Impact of acyclovir on genital and plasma HIV-1 RNA, genital herpes simplex virus type 2 DNA, and ulcer healing among HIV-1-infected African women with herpes ulcers: a randomized placebo-controlled trial.
BACKGROUND
Little is known about the impact of episodic treatment of herpes on human immunodeficiency virus type 1 (HIV-1).


METHODS
Women from Ghana and the Central African Republic who had genital ulcers were enrolled in a randomized, double-blind, placebo-controlled trial of acyclovir plus antibacterials and were monitored for 28 days. Ulcer etiologies and detection of lesional HIV-1 RNA were determined by polymerase chain reaction (PCR). Cervicovaginal HIV-1 RNA and herpes simplex virus type 2 (HSV-2) DNA and plasma HIV-1 RNA were quantitated by real-time PCR. Primary analyses included 118 HIV-1-infected women with HSV-2 ulcers (54 of whom were given acyclovir and 64 of whom were given placebo).


RESULTS
Acyclovir had little impact on (1) detection of cervicovaginal HIV-1 RNA (risk ratio [RR], 0.96; 95% confidence interval [CI], 0.8-1.2) at day 7 of treatment, (2) the mean cervicovaginal HIV-1 RNA load (-0.06 log(10) copies/mL; 95% CI, -0.4 to 0.3 log(10) copies/mL) at day 7 of treatment, or (3) the plasma HIV-1 RNA load (+0.09 log(10) copies/mL; 95% CI, -0.1 to 0.3 log(10) copies/mL) at day 14 of treatment. At day 7, women receiving acyclovir were less likely to have detectable lesional HIV-1 RNA (RR, 0.70; 95% CI, 0.4-1.2) or cervicovaginal HSV-2 DNA (RR, 0.69; 95% CI, 0.4-1.3), had a lower quantity of HSV-2 DNA (-0.99 log(10) copies/mL; 95% CI, -1.8 to -0.2 log(10) copies/mL), and were more likely to have a healed ulcer (RR, 1.26; 95% CI, 0.9-1.9).


CONCLUSIONS
Episodic therapy for herpes reduced the quantity of cervicovaginal HSV-2 DNA and slightly improved ulcer healing, but it did not decrease genital and plasma HIV-1 RNA loads.


BACKGROUND
ClinicalTrials.gov identifier NCT00158483 .
Mayaud
Philippe
P
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. philippe.mayaud@lshtm.ac.uk
Legoff
Jérôme
J
Weiss
Helen A
HA
Grésenguet
Gérard
G
Nzambi
Khonde
K
Bouhlal
Hicham
H
Frost
Eric
E
Pépin
Jacques
J
Malkin
Jean-Elie
JE
Hayes
Richard J
RJ
Mabey
David C W
DC
Bélec
Laurent
L
D000212:Acyclovir / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D002488:Central African Republic / Q000453:epidemiology; D004279:DNA, Viral / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005869:Ghana / Q000453:epidemiology; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006558:Herpes Genitalis / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D012367:RNA, Viral / Q000097:blood / Q000378:metabolism
D000998:Antiviral Agents; D004279:DNA, Viral; D012367:RNA, Viral; D000212:Acyclovir