Drug–Drug Interactions, Effectiveness, and Safety of Hormonal Contraceptives in Women Living with HIV

Scarsi, Kimberly K.; Darin, Kristin M.; Chappell, Catherine A.; Nitz, Stephanie M.; Lamorde, Mohammed

doi:10.1007/s40264-016-0452-7

Cited by 48 publications

(49 citation statements)

References 85 publications

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“…Antiretrovirals, including NNRTIs, PIs, and cobicistat-boosted agents, influence the activity of CYP3A4 and 2B6 enzymes; NNRTIs are specifically implicated in CYP3A4 induction [14]. Generally, NRTIs and INSTIs are not considered significant inhibitors, inducers, or substrates of CYP450 enzymes, and, therefore, unlikely to influence hormonal contraceptive exposure [14,15]. Two recent systematic reviews on DDIs between hormonal contraceptives and antiretrovirals for women living with HIV thoroughly cover the aforementioned aspects [15,16].…”

Section: General Principles For Contraceptive Provisionmentioning

confidence: 99%

“…Generally, NRTIs and INSTIs are not considered significant inhibitors, inducers, or substrates of CYP450 enzymes, and, therefore, unlikely to influence hormonal contraceptive exposure [14,15]. Two recent systematic reviews on DDIs between hormonal contraceptives and antiretrovirals for women living with HIV thoroughly cover the aforementioned aspects [15,16]. In Section 3, we highlight pertinent findings for each combination of contraceptive method and antiretroviral classes.…”

Section: General Principles For Contraceptive Provisionmentioning

confidence: 99%

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Current and future contraceptive options for women living with HIV

Patel

Bukusi

Baeten

2017

Expert Opinion on Pharmacotherapy

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Introduction Among women living with HIV, half of the pregnancies are unintended. Effective contraception can prevent unintended pregnancies and consequently reduce maternal mortality and perinatal transmission of HIV. While contraceptive options available for all women also apply to women living with HIV, specific considerations exist to the use of contraception by women living with HIV. Areas covered First, general principles guiding the use of contraception among women living with HIV are discussed, such as choice, method mix, relative effectiveness, and drug-drug interactions. Second, a detailed discussion of each contraceptive method and issues surrounding the use of that method, such as drug-drug interactions, follows. Third, future contraceptive options in advanced development for use by women or men are briefly discussed. Expert opinion Contraceptive methods available to all women should also be accessible to women living with HIV. When the relative effectiveness of a contraceptive method is reduced, for example due to drug-drug interactions with antiretrovirals, the method should still be made available to women living with HIV with the appropriate information sharing and counseling. Greater research on various aspects of contraceptive use by women living with HIV and more comprehensive testing of co-administration of hormonal contraceptives and common medications used by these women are warranted.

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Section: General Principles For Contraceptive Provisionmentioning

confidence: 99%

Section: General Principles For Contraceptive Provisionmentioning

confidence: 99%

Current and future contraceptive options for women living with HIV

Patel

Bukusi

Baeten

2017

Expert Opinion on Pharmacotherapy

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“…For example, three pregnancies were reported in a total of twenty study participants on EFV-based ART while using the LNG implant and these pregnancies were associated with low plasma LNG concentrations [13]. In addition, retrospective analyses confirm that contraceptive failures are more frequent in women receiving EFV-based ART in combination with contraceptive implants [19, 20, 35]. Thus, decreased ENG exposure in the setting of concomitant EFV-based ART reported here is concerning for increased risk of contraceptive failures.…”

Section: Discussionmentioning

confidence: 99%

Efavirenz decreases etonogestrel exposure

Chappell

Lamorde

Nakalema

et al. 2017

Aids

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Objectives The primary objective of this study was to characterize the pharmacokinetics of etonogestrel (ENG) released from a contraceptive implant in Ugandan women living with HIV who were receiving efavirenz (EFV)- or nevirapine (NVP)-based antiretroviral therapy (ART), compared to ART-naïve women over 24 weeks. Design Non-randomized, parallel-group study with 3 arms: ART-naïve, NVP-, or EFV-based ART (N=20 per group). Methods Sparse pharmacokinetic sampling of ENG, NVP or EFV were performed at screening, entry, and then 1, 4, 12 and 24 weeks post-implant insertion. The primary endpoint was ENG concentrations at week 24, compared between the ART-naïve group and each ART group, using geometric mean ratio (GMR) with 90% confidence intervals. Results Sixty participants competed the study and data from 58 participants are included; one participant each was excluded from the NVP group and EFV group due to a sample processing error and ART nonadherence, respectively. At week 24, geometric mean (GM) ENG was 362, 341, and 66 pg/mL in the ART-naïve, NVP, and EFV groups, respectively [GMR: NVP:ART-naïve 0.94 (0.90–1.01); EFV:ART-naïve 0.18 (0.17–0.20)]. NVP and EFV concentrations were lower at week 24 compared to pre-implant [NVP: GM 5.7 versus 6.8 mg/L, respectively, GMR 0.84 (0.83–0.85); EFV: GM 3.6 versus 4.9mg/L, respectively, GMR 0.73 (0.69–0.80)]. Conclusions After 24 weeks of combined use, ENG exposure was 82% lower in women using EFV-based ART compared to ART-naïve women. In contrast, NVP did not significantly impact ENG exposure. These results raise concerns about reduced effectiveness of implantable contraception for women taking EFV-based ART.

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“…For women with or at risk for HIV-1, concurrent use of hormonal contraceptives for pregnancy prevention and antiretrovirals for HIV-1 treatment or prevention could result in potential drug-drug interactions that may diminish contraceptive effectiveness[2, 3]. Contraceptive hormones are metabolized by hepatic cytochrome P450 enzymes, and certain non-nucleoside reverse transcriptase inhibitors (NNRTIs) can induce cytochrome P450 enzymes leading to reduced plasma progestin concentrations, with some NNRTIs having a greater impact on progestin pharmacokinetics than others[4-8].…”

Section: Introductionmentioning

confidence: 99%

“…Contraceptive hormones are metabolized by hepatic cytochrome P450 enzymes, and certain non-nucleoside reverse transcriptase inhibitors (NNRTIs) can induce cytochrome P450 enzymes leading to reduced plasma progestin concentrations, with some NNRTIs having a greater impact on progestin pharmacokinetics than others[4-8]. Among HIV-1 infected women, use of the NNRTI efavirenz as part of combination HIV-1 treatment has been associated with a reduced effectiveness of contraceptive implants[3, 6, 7, 9]. …”

Section: Introductionmentioning

confidence: 99%

Brief Report: Dapivirine Vaginal Ring Use Does Not Diminish the Effectiveness of Hormonal Contraception

Balkus

Palanee‐Phillips²,

Reddy

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objective To evaluate the potential for a clinically relevant drug-drug interaction with concomitant use of a dapivirine vaginal ring, a novel antiretroviral-based HIV-1 prevention strategy, and hormonal contraception by examining contraceptive efficacies with and without dapivirine ring use. Design A secondary analysis of women participating in MTN-020/ASPIRE, a randomized, double-blind, placebo-controlled trial of the dapivirine vaginal ring for HIV-1 prevention. Methods Use of a highly effective method of contraception was an eligibility criterion for study participation. Urine pregnancy tests were performed monthly. Pregnancy incidence by arm was calculated separately for each hormonal contraceptive method and compared using an Andersen-Gill proportional hazards model stratified by site and censored at HIV-1 infection. Results Of 2629 women enrolled, 2310 women returned for follow-up and reported using a hormonal contraceptive method at any point during study participation (1139 in the dapivirine arm, 1171 in the placebo arm). Pregnancy incidence in the dapivirine arm versus placebo among women using injectable depot medroxyprogesterone acetate was 0.43% vs. 0.54%, among women using injectable norethisterone enanthate was 1.15% vs. 0%, among women using hormonal implants was 0.22% vs. 0.69%, and among women using oral contraceptive pills was 32.26% vs. 28.01%. Pregnancy incidence did not differ by study arm for any of the hormonal contraceptive methods. Conclusions Use of the dapivirine ring does not reduce the effectiveness of hormonal contraceptives for pregnancy prevention. Oral contraceptive pill use was associated with high pregnancy incidence, potentially due to poor pill adherence. Injectable and implantable methods were highly effective in preventing pregnancy.

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Drug–Drug Interactions, Effectiveness, and Safety of Hormonal Contraceptives in Women Living with HIV

Cited by 48 publications

References 85 publications

Current and future contraceptive options for women living with HIV

Current and future contraceptive options for women living with HIV

Efavirenz decreases etonogestrel exposure

Brief Report: Dapivirine Vaginal Ring Use Does Not Diminish the Effectiveness of Hormonal Contraception

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