despite substantial counseling efforts, drug adherence appeared to be low. (Supported by the U.S. Agency for International Development and others; FEM-PrEP ClinicalTrials.gov number, NCT00625404.).
FHI 360, Research Triangle Park, North Carolina, USA. lvandamme@fhi360.org
Lut
L
Van Damme
Amy
A
Corneli
Khatija
K
Ahmed
Kawango
K
Agot
Johan
J
Lombaard
Saidi
S
Kapiga
Mookho
M
Malahleha
Fredrick
F
Owino
Rachel
R
Manongi
Jacob
J
Onyango
Lucky
L
Temu
Modie Constance
MC
Monedi
Paul
P
Mak'Oketch
Mankalimeng
M
Makanda
Ilse
I
Reblin
Shumani Elsie
SE
Makatu
Lisa
L
Saylor
Haddie
H
Kiernan
Stella
S
Kirkendale
Christina
C
Wong
Robert
R
Grant
Angela
A
Kashuba
Kavita
K
Nanda
Justin
J
Mandala
Katrien
K
Fransen
Jennifer
J
Deese
Tania
T
Crucitti
Timothy D
TD
Mastro
Douglas
D
Taylor
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016022:Case-Control Studies; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004311:Double-Blind Method; D004338:Drug Combinations; D024882:Drug Resistance, Viral; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000453:epidemiology / Q000517:prevention & control*; D006679:HIV Seropositivity; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D055118:Medication Adherence; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D012309:Risk-Taking; D012725:Sexual Behavior / Q000706:statistics & numerical data; D000068698:Tenofovir; D017211:Treatment Failure; D019562:Viral Load; D055815:Young Adult
D044966:Anti-Retroviral Agents; D004338:Drug Combinations; D063065:Organophosphonates; D012367:RNA, Viral; D003841:Deoxycytidine; D000068698:Tenofovir; D000410:Alanine Transaminase; D000068679:Emtricitabine; D000225:Adenine