Variability of HIV-1 in the female genital reservoir during genital reactivation of herpes simplex virus type 2 (HSV-2).

Clinical and subclinical genital HSV-2 reactivations have been associated with increases of HIV-1 genital shedding. Whether herpes simplex virus type 2 (HSV-2) shedding contributes to the selection of specific genital HIV-1 variants remains unknown. We evaluated the genetic diversity of genital and blood HIV-1 RNA and DNA in 14 HIV-1-/HSV-2- co-infected women, including 7 with HSV-2 genital reactivation and 7 without as controls. HIV-1 DNA and HIV-1 RNA env V1-V3 sequences in paired blood and genital samples were compared. The Herpes selection pressure on HIV was estimated with the number of synonymous (dS) and non-synonymous substitutions (dN) and the dS/dN ratio within HIV quasi-species. HIV-1 RNA levels in cervicovaginal secretions were higher in women with HSV-2 replication than in controls (p=0.02). Plasma HIV-1 RNA and genital HIV-1 RNA and DNA were genetically compartmentalized. No difference in dS, dN and dS/dN ratios was observed between the study groups for both genital HIV-1 RNA and plasma HIV-1 RNA. In contrast, dS and dN in genital HIV-1 DNA were significantly higher in patients with genital herpes reactivation (p<0.01 and p<0.05, respectively). The mean of dS/dN ratio in genital HIV-1 DNA was slightly higher in patients with herpetic genital replication, indicating a trend for a purifying selection (p=0.056). HSV-2 increased genetic diversity of genital HIV-1 DNA. These observations confirm molecular interactions between HSV-2 and HIV-1 at the genital tract level.