Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana.
BACKGROUND
Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus (HIV) among men who have sex with men; however, the efficacy among heterosexuals is uncertain.


METHODS
We randomly assigned HIV-seronegative men and women to receive either tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or matching placebo once daily. Monthly study visits were scheduled, and participants received a comprehensive package of prevention services, including HIV testing, counseling on adherence to medication, management of sexually transmitted infections, monitoring for adverse events, and individualized counseling on risk reduction; bone mineral density testing was performed semiannually in a subgroup of participants.


RESULTS
A total of 1219 men and women underwent randomization (45.7% women) and were followed for 1563 person-years (median, 1.1 years; maximum, 3.7 years). Because of low retention and logistic limitations, we concluded the study early and followed enrolled participants through an orderly study closure rather than expanding enrollment. The TDF-FTC group had higher rates of nausea (18.5% vs. 7.1%, P<0.001), vomiting (11.3% vs. 7.1%, P=0.008), and dizziness (15.1% vs. 11.0%, P=0.03) than the placebo group, but the rates of serious adverse events were similar (P=0.90). Participants who received TDF-FTC, as compared with those who received placebo, had a significant decline in bone mineral density. K65R, M184V, and A62V resistance mutations developed in 1 participant in the TDF-FTC group who had had an unrecognized acute HIV infection at enrollment. In a modified intention-to-treat analysis that included the 33 participants who became infected during the study (9 in the TDF-FTC group and 24 in the placebo group; 1.2 and 3.1 infections per 100 person-years, respectively), the efficacy of TDF-FTC was 62.2% (95% confidence interval, 21.5 to 83.4; P=0.03).


CONCLUSIONS
Daily TDF-FTC prophylaxis prevented HIV infection in sexually active heterosexual adults. The long-term safety of daily TDF-FTC prophylaxis, including the effect on bone mineral density, remains unknown. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health; TDF2 ClinicalTrials.gov number, NCT00448669.).
Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, USA. mthigpen@cdc.gov
Michael C
MC
Thigpen
Poloko M
PM
Kebaabetswe
Lynn A
LA
Paxton
Dawn K
DK
Smith
Charles E
CE
Rose
Tebogo M
TM
Segolodi
Faith L
FL
Henderson
Sonal R
SR
Pathak
Fatma A
FA
Soud
Kata L
KL
Chillag
Rodreck
R
Mutanhaurwa
Lovemore Ian
LI
Chirwa
Michael
M
Kasonde
Daniel
D
Abebe
Evans
E
Buliva
Roman J
RJ
Gvetadze
Sandra
S
Johnson
Thom
T
Sukalac
Vasavi T
VT
Thomas
Clyde
C
Hart
Jeffrey A
JA
Johnson
C Kevin
CK
Malotte
Craig W
CW
Hendrix
John T
JT
Brooks
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects; D003268:Contraception Behavior / Q000706:statistics & numerical data; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000517:prevention & control*; D006679:HIV Seropositivity; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D015498:HIV-2 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000097:blood; D012725:Sexual Behavior / Q000706:statistics & numerical data; D000068698:Tenofovir; D019562:Viral Load; D055815:Young Adult
D044966:Anti-Retroviral Agents; D063065:Organophosphonates; D012367:RNA, Viral; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine