A Tunable, Biodegradable, Thin-Film Polymer Device as a Long-Acting Implant Delivering Tenofovir Alafenamide Fumarate for HIV Pre-exposure Prophylaxis

Schlesinger, Erica; Johengen, Daniel; Luecke, Ellen; Rothrock, Ginger; McGowan, Ian; Straten, Ariane van der; Desai, Tejal A.

doi:10.1007/s11095-016-1904-6

Cited by 88 publications

(95 citation statements)

References 21 publications

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“…A single oral dose of only 10 mg of EFdA in humans inhibited replication for at least 1 week, 17 and studies in rats involving an implant suggested that greater than 6 months' release of EFdA at adequate levels may be feasible 17 . Although EFdA is only in early-stage development, TAF is another NRTI that is already approved as an oral agent and is now being explored as an agent to be released from several different types of long-acting implants 18 , 19 . And GS-9131 is an early-stage NRTI prodrug with a structure and potency somewhat similar to TAF, but with a very robust barrier to resistance and unique resistance profile 15 .…”

Section: New Arvs May Help Overcome These Downsidesmentioning

confidence: 99%

“…While developing such biodegradable implants has long been a goal for long-acting reversible contraception, it has proved elusive due to several potential challenges, including a prolonged tail of low levels of the active agent and the possibility of dumping large amounts of the agent when the implant terminally biodegrades. However, new designs for biodegradable implants may overcome these challenges for ARVs, such as a thin-film polymer device that contains a thin biodegradable coat and a reservoir filled with an ARV (TAF, noted above, is an ARV that is being used in one investigational device) 18 . The ARV diffuses through the membrane, allowing the reservoir to gradually empty after which the outer coat biodegrades, thereby decoupling the biodegradation from the release and hopefully avoiding dumping or a prolonged tail.…”

Section: Implants That Are Easier To Implement: Biodegradable and Refmentioning

confidence: 99%

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Long-Acting HIV Treatment and Prevention: Closer to the Threshold

Barnhart

2017

Glob Health Sci Pract

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Substantial progress has been made toward viable, practical long-acting approaches to deliver HIV treatment and prevention through: (1) continued improvements in long-acting antiretrovirals (ARVs); (2) better innovative delivery systems; and (3) collaboration of willing partners to advance new ARVs. More progress on those 3 fronts is still needed to arrive at the goal of optimized HIV treatment and prevention for all who would benefit—and of finally controlling the HIV epidemic.

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Section: New Arvs May Help Overcome These Downsidesmentioning

confidence: 99%

Section: Implants That Are Easier To Implement: Biodegradable and Refmentioning

confidence: 99%

Long-Acting HIV Treatment and Prevention: Closer to the Threshold

Barnhart

2017

Glob Health Sci Pract

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“…For example, long-acting injectable antiretrovirals, rilpivirine and cabotegravir, have shown promising results for treatment of HIV in phase 2 clinical trials [93]. Implants embedded with long-acting antiretrovirals are also under development [94,95]. If successful, such long-acting antiretroviral formulations for HIV treatment could be combined with contraceptives for pregnancy prevention.…”

Section: Future Contraceptive Optionsmentioning

confidence: 99%

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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“…Other PrEP products (e.g. dapivirine, tenofovir alafenamide (TAF), and maraviroc rings, biodegradable tenofovir (TFV) films, cabotegravir injections, TAF or maraviroc pills, TFV implants), are at various stages of the research and development process and are promising, longer-acting HIV prevention options (9 ■ ,10 ■ ,11 ■ ,12). However, it has recently been hypothesized that the efficacy of topically-applied PrEP products may be moderated by vaginosis dysbiosis, a general term indicating that vaginal microbiota are sub-optimal (13 ■■ ).…”

Section: Introductionmentioning

confidence: 99%

The Vaginal Microbiome and its Potential to Impact Efficacy of HIV Pre-exposure Prophylaxis for Women

Velloza

Heffron

2017

Curr HIV/AIDS Rep

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Purpose of review This review describes existing evidence addressing the potential modulation of PrEP products, specifically 1% tenofovir (TFV) gel and oral tenofovir-based PrEP, by vaginal dysbiosis and discusses future considerations for delivering novel, long-acting PrEP products to women at high-risk for vaginal dysbiosis and HIV. Recent findings We describe results from analyses investigating the modification of PrEP efficacy by vaginal dysbiosis and studies of biological mechanisms that could render PrEP ineffective in the presence of specific microbiota. A secondary analysis from the CAPRISA-004 cohort demonstrated that there is no effect of the 1% TFV gel in the presence of non-Lactobacillus dominant microbiota. Another recent analysis comparing oral tenofovir-based PrEP efficacy among women with and without bacterial vaginosis in the Partners PrEP Study found that oral PrEP efficacy is not modified by bacterial vaginosis. Gardnerella vaginalis, commonly present in women with vaginal dysbiosis, can rapidly metabolize TFV particularly when it is locally applied and thereby prevent TFV integration into cells. Given that vaginal dysbiosis appears to modulate efficacy for 1% TFV gel but not for oral tenofovir-based PrEP, vaginal dysbiosis is potentially less consequential to HIV protection from TFV in the context of systemic drug delivery and high product adherence. Summary Vaginal dysbiosis may undermine the efficacy of 1% TFV gel to protect women from HIV but not the efficacy of oral PrEP. Ongoing development of novel ring, injectable, and film-based PrEP products should investigate whether vaginal dysbiosis can reduce efficacy of these products, even in the presence of high adherence.

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A Tunable, Biodegradable, Thin-Film Polymer Device as a Long-Acting Implant Delivering Tenofovir Alafenamide Fumarate for HIV Pre-exposure Prophylaxis

Cited by 88 publications

References 21 publications

Long-Acting HIV Treatment and Prevention: Closer to the Threshold

Long-Acting HIV Treatment and Prevention: Closer to the Threshold

Current and future contraceptive options for women living with HIV

The Vaginal Microbiome and its Potential to Impact Efficacy of HIV Pre-exposure Prophylaxis for Women

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