Pharmacokinetic and Clinical Associations Between Doravirine-Containing Antiretroviral Therapy and Injectable and Implantable Hormonal Contraceptive Methods Among Women Living With Human Immunodeficiency Virus in South Africa.

Details

• Alternative Title:
  The Journal of Infectious Diseases, 2025, v. 232, no. 1: Pharmacokinetic and Clinical Associations Between Doravirine-Containing Antiretroviral Therapy and Injectable and Implantable Hormonal Contraceptive Methods Among Women Living With Human Immunodeficiency Virus in South Africa.
• Journal Article:
  The Journal of Infectious Diseases
• Personal Author:
  Patel, Rena C. ; Ndlovu, Nkosiphile ; Maheria, Pooja ; Kgoa, Reolebogile ; Kew, Lindsay ; Kapa, La-Donna ; Reddy, Krishnaveni ; Govindasami, Merusha ; Matswake, Nomasonto ; Sigcu, Nompumelelo ; Seedat, Mohammed ; Shale, Lerato ; Yongo, Nashon ; Hassan, Shukri A. ; Williams, Tommy L. ; Erikson, David W. ; Scarsi, Kimberly K. ; Palanee-Phillips, Thesla
• Description:
  Drug resistance and intolerance of dolutegravir-containing antiretroviral therapy (ART) are rising in low- and middle-income countries, resulting in a potentially increased use of doravirine-containing ART use. There are knowledge gaps regarding doravirine and hormonal contraceptive drug-drug interactions among women living with human immunodeficiency virus (HIV).
  
  We conducted a 5-parallel-group, prospective pharmacokinetic study among women living with HIV aged 18-45 years in Johannesburg, South Africa, between November 2021 and February 2024. We included a sixth, historical comparator group from a Kenyan study. After a ≥6-week lead-in period with doravirine-containing ART, participants initiated injectable medroxyprogesterone acetate (MPA), implantable etonogestrel (ENG), or nonhormonal intrauterine device contraception and were observed every 2-4 weeks for an additional 12 or 24 weeks. We analyzed serum MPA and ENG and plasma doravirine or dolutegravir concentrations per visit, using validated liquid chromatography-mass spectrometry assays. We assessed log-transformed concentrations of each drug with geometric mean ratios (90% confidence intervals) and a multivariate model adjusted for age and body mass index. We described safety, tolerability, and effectiveness (HIV RNA <40 copies/mL) of doravirine-containing ART.
  
  A total of 128 participants are included in this analysis. There were no significant reductions in the MPA, ENG, or doravirine concentrations. A total of 8 (3%) adverse events grade ≥2 were considered attributable to doravirine-containing ART and 22 (8%) to the contraceptive method. ART satisfaction was 100%, and viral suppression at study exit ranged from 86% to 96%.
  
  We found no detrimental bidirectional drug-drug interactions and few adverse events between doravirine and hormonal contraceptives.
• Content Notes:
  Author manuscript
• Subjects:
  • Humans
  • Female
  • Adult
  • Pyridones
  • HIV Infections
  • Prospective Studies
  • Middle Aged
  • Young Adult
  • Triazoles
  • Adolescent
  More +
• Keywords:
  • drug-drug interactions
  • pharmacokinetic study
  • hormonal contraception
  • doravirine-containing ART
  • South Africa
• Source:
  The Journal of Infectious Diseases, 2025, v. 232, no. 1
• DOI:
  https://doi.org/10.1093/infdis/jiaf196
• ISSN:
  0022-1899 ; 1537-6613
• Pubmed ID:
  40261052
• Pubmed Central ID:
  PMC12447852
• Document Type:
  Text
• Funding:
  P51 OD011092/OD/NIH HHSUnited States/ ; P51 OD011092/CD/ODCDC CDC HHSUnited States/
• Genre:
  Journal Article
• Place as Subject:
  South Africa
• Pages in Document:
  79-89 (21 pdf pages)
• Volume:
  232
• Issue:
  1
• Download URL:
  https://stacks.cdc.gov/view/cdc/261467/cdc_261467_DS1.pdf
• File Type:
  [PDF - 678.75 KB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:88fce7730112f894bb4ffb683fd8b6c7c18cd4d4ebb44659230a35454a13d0522a342cdaaa7052b57e7a73ea986cddb6aace0a9a4637b3dcd577dd5d8090df47