Is a lower-dose, subcutaneous contraceptive injectable containing depot medroxyprogesterone acetate likely to impact women's risk of HIV?

Polis, Chelsea B.; Achilles, Sharon L.; Hel, Zdeněk; Hapgood, Janet P.

doi:10.1016/j.contraception.2017.12.003

Cited by 18 publications

(16 citation statements)

References 77 publications

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“…The pharmacokinetic data from studies of DMPA and NET-EN show large interindividual and interstudy variability. Differences across studies may be impacted by differences in study design, including numbers of women investigated, women's demographic characteristics (ethnicity, race, body mass index, weight and metabolism), number of injections, injection sites, and time and frequency of measurements [14] , [19] . Assay methodologies to measure progestins have evolved over time to be more sensitive and specific; however, this can further complicate interpretation when comparing data from newer and older studies [20] , [21] , [22] .…”

Section: Pharmacologic Biologic and Epidemiologic Studies Of Dmpa Anmentioning

confidence: 99%

“…However, data from non-head-to-head studies suggest that serum MPA concentrations may be greater during the first 30 days after injection of DMPA-IM relative to DMPA-SC [19] , [25] , [26] , [27] . More than 30 days following injection, serum MPA concentrations appear similar in women receiving DMPA-IM and DMPA-SC injections, although comparisons are complicated by lack of a head-to-head study [19] , [25] , [26] , [28] . A postmarketing study designed to compare efficacy, safety and acceptability of DMPA-SC with DMPA-IM suggested no difference in minimum concentration ( C min ) at 90 days following injection, even subsequent to multiple injections, but did not evaluate C max [29] .…”

Section: Pharmacologic Biologic and Epidemiologic Studies Of Dmpa Anmentioning

confidence: 99%

“…For example, in women, NET has been shown to be converted to ethinyl estradiol, a potent estrogen, which binds to and activates the estrogen receptor [59] . For DMPA, further clinical studies are needed to determine whether different routes of administration (e.g., IM versus SC) or sites of subcutaneous injection (e.g., abdomen, thigh, arm) result in different receptor-mediated responses [19] , [25] , [26] , [28] , [54] , [55] , [61] . The differential binding affinity of MPA and NET for the glucocorticoid receptor may underlie key differences in biological impacts [52] , [54] , [55] including potential differences in HIV susceptibility [14] , [24] .…”

Section: Pharmacologic Biologic and Epidemiologic Studies Of Dmpa Anmentioning

confidence: 99%

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Pharmacokinetic, biologic and epidemiologic differences in MPA- and NET-based progestin-only injectable contraceptives relative to the potential impact on HIV acquisition in women

et al. 2019

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Access to safe and effective contraceptive choices is a reproductive right and contributes tremendously to improvements in maternal and child health. Progestin-only injectables, particularly intramuscularly injected depot medroxyprogesterone acetate (DMPA-IM), have received increased attention given findings suggesting a potential association with increased HIV risk. For women at high risk of HIV, the World Health Organization's Medical eligibility criteria for contraceptive use currently aggregate recommendations for all progestin-only injectables, including DMPA-IM, subcutaneously injected DMPA (DMPA-SC) and intramuscularly injected norethindrone/ norethisterone enanthate (NET-EN), except in the case of some drug interactions. We considered whether published data indicate differences or similarities between these injectables relevant to risk of acquiring HIV. In vitro data confirm different biological activities of these distinct progestins, including that MPA, and not NET, binds and activates the glucocorticoid receptor resulting in different biological effects relevant to immune function. Limited clinical data suggest changes in immunologic activity following DMPA-IM and NET-EN initiation, but interstudy variation and study design differences diminish ability to determine clinical relevance and the degree to which DMPA-IM and NET-EN could act differentially. The highest-quality epidemiologic studies suggest a potential 40% increase in HIV incidence in users of DMPA-IM relative to women not using hormonal contraception but no significant increase in risk in users of NET-EN. In our opinion, most of the available biologic activity and epidemiologic data indicate that DMPA and NET-EN are likely to act differently, and data remain too limited to evaluate differences between DMPA-IM and DMPA-SC.

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Section: Pharmacologic Biologic and Epidemiologic Studies Of Dmpa Anmentioning

confidence: 99%

Section: Pharmacologic Biologic and Epidemiologic Studies Of Dmpa Anmentioning

confidence: 99%

Section: Pharmacologic Biologic and Epidemiologic Studies Of Dmpa Anmentioning

confidence: 99%

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Pharmacokinetic, biologic and epidemiologic differences in MPA- and NET-based progestin-only injectable contraceptives relative to the potential impact on HIV acquisition in women

et al. 2019

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“…6 Since 2016, there is substantial new clinical and in vitro biological and animal data that are largely consistent with increased HIV acquisition for DMPA-IM users via several mechanisms. [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52] An interesting argument was made in the WHO 2019 guidelines 6 on this issue: ''The GDG recognized that the ECHO trial did not address the etiological or causal question of whether DMPA increases the risk of HIV acquisition when compared with not using any contraception'' followed shortly thereafter by: ''Furthermore, the GDG noted that the high incidence of HIV infection experienced by each contraceptive group during the ECHO trial was similar to the background incidence assumed when designing the trial. This was deemed to be indirect evidence addressing the question, suggesting no increased risk of HIV acquisition among users of these contraceptives compared with women not using any contraception.''…”

