Roles of clinical and subclinical reactivated herpes simplex virus type 2 infection and human immunodeficiency virus type 1 (HIV-1)-induced immunosuppression on genital and plasma HIV-1 levels.
- Department for International Development
- 1 January 2008
- Burkina Faso
- Document Type:
- Journal Article
- Weiss, H.A., Nagot, N., Ouedraogo, A., Defer, M.C., van de Perre, P. Mayaud, P., Segondy, M., Konate, I., Foulongne, V., Sanon, A., Becquart, P., Sawadogo, A., and ANRS 1285 Study Group
Background: Few longitudinal studies have described the interactions between reactivation of herpes simplex virus type 2 (HSV-2) infection (hereafter, “HSV-2 reactivation”) and genital and systemic replication of human immunodeficiency virus type 1 (HIV-1). Methods: Women in Burkina Faso who were seropositive for both HIV-1 and HSV-2 were enrolled in a randomized placebo-controlled trial of therapy to suppress reactivation of HSV-2 infection (hereafter, “HSV suppressive therapy”). During the baseline phase, 6 enriched cervicovaginal lavage specimens were obtained over 12 weeks to detect and quantify the HIV-1 RNA and HSV-2 DNA loads. Results: Women with genital ulcer disease (GUD) detected at least once were more likely than women in whom GUD was not detected (risk ratio [RR], 1.23; 95% confidence interval [CI], 1.09–1.37) to have genital HIV-1 RNA detected during at least one visit. Similarly, women with genital HSV-2 DNA detected during at least one clinic visit were more likely than women in whom genital HSV-2 DNA was not detected (RR, 1.17; 95% CI, 1.01–1.34) to have genital HIV-1 RNA detected at least once. In addition, the mean genital HIV-1 RNA loads for women with GUD detected during at least one visit and women with HSV-2 genital shedding detected during at least one visit were greater than for women in whom genital HSV-2 DNA or GUD was never detected. The plasma HIV-1 RNA load was increased among women for whom at least one visit revealed GUD (+0.25 log10 copies/mL; 95% CI, −0.05–0.55) or genital HSV-2 DNA (+0.40 log10 copies/mL; 95% CI, 0.15–0.66), compared with women who did not experience GUD or HSV-2 genital shedding, respectively. The association of HSV-2 reactivations with HIV-1 replication tended to be stronger in patients with a higher CD4+ cell count (i.e., >500 cells/μL). The contribution of HSV-2 to HIV-1 replication among women with CD4+ cell count of 500 cells/μL was reduced because almost all experienced HIV-1 genital shedding. Conclusions: Both clinical and subclinical HSV-2 reactivations play a role in increasing the rate of HIV-1 replication. HSV suppressive therapy is a promising tool for HIV control. Initiation of such therapy when the CD4+ cell count is >500 cells/μL deserves further investigation.
Journal of Infectious Diseases (2008) 198 (2) pp. 241-249 [DOI: 10.1086/589621].
Published: 1 January 2008