Tenofovir Diphosphate Concentrations in Dried Blood Spots From Pregnant and Postpartum Adolescent and Young Women Receiving Daily Observed Pre-exposure Prophylaxis in Sub-Saharan Africa

Lynda Stranix-Chibanda; Peter L Anderson; Deborah Kacanek; Sybil Hosek; Sharon Huang; Teacler G Nematadzira; Frank Taulo; Violet Korutaro; Clemensia Nakabiito; Maysebole Masenya; Kathryn Lypen; Emily Brown; Mustafa E Ibrahim; Jenna Yager; Lubbe Wiesner; Benjamin Johnston; K Rivet Amico; James F Rooney; Nahida Chakhtoura; Hans M L Spiegel; Benjamin H Chi; IMPAACT 2009 Team

doi:10.1093/cid/ciaa1872

Tenofovir Diphosphate Concentrations in Dried Blood Spots From Pregnant and Postpartum Adolescent and Young Women Receiving Daily Observed Pre-exposure Prophylaxis in Sub-Saharan Africa

Clin Infect Dis. 2021 Oct 5;73(7):e1893-e1900. doi: 10.1093/cid/ciaa1872.

Authors

Lynda Stranix-Chibanda^{1

2}, Peter L Anderson³, Deborah Kacanek⁴, Sybil Hosek⁵, Sharon Huang⁴, Teacler G Nematadzira², Frank Taulo⁶, Violet Korutaro⁷, Clemensia Nakabiito⁸, Maysebole Masenya⁹, Kathryn Lypen¹⁰, Emily Brown¹⁰, Mustafa E Ibrahim³, Jenna Yager³, Lubbe Wiesner¹¹, Benjamin Johnston¹², K Rivet Amico¹³, James F Rooney¹⁴, Nahida Chakhtoura¹⁵, Hans M L Spiegel¹⁶, Benjamin H Chi¹⁷; IMPAACT 2009 Team

Collaborators

IMPAACT 2009 Team:
Vongai Chanaiwa, Suzen Maonera, Lucia Mungate, Sharon Kunkanga Mambiya, Abigail Mnemba, Flora Chithila, Phionah Nakabuye, Muzamil Nsibuka Kisekka, Victoria Ndyanabangi, Brenda Gati Mirembe, Phionah Kibalama Ssemambo, Annette Miwanda Ssekasi, Elizea Horne, Siphokazi Sibisi, Janet Grab

Affiliations

¹ University of Zimbabwe, Harare, Zimbabwe.
² University of Zimbabwe Clinical Trials Research Centre, Harare, Zimbabwe.
³ University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
⁴ Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
⁵ John H. Stroger Jr. Hospital of Cook County, Chicago, Illinois, USA.
⁶ College of Medicine-Johns Hopkins Research Project, Blantyre, Malawi.
⁷ Baylor College of Medicine Children's Foundation-Uganda, Kampala, Uganda.
⁸ Makerere University-Johns Hopkins University, Kampala, Uganda.
⁹ Wits Reproductive Health and HIV Institute, Johannesburg, South Africa.
¹⁰ FHI 360, Durham, North Carolina, USA.
¹¹ Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
¹² Frontier Science Foundation, Inc, Amherst, New York, USA.
¹³ University of Michigan, Ann Arbor, Michigan, USA.
¹⁴ Gilead Sciences, Inc, Foster City, California, USA.
¹⁵ National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
¹⁶ Kelly Government Solutions, Contractor to National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland, USA.
¹⁷ University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Abstract

Background: Intracellular tenofovir diphosphate (TFV-DP) concentration in dried blood spots (DBSs) is used to monitor cumulative pre-exposure prophylaxis (PrEP) adherence. We evaluated TFV-DP in DBSs following daily oral PrEP (emtricitabine 200 mg/tenofovir diphosphate 300 mg) among pregnant and postpartum adolescent girls and young women (AGYW).

Methods: Directly observed PrEP was administered for 12 weeks in a pregnancy (14-24 weeks' gestation, n = 20) and postpartum (6-12 weeks postpartum, n = 20) group of AGYW aged 16-24 years in sub-Saharan Africa. Weekly DBS TFV-DP was measured by validated liquid chromatography-tandem mass spectrometry assay. Week 12 TFV-DP distributions were compared between groups with Wilcoxon test. Population pharmacokinetic models were fit to estimate steady-state concentrations and create benchmarks for adherence categories. Baseline correlates of TFV-DP were evaluated.

Results: Median age was 20 (IQR, 19-22) years. Of 3360 doses, 3352 (>99%) were directly observed. TFV-DP median (IQR) half-life was 10 (7-12) days in pregnancy and 17 (14-21) days postpartum, with steady state achieved by 5 and 8 weeks, respectively. Observed median (IQR) steady-state TFV-DP was 965 fmol/punch (691-1166) in pregnancy versus 1406 fmol/punch (1053-1859) postpartum (P = .006). Modeled median steady-state TFV-DP was 881 fmol/punch (667-1105) in pregnancy versus 1438 fmol/punch (1178-1919) postpartum. In pooled analysis, baseline creatinine clearance was associated with observed TFV-DP concentrations.

Conclusions: TFV-DP in African AGYW was approximately one-third lower in pregnancy than postpartum. These Population-specific benchmarks can be used to guide PrEP adherence support in pregnant/postpartum African women.

Clinical trials registration: NCT03386578.

Keywords: PrEP in pregnancy; adolescence; intracellular TFV-DP.

Publication types

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

MeSH terms

Adenine / analogs & derivatives
Adolescent
Africa South of the Sahara
Anti-HIV Agents* / therapeutic use
Female
HIV Infections* / drug therapy
HIV Infections* / prevention & control
Humans
Medication Adherence
Organophosphates
Postpartum Period
Pre-Exposure Prophylaxis*
Pregnancy
Young Adult

Tenofovir Diphosphate Concentrations in Dried Blood Spots From Pregnant and Postpartum Adolescent and Young Women Receiving Daily Observed Pre-exposure Prophylaxis in Sub-Saharan Africa

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