The Dual Prevention Pill (DPP) is a daily oral pill containing oral pre-exposure prophylaxis (PrEP) for protection against HIV and a combined oral contraceptive (COC) for the prevention of unintended pregnancy, currently under development. However, little is known about healthcare providers' (HCPs) perspectives on this potential new multipurpose prevention technology (MPT). A more granular understanding of HCP views about the DPP may support efforts to ensure equitable introduction of and access to this innovative technology. We conducted in-depth interviews with 17 HCPs working at family planning (FP) and HIV service sites in Johannesburg, South Africa. We used a qualitative framework analysis to examine HCP perspectives on potential end-users, the DPP concept and health system-related considerations. HCPs articulated that the DPP would meet the needs of their clients, contribute to more efficient and effective integrated sexual and reproductive health service delivery and meet broader community goals for the reduction in HIV infections and unintended pregnancies. HCPs noted concerns and potential challenges with the product’s daily dosing regimen, potential for exacerbated side effects (compared to oral PrEP or COCs taken alone) and potential ethical considerations about offering the DPP to adolescents. HCPs felt the DPP should be available through public health care facilities to maximise outreach and ensure appropriate care, and discussed community-based delivery options for expanded outreach. They also noted the need to address provider biases, particularly when serving adolescents, as well as the accompanying demand creation efforts with end-users and educational campaigns in the community. Understanding providers’ support for the DPP, as well as the potential challenges they foresee, should inform market introduction strategies, clinic counselling guidelines and provider training for the DPP. We underscore the need to engage with HCPs early (prior to product introduction) to understand local barriers and facilitators to ensure quality sustained rollout and support for MPTs.

INTRODUCTION:Oral preexposure prophylaxis (PrEP) is safe and effective for HIV prevention, but use among women has been suboptimal. A dual prevention pill (DPP) coformulating PrEP and a combined oral contraceptive (COC) may increase PrEP use. METHODS:We conducted a crossover study comparing an overencapsulated PrEP and COCs capsule (DPP) with PrEP and COCs taken separately (2-pill regimen [2 PR]) among in Johannesburg, South Africa. We randomized (1:1) 18- to 40-year-old female participants to regimen sequence: DPP followed by 2 PR for ∼3 months each, or the reverse, plus an optional choice period (≤6 m). Primary outcomes were stated regimen "preference" after the crossover period (exact binomial test; proportion = 0.5) and "adherence" defined as tenofovir diphosphate (TFV-DP) levels in monthly dried blood spots (DBS) indicating ≥4 PrEP doses/week (mixed-effects logistic regression). Safety and acceptability were secondary outcomes. RESULTS:Of 96 participants (mean age, 27.4 years) enrolled, 85 completed the crossover period (August 2022-January 2024), 62% of whom preferred the 2 PR vs 38% the DPP capsule (P = 0.037). Few participants (7%) were always adherent (per DBS samples) and <25% were ever adherent (≥1 DBS sample indicating adherence), with no difference by regimen (P > 0.05). Most adverse events were mild/moderate and similar between the regimens. More than 80% found both regimens easy to use, although >75% reported challenges swallowing the DPP and/or PrEP tablet. CONCLUSIONS:Although more participants preferred the 2 PR, a substantial minority preferred the DPP, highlighting the importance of choice. Adherence to both regimens was low. Studies with the smaller coformulated tablet will be important for assessing the DPP's ultimate impact on HIV prevention. CLINICAL TRIAL NUMBER:NCT04778527.

Background:We assessed US women's preferences to inform development of a novel nonhormonal multipurpose prevention technology (MPT)-a vaginal ring to prevent pregnancy, HIV, sexually transmitted infections (STIs), and bacterial vaginosis (BV). Methods:In cross-sectional online surveys with US women ages 18-49 currently/interested in using contraception, we conducted a discrete choice experiment (DCE) comprising 7 MPT ring attributes. Mixed multinomial logit models examined relative attribute importance and sub-population preferences. Results:Of 2,105 survey completers (mean age 31) from all 50 states (Dec 2023 to Jan 2024), 53% were married/cohabiting, 57% had ≥1 child, 43% ever had an unintended pregnancy, and 9% had an STI in the past year. Participants valued effectiveness for contraception about twice as much as for HIV prevention and about 3 times that of STI prevention. Younger women (18-29 vs. 30-49) desired higher pregnancy and HIV prevention effectiveness. Women who were worried about HIV valued effectiveness for HIV and pregnancy similarly. While most women valued BV prevention and no menstrual side effects, a nonhormonal formulation mattered only to women averse to hormonal contraception (61%) and on-demand use (vs. continuous-use only) was not preferred. Women were willing to trade off some pregnancy prevention effectiveness for other desired attributes. Overall, 73% reported being likely/very likely to use a nonhormonal MPT ring at moderate protection levels (80% pregnancy, 50% HIV/STIs). Conclusions:Interest in an MPT ring was strong, even with conservative effectiveness estimates. Preferences and desired levels of prevention effectiveness and nonhormonal options were shaped by contraceptive history and personal context.

Adolescent girls and young women (AGYW) in Zimbabwe bear a double burden of HIV and unmet need despite the progress made in provision of family planning and oral pre-exposure prophylaxis (PrEP). We elicited opinions from AGYW and health care providers (HCPs) about a dual prevention pill (DPP) in development that combines oral contraceptives (OCs) with oral PrEP to simultaneously prevent unintended pregnancy and HIV, and potentially increase uptake and adherence to oral PrEP. We enrolled 44 participants (March-June 2021) and conducted 12 in-depth interviews with HCPs (nurses, counselors, social workers, pharmacists, clinicians) from public and private health facilities offering HIV and family planning services in Harare, and four focus group discussions (FGDs) with 32 AGYW who were current OC users, stratified by age (16-19, 20-24). The HCPs and AGYW welcomed the idea of the DPP. Both groups perceived the benefits of the DPP as lessening the burden of taking two separate pills and giving AGYW the option to protect themselves discreetly, potentially increasing adherence and ease of use. HCP's had favorable attitudes toward the DPP and highlighted that the DPP regimen is already similar to the OCs women are taking and would allow for regular menses and quick return to fertility. Despite concerns about potential side effects and lack of protection against sexually transmitted infections (STIs) other than HIV, HCPs noted the potential benefits of the DPP in reducing their workload and increasing the uptake of PrEP services. From the end user perspective, the DPP size, color, and packaging should be appealing and distinct from HIV medications to minimize stigma. Clear guidelines are deemed necessary for DPP service provision for adolescents, emphasizing the importance of tailored approaches for different age groups. Educating male partners and the broader community about the DPP could enhance its use among AGYW.

BACKGROUND: No empirical data support the 54 to 58 mm external diameter of intravaginal rings currently available and in development for contraception and other indications. Understanding how external diameter affects preference, adherence, and acceptability is critical for optimizing future product development. OBJECTIVE: Our primary objectives were to determine which of 3 nonmedicated rings of differing external diameters was preferred and yielded the highest adherence. Secondary objectives were comparing acceptability, patterns of adherence, and safety of the 3 rings. STUDY DESIGN: In an open-label, 3-way crossover trial, healthy, HIV-uninfected, monogamous, sexually active, nonpregnant, 18-year-old to 40-year-old cisgender women and their male partners in Atlanta, GA and the Bronx, NY were randomly assigned to the sequence of using 3 non-medicated silicone rings (46 mm, 56 mm, and 66 mm external diameters) continuously for approximately 30 days each (90 days total; November 2021 to December 2022). We tested whether end-of-study preference for any of the 3 rings was greater than 0.33 (binomial proportion, exact test). We used mixed-effect regression models with random intercepts by participants to compare adherence (ring never out for more than 30 minutes in 24 hours) and probability of removals (including reasons for removal), expulsions, and the ring being out of the vagina all day, per ring, per day of use with the 56-mm ring as the reference group and to compare scores on a novel 19-item acceptability scale with items related to ease and experience of use and impact on sex. RESULTS: Of 24 women, 23 completed the study (median age: 26.7 years [standard deviation: 3.78]). Most were college graduates (92%), White (63%), non-Hispanic (79%), single (79%), and nulliparous (92%). At the end of the study, 59% preferred the smallest (46 mm) ring versus 18% each for the 56-mm and 66-mm rings (P=.0045). The proportion of participants who were adherent did not differ by ring (46 mm, 78%; 56 mm, 75%; 66 mm, 59%; P=.30); however, odds of expulsion were higher for the 46-mm (odds ratio: 5.72; 95% confidence interval: 1.25-26.1) and 66-mm (odds ratio: 25.9; 95% confidence interval: 6.11-109) rings than for the 56-mm ring. The 66-mm ring also had greater odds of being out (removal or expulsion, any length of time) than the 56-mm ring (odds ratio: 6.50; 95% confidence interval: 3.46-12.2). Mean acceptability scale scores were identical (4.54/5) for the 46-mm and 56-mm (smallest and medium) rings and significantly higher than for the largest, 66-mm ring (3.94/5; P<.001). CONCLUSION: Although the 46-mm ring was preferred by more women and had higher rates of adherence compared to the other 2 rings, the 56-mm ring was rated as equally acceptable with significantly fewer reports of expulsions/removals compared to the other 2 rings. These data confirm that the current 54 to 58 mm diameter of vaginal rings on the market and in development is acceptable and performs well. Future studies should explore the effect of other mechanical attributes, such as compressibility, on preference, adherence, and acceptability, as well as investigating ring characteristics in other populations.

End-user feedback early in product development is important for optimizing multipurpose prevention technologies for HIV and pregnancy prevention. We evaluated the acceptability of the 90-day dapivirine levonorgestrel ring (DPV-LNG ring) used for 14 days compared to a dapivirine-only ring (DVR-200mg) in MTN-030/IPM 041 (n = 23), and when used for 90 days cyclically or continuously in MTN-044/IPM 053/CCN019 (n = 25). We enrolled healthy, non-pregnant, HIV-negative women aged 18-45 in Pittsburgh, PA and Birmingham, AL (MTN-030 only). Self-reports of vaginal bleeding and adherence (ring removals, expulsions) were collected via daily short message service. Acceptability data were recorded in face-to-face interviews at study exit. We assessed differences in acceptability by product characteristics and adherence; and associations between baseline characteristics/demographics, number of bleeding days, adherence, and overall acceptability. Most (21/23) women in the 14-day MTN-030 study and about half (13/25) in the 90-day MTN-044 study liked their assigned rings. In MTN-030 there were no significant associations between any variables and overall acceptability of either ring. In MTN-044, women who disliked the DPV-LNG ring had a significantly higher incidence of unanticipated vaginal bleeding, and reporting that vaginal bleeding changes were unacceptable than those who liked it. Although we found no overall association between adherence and acceptability, significantly more women who disliked (versus liked) the DPV-LNG ring reported expulsions during toileting. The DPV-LNG ring could meet the needs of women seeking simultaneous protection from HIV and unintended pregnancy. Addressing issues related to vaginal bleeding and expulsions early in product development will likely enhance acceptability of the DPV-LNG ring. Trial registration: Clinical Trial Registration: MTN-030/IPM 041: ClinicalTrials.gov NCT02855346; MTN-044/IPM 053/CCN019: ClinicalTrials.gov NCT03467347.

Adolescent girls and young women (AGYW) in sub-Saharan Africa are at risk for HIV/unintended pregnancy. Adherence and continuation to effective oral pre-exposure prophylaxis (PrEP) are limited in AGYW. We hypothesized that an over-encapsulated dual prevention pill (DPP) combining PrEP + oral contraceptive (OC) would be preferred, acceptable, and improve adherence compared to PrEP alone. We randomized HIV-uninfected, 16-24 year-olds 1:1 to use DPP or 2-pill regimen (2PR -PrEP and OCs separately) for three 28-day cycles each. We compared preference for DPP vs. 2PR (exact binomial test) and regimen effects on four acceptability domains: use attributes, product attributes, side effects, impact on sex (Wilcoxon signed-rank tests). Adherence was compared by regimen and sequence (mixed-effects logistic regression) using self-report, pill-count, tenofovir-diphosphate levels in dried blood spots (DBS), indicating ≥ 4 doses per week(≥ 500 fmol/punch at Month 1 and ≥ 700 fmol/punch at Months 2-6). 26/30 participants (mean age 19.4years) completed the study (Nov 2022-Sept 2023). 62% preferred DPP, 38% 2PR (p = 0.24). Most rated both regimens as acceptable, with no differences between them (all p > 0.05). Adherence was high by self-report (98%) and pill-count (97%), but low based on DBS results (DPP: mean 392 fmol/punch, 2PR: mean 384 fmol/punch); with only 10% consistently adherent. There was no difference in adherence by regimen, though odds were higher in period 1 vs. 2 (AOR 3.7; 95% CI 1.10-12.8). Both regimens were safe; 2 pregnancies occurred during the DPP regimen, with no HIV seroconversions. No significant differences in preference, acceptability, and adherence between DPP and 2PR were found in this study. Adherence was low and waned over time. A larger study with a smaller co-formulated DPP may better inform its impact on HIV and pregnancy prevention.The study has been registered at ClinicalTrials.gov Identifier NCT04778514.

BACKGROUND:Oral pre-exposure prophylaxis (PrEP) is effective for HIV prevention , yet use has been inconsistent in adolescent girls and young women (AGYW). We compared PrEP with the dapivirine vaginal ring (ring) among AGYW in MTN-034 (REACH). METHODS:We randomized 247 16-21-yr-old AGYW (South Africa, Uganda, Zimbabwe) to the sequence of using the ring and oral PrEP for 6 m each (February 2019-September 2021). Participants rated overall product acceptability (1, dislike very much to 5, like very much) after 3 m and 6 m, and product characteristics/use attributes after 3 m. We compared proportions of participants rating each product a "5" (binomial model with generalized estimating equations). We assessed associations between product characteristics/use attribute ratings at 3 m and overall acceptability after 6 m (χ 2 ). RESULTSOVERALL,:65% and 41% of participants rated the ring versus PrEP a "5" (adjusted risk difference [aRD] 24%, 95% CI: 15%, 32%; P < 0.001). For both products, high overall acceptability was associated with "excellent" self-rated adherence (ring, P < 0.001; PrEP, P = 0.03), product appearance (ring, P = 0.005; PrEP, P < 0.001), and ease of use (ring, P = 0.001; PrEP, P = 0.003). Not worrying about/or experiencing side effects were also associated with high acceptability of oral PREP. CONCLUSIONS:The dapivirine ring was highly acceptable to substantially more individuals than oral PrEP, although a significant minority rated oral PrEP highly, even after using the ring. As has been found in the contraceptive field, offering AGYW a choice of PrEP products is likely to increase the use of any HIV prevention method in this vulnerable population.

OBJECTIVE:Intravaginal rings (IVRs) are marketed or in development for contraception and other indications. We sought to develop and validate the IVR Acceptability Scale (IVR-AS) as a multidimensional, standardized tool for assessing IVR acceptability among end-users in the United States. METHODS:Scale items reflect specific aspects of IVR acceptability for women and male partners. Response options range from 1 (not-at-all acceptable) to 5 (highly acceptable). We evaluated the IVR-AS within a randomized, crossover clinical trial of three nonmedicated silicone IVRs of differing external diameters (46, 56, 66 mm) in heterosexual couples who used each for ~30 days, then completed a self-administered survey. We conducted exploratory factor analysis and multivariable regression to assess convergent validity. Follow-up in-depth interviews with all participants explored scale salience. RESULTS:Twenty-four couples participated (mean age 27). The final 19-item women's scale (Cronbach's alpha = 0.93) included six subdimensions: ease of use; experience and sensation; effect on sexual desire/engagement, and effect on vaginal sex (all alphas > 0.78). The final eight-item men's scale comprised two subdimensions: effect on sexual desire/engagement and effect on vaginal sex (all alphas > 0.89). For both sexes, higher overall/subdimension scores were consistently associated with favorable assessments of the ring, for example, ease of insertion/removal; adherence (most p < 0.001). The 46/56 mm IVRs had higher overall and subdimension scores than the 66 mm IVR (most p < 0.001). Qualitative reports reinforced the salience of scale subdimensions and item content. CONCLUSION:The IVR-AS captures multiple dimensions of IVR acceptability among women and their partners. The scales demonstrated excellent reliability and convergent validity. Further validation is warranted in future studies. TRIAL REGISTRATION:Clinical Trials.gov: NCT05128136. https://clinicaltrials.gov/study/NCT05128136?intr=non-medicated%20silicone%20ring&rank=2.

Introduction Oral pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention method; however, uptake and persistence have been low among southern African women. A dual prevention pill (DPP) that combines PrEP with oral contraception (OC) may increase PrEP use and better meet women’s sexual and reproductive health needs. We will gauge the DPP’s acceptability in two cross-over clinical trials.Methods and analysis PC952 (Zimbabwe) and PC953 (South Africa) will compare acceptability, adherence and preference for an over-encapsulated DPP versus PrEP and OCs taken separately. HIV-negative, non-pregnant cisgender females in Johannesburg, South Africa (n=96, 16–40 years) and Harare, Zimbabwe (n=30, 16–24 years) will be randomised 1:1 to the order of regimens—DPP or two separate tablets—each used for three 28-day cycles, followed by a 6-month choice period in South Africa. Monthly clinic visits include HIV and pregnancy testing; safety assessments and risk reduction and adherence counselling. We will assess adherence (monthly) based on tenofovir diphosphate drug levels in dried blood spots and by self-report. We will evaluate acceptability (monthly) and preference (end of cross-over) via computer-assisted self-interviewing and in-depth interviews with a subset of participants. Data collection started in September 2022 and ended in January 2024.Ethics and dissemination PC952 was approved by the Ministry of Health and Child Care, Medical Research Council, Research Council and Medicines Control Authority of Zimbabwe; the Chitungwiza City Health Ethics Committee; and the Joint Research Ethics Committee for the University of Zimbabwe Faculty of Medicine and Health Sciences and Parirenyatwa Group of Hospitals. PC953 was approved by the South African Health Products Regulatory Authority and the University of the Witwatersrand’s Human Research Ethics Committee. The Population Council IRB approved both studies. We will disseminate results in open-access journals, clinical trials registries, and at local and international meetings and conferences.Trial registration numbers NCT04778514, NCT04778527.

Abstract Background HIV incidence remains high in South Africa, with ~ 60% of all new HIV infections among adolescent girls and women (Country factsheets HIV and AIDS Estimates, 2022). Oral pre-exposure prophylaxis (PrEP), approved for HIV prevention in South Africa since 2015, is hampered by low uptake and adherence, particularly among adolescent girls and young women (AGYW). Combining oral PrEP with oral contraceptives could increase PrEP uptake, persistence and address unmet needs for contraception. We investigated the acceptability of a dual prevention pill (DPP), combining oral PrEP and a combined oral contraceptive (COC) for HIV and pregnancy prevention among women in Johannesburg, South Africa. Methods Between March-July 2021, we conducted 12 focus group discussions (FGDs) with adolescent girls and women (n = 74) aged 16–40 stratified by ages (16–17, 18–24, 25–40), half of whom were COC users. We explored adolescent girls and women’s opinions about the DPP concept, existing HIV and pregnancy prevention options, and input on perceived facilitators and barriers to DPP use. FGDs were conducted in English or isiZulu, using a standardized interview guide. FGDs were audio-recorded, transcribed to English and analyzed using ethnographic content analysis. Results The majority viewed the DPP favorably as a multipurpose option preventing unplanned pregnancy and HIV. Most saw it as a convenient “two-in-one” solution, requiring one clinic visit for both PrEP and COCs. AGYW were viewed as the most likely to benefit from the DPP due to the likelihood of multiple partners and unplanned sex, possibly preventing school dropout from unplanned pregnancy or HIV acquisition. The DPP was perceived to be more reliable than condoms, especially when condom negotiation is limited. Benefits were also seen by participants in rape cases, protecting against pregnancy and HIV. DPP use barriers included side effect concerns, unsupportive partners and judgmental healthcare providers. Conclusions/significance The DPP was perceived as acceptable for HIV and pregnancy prevention to AGYW in Johannesburg and its dual indications helpful in supporting improved PrEP uptake and persistence. DPP implementation programs need to consider solutions to potential barriers, like education on DPP benefits, coupled with reliable side effect support and healthcare provider sensitization as part of routine sexual health services to encourage uptake and adherence.

EDITORIAL article Front. Reprod. Health, 27 February 2024Sec. HIV and STIs Volume 6 - 2024 | https://doi.org/10.3389/frph.2024.1384153

BACKGROUND: The US Food and Drug Administration-approved segesterone acetate and ethinyl estradiol ring-shaped contraceptive vaginal system, known as Annovera (Sever Pharma Solutions/QPharma, Malm & ouml;, Sweden), was inserted and removed under a woman's control for a 21 day in and 7 day out regimen for up to 13 cycles of use. OBJECTIVE: We aimed to describe the patterns of ring expulsion over time, to identify potential predictors of expulsion, and to evaluate the impact of expulsions on method discontinuation and pregnancy risk. STUDY DESIGN: Using data from 2064 participants who were enrolled in 2 multinational phase 3 clinical trials on the use of this contraceptive vaginal system, we examined data from participants' daily diaries for documentation of complete ring expulsion. We modeled the odds of reported expulsions over time with adjustment for background and demographic characteristics using mixed-effects logistic regression models with random intercepts. We compared the probability of continuation between those who did and those who did not report expulsions in the first cycle of use using survival analysis and hazards modeling. To determine if expulsions during the first cycle of use affected the risk for pregnancy, we calculated Pearl Indices. RESULTS: Most participants (75%) never experienced any expulsions during any cycle of use, and 91% to 97% did not experience an expulsion during any 1 cycle. The incidence of expulsion was highest in cycle 1 (9%). The odds of experiencing expulsions decreased by half in cycles 2 to 8 when compared with cycle 1 (0.48; 95% confidence interval, 0.40-0.58), and in cycles 9 to 13, expulsions were about a third of that in cycle 1 (0.32; 95% confidence interval, 0.26-0.41). Of those who did experience expulsions, most (62%-84%) experienced <2 expulsions per cycle. Participants from study sites in Latin America vs those in the United States had higher odds of not experiencing an expulsion (odds ratio, 1.95; 95% confidence interval, 1.45-2.63). Women with a higher education level had higher odds of experiencing an expulsion. Notably, parity, age, and body mass index were not associated with expulsion. Participants who experienced any expulsions in cycle 1 were more likely to discontinue use early (hazard ratio, 1.28; 95% confidence interval, 1.14-1.43) than participants who did not have an expulsion. The Pearl Index for participants who had expulsions during cycle 1 was 3.99 (95% confidence interval, 1.29-9.31), which was higher than that among participants who reported no expulsions (Pearl Index, 2.39; 95% confidence interval, 1.61-3.41), but the overlapping confidence intervals indicate that there is not sufficient evidence to demonstrate an association between expulsions and pregnancy risk. CONCLUSION: Expulsions were infrequent overall, decreased with subsequent cycles of use, and were not associated with body mass index or parity. Early discontinuation of product use was higher among participants who experienced an expulsion during cycle 1. Although it is unclear whether pregnancy risk was associated with expulsions, early recognition of expulsions among users may identify those at higher risk for discontinuation and may highlight when enhanced anticipatory counselling and guidance may be advantageous.

We evaluated correlates of adherence to PrEP, including daily oral tenofovir disoproxil fumarate in combination emtricitabine (oral FTC/TDF) and the monthly dapivirine ring (ring)among adolescent girls and young women (AGYW) in the MTN-034/REACH study. We enrolled 247 AGYW aged 16–21 years in South Africa, Uganda and Zimbabwe (ClinicalTrials.gov: NCT03074786). Participants were randomized to the order of oral FTC/TDF or ring use for 6 months each in a crossover period, followed by a 6-month choice period. We assessed potential adherence correlates—individual, interpersonal, community, study, and product-related factors—quarterly via self-report. We measured biomarkers of adherence monthly; high adherence was defined as > 4 mg dapivirine released from returned rings or intracellular tenofovir diphosphate levels ≥ 700 fmol/punch from dried blood spots (DBS). We tested associations between correlates and objective measures of high adherence using generalized estimating equations. High adherence to oral FTC/TDF was significantly associated with having an older primary partner (p = 0.04), not having exchanged sex in the past 3 months (p = 0.02), and rating oral FTC/TDF as highly acceptable (p = 0.003). High ring adherence was significantly associated with unstable housing (p = 0.01), disclosing ring use to a male family member (p = 0.01), and noting a social benefit from study participation (p = 0.03). All associations were moderate, corresponding to about 6

BACKGROUND:On demand, topical PrEP is desired by those preferring episodic, nonsystemic PrEP. PC-1005 gel (MIV-150, zinc, and carrageenan) exhibits in vitro antiviral HIV-1, human papillomavirus (HPV), and herpes simplex virus type 2 (HSV-2) activity, attractive for a multipurpose prevention technology candidate. We evaluated the safety, pharmacokinetics, and antiviral effect of rectally applied PC-1005. METHODS:HIV-uninfected adults received a series of 3 rectal PC-1005 doses-4, 16, and 32 mL separated by 2-week washout periods. Following each dose, plasma, rectal fluid and tissue, and vaginal fluid were collected over 48 hours. RESULTS:Thirteen adults enrolled; 12 completed all 3 doses. All 13 adverse events reported were grade 1 or 2; 5 were judged study drug related. Plasma MIV-150 peaked 1-2 h after dosing with a median peak concentrations range of 0.07-0.23 ng/mL and median half-life range of 4.9-7.4 hours across dose volumes; median concentrations were below assay quantitation limits (BLQ) 24 hours after dosing. Rectal tissue MIV-150 peaked 0.5-1 hours after dosing at 1.4 ng/g (ng/mL) (0.8, 1.9), 46.0 (30.7, 831.0), and 79.7 (11.9, 116.0), respectively, after each dose volume; median tissue concentrations were BLQ beyond 5 hours for all doses. All vaginal fluid samples were BLQ. Ex vivo antiviral assays showed 5 hours of antiviral HPV and HSV effects but no anti-HIV activity. CONCLUSIONS:MIV-150 rectal tissue concentrations were below the 100 ng/g target concentration and transient. Ex vivo assays demonstrated antiviral HSV and HPV effects but not against HIV. PC-1005 requires a more potent antiviral and longer-lasting formulation for further consideration as a multipurpose prevention technology candidate. CLINICAL TRIALS:NCT03408899.

INTRODUCTION:Adolescent girls and young women (AGYW) in sub-Saharan Africa are disproportionately affected by the HIV epidemic and face an array of challenges using proven behavioral and biomedical prevention methods. To address the urgent need for expanding prevention options, we evaluated the baseline preferences of HIV prevention methods among participants enrolled in the MTN-034/REACH crossover trial along with their stated product preference prior to product initiation. METHODS:AGYW aged 16-21 years were enrolled at 4 study sites: Cape Town and Johannesburg, South Africa; Kampala, Uganda; and Harare, Zimbabwe and randomly assigned to the sequence of using oral PrEP and the dapivirine ring for 6 months each, followed by a choice period in which they could choose either product (or neither) for an additional six months. Eligible AGYW were HIV-negative, not pregnant and using effective contraception for at least two months prior to enrollment. Descriptive statistics were used to summarize demographic and behavioral data while multinomial analysis was used to determine predictors of stated product preference (ring or oral PrEP). RESULTS:Of the 247 AGYW enrolled in REACH, 34% were aged 16-17 and 89% had a primary partner.The median age of sexual debut was 16 years and 40% had ever been pregnant. At screening, 35% of participants were diagnosed with a sexually transmitted infection (STI), 39% had an AUDIT-C score associated with harmful drinking and 11% reported intimate partner violence in the past 6 months. Overall, 28% of participants, had CESD-10 scores suggestive of depressive symptoms (≥12) in the past week. At baseline, similar proportions stated a preference for the ring and oral PrEP (38.1% and 40.5% respectively), with 19% of participants stating they preferred both products equally. Only study site was significantly associated with product preference (P<0.05) with AGYW from Johannesburg having higher odds of preferring the ring and those from Kampala having higher odds of preferring both options equally. CONCLUSIONS:We successfully enrolled African AGYW with a clear unmet need for HIV prevention. The balanced preference between the two products suggests that multiple biomedical prevention options may be appealing to this age group and could address their prevention needs.