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The prevention of HIV and unintended pregnancies is a public health priority. Multi-purpose prevention technologies capable of long-acting HIV and pregnancy prevention are desirable for women. Here, we utilized a preclinical macaque model to evaluate the pharmacokinetics of biodegradable ε-polycaprolactone implants delivering the antiretroviral islatravir (ISL) and the contraceptive etonogestrel (ENG). Three implants were tested: ISL-62 mg, ISL-98 mg, and ENG-33 mg. Animals received one or two ISL-eluting implants, with doses of 42, 66, or 108 µg of ISL/day with or without an additional ENG-33 mg implant (31 µg/day). Drug release increased linearly with dose with median [range] plasma ISL levels of 1.3 [1.0-2.5], 1.9 [1.2-6.3] and 2.8 [2.3-11.6], respectively. The ISL-62 and 98 mg implants demonstrated stable drug release over three months with ISL-triphosphate (ISL-TP) concentr54ations in PBMCs above levels predicted to be efficacious for PrEP. Similarly, ENG implants demonstrated sustained drug release with median [range] plasma ENG levels of 495 [229-1110] pg/mL, which suppressed progesterone within two weeks and showed no evidence of altering ISL pharmacokinetics. Two of the six ISL-98 mg implants broke during the study and induced implant-site reactions, whereas no reactions were observed with intact implants. We show that ISL and ENG biodegradable implants are safe and yield sufficient drug levels to achieve prevention targets. The evaluation of optimized implants with increased mechanical robustness is underway for improved durability and vaginal efficacy in a SHIV challenge model.
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Introduction: Women in sub-Saharan Africa (SSA) experience disproportionately high rates of HIV infection and unintended pregnancy compared to their age-matched counterparts in other regions of the world. Multipurpose prevention technologies (MPTs) that offer protection against HIV and unintended pregnancy in a single product stand to address these dual sexual and reproductive health needs simultaneously. The aim of this scoping review is to identify factors that are important for optimizing the likelihood of MPT adoption by end users in SSA. Methods: Study inclusion criteria included MPT research (HIV and pregnancy prevention dual indication) published or presented in English from 2000 to 2022 and conducted in SSA amongst end-users (women aged 15-44), male partners, health care providers, and community stakeholders. References were identified by searching peer reviewed literature, grey literature, conference presentations (2015-2022), grant databases, and outreach to MPT subject matter experts. Of 115 references identified, 37 references met inclusion criteria and were extracted for analysis. A narrative synthesis approach was used to summarize findings within and across MPT products. Results: Studies were identified from six countries in SSA and a substantial proportion included a South African (n = 27) and/or Kenyan (n = 16) study site. Most studies utilized a qualitative study design (n = 22) and evaluated MPT acceptability and preferences by presenting hypothetical products through images or a list of product attributes (n = 21). The vaginal ring (n = 20), oral tablet (n = 20), and injection (n = 15) were examined most frequently. Across studies, there was high acceptability and demand for an HIV and pregnancy prevention MPT. End users valued choice in prevention product type as well as discreetness and long-acting options. Provider counseling and community sensitization were reported as essential for future introduction of novel MPT delivery forms. Conclusion: Recognizing the heterogeneity of women's preferences and changing reproductive and sexual health needs over the life course, choice is important in the delivery of pregnancy and HIV prevention products as well as amongst MPT products with distinct product profiles. End user research with active MPTs, vs. hypothetical or placebo MPTs, is necessary to advance understanding of end-user preferences and acceptability of future products.
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INTRODUCTION: The effectiveness of HIV pre-exposure prophylaxis (PrEP) requires consistent and correct product use, thus a deeper understanding of women's stated product formulation preferences, and the correlates of those preferences, can help guide future research. VOICE-D (MTN-003D), a qualitative ancillary study conducted after the VOICE trial, retrospectively explored participants' tablet and gel use, as well as their preferences for other potential PrEP product formulations. METHODS: We conducted an analysis of quantitative and qualitative data from VOICE-D participants. During in-depth interviews, women were presented with pictures and descriptions of eight potential PrEP product formulations, including the oral tablet and vaginal gel tested in VOICE, and asked to discuss which product formulations they would prefer to use and why. Seven of the original product formulations displayed were combined into preferred product formulation categories based on exploratory factor and latent class analyses. We examined demographic and behavioural correlates of these preferred product formulation categories. In-depth interviews with participants were conducted, coded, and analysed for themes related to product preference. RESULTS: Of the 68 female participants who completed in-depth interviews (22 South Africa, 24 Zimbabwe, 22 Uganda), median age was 28 (range 21-41), 81% were HIV negative, and 49% were married or living with a partner. Four preferred product formulation categories were identified via exploratory factor analysis: 1) oral tablets; 2) vaginal gel; 3) injectable, implant, or vaginal ring; and 4) vaginal film or suppository. A majority of women (81%) expressed a preference for product formulations included in category 3. Characteristics significantly associated with each preferred product category differed. Attributes described by participants as being important in a preferred product formulation included duration of activity, ease of use, route of administration, clinic- versus self-administration, and degree of familiarity with product. CONCLUSIONS: While there was interest in a variety of potential PrEP product formulations, a majority of VOICE-D participants preferred long-acting methods. More research is needed to gain insight into end-users' product formulation preference to inform messaging and market segmentation for different PrEP products and resources to invest in products that target populations are most interested in using. CLINICAL TRIAL NUMBER: NCT02358616.
