Depot Medroxyprogesterone Acetate and the Vaginal Microbiome as Modifiers of Tenofovir Diphosphate and Lamivudine Triphosphate Concentrations in the Female Genital Tract of Ugandan Women: Implications for Tenofovir Disoproxil Fumarate/Lamivudine in Preexposure Prophylaxis

Clin Infect Dis. 2020 Apr 10;70(8):1717-1724. doi: 10.1093/cid/ciz443.


Background: Effective concentrations of antiretrovirals in the female genital tract (FGT) are critical for suppression of viral shedding or effective preexposure prophylaxis. The disposition of tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) in the FGT have been previously described. Despite widespread use, however, lamivudine triphosphate (3TC-TP) exposure in the FGT is unknown. Depot medroxyprogesterone acetate (DMPA) and vaginal dysbiosis have been implicated in increased risk of human immunodeficiency virus (HIV) acquisition, but whether they alter TFV-DP or 3TC-TP exposure, and therefore compromise prevention efficacy, is unknown.

Methods: Fifty premenopausal women living with HIV in Kampala, Uganda, and receiving daily tenofovir disoproxil fumarate/lamivudine were recruited. Ectocervical biopsies were obtained for quantification of TFV-DP and 3TC-TP using liquid chromatography-mass spectrometry. 16S ribosomal RNA gene sequencing was performed on DNA extracted from vaginal swabs. Wilcoxon rank-sum was used to test for differences between contraceptive groups.

Results: 3TC-TP concentrations were on average 17-fold greater than TFV-DP concentrations in cervical tissues. TFV-DP concentrations in cervical biopsies were 76% greater in DMPA users compared with women using nonhormonal contraception (n = 23 per group). Abundance of Lactobacillus in vaginal swabs was correlated with 3TC-TP concentrations in cervical tissues.

Conclusions: We found that TFV-DP concentrations were significantly greater in DMPA users compared with women using nonhormonal contraception, suggesting that prevention efficacy is unlikely to be compromised by DMPA use. Similar to reports of FTC-TP, 3TC-TP exposure was significantly greater than TFV-DP in cervical tissue and was correlated with abundance of Lactobacillus. These data support lamivudine as an option for preexposure prophylaxis.

Clinical trials registration: NCT03377608.

Keywords: DMPA; HIV; PrEP; lamivudine; microbiome; tenofovir.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Anti-HIV Agents* / therapeutic use
  • Cytidine Triphosphate / analogs & derivatives
  • Dideoxynucleotides
  • Emtricitabine / therapeutic use
  • Female
  • HIV Infections* / drug therapy
  • HIV Infections* / prevention & control
  • Humans
  • Lamivudine / analogs & derivatives
  • Lamivudine / therapeutic use
  • Medroxyprogesterone Acetate / therapeutic use
  • Microbiota*
  • Organophosphates
  • Pre-Exposure Prophylaxis*
  • Tenofovir / therapeutic use
  • Uganda


  • Anti-HIV Agents
  • Dideoxynucleotides
  • Organophosphates
  • lamivudine triphosphate
  • tenofovir diphosphate
  • Lamivudine
  • Cytidine Triphosphate
  • Tenofovir
  • Medroxyprogesterone Acetate
  • Emtricitabine
  • Adenine

Associated data