Genital tract viral load in HIV Type 1-positive women correlates with specific cytokine levels in cervical-vaginal secretions but is not a determinant of infectious virus or anti-HIV activity

Abstract

As the AIDS epidemic continues with women being disproportionately affected, it is crucial to understand factors that predict the risk of heterosexual HIV-1 transmission. We investigated whether genital tract viral load (GTVL) in cervical-vaginal lavages (CVL) from HIV-1-positive women with moderately low CD4 T cell counts correlates with cytokine levels, antimicrobial concentrations, and intrinsic anti-HIV activity. CVL were collected from 19 HIV-1-positive women with moderately low CD4 T cell counts [mean 381 cells/mm(3) (227-536 cells/mm(3))]. None of the women was on antiretroviral therapy. The women were categorized into those with detectable GTVL or those with undetectable GTVL (detectable GTVL RNA levels > 400 copies/ml). Women were also categorized according to bacterial vaginosis (BV) status irrespective of GTVL. The TZM-bl assay was used to determine the presence of infectious virus and anti-HIV activity. Significantly higher levels of RANTES, Eotaxin, Fractalkine, IL-1α, IL-6, MCP-1, MIP1β, MIP1α, TNF-α, and GM-CSF were observed in women with detectable GTVL compared to women with undetectable GTVL. No significant differences were observed in the following cytokines and chemokines: G-CSF, IL-1RA, IL-8, and IP-10. GTVL did not correlate either with antimicrobials known to have anti-HIV activity or with the presence of infectious virus. BV status did not have a significant effect on anti-HIV activity. These findings further our understanding of the role of GTVL in determining the cytokine and chemokine milieu in the female reproductive tract.

FIG. 1.

Determination of the presence of infectious HIV-1 in 19 HIV⁺ women with detectable genital tract viral load (GTVL RNA levels > 400 copies/ml) and undetectable GTVL (GTVL RNA levels < 400 copies/ml). Cervical-vaginal lavages (CVL) were diluted 1:4 and added directly to TZM-bl cells. The assay was terminated 48 h postinfection and HIV-1 infection was quantified by measuring luciferase reporter gene activity using a luminometer and expressed as relative light units (RLU). Each data point in the graph represents one individual patient. In the negative control (media only) column and in the positive control [media+IIIB (X4-tropic) or BaL (R5-tropic)] each point represents replicate wells. There was no infectious HIV-1 in both detectable and undetectable GTVL groups.

FIG. 2.

Measurement of anti-HIV activity in HIV⁺ women with detectable GTVL (GTVL RNA levels > 400 copies/ml) and undetectable GTVL (GTVL RNA levels < 400 copies/ml). CVL were diluted 1:4 and incubated with HIV-1 IIIB (X4-tropic) and BaL (R5-tropic) at a multiplicity of infection (MOI) of 1.0 for 1 h at 37°C prior to infecting TZM-bl cells. Data points in each graph represent one individual patient. Media was set up as negative control, and replicate wells of virus (IIIB and BaL) were set up as positive controls.