Long-term impact of acyclovir suppressive therapy on genital and plasma HIV RNA in Tanzanian women: a randomized controlled trial.
BACKGROUND
Herpes simplex virus (HSV) suppressive therapy reduces genital and plasma human immunodeficiency virus type 1 (HIV-1) RNA over periods up to 3 months, but the long-term effect is unknown.


METHODS
A total of 484 HIV-1 and HSV type 2 seropositive Tanzanian women aged 16-35 years were enrolled in a randomized placebo-controlled trial of acyclovir administered at a dosage of 400 mg twice daily. Cervico-vaginal lavage and blood samples were collected at 6 months, 12 months, and 24 months for quantification of genital and plasma HIV-1 RNA and genital HSV DNA. Primary outcomes were detection and quantity of cervico-vaginal HIV-1 RNA at 6 months.


RESULTS
At 6 months, there was little difference between the acyclovir and placebo arms for cervico-vaginal HIV-1 RNA detection (88 [ 41 .3%] of 213 vs 84 [ 44 .0%] of 191; odds ratio [OR], 0.90; 95% confidence interval [CI], 0.60-1.33), HSV DNA detection (20 [ 9 .4%] of 213 vs 22 [ 11 .5%] of 191; OR, 0.80; 95% CI, 0.42-1.51), genital HIV or HSV loads, or plasma HIV-1 RNA load. Estimated median adherence was 91%. There was a suggestion of an impact on cervico-vaginal HIV-1 RNA detection among women with estimated adherence 90% (OR, 0.74; 95% CI, 0.50-1.09) when data from all 3 visits were included.


CONCLUSIONS
Acyclovir administered at a dosage of 400 mg twice daily is unlikely to be a useful long-term intervention to reduce HIV transmission. The lack of effect on HIV may be attributable to suboptimal adherence or treatment regimen.
Tanton
Clare
C
London School of Hygiene and Tropical Medicine, London, United Kingdom. ctanton@gum.ucl.ac.uk
Weiss
Helen A
HA
Rusizoka
Mary
M
Legoff
Jerome
J
Changalucha
John
J
Baisley
Kathy
K
Mugeye
Kokugonza
K
Everett
Dean
D
Belec
Laurent
L
Clayton
Tim C
TC
Ross
David A
DA
Hayes
Richard J
RJ
Watson-Jones
Deborah
D
D000212:Acyclovir / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000032:analysis / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects; D006558:Herpes Genitalis / Q000188:drug therapy / Q000635:transmission; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006801:Humans; D010349:Patient Compliance; D012367:RNA, Viral / Q000032:analysis / Q000097:blood; D013636:Tanzania; D013997:Time Factors; D014621:Vagina / Q000821:virology; D055815:Young Adult
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D004279:DNA, Viral; D012367:RNA, Viral; D000212:Acyclovir