HIV Prevention: A Tissue Model to Determine Effective Antiretroviral Concentration Targets (2011)

Undergraduates: Allison Hastings, Melanie Nicol

Faculty Advisor: Angela Kashuba
Department: Biology

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Background: In 2008, the WHO estimated that in low-mid income countries, for every 1 person treated for HIV infection, 2-3 were newly-infected. Therefore prevention, in addition to treatment, of HIV is required to significantly impact the epidemic. Objectives: My goal was to use a novel mucosal tissue explant culture system to determine effective antiretroviral concentration targets for HIV prevention. HIV target cell and receptor quantification in tissue was performed, drug stability was assessed, and drug response and model functionality in TZM cells and mucosal tissue were compared. Methods: HIV target cells and receptors were quantified by immunohistochemistry. Drug stability under defined culture conditions was measured across 72 hours. Drug efficacy was evaluated by incubating 0.1-10000 ng/mL of maraviroc, nevirapine, and tenofovir in TZM cells before HIV exposure. HIV infection was quantified by p24 ELISA. Results: CD3+ and CD4+ cells are more prevalent in rectal tissue than in vaginal tissue (mean 94 and 47 versus 40 and 24, respectively). Drug concentrations remained stable in culture over 30 hours. Each drug completely inhibited HIV infection in TZM cells at concentrations of 1000-10000ng/mL. Conclusions: Each drug was stable in culture conditions and could potently inhibit HIV replication. Target cell populations differ in each mucosal tissue. Thus, drug effects should be evaluated in each tissue independently for evidence of efficacy against HIV transmission.