Cervicovaginal HIV-1 and herpes simplex virus type 2 shedding during genital ulcer disease episodes.

Author(s): LeGoff J, Weiss HA, Gresenguet G, Nzambi K, Frost E, Hayes RJ, Mabey DC, Malkin JE, Mayaud P, Belec L

Affiliation(s): Universite Paris Descartes Equipe Immunite et Biotherapie Muqueuse, Unite INSERM Internationale U743 (Immunologie Humaine), Centre de Recherches Biomedicales des Cordeliers, 15 rue de l'Ecole de Medecine, 75270 Paris Cedex 06, France.

Publication date & source: 2007-07-31, AIDS., 21(12):1569-78.

Publication type: Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

OBJECTIVE: To investigate correlates of herpes simplex virus type 2 (HSV-2) DNA and HIV-1 RNA among women with genital ulcer disease (GUD). DESIGN: Baseline data from a randomized placebo-controlled trial of episodic herpes treatment in Ghana and the Central African Republic. METHODS: GUD aetiology was determined by polymerase chain reaction (PCR) from a lesional swab. Real-time PCR was used to quantify HIV-1 RNA, and HSV-2 DNA in cervicovaginal lavages (CVL) and HIV-1 RNA in plasma. Genital infection was defined as the presence of virus in the lesion or CVL. RESULTS: Of 441 women enrolled, 79.0% were HSV-2 seropositive, 46.6% were HIV-1 seropositive, and 50.0% had an HSV-2 ulcer. Among 180 HSV-2/HIV-1 co-infected women, cervicovaginal HIV-1 RNA was detected more frequently in women with HSV-2 ulcers (67.9%) or cervicovaginal HSV-2 DNA only (72.3%) compared with women without genital HSV-2 infection (42.4%) (P = 0.004). Women with genital HSV-2 infection had higher median cervicovaginal HIV-1-RNA loads (3.14 log10 copies/mL versus 2.10 log10 copies/mL; P = 0.003), higher plasma HIV-1-RNA loads (median 5.10 versus 4.65 log10 copies/mL; P = 0.07), and lower median CD4 cell counts) (198 versus 409 cells/mm, P = 0.03). Cervicovaginal HIV-1 RNA and HSV-2 DNA were significantly correlated after adjusting for plasma HIV-1 RNA and CD4 cell counts (P < 0.001) and a 10-fold increase in cervicovaginal HSV-2 DNA was associated with a 1.7-fold increase in plasma HIV-1 RNA (P = 0.003). CONCLUSION: Genital HSV-2 infection is associated with increased cervicovaginal and plasma HIV-1 RNA among co-infected women with genital ulcers, independently of the level of immunodeficiency, highlighting the close interaction between these two viruses and the role of HSV-2 as a co-factor for the sexual transmission of HIV-1.