Determinants of HIV shedding in the lower genital tract of women

Abstract

Heterosexual spread of HIV remains the major risk factor for transmission worldwide. Genital secretions from the infected partner contain both cell-free and cell-associated virus. Although the exact mechanism of heterosexual transmission is unknown, genital virus plays an important role. Decreasing the genital shedding of HIV is an important step in slowing the spread of the disease. Recent studies have shown that antiretroviral penetration into the genital tract varies by class and that antiretroviral therapy significantly decreases HIV levels. Compartmentalization between the blood and genital tract is based on viral load levels, resistant variants, viral diversity, and coreceptor usage. HSV-2, lack of lactobacilli, and plasma cell endometritis increased HIV genital shedding. HSV-2 suppressive therapy significantly reduces plasma and genital tract viral load. Data are conflicting on the effect of hormonal contraception on HIV genital shedding. Further studies are needed to translate these findings into decreased spread on a population level.

Genital Tract, Cord Blood, and Amniotic Fluid Exposures of Seven Antiretroviral Drugs during and after Pregnancy in Human Immunodeficiency Virus Type 1-Infected Women

“…HIV genital tract shedding has been seen in patients on ARV. Therefore, even lower exposure in the genital tract during pregnancy may result in increased risk of the mother shedding and transmitting HIV to the baby (1,21). Fortunately, no infants in this study became infected with HIV despite these decreased ARV concentrations in the genital tract.…”

Care of the human immunodeficiency virus–infected menopausal woman

“…When women are co-infected with other sexually transmitted infections, however, their HIV viral load may increase as well as viral shedding and infectivity (47). Hence, seropositive women should all be screened for treatable sexuallly transmitted infections including syphilus, gonorrhea, trichomonas, and chlamydia yearly if they are sexually active, and more often with symptoms or high risk behaviors (48).…”

Antiretroviral drug concentrations in the male and female genital tract: implications for the sexual transmission of HIV

“…At the other end of the spectrum is the view that the degree of compartmentalization between the genital tract and peripheral circulation can be significant as evidenced by discordant viral evolution [1,2,5,12], differences in viral load responses to ART [13,14 ,15 ,16-19], differences in viral tropism [3] and local responses to sexually transmitted infections [10]. Many of these factors have recently been reviewed by Anderson and Cu-uvin [20 ]. In this article, we examine more recent data on the different disposition of antiretroviral agents into the genital tract.…”

“…No drug levels were measured in this study and nNRTI use was divided between efavirenz and nevirapine. The determinants of shedding in the female genital tract (other than ART) have recently been the subject of an excellent review by Anderson and Cu-uvin[20 ].There appear to be several patterns of drug penetration into the male and female genital tract. In addition, there appear to be different patterns of genital shedding under the influence of ART.…”