Section: What Do the Echo Results Tell Us About The Risks Of Hiv Acqumentioning

confidence: 99%

“…The metaanalysis of observational data for DMPA-IM relative to no contraception or mainly condom use are currently the best estimate of the HIV risks associated with DMPA-IM and are mostly consistent with a large body of other clinical, animal, and laboratory studies indicating several plausible biological mechanisms whereby DMPA-IM may increase HIV acquisition relative to no contraception. [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52]72 The ECHO trial results on relative HIV risks between the three methods are subject to several limitations and uncertainties. They provide evidence that the LNG implant may be associated with lower HIV risk than DMPA-IM and the copper-IUD.…”

Section: What Do the Echo Results Tell Us About The Risks Of Hiv Acqumentioning

confidence: 99%

Is the Injectable Contraceptive Depo-Medroxyprogesterone Acetate (DMPA-IM) Associated with an Increased Risk for HIV Acquisition? The Jury Is Still Out

Hapgood

2020

AIDS Research and Human Retroviruses

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Intramuscular depo-medroxyprogesterone acetate (DMPA-IM) is the most widely used hormonal contraceptive in sub-Saharan Africa. Previous meta-analyses of observational studies found a significant 40%-50% increased risk associated with DMPA-IM use, relative to no contraception or infrequent condom use. This raised substantial concerns, although these studies had important limitations. Consequently, the open-label randomized Evidence for Contraceptive Options and HIV Outcomes trial was conducted, designed primarily to detect a 50% or greater difference in HIV risk between DMPA-IM, the levonorgestrel (LNG) implant, and the copper-intrauterine device. The ECHO study, published in July 2019, concluded that there is no substantial difference in HIV risk among the methods evaluated, and that all three methods are safe and highly effective. In response, the WHO relaxed the Medical Eligibility Criteria for DMPA-IM use among women at high HIV risk in August 2019. However, two of the three comparisons in the ECHO trial could rule out neither a 50% increase nor no change in HIV risk for one contraceptive compared with another. The study had limitations and the results contained considerable uncertainty. They also did not inform on associated HIV risk for any one of the individual methods due to the absence of a control group such as no contraception or only infrequent condom use. The HIV risks associated with LNG implant and copper-IUD relative to no contraception or infrequent condom use are unknown and these cannot be seen as controls, nor did the authors claim them to be. The results will be discussed in the context of their limitations, what they add to the body of work to date on contraception and HIV acquisition, and the implications of the findings and reports thereof for future research and contraceptive choice.

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Task-shifting the provision of DMPA-SC in the DR Congo: Perspectives from two different groups of providers

et al. 2018

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ObjectivesTo document the experience of three groups of Family Planning service providers participating in task-shifting for the provision of subcutaneous depot-medroxyprogesterone acetate (DMPA-SC) at the community level in the DRC.Study designThis article compares results from interviews with DMPA-SC providers in two separate pilot studies: 1) 53 medical and nursing school students teaching women how to self-inject (2016–2017); and 2) 34 lay community health workers providing DMPA-SC in rural areas of Lualaba (2017). All providers gave information on socio-demographic characteristics, recruitment,) training, supervision, experience and satisfaction with the provision of DMPA-SC. The paper examines variations in responses from the different provider cadres.ResultsDespite substantive variations in provider profiles in terms of age, educational and marital status, reported levels of satisfaction with offering DMPA-SC in the community were consistently high. Over 90% of all providers declared being comfortable or very comfortable interacting with FP clients, and more than three quarters of them were very comfortable performing an injection. Over 90% of Lualaba providers and over 80% of student providers gave correct responses to DMPA-SC protocol questions regarding referral of clients to facilities and side-effects management. The vast majority declared being (very) satisfied with their experience providing DMPA-SC.ConclusionsProviders with and without a clinical background, when properly trained and supervised, can provide DMPA-SC at the community level in both urban and rural settings of the DRC. Support strategies from the Family Planning environment (continuous contraceptive supplies and adequate referral system to fixed facilities) are key to engaging community health workers and sustainably leveraging task-shifting opportunities.Implication statementThis study provides additional evidence on the acceptability and feasibility of task-shifting in relation to DMCP-SC and supports further scale-up efforts.

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Is a lower-dose, subcutaneous contraceptive injectable containing depot medroxyprogesterone acetate likely to impact women's risk of HIV?

Cited by 18 publications

References 77 publications

Pharmacokinetic, biologic and epidemiologic differences in MPA- and NET-based progestin-only injectable contraceptives relative to the potential impact on HIV acquisition in women

Pharmacokinetic, biologic and epidemiologic differences in MPA- and NET-based progestin-only injectable contraceptives relative to the potential impact on HIV acquisition in women

Is the Injectable Contraceptive Depo-Medroxyprogesterone Acetate (DMPA-IM) Associated with an Increased Risk for HIV Acquisition? The Jury Is Still Out

Task-shifting the provision of DMPA-SC in the DR Congo: Perspectives from two different groups of providers

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