Adherence to event‐driven HIV PrEP among men who have sex with men in Amsterdam,the Netherlands: analysis based on online diary data, 3‐monthly questionnaires and intracellular TFV‐DP

IntroductionEvent‐driven pre‐exposure prophylaxis (edPrEP) with oral tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) is highly effective for preventing HIV acquisition in men who have sex with men (MSM) and is preferred over daily PrEP by some MSM. However, it is largely unknown how well MSM adhere to edPrEP. We then aimed to assess PrEP protection during CAS among MSM using edPrEP and participating in the Amsterdam PrEP demonstration project (AMPrEP).MethodsWe analysed data from participants enrolled in AMPrEP who were taking edPrEP. We measured adherence through (1) a mobile application in which sexual behaviour and PrEP‐use were recorded daily, (2) three‐monthly self‐completed questionnaires and (3) dried blood spot (DBS) samples collected around six, twelve and twenty‐four months after PrEP initiation. We assessed the proportion of days with condomless anal sex (CAS) acts that were protected by PrEP, per partner type (i.e. steady partners, known casual partners, unknown casual partners), and the proportion of three‐month periods during which PrEP was correctly used. Intracellular TFV‐diphosphate (TFV‐DP) concentrations were determined from DBS. Good adherence was defined as at least one tablet before and one tablet within 48 hours after a CAS act.ResultsBetween 11 September 2015 and 6 October 2019, 182 of 376 MSM (48.4%) used edPrEP for at least one three‐month period. Of the 8224 CAS days that were reported in the app during edPrEP‐use, we observed good protection for most CAS days involving steady partners (n = 1625/2455, 66.9%), known casual partners (n = 3216/3472, 92.6%) and unknown casual partners (n = 2074/2297, 90.3%). Men reported consistently correct PrEP‐use in 851 (81.4%) of the 1046 three‐month periods of edPrEP‐use. The median TFV‐DP concentration was 591 fmol/sample (interquartile range = 270 to 896).ConclusionsAdherence to edPrEP was high as determined from the online app and questionnaire. DBS measurements were consistent with two to three tablets per week on average.     

Increasing awareness of HIV pre‐exposure prophylaxis (PrEP) and willingness to use HIV PrEP among men who have sex with men: a systematic review and meta‐analysis of global data

IntroductionIntegrated knowledge regarding pre‐exposure prophylaxis (PrEP) awareness and willingness to use PrEP can be useful for HIV prevention in high incidence groups. This review summarizes the awareness of PrEP and willingness to use PrEP among men who have sex with men (MSM).MethodsOnline electronic databases were searched before 31 August 2021. A meta‐analysis was conducted to pool studies analysing PrEP awareness and willingness to use PrEP. LOESS regression and linear regression were applied to fit the trends over time for the proportion of MSM aware of PrEP and willing to use PrEP. Dose–response meta‐analysis (DRMA) was conducted by a restricted cubic spline model to explore the relationship between willingness to use PrEP and selected factors.Results and DiscussionA total of 156 articles involving 228,403 MSM were included. The pooled proportions of MSM aware of PrEP and willing to use PrEP were 50.0 (95% CI: 44.8–55.2) and 58.6% (95% CI: 54.8–62.4), respectively. PrEP awareness varied among countries with different economic status and different WHO regions, among different publication and research years, PrEP types and support policies. PrEP willingness differed among countries with different economic status and groups with different risks of HIV. The awareness of PrEP increased from 2007 to 2019 with a slope of 0.040260 (p<0.0001), while the proportion of MSM willing to use PrEP decreased from 2007 to 2014 (slope = –0.03647, p = 0.00390) but increased after 2014 (slope = 0.04187, p = 0.03895). The main facilitators of willingness to use PrEP were PrEP awareness, condomless sexual behaviours, high perceived risk of HIV infection and influence of social network. The main barriers were doubts about the efficacy and side effects of PrEP. DRMA results indicated that MSM with more sexual partners and lower level of education were more willing to use PrEP. No publication bias was observed.ConclusionsThe proportions of PrEP awareness and willingness to use PrEP among MSM have increased since 2014, although the awareness was low and the willingness was moderate. Improving awareness of PrEP through increasing access to PrEP‐related health education and enhancing risk perceptions of HIV infection could have positive effects on the willingness to use PrEP among MSM.     

HIV prevention: better choice for better coverage

IntroductionAntiretroviral‐based pre‐exposure prophylaxis (PrEP) is today an established, effective and safe method of HIV prevention used in multiple countries worldwide by a broad range of populations at risk of HIV infection. Biomedical innovations are critical in supporting the primary prevention of HIV; however, their potential can only be maximized if end‐user challenges are recognized, described and used to develop next‐generation models.DiscussionFirst‐generation PrEP, a daily oral pill, is highly efficacious, discreet and affords users the ability to commence and conclude treatment rapidly. However, consistent daily adherence and persistence is challenging, especially among younger populations, due in part to side effects, the risk of stock‐outs and a lack of pill storage options. Second‐generation PrEP, longer acting agents that require less frequent dosing, could overcome such challenges. Agents that have shown efficacy in clinical trials include a monthly vaginal ring and PrEP injectables to be administered every 8 weeks, while products in development include 6 monthly injectables, oral therapy that uses monthly rather than daily pills, implants and the potential for long‐acting passive immunization.ConclusionsSecond‐generation PrEP agents will have the potential to offer improved adherence and less frequent reminders once they have undergone further development and the delivery systems that will best support them have been established. In order to pursue global UNAIDS targets of reducing new HIV infections to fewer than 500,000 annually by 2025, and to ensure that all people have access to prevention options that meet their specific prevention needs, both early and next‐generation PrEP options are needed.     

Choosing event‐driven and daily HIV pre‐exposure prophylaxis – data from two European PrEP demonstration projects among men who have sex with men

IntroductionDaily and event‐driven PrEP are both efficacious in reducing the risk for HIV infection. However, the practice of event‐driven PrEP (edPrEP) is less well studied, in particular when provided as an alternative to daily PrEP. We studied regimen preferences and switches, and sexually transmitted infection (STI) incidence.MethodsWe analysed pooled data from two prospective cohort studies among MSM: Be‐PrEP‐ared, Belgium and AMPrEP, the Netherlands. In both projects, participants could choose between daily and edPrEP at three‐monthly study visits, when they were also screened for sexually transmitted infections including hepatitis C (HCV). We assessed the proportion choosing each regimen, and the determinants of choosing edPrEP at baseline. Additionally, we compared the incidence rates (IRs) of HCV, syphilis and chlamydia or gonorrhoea between regimens using Poisson regression. The study period was from 3 August 2015 until 24 September 2018.Results and discussionWe included 571 MSM, of whom 148 (25.9%) chose edPrEP at baseline. 31.7% of participants switched regimen at least once. After 28 months, 23.5% used edPrEP. Older participants (adjusted odds ratio (aOR) = 1.38 per 10 years, 95% confidence interval (CI) = 1.15 to 1.64) and those unemployed (aOR = 1.68, 95% CI = 1.03 to 1.75) were more likely to initially choose edPrEP. IR of HCV and syphilis did not differ between regimens, but the IR of chlamydia/gonorrhoea was higher among daily users (adjusted incidence rate ratio = 1.61, 95% CI = 1.35 to 1.94).ConclusionsA quarter of participants chose edPrEP at baseline and at 28 months this proportion was similar. Although the IR of HCV and syphilis were similar in the two regimens, the lower incidence of chlamydia and gonorrhoea among edPrEP users may suggest that less frequent STI testing of this group could be considered.     

Preference for daily versus on‐demand pre‐exposure prophylaxis for HIV and correlates among men who have sex with men: the China Real‐world Oral PrEP Demonstration study

IntroductionThis study explores the preference for daily versus on‐demand pre‐exposure prophylaxis (PrEP) among men who have sex with men (MSM) in developing countries when both regimens are available.MethodsFrom 11 December 2018 to 19 October 2019, we recruited MSM for an open‐label real‐world PrEP demonstration study in four major cities in China. Subjects selected their preferred PrEP (oral tenofovir/emtricitabine) regimen (daily vs. on‐demand) at recruitment and underwent on‐site screening before initiation of PrEP. We used logistic regression to assess preference for daily PrEP and correlates.ResultsOf 1933 recruited MSM, the median age was 29 years, 7.6% was currently married to or living with a female; the median number of male sexual partners was four and 6.1% had used post‐exposure prophylaxis (PEP) in the previous six months. HIV infection risk was subjectively determined as very high (>75%) in 7.0% of subjects, high (50% to 75%) in 13.3%, moderate (25% to 49%) in 31.5% and low or none (0% to 24%) in 48.1%. On average, participants preferred on‐demand PrEP over daily PrEP (1104 (57.1%) versus 829 (42.9%)) at recruitment. In multivariable analysis, currently being married to or living with a female was associated with 14.6 percentage points lower preference for daily PrEP (marginal effect = −0.146 [95% CI: −0.230, −0.062], p = 0.001); whereas the number of male sexual partners (marginal effect = 0.003 [95% CI: 0.000, 0.005], p = 0.034) and a subjective assessment of being very high risk of HIV infection (vs. low and no risk, marginal effect size = 0.105 [95% CI: 0.012, 0.198], p = 0.027) were associated with increased preference for daily versus on‐demand PrEP. Among the 1933 potential participants, 721 (37.3%) did not attend the subsequent on‐site screening. Lower‐income, lower education level, lower subjective expected risk of HIV infection risk and younger age positively correlated with the absence of on‐site screening.ConclusionsMSM in China prefer both daily and on‐demand PrEP when both regimens are provided free. Social structural factors and subjective risk of HIV infection have significant impacts on PrEP preference and use. The upcoming national PrEP guideline should consider incorporating both regimens and the correlates to help implement PrEP in China.     

Comparison between daily and on‐demand PrEP (pre‐exposure prophylaxis) regimen in covering condomless anal intercourse for men who have sex with men in Hong Kong: A randomized,controlled, open‐label,crossover trial

IntroductionBoth daily and on‐demand regimens have been proven effective for pre‐exposure prophylaxis (PrEP) against HIV in men who have sex with men (MSM). We aimed to compare the two regimens on their coverage of condomless anal intercourse (CLAI) in MSM.MethodsA randomized, controlled, open‐label, crossover trial was conducted in a teaching hospital in Hong Kong. Participants were sexually active HIV‐negative MSM aged 18 years or above with normal renal function and without chronic hepatitis B infection. Oral tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg (TDF/FTC) tablets were prescribed for PrEP. After a 2‐week lead‐in with daily TDF/FTC for treatment‐naïve MSM for tolerance assessment, participants were randomly assigned in a 1:1 ratio with a block size of four to either daily‐first or on‐demand‐first arm based on the IPERGAY study, for receiving PrEP for 16 weeks, then crossed‐over to the alternative regimen for another 16 weeks. The primary outcome was the proportion of days with PrEP‐covered CLAI by intention‐to‐treat analysis. The trial is registered with the CCRB Clinical Trials Registry, CUHK, CUHK_CCRB00606, and is closed to accrual.ResultsBetween 25 August 2018 and 23 March 2019, 119 eligible participants were assigned to daily‐first arm (n = 59) and on‐demand‐first arm (n = 60) with an 87% overall completion rate (n = 103). With 96% and 54% of days on PrEP during daily and on‐demand periods, respectively, the proportion of days with PrEP‐covered CLAI between two arms were not statistically different (92% vs. 92%, p = 0.93). About half (47%) were diagnosed with at least one episode of incident sexually transmitted infection. Mild and time‐limited adverse events, including diarrhoea, headache, nausea and dizziness, were reported in 37 (31%) and 10 (8%) during the daily and on‐demand periods, respectively. At the end of the study, a similar proportion favoured daily or on‐demand regimen.ConclusionsHigh prevention‐effective adherence, as reflected from the coverage of CLAI, was achievable by either daily or on‐demand PrEP among MSM, albeit a higher number of tablets taken for daily PrEP. As both regimens were well accepted, a flexible approach adopting either or both regimens with possible switching is warranted in order to suit individual health needs.     

Association between HIV PrEP indications and use in a national sexual network study of US men who have sex with men

IntroductionHIV pre‐exposure prophylaxis (PrEP) is effective in preventing HIV transmission. United States Public Health Service (USPHS) clinical practice guidelines define biobehavioral indications for initiation. To assess guideline implementation, it is critical to quantify PrEP nonusers who are indicated and PrEP users who are not indicated. We sought to estimate current PrEP use among US men who have sex with men (MSM), characterize whether their PrEP use aligned with their current indications for PrEP, and assess whether the association between PrEP indications and PrEP use differed by demography or geography.MethodsUsing data from a US web‐based sexual network study of MSM between 2017 and 2019, we measured PrEP usage and assessed whether respondents met indications for PrEP. Log‐binomial regression was used to estimate the relationship between PrEP indications and PrEP use, with adjustment for geography, age and race/ethnicity.ResultsOf 3508 sexually active, HIV‐negative MSM, 34% met indications for PrEP. The proportion with current PrEP use was 32% among MSM meeting indications and 11% among those without indications. Nearly 40% of those currently using PrEP did not meet indications for PrEP, and 68% of MSM with indications for PrEP were not currently using PrEP. After adjusting for geography and demographics, MSM with PrEP indications were about three times as likely to be currently using PrEP. This association varied slightly, but not significantly, by geographic region, age and race/ethnicity.ConclusionsIndications for PrEP strongly predicted current PrEP use among US MSM. However, we identified substantial misalignment between indications and use in both directions (indicated MSM who were not benefitting from PrEP, and MSM taking PrEP while not presently being indicated). PrEP underuse by those at greatest risk for HIV acquisition may limit the projected impact of PrEP implementation, despite reported increases in PrEP provision. This calls for further implementation efforts to improve PrEP delivery to those most in need during periods of elevated sexual risk and to close the gap between indications and uptake.     

A multi‐country cross‐sectional study to assess predictors of daily versus on‐demand oral pre‐exposure prophylaxis in youth from South Africa,Uganda and Zimbabwe

IntroductionSub‐Saharan Africa (SSA) carries the burden of the HIV epidemic, especially among adolescents and young people (AYP). Little is known about pre‐exposure prophylaxis (PrEP) uptake and preferences among AYP in SSA. We describe preferences for daily and on‐demand PrEP among AYP in South Africa, Uganda and Zimbabwe.MethodsA cross‐sectional survey was conducted in 2019 among 13‐ to 24‐year olds, capturing socio‐demographics, HIV risk behaviours and preferences for daily or on‐demand PrEP. Logistic regression models were used to estimate odds ratios, adjusting for site, sex and age.Results and discussionA total of 1330 participants from Cape Town (n = 239), Johannesburg (n = 200), Entebbe (n = 491) and Chitungwiza (n = 400) were enrolled; 673 (51%) were male, and the median age was 19 years (interquartile range 17–22 years). Of 1287 participants expressing a preference, 60% indicated a preference for on‐demand PrEP with differences by site (p < 0.001), sex (p < 0.001) and age group (p = 0.003). On‐demand PrEP was most preferred in Entebbe (75%), among males (65%) versus females (54%) and in older participants (62% in 18‐ to 24‐year‐olds vs. 47% in 13‐ to 15‐year‐olds). After adjusting for site, sex and age group, preference for on‐demand PrEP decreased as sex frequency over the past month increased (p‐trend = 0.004) and varied with the number of partners in the last 6 months, being least popular among those reporting four or more partners (p = 0.02). Participants knowing further in advance that they were likely to have sex were more likely to prefer on‐demand PrEP (p‐trend = 0.02). Participants having a larger age gap with their most recent partner and participants whose last partner was a transactional sex partner or client were both less likely to prefer on‐demand compared to daily PrEP (p = 0.05 and p = 0.09, respectively). Participants who knew their most recent partner was living with HIV or who did not know the HIV status of their most recent partner were less likely to prefer on‐demand PrEP (p = 0.05).ConclusionsOur data show that AYP in four SSA communities prefer on‐demand over daily PrEP options, with differences seen by site, age and sex. PrEP demand creation needs to be reviewed, optimized and tailored to socio‐demographic differences and designed in conjunction with AYP.     

Oral pre‐exposure prophylaxis preference,uptake, adherence and continuation among adolescent girls and young women in Kampala,Uganda: a prospective cohort study

IntroductionOral pre‐exposure prophylaxis (PrEP) has been scaled up; however, data from real‐world settings are limited. We studied oral PrEP preference, uptake, adherence and continuation among adolescent girls and young women (AGYW) vulnerable to HIV in sub‐Saharan Africa.MethodsWe conducted a prospective cohort study among 14‐ to 24‐year‐old AGYW without HIV who were followed for 12 months in Kampala, Uganda. Within at least 14 days of enrolment, they received two education sessions, including demonstrations on five biomedical interventions that are; available (oral PrEP), will be available soon (long‐acting injectable PrEP and anti‐retroviral vaginal ring) and in development (PrEP implant and HIV vaccine). Information included mode and frequency of delivery, potential side effects and method availability. Volunteers ranked interventions, 1 = most preferred to 5 = least preferred. Oral PrEP was “preferred” if ranked among the top two choices. All were offered oral PrEP, and determinants of uptake assessed using Poisson regression with robust error variance. Adherence was assessed using plasma tenofovir levels and self‐reports.ResultsBetween January and October 2019, 532 volunteers were screened; 285 enrolled of whom 265 received two education sessions. Mean age was 20 years (SD±2.2), 92.8% reported paid sex, 20.4% reported ≥10 sexual partners in the past 3 months, 38.5% used hormonal contraceptives, 26.9% had chlamydia, gonorrhoea and/or active syphilis. Of 265 volunteers, 47.6% preferred oral PrEP. Willingness to take PrEP was 90.2%; however, uptake was 30.6% (n = 81). Following enrolment, 51.9% started PrEP on day 14 (same day PrEP offered), 20.9% within 30 days and 27.2% after 30 days. PrEP uptake was associated with more sexual partners in the past 3 months: 2–9 partners (aRR = 2.36, 95% CI: 1.20–4.63) and ≥10 partners (aRR 4.70, 95% CI 2.41–9.17); oral PrEP preference (aRR 1.53, 95% CI 1.08–2.19) and being separated (aRR 1.55, 95% CI 1.04–2.33). Of 100 samples from 49 volunteers during follow up, 19 had quantifiable tenofovir levels (>10 μg/L) of which only three were protective (>40 μg/L).ConclusionsHalf of AGYW preferred oral PrEP, uptake and adherence were low, uptake was associated with sexual behavioural risk and oral PrEP preference. Development of alternative biomedical products should be expedited to meet end‐user preferences and, community delivery promoted during restricted movement.     

Preference for using a variety of future HIV pre‐exposure prophylaxis products among men who have sex with men in three US cities

BackgroundDaily oral pre‐exposure prophylaxis (PrEP) is available and recommended for men who have sex with men (MSM) at risk for HIV infection. Other HIV prevention products are being developed, including long‐acting injectable (LAI) and event‐based oral and topical formulations. Understanding preferences for potential products by MSM can help direct further development of prevention messaging.MethodsWe present baseline data from HIV‐negative participants enrolled in the US Mobile Messaging for Men (M‐cubed) Study. Participants were asked their likelihood of and rank order preference for using daily oral PrEP and various potential prevention products (one‐ to ‐three‐month injections, 2‐1‐1 sexual event oral dosing, anal or penile gel, or anal suppository), and their sociodemographic characteristics. Bivariate and multivariable logistics regression assessed demographic associations with likelihood of use and rank order preference.ResultsOverall, most MSM reported a likelihood of using LAI (74%), sexual event‐based pills (67%) and penile gel (64%). Men who reported recent unprotected (condomless and PrEPless) anal sex most preferred a penile gel formulation (74%), followed closely by LAI and event‐based pills (73% each). Current PrEP users (vs. non‐users) had greater odds of reporting likelihood to use LAI (AOR = 3.29, 95% CI = 2.12 to 5.11), whereas men reporting recent unprotected anal sex had a greater odds of likelihood to use a penile gel (AOR = 1.79, 95% CI = 1.27 to 2.52) and an anal suppository (AOR = 1.48, 95% CI = 1.08 to 2.02). Hispanic/Latino (vs. White) MSM (AOR = 2.29, 95% CI = 1.40 to 3.73) and, marginally, Black MSM (AOR = 1.54, 95% CI = 1.00 to 2.38) had greater odds of reporting likelihood to use penile gel. Similar patterns were found for rank ordering preference of products, including condoms.ConclusionsMost MSM were interested in using various potential future HIV prevention products, especially LAI. However, two typologies of potential users emerged: men who prefer sexual event‐based methods (condoms, event‐based pill, sexual gels and suppositories) and men who prefer non‐sexual event‐based methods (daily pill, LAI). Men who reported recent unprotected anal sex preferred a penile gel product most, followed closely by sexual event‐based pills and LAI. Racial/ethnic differences were noted as well. These findings on product preferences can help in formulation development and messaging.     

Assessing the performance of international pre‐exposure prophylaxis (PrEP) eligibility guidelines in a cohort of Chinese MSM,Beijing, China 2009 to 2016

IntroductionPrEP is a powerful HIV prevention tool, and locally relevant eligibility criteria are necessary to optimize the prevention impact of PrEP. We assessed performance of existing national and international PrEP eligibility criteria to predict future HIV seroconversion among MSM in Beijing, China.MethodsParticipants were MSM aged ≥18 years who enrolled in a cohort study between July 2009 and March 2016. Participants completed HIV testing, syphilis testing, and a questionnaire on recent sexual health behaviours at each follow‐up visit and were followed until HIV seroconversion or dropout. We assessed PrEP eligibility at the most recent follow‐up visit prior to the final study visit. Participants were classified as indicated for