Next generation PrEP—multipurpose technologies in macaques

Editor’s notes: Adherence is an issue not only for oral PrEP but also for topical PrEP.  Two large studies of an intra-vaginal ring releasing dapivirine both showed some overall efficacy in the primary analysis, but suggested that very high adherence would be needed to achieve reliable protection from HIV.  One reason for poor adherence, particularly among the youngest women in the studies, may be that young women do not seriously consider the chance that they might acquire HIV infection from a romantic partner.  Adherence to modern family planning methods has been improved through the use of long-acting reversible products including injections, implants, rings and intra-uterine devices. This has led to enthusiasm for multipurpose technologies that might offer women not only protection against unwanted pregnancies, but also protection from HIV or from other sexually transmitted such as herpes simplex virus.  Smith and colleagues present some data from early studies of one such device.  They made silicone rings with pods that could deliver hormonal contraception as well as tenofovir alafenamide (against HIV) and acyclovir (against HSV).  These rings were shown in macaques to release their different components satisfactorily into the vaginal tissues and systemic circulation at levels that would be predicted to be highly effective.  Modern contraceptives are highly effective and hugely important as a means for women to regulate their own fertility.  As has been seen with the dapivirine ring studies, adherence to intravaginal products is likely not be as high as can be achieved with injections or implants.  So the balance between contraceptive efficacy and the potential benefits of additional prevention tools for HIV and other sexually transmitted infections will need to be weighed carefully.  On the other hand, the increasing worry that DMPA may actually increase the risk of HIV acquisition (as discussed in previous issues) makes research to broaden the choices for women’s reproductive and sexual health even more important.

Novel multipurpose pod-intravaginal ring for the prevention of HIV, HSV, and unintended pregnancy: Pharmacokinetic evaluation in a macaque model.

Smith JM, Moss JA, Srinivasan P, Butkyavichene I, Gunawardana M, Fanter R, Miller CS, Sanchez D, Yang F, Ellis S, Zhang J, Marzinke MA, Hendrix CW, Kapoor A, Baum MM. PLoS One. 2017 Oct 5;12(10):e0185946. doi: 10.1371/journal.pone.0185946. eCollection 2017.

Globally, women bear an uneven burden for sexual HIV acquisition. Results from two clinical trials evaluating intravaginal rings (IVRs) delivering the antiretroviral agent dapivirine have shown that protection from HIV infection can be achieved with this modality, but high adherence is essential. Multipurpose prevention technologies (MPTs) can potentially increase product adherence by offering protection against multiple vaginally transmitted infections and unintended pregnancy. Here we describe a coitally independent, long-acting pod-IVR MPT that could potentially prevent HIV and HSV infection as well as unintended pregnancy. The pharmacokinetics of MPT pod-IVRs delivering tenofovir alafenamide hemifumarate (TAF2) to prevent HIV, acyclovir (ACV) to prevent HSV, and etonogestrel (ENG) in combination with ethinyl estradiol (EE), FDA-approved hormonal contraceptives, were evaluated in pigtailed macaques (N = 6) over 35 days. Pod IVRs were exchanged at 14 days with the only modification being lower ENG release rates in the second IVR. Plasma progesterone was monitored weekly to determine the effect of ENG/EE on menstrual cycle. The mean in vivo release rates (mg d-1) for the two formulations over 30 days ranged as follows: TAF2 0.35-0.40; ACV 0.56-0.70; EE 0.03-0.08; ENG (high releasing) 0.63; and ENG (low releasing) 0.05. Mean peak progesterone levels were 4.4 ± 1.8 ng mL-1 prior to IVR insertion and 0.075 ± 0.064 ng mL-1 for 5 weeks after insertion, suggesting that systemic EE/ENG levels were sufficient to suppress menstruation. The TAF2 and ACV release rates and resulting vaginal tissue drug concentrations (medians: TFV, 2.4 ng mg-1; ACV, 0.2 ng mg-1) may be sufficient to protect against HIV and HSV infection, respectively. This proof of principle study demonstrates that MPT-pod IVRs could serve as a potent biomedical prevention tool to protect women's sexual and reproductive health and may increase adherence to HIV PrEP even among younger high-risk populations.

Abstract  Full-text [free] access

Basic science
Northern America
United States of America
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