Effect of herpes simplex suppression on incidence of HIV among women in Tanzania.
BACKGROUND
Infection with herpes simplex virus type 2 (HSV-2) is associated with an increased risk of acquiring infection with the human immunodeficiency virus (HIV). This study tested the hypothesis that HSV-2 suppressive therapy reduces the risk of HIV acquisition.


METHODS
Female workers at recreational facilities in northwestern Tanzania who were 16 to 35 years of age were interviewed and underwent serologic testing for HIV and HSV-2. We enrolled female workers who were HIV-seronegative and HSV-2-seropositive in a randomized, double-blind, placebo-controlled trial of suppressive treatment with acyclovir (400 mg twice daily). Participants attended mobile clinics every 3 months for a follow-up period of 12 to 30 months, depending on enrollment date. The primary outcome was the incidence of infection with HIV. We used a modified intention-to-treat analysis; data for participants who became pregnant were censored. Adherence to treatment was estimated by a tablet count at each visit.


RESULTS
A total of 821 participants were randomly assigned to receive acyclovir (400 participants) or placebo (421 participants); 679 (83%) completed follow-up. Mean follow-up for the acyclovir and placebo groups was 1.52 and 1.62 years, respectively. The incidence of HIV infection was 4.27 per 100 person-years (27 participants in the acyclovir group and 28 in the placebo group), and there was no overall effect of acyclovir on the incidence of HIV (rate ratio for the acyclovir group, 1.08; 95% confidence interval, 0.64 to 1.83). The estimated median adherence was 90%. Genital HSV was detected in a similar proportion of participants in the two study groups at 6, 12, and 24 months. No serious adverse events were attributable to treatment with acyclovir.


CONCLUSIONS
These data show no evidence that acyclovir (400 mg twice daily) as HSV suppressive therapy decreases the incidence of infection with HIV. (Current Controlled Trials number, ISRCTN35385041 [controlled-trials.com].).
Watson-Jones
Deborah
D
London School of Hygiene and Tropical Medicine, London. deborah.watson-jones@lshtm.ac.uk
Weiss
Helen A
HA
Rusizoka
Mary
M
Changalucha
John
J
Baisley
Kathy
K
Mugeye
Kokugonza
K
Tanton
Clare
C
Ross
David
D
Everett
Dean
D
Clayton
Tim
T
Balira
Rebecca
R
Knight
Louise
L
Hambleton
Ian
I
Le Goff
Jerome
J
Belec
Laurent
L
Hayes
Richard
R
D000212:Acyclovir / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005836:Genitalia, Female / Q000821:virology; D006678:HIV; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000453:epidemiology / Q000517:prevention & control*; D006558:Herpes Genitalis / Q000188:drug therapy*; D018258:Herpesvirus 2, Human / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D010349:Patient Compliance; D012725:Sexual Behavior; D013636:Tanzania / Q000453:epidemiology
D000914:Antibodies, Viral; D000998:Antiviral Agents; D015483:HIV Antibodies; D000212:Acyclovir