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A pharmacokinetic and pharmacogenetic evaluation of contraceptive implants and antiretroviral therapy among women in Kenya and Uganda.
AIDS 2019; 33(13):1995-2004AIDS

Abstract

OBJECTIVES

To evaluate pharmacokinetics and pharmacogenetics of contraceptive implant progestin concentrations in HIV-positive women initiating efavirenz (EFV)-containing or nevirapine (NVP)-containing antiretroviral therapy (ART).

DESIGN

We analyzed stored samples from women self-reporting implant use in the Partners PrEP Study.

METHODS

Plasma samples collected every 6 months were analyzed for levonorgestrel and etonogestrel concentrations. Progestin concentrations from samples collected after ART initiation were compared with pre-ART concentrations for intraindividual comparisons. We used adjusted linear mixed models to compare hormone concentrations between individuals on EFV and NVP to a no ART group. We then evaluated whether possessing certain alleles with known or possible influences on EFV, NVP, or progestin metabolism were associated with changes in progestin concentrations or modified the association between ART use and progestin concentrations.

RESULTS

Our analysis included 11 women who initiated EFV, 13 who initiated NVP, and 36 who remained ART-naive. In the EFV group, the adjusted geometric mean ratio (aGMR) of levonorgestrel was 0.39 [90% confidence intervals (0.31, 0.49); P < 0.001] and the etonogestrel aGMR was 0.51 (0.34, 0.76; P = 0.006) compared with the control group. No difference was observed in the NVP group compared with controls [levonorgestrel 0.93 (0.74, 1.18); P = 0.64; etonogestrel 1.07 (0.77, 1.50); P = 0.73]. Possession of four allele variants were found to result in further reductions in progestin concentrations among those receiving EFV.

CONCLUSION

Concomitant use of EFV significantly reduces levonorgestrel or etonogestrel concentrations by 61 and 49%, respectively, compared with no ART use. We also report allelic variants in hepatic enzymes that influenced the extent of the observed drug-interaction between progestins and EFV.

Authors+Show Affiliations

Department of Medicine. Department of Global Health.Department of Epidemiology.Department of Global Health.Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, California.Endocrine Technologies Core, Oregon National Primate Research Center, Beaverton, Oregon.Endocrine Technologies Core, Oregon National Primate Research Center, Beaverton, Oregon.Department of Pharmaceutics, University of Washington, Seattle, Washington.Department of Pharmaceutics, University of Washington, Seattle, Washington.Global Health, Population, and Nutrition, FHI 360, Durham, North Carolina.Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.Department of Medicine. Department of Global Health.Department of Global Health. Center for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.Department of Medicine. Department of Global Health. Department of Epidemiology.Department of Pharmacy Practice and Science, University of Nebraska Medical Center, Omaha, Nebraska, USA.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31306173

Citation

Patel, Rena C., et al. "A Pharmacokinetic and Pharmacogenetic Evaluation of Contraceptive Implants and Antiretroviral Therapy Among Women in Kenya and Uganda." AIDS (London, England), vol. 33, no. 13, 2019, pp. 1995-2004.
Patel RC, Stalter RM, Thomas KK, et al. A pharmacokinetic and pharmacogenetic evaluation of contraceptive implants and antiretroviral therapy among women in Kenya and Uganda. AIDS. 2019;33(13):1995-2004.
Patel, R. C., Stalter, R. M., Thomas, K. K., Tamraz, B., Blue, S. W., Erikson, D. W., ... Scarsi, K. K. (2019). A pharmacokinetic and pharmacogenetic evaluation of contraceptive implants and antiretroviral therapy among women in Kenya and Uganda. AIDS (London, England), 33(13), pp. 1995-2004. doi:10.1097/QAD.0000000000002308.
Patel RC, et al. A Pharmacokinetic and Pharmacogenetic Evaluation of Contraceptive Implants and Antiretroviral Therapy Among Women in Kenya and Uganda. AIDS. 2019 Nov 1;33(13):1995-2004. PubMed PMID: 31306173.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A pharmacokinetic and pharmacogenetic evaluation of contraceptive implants and antiretroviral therapy among women in Kenya and Uganda. AU - Patel,Rena C, AU - Stalter,Randy M, AU - Thomas,Katherine K, AU - Tamraz,Bani, AU - Blue,Steven W, AU - Erikson,David W, AU - Kim,Christina J, AU - Kelly,Edward J, AU - Nanda,Kavita, AU - Kourtis,Athena P, AU - Lingappa,Jairam R, AU - Mugo,Nelly, AU - Baeten,Jared M, AU - Scarsi,Kimberly K, AU - ,, PY - 2020/11/01/pmc-release PY - 2019/7/16/pubmed PY - 2019/7/16/medline PY - 2019/7/16/entrez SP - 1995 EP - 2004 JF - AIDS (London, England) JO - AIDS VL - 33 IS - 13 N2 - OBJECTIVES: To evaluate pharmacokinetics and pharmacogenetics of contraceptive implant progestin concentrations in HIV-positive women initiating efavirenz (EFV)-containing or nevirapine (NVP)-containing antiretroviral therapy (ART). DESIGN: We analyzed stored samples from women self-reporting implant use in the Partners PrEP Study. METHODS: Plasma samples collected every 6 months were analyzed for levonorgestrel and etonogestrel concentrations. Progestin concentrations from samples collected after ART initiation were compared with pre-ART concentrations for intraindividual comparisons. We used adjusted linear mixed models to compare hormone concentrations between individuals on EFV and NVP to a no ART group. We then evaluated whether possessing certain alleles with known or possible influences on EFV, NVP, or progestin metabolism were associated with changes in progestin concentrations or modified the association between ART use and progestin concentrations. RESULTS: Our analysis included 11 women who initiated EFV, 13 who initiated NVP, and 36 who remained ART-naive. In the EFV group, the adjusted geometric mean ratio (aGMR) of levonorgestrel was 0.39 [90% confidence intervals (0.31, 0.49); P < 0.001] and the etonogestrel aGMR was 0.51 (0.34, 0.76; P = 0.006) compared with the control group. No difference was observed in the NVP group compared with controls [levonorgestrel 0.93 (0.74, 1.18); P = 0.64; etonogestrel 1.07 (0.77, 1.50); P = 0.73]. Possession of four allele variants were found to result in further reductions in progestin concentrations among those receiving EFV. CONCLUSION: Concomitant use of EFV significantly reduces levonorgestrel or etonogestrel concentrations by 61 and 49%, respectively, compared with no ART use. We also report allelic variants in hepatic enzymes that influenced the extent of the observed drug-interaction between progestins and EFV. SN - 1473-5571 UR - https://www.unboundmedicine.com/medline/citation/31306173/A_pharmacokinetic_and_pharmacogenetic_evaluation_of_contraceptive_implants_and_antiretroviral_therapy_among_women_in_Kenya_and_Uganda L2 - http://Insights.ovid.com/pubmed?pmid=31306173 DB - PRIME DP - Unbound Medicine ER -