Antiretroviral prophylaxis for HIV prevention in heterosexual men and women.
BACKGROUND
Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations.


METHODS
We conducted a randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1-serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1-seronegative partner in each couple was randomly assigned to one of three study regimens--once-daily tenofovir (TDF), combination tenofovir-emtricitabine (TDF-FTC), or matching placebo--and followed monthly for up to 36 months. At enrollment, the HIV-1-seropositive partners were not eligible for antiretroviral therapy, according to national guidelines. All couples received standard HIV-1 treatment and prevention services.


RESULTS
We enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned to TDF, 1579 to TDF-FTC, and 1584 to placebo. For 62% of the couples followed, the HIV-1-seronegative partner was male. Among HIV-1-seropositive participants, the median CD4 count was 495 cells per cubic millimeter (interquartile range, 375 to 662). A total of 82 HIV-1 infections occurred in seronegative participants during the study, 17 in the TDF group (incidence, 0.65 per 100 person-years), 13 in the TDF-FTC group (incidence, 0.50 per 100 person-years), and 52 in the placebo group (incidence, 1.99 per 100 person-years), indicating a relative reduction of 67% in the incidence of HIV-1 with TDF (95% confidence interval [CI], 44 to 81; P<0.001) and of 75% with TDF-FTC (95% CI, 55 to 87; P<0.001). Protective effects of TDF-FTC and TDF alone against HIV-1 were not significantly different (P=0.23), and both study medications significantly reduced the HIV-1 incidence among both men and women. The rate of serious adverse events was similar across the study groups. Eight participants receiving active treatment were found to have been infected with HIV-1 at baseline, and among these eight, antiretroviral resistance developed in two during the study.


CONCLUSIONS
Oral TDF and TDF-FTC both protect against HIV-1 infection in heterosexual men and women. (Funded by the Bill and Melinda Gates Foundation; Partners PrEP ClinicalTrials.gov number, NCT00557245.).
Department of Global Health, University of Washington, Seattle, WA 98104, USA. jbaeten@uw.edu
Jared M
JM
Baeten
Deborah
D
Donnell
Patrick
P
Ndase
Nelly R
NR
Mugo
James D
JD
Campbell
Jonathan
J
Wangisi
Jordan W
JW
Tappero
Elizabeth A
EA
Bukusi
Craig R
CR
Cohen
Elly
E
Katabira
Allan
A
Ronald
Elioda
E
Tumwesigye
Edwin
E
Were
Kenneth H
KH
Fife
James
J
Kiarie
Carey
C
Farquhar
Grace
G
John-Stewart
Aloysious
A
Kakia
Josephine
J
Odoyo
Akasiima
A
Mucunguzi
Edith
E
Nakku-Joloba
Rogers
R
Twesigye
Kenneth
K
Ngure
Cosmas
C
Apaka
Harrison
H
Tamooh
Fridah
F
Gabona
Andrew
A
Mujugira
Dana
D
Panteleeff
Katherine K
KK
Thomas
Lara
L
Kidoguchi
Meighan
M
Krows
Jennifer
J
Revall
Susan
S
Morrison
Harald
H
Haugen
Mira
M
Emmanuel-Ogier
Lisa
L
Ondrejcek
Robert W
RW
Coombs
Lisa
L
Frenkel
Craig
C
Hendrix
Namandjé N
NN
Bumpus
David
D
Bangsberg
Jessica E
JE
Haberer
Wendy S
WS
Stevens
Jairam R
JR
Lingappa
Connie
C
Celum
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*; D003268:Contraception Behavior / Q000706:statistics & numerical data; 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; D020010:Heterosexuality; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D011247:Pregnancy; D012367:RNA, Viral / Q000097:blood; D012725:Sexual Behavior / Q000706:statistics & numerical data; D000068698:Tenofovir; D055815:Young Adult
D044966:Anti-Retroviral Agents; D004338:Drug Combinations; D063065:Organophosphonates; D012367:RNA, Viral; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine