Significant Decrease of Ethinylestradiol With Nevirapine, and of Etonogestrel With Efavirenz in HIV-Positive Women

Landolt, Nadia Kancheva; Phanuphak, Nittaya; Ubolyam, Sasiwimol; Pinyakorn, Suteeraporn; Kerr, Stephen J.; Ahluwalia, Jennisa; Thongpaeng, Parawee; Thammajaruk, Narukjaporn; Cremers, Serge; Thomas, Tiffany; Chaithongwongwatthana, Surasith; Lange, Joep M. A.; Ananworanich, Jintanat

doi:10.1097/qai.0000000000000134

Cited by 84 publications

(27 citation statements)

References 20 publications

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“…The studies were all conducted in non-TGW, with 10 to 34 participants. In all but five studies [87,88,95,96,98], the participants were all HIV-negative.…”

Section: Resultsmentioning

confidence: 99%

Transgender women, hormonal therapy and HIV treatment: a comprehensive review of the literature and recommendations for best practices

Radix

Sevelius

Deutsch

2016

Journal of the International AIDS Society

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IntroductionStudies have shown that transgender women (TGW) are disproportionately affected by HIV, with an estimated HIV prevalence of 19.1% among TGW worldwide. After receiving a diagnosis, HIV-positive TGW have challenges accessing effective HIV treatment, as demonstrated by lower rates of virologic suppression and higher HIV-related mortality. These adverse HIV outcomes have been attributed to the multiple sociocultural and structural barriers that negatively affect their engagement within the HIV care continuum. Guidelines for feminizing hormonal therapy among TGW recommend combinations of oestrogens and androgen blockers. Pharmacokinetic studies have shown that certain antiretroviral therapy (ART) agents, such as protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and cobicistat, interact with ethinyl estradiol, the key oestrogen component of oral contraceptives (OCPs). The goal of this article is to provide an overview of hormonal regimens used by TGW, to summarize the known drug-drug interactions (DDIs) between feminizing hormonal regimens and ART, and to provide clinical care recommendations.MethodsThe authors identified English language articles examining DDIs between oestrogen therapy, androgen blockers and ART published between 1995 and 2015 using PubMed, Cumulative Index to Nursing and Allied Health Literature and EBSCOhost.Results and DiscussionPublished articles predominantly addressed interactions between ethinyl estradiol and NNRTIs and PIs. No studies examined interactions between ART and the types and doses of oestrogens found in feminizing regimens. DDIs that may have the potential to result in loss of virologic suppression included ethinyl estradiol and amprenavir, unboosted fosamprenavir and stavudine. No clinically significant DDIs were noted with other anti-retroviral agents or androgen blockersConclusionsThere are insufficient data to address DDIs between ART and feminizing hormone regimens used by TGW. There is an urgent need for further research in this area, specifically pharmacokinetic studies to study the direction and degree of interactions between oral, injectable and transdermal estradiol and ART. Clinicians need to be vigilant about possible interactions and monitor hormone levels if concerns arise. More research is also needed on the provision of hormone therapy and gender-affirming care on the long-term health outcomes of HIV-positive TGW.

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“…The studies were all conducted in non-TGW, with 10 to 34 participants. In all but five studies [87,88,95,96,98], the participants were all HIV-negative.…”

Section: Resultsmentioning

confidence: 99%

Transgender women, hormonal therapy and HIV treatment: a comprehensive review of the literature and recommendations for best practices

Radix

Sevelius

Deutsch

2016

Journal of the International AIDS Society

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“…Studies have found no effect of EFV on progesterone levels when using DMPA [8,10,16], but significantly lower progesterone levels among implant users [17–19,15], along with contraceptive failure rates up to 15% among levonorgestrel implant users [20–22]. Evidence regarding EFV and OCs is very limited, suggesting lower progesterone levels but not necessarily increased ovulation on EFV [13,23,24]. The existing evidence has led at least one national health department in Africa to recommend against implant use for women on EFV [25].…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of hormonal contraception in HIV-infected women using antiretroviral therapy

Pyra

Heffron

Mugo

et al. 2015

Aids

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Objective To assess whether antiretroviral therapy (ART) may diminish the effectiveness of hormonal contraceptive methods. Methods Using data from 5,153 HIV-infected women followed prospectively one to three years in three HIV prevention studies in Africa, we compared incident pregnancy rates by contraceptive method (implant, injectable, oral, or none) and ART use. Multivariable Cox regression models were used to determine adjusted hazard ratios (aHR) and test interactions between each method and ART use. Results During follow-up, 9% of women ever used implants, 40% used injectables, and 14% used oral contraceptives; 31% of women ever used ART, mostly nevirapine (75% of ART users) or efavirenz-based (15%). Among women not using contraception, pregnancy rates were 13.2 and 22.5 per 100 women-years for those on and not on ART, respectively. Implants greatly reduced the incidence of pregnancy among both women on ART (aHR 0.06, 95% CI 0.01-0.45) and not on ART (aHR 0.05, 95% CI 0.02-0.11). Injectables (aHR 0.18 on ART and aHR 0.20 not on ART) and oral contraceptives (aHR 0.37 on ART and aHR 0.36 not on ART) also reduced pregnancy risk, though by lesser degrees. ART use did not significantly diminish contraceptive effectiveness, although all methods showed non-statistically significant reduced effectiveness when concurrently using efavirenz. Conclusion Hormonal contraceptive methods are highly effective in reducing pregnancy risk in HIV-infected women, including those concurrently using ART. Studies of potential interactions between ART and contraceptives should evaluate real-world effectiveness of contraceptive methods; in this study, implants were the most effective method to prevent pregnancy, even during ART use.

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“…Landolt et al compared the pharmacokinetics of ethinyl estradiol/desogestrel in HIV-positive women receiving ART to HIV-negative women. In that study, women receiving nevirapine-based ART had etonogestrel (the active metabolite of desogestrel) concentrations 22% lower and ethinyl estradiol concentrations 58% lower than HIV-negative individuals [45]. However, no participant receiving nevirapine-based ART had luteal activity, despite the decrease in etonogestrel and ethinyl estradiol exposure [46].…”

Section: 0 Drug-drug Interactions Between Hormonal Contraceptives Amentioning

confidence: 99%

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

et al. 2016

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Family planning options, including hormonal contraceptives, are essential for improving reproductive health among the more than 17 million women living with human immunodeficiency virus (HIV) worldwide. For these women, prevention of unintended pregnancy decreases maternal and child mortality, as well as reduces the risk of perinatal HIV transmission. Similarly, treatment of HIV with antiretroviral therapy (ART) is essential for reducing morbidity and mortality among HIV-positive individuals, as well as preventing HIV transmission between sexual partners or from mother to child. Importantly, despite the benefits of hormonal contraceptives, barriers to effective family planning methods exist for HIV-positive women. Specifically, drug-drug interactions can occur between some antiretroviral medications and some hormonal contraceptives, which may influence both contraceptive efficacy and tolerability. In addition, safety concerns have been raised about the impact of hormonal contraceptives on HIV disease progression, tolerability and the risk of female-to-male HIV transmission. This review article summarizes the potential for drug-drug interactions, tolerability, and contraceptive effectiveness when hormonal contraceptives are combined with ART. In addition, the evidence surrounding the influence of hormonal contraceptives on HIV transmission and HIV disease progression in women living with HIV are summarized.

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Significant Decrease of Ethinylestradiol With Nevirapine, and of Etonogestrel With Efavirenz in HIV-Positive Women

Cited by 84 publications

References 20 publications

Transgender women, hormonal therapy and HIV treatment: a comprehensive review of the literature and recommendations for best practices

Transgender women, hormonal therapy and HIV treatment: a comprehensive review of the literature and recommendations for best practices

Effectiveness of hormonal contraception in HIV-infected women using antiretroviral therapy

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

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