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.
London School of Hygiene and Tropical Medicine, London, United Kingdom. ctanton@gum.ucl.ac.uk
Clare
C
Tanton
Helen A
HA
Weiss
Mary
M
Rusizoka
Jerome
J
Legoff
John
J
Changalucha
Kathy
K
Baisley
Kokugonza
K
Mugeye
Dean
D
Everett
Laurent
L
Belec
Tim C
TC
Clayton
David A
DA
Ross
Richard J
RJ
Hayes
Deborah
D
Watson-Jones
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