Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus.
BACKGROUND
Epidemiologic data suggest that infection with herpes simplex virus type 2 (HSV-2) is associated with increased genital shedding of human immunodeficiency virus type 1 (HIV-1) RNA and HIV-1 transmissibility.


METHODS
We conducted a randomized, double-blind, placebo-controlled trial of HSV suppressive therapy with valacyclovir (at a dose of 500 mg twice daily) in Burkina Faso among women who were seropositive for HIV-1 and HSV-2; all were ineligible for highly active antiretroviral therapy. The patients were followed for 24 weeks (12 weeks before and 12 weeks after randomization). Regression models were used to assess the effect of valacyclovir on the presence and quantity of genital and plasma HIV-1 RNA and genital HSV-2 DNA during treatment, adjusting for baseline values, and to evaluate the effect over time.


RESULTS
A total of 140 women were randomly assigned to treatment groups; 136 were included in the analyses. At enrollment, the median CD4 cell count was 446 cells per cubic millimeter, and the mean plasma viral load was 4.44 log10 copies per milliliter. With the use of summary-measures analysis, valacyclovir therapy was found to be associated with a significant decrease in the frequency of genital HIV-1 RNA (odds ratio, 0.41; 95% confidence interval [CI], 0.21 to 0.80) and in the mean quantity of the virus (log(10) copies per milliliter, -0.29; 95% CI, -0.44 to -0.15). However, there was no significant decrease in detection of HIV (risk ratio, 0.93; 95% CI, 0.81 to 1.07). HSV suppressive therapy also reduced the mean plasma HIV-1 RNA level by 0.53 log(10) copy per milliliter (95% CI, -0.72 to -0.35). Repeated-measures analysis showed that these effects became significantly stronger during the 3 months of follow-up.


CONCLUSIONS
HSV suppressive therapy significantly reduces genital and plasma HIV-1 RNA levels in dually infected women. This finding may have important implications for HIV control. (ClinicalTrials.gov number, NCT00158509 [ClinicalTrials.gov].).
Nagot
Nicolas
N
Centre Muraz, Bobo-Dioulasso, Burkina Faso. n_nagot@hotmail.com
Ouédraogo
Abdoulaye
A
Foulongne
Vincent
V
Konaté
Issouf
I
Weiss
Helen A
HA
Vergne
Laurence
L
Defer
Marie-Christine
MC
Djagbaré
Didier
D
Sanon
Anselme
A
Andonaba
Jean-Baptiste
JB
Becquart
Pierre
P
Segondy
Michel
M
Vallo
Roselyne
R
Sawadogo
Adrien
A
Van de Perre
Philippe
P
Mayaud
Philippe
P
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002584:Cervix Uteri / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D006558:Herpes Genitalis / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D012367:RNA, Viral / Q000032:analysis* / Q000097:blood; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects; D017201:Virus Shedding / Q000187:drug effects
D000998:Antiviral Agents; D012367:RNA, Viral; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir