ArticleThe Journal of infectious diseases2024
Female Genital Tract Host Factors and Tenofovir and Lamivudine Active Metabolites.
Article in The Journal of infectious diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Prevotella bivia Influences Antiretroviral Pharmacokinetics and Viral Replication in an Ex Vivo Vaginal Tissue Model.Clinical and translational science · 2026Article
- The female microbiome in HIV prevention, pathogenesis, and treatment.Current opinion in HIV and AIDS · 2026Review
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Authors and funding
8 authors.
Funding
Abstract
backgroundWe previously reported the effect of contraception on cervical tenofovir concentrations in Ugandan women with human immunodeficiency virus (HIV). Here we explored the role of cervicovaginal cytokines and drug metabolizing enzymes and transporters (DMETs) to elucidate female genital tract (FGT) drug disposition in a Ugandan cohort.
methodsCervicovaginal fluid and cervical biopsies were collected from Ugandan women with HIV receiving tenofovir/lamivudine-based therapy and intramuscular depot medroxyprogesterone acetate (n = 25), copper intrauterine device (cuIUD; n = 12), or condoms (n = 13) as contraception. Cytokines were measured in cervicovaginal fluid (CVF). Ectocervical tenofovir diphosphate (TFVdp), lamivudine triphosphate (3TCtp), and deoxyadenosine triphosphate (dATP)/deoxycytidine triphosphate (dCTP) concentrations and immune marker/DMET gene expression were measured in cervical biopsies.
resultsCervical 3TCtp was not correlated with any CVF cytokines. Cervical TFVdp was correlated with IL-10, IL-7, and IL-17 in CVF. CCR5 mRNA expression in cervical biopsies was higher in cuIUD users versus condom users. Using multivariable linear regression, CVF IL-17, tissue dATP, plasma estradiol, and plasma tenofovir were all significant predictors of cervical TFVdp. Tissue dCTP and plasma lamivudine were significant predictors of cervical 3TCtp.
conclusionsTFVdp concentrations in cervix appear to be influenced by local inflammation. In contrast, 3TCtp FGT exposure was not affected by genital inflammation or DMETs. CuIUD users have more immune cells present, which may in turn influence local TFVdp disposition. MAIN FINDING: We investigated changes in tenofovir diphosphate and lamivudine triphosphate due to the microbiome and inflammation. While lamivudine triphosphate was not affected by either, tenofovir diphosphate appeared to be affected by local inflammation. Specifically, Th17 cells may influence tenofovir disposition.
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