Background:  HIV-1 RNA is the most significant determinant of cervical HIV-1 shedding. Shedding has also been related to sexually transmitted diseases and cervical inflammation. The mechanism by which this occurs is poorly understood. There is evidence that systemic immune activation promotes viral entry, and replication and HIV disease progression. However, the effect of immune activation on local genital HIV shedding has not been characterized.
Methods:  This study included 225 HIV⁺ women enrolled in the Women’s Interagency HIV Study, who had paired plasma and cervicovaginal lavage specimens available for evaluation. Clinical assessments, HIV-1 RNA in plasma and genital secretions, and markers of activation (CD8⁺CD38⁺DR⁺ and CD4⁺CD38⁺DR⁺) were evaluated. HIV-1 shedding was defined as ≥ 176 copies/mL. We tested associations with HIV genital shedding using logistic regression, accounting for multiple visits per subject.
Results:  Over the course of the study, 225 HIV⁺ women had 568 genital evaluations, accounting for 157 shedding visits. The mean number of shedding visits was 1.62 per subject. In the multivariate model adjusting for covariates (CD4, HAART, genital infections), genital shedding was significantly associated with CD8⁺CD38⁺DR⁺ (OR 1.94, 95%CI 1.01 to 3.75) and CD4⁺CD38⁺DR⁺ (OR 1.72, 95%CI 1.01 to 2.94) immune activation. In addition, lack of immune activation was protective for shedding. When controlling for all covariates, including HIV viral load, only lack of immune activation was protective for HIV genital shedding, CD4⁺CD38^–DR^– (OR 0.54, 95%CI 0.32 to 0.92).
Conclusions:  Immune activation was significantly associated with HIV RNA-1 genital shedding. In particular, lack of immune activation was protective for genital shedding. This study suggests that the pathophysiologic mechanism of HIV genital shedding may be related to immune activation. As a consequence of immune activation, local HIV RNA-1 replication may be enhanced, and thus increase the transmission and acquisition of HIV infection.