154LB
Impact of HSV-2 Suppressive Therapy on Genital and Plasma HIV-1 RNA in HIV-1 and HSV-2-seropositive Women Not Taking ART: A Randomized, Placebo-controlled Trial in Johannesburg, South Africa
Sinead Delany*1,2, Sinead Delany*1,2, P Mayaud2, T Clayton2, N Mlaba1, G Akpomiemie1, K Hira3, A Capovilla3, W Stevens3, and H Rees1
1Reproductive Health & HIV Res Unit, Johannesburg, South Africa; 2London Sch of Hygiene & Tropical Med, UK; and 3Univ of the Witwatersrand, Johannesburg, South Africa
Background: Randomized,
controlled trials are required to demonstrate that herpes simplex virus type II
(HSV-2) enhances both HIV disease progression and infectiousness, by
stimulating HIV replication.
Methods: We conducted a randomized, double-blind, placebo-controlled
trial of acyclovir (ACV) suppressive treatment (400 mg twice daily for 3
months) among HIV-1- and HSV-2-seropositive women who did not require HAART. We
evaluated the effect of treatment on genital HIV-1 RNA, and on HIV-1 plasma
viral load, CD4 count, and genital HSV-2. Participants were assessed at two
pre-randomisation visits one week apart, and then monthly for 3 months after
randomization. At each visit, a cervico-vaginal lavage was collected for HIV-1
RNA and HSV-2 DNA detection and quantitation by real-time polymerase chain
reaction. Primary analyses were based on intent-to-treat approach at month 3.
Effect of treatment on detection of either genital HIV-1 RNA or HSV-2 DNA was
estimated using a risk ratio with 95% confidence intervals. Linear regression was used to estimate the
impact of treatment on the mean quantity of genital and plasma HIV-1 RNA and
CD4 count. Ordered logistic regression was used to estimate the effect of
treatment on frequency of viral shedding over all follow-up visits.
Results: We randomized 300 women to ACV (n
= 152) or placebo (n = 148); 91% of
visits were completed. Median CD4 count
was 474 cells/μL and mean HIV-1 plasma viral load
was 4.13 log10
copies/mL at baseline. There was little evidence that, compared to placebo, ACV
influenced detection (RR = 0.89, 95%CI 0.70 to 1.13) and quantity of genital
HIV-1 RNA among those who shed (coefficient = 0.13, 95%CI –0.13 to 0.39) at
month 3. However, ACV significantly decreased the frequency of HIV-1 shedding
over all follow-up visits (adjusted OR = 0.56, 95%CI 0.36 to 0.88). HIV-1 plasma viral load was also
significantly decreased in the ACV group by an average 0.37 log10
copies/mL (95%CI –0.56 to –0.18). There was little evidence of an effect of ACV
on CD4 count at month 3. ACV reduced both the clinical (RR = 0.42, 95%CI 0.22
to 0.84) and subclinical detection of HSV-2 (RR = 0.35, 95%CI 0.18 to 0.66).
Conclusions: HSV-2 suppressive therapy, by reducing HIV-1
plasma viral load and altering the pattern of genital HIV-1 shedding, may
contribute to the reduction in sexual transmission of HIV-1 and may delay the
requirement for HAART initiation.
|
