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Effect of Hormonal Contraception on Pharmacokinetics of Vaginal Tenofovir in Healthy Women

Increased Tenofovir Diphosphate in Injectable Depot Medroxyprogesterone Acetate Users

Thurman, Andrea R., MD*; Schwartz, Jill L., MD, MPH*; Brache, Vivian, BS; Chen, Beatrice A., MD, MPH; Chandra, Neelima, PhD*; Kashuba, Angela D.M., PharmD§; Weiner, Debra H., MPH; Mauck, Christine, MD*; Doncel, Gustavo F., MD, PhD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: January 1, 2019 - Volume 80 - Issue 1 - p 79–88
doi: 10.1097/QAI.0000000000001864
Clinical Science

Objective: Endogenous and exogenous contraceptive hormones may affect mucosal pharmacokinetics (PKs) of topical antiretrovirals such as tenofovir. We present PK data from healthy women using tenofovir vaginal gel, at baseline (follicular and luteal phases) and after oral contraceptive pill (OCP) or depot medroxyprogesterone acetate (DMPA) use.

Methods: CONRAD A10-114 was a prospective, interventional, open-label, parallel study. We enrolled 74 women and 60 completed the study (32 and 28 who selected OCPs or DMPA, respectively). Participants used 2 doses of tenofovir gel separated by 2 hours, without intercourse, and were examined 3 or 11 hours after the last dose. We assessed pharmacokinetics in plasma, cervicovaginal (CV) aspirate, and vaginal tissue.

Results: In general, there were no significant differences in mucosal tenofovir and tenofovir diphosphate concentrations (P > 0.23) in the follicular and luteal phases, except for lower mean tenofovir tissue concentrations (P < 0.01) in the follicular phase. Tenofovir concentrations significantly decreased in CV aspirate (P < 0.01) after contraceptive use, but overall remained very high (>106 ng/mL). Mean tissue tenofovir diphosphate increased to 6229 fmol/mg after DMPA use compared with 3693 and 1460 fmol/mg in the follicular and luteal phases, respectively (P < 0.01). The molecular conversion of tenofovir into tenofovir diphosphate was more effective in DMPA users (molecular ratio of 2.02 versus 0.65 luteal phase, P < 0.01).

Conclusions: Both menstrual cycle phase and exogenous hormones affect topical tenofovir mucosal and systemic PKs. However, high levels of tenofovir and tenofovir diphosphate were observed in the CV mucosa in the presence or absence of OCPs and DMPA, with tissue levels exceeding benchmarks of predicted mucosal anti-HIV efficacy (tenofovir >1.00 ng/mL in CV aspirate and tenofovir diphosphate >1000 fmol/mg).

*CONRAD, Eastern Virginia Medical School, Norfolk and Arlington, VA;

Profamilia, Santo Domingo, Dominican Republic;

University of Pittsburgh, Magee-Women's Research Institute, Pittsburgh, PA;

§University of North Carolina, Chapel Hill, NC; and

FHI360, Durham, NC.

Correspondence to: Andrea R. Thurman, MD, CONRAD, Eastern Virginia Medical School, 601 Colley Avenue, Norfolk, VA 23507 (e-mail:

Supported by the United States Agency for International Development (USAID) and the President's Emergency Plan for AIDS Relief (PEPFAR) under Cooperative Agreements GPO-A-00-08-00005-00 and AID-OAA-A-14-00011.

The contents are the sole responsibility of the authors and do not necessarily reflect the views of their institutions, USAID or the United States Government.

The authors have no conflicts of interest to disclose.

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The contents are the sole responsibility of the authors and do not necessarily reflect the views of their institutions, USAID or the United States Government.

Received May 31, 2018

Accepted September 03, 2018

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