The Genital Tract as a Sanctuary Site for HIV

Angela DM Kashuba, BScPhm, PharmD, DABCP

Associate Professor of Pharmacy; Associate Director, The University of North Carolina Center for AIDS Research Clinical Pharmacology/Analytical Chemistry Core; Pharmacologist; School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC (USA)

The current predominant mode of HIV transmission worldwide is through heterosexual contact.  Sexual transmission of HIV can be related to the concentration of virus present in the infectious inoculum; genital fluid.  In some investigations, blood HIV RNA concentrations can be correlated with the HIV RNA concentrations in genital fluid.  However, local replication of HIV is possible, particularly in the presence of inflammation.  In general, aggressive antiretroviral therapy can be expected to reduce the concentration of HIV RNA in genital fluids, and in some cases, can be sustained for long periods of time.  However, even in such patients, HIV can still be occasionally detected intermittently in culture, or HIV DNA can be recovered from the cellular fraction in some patients.  These data suggest that replication-competent (and transmissible) HIV can still be found in the genital tract of some subjects on antiretroviral therapy, despite undetectable active HIV replication. Incomplete suppression of viral replication in the genital tract, with the development of resistance, has been documented for both men and women on antiretroviral therapy.  These variants can clearly be transmitted through sexual contact.  Recent studies of the level of HIV resistance in newly diagnosed infections demonstrate a low level of genotypic and phenotypic resistance to all classes of antiviral drugs.

With the genital tract being a sanctuary site for HIV-1 replication, understanding antiretroviral pharmacology in the genital tract is critically important, as these therapies have the potential to decrease sexual transmission of HIV by reducing HIV RNA and rendering the infected person less infectious, or by pre- or post-exposure prophylaxis. Low concentrations of ARVs in the GT may render pre- and post-exposure prophylaxis regimens ineffective, and may result in the emergence of drug resistant HIV mutations that could impact HIV transmission to others, and result in antiretroviral failure in an individual patient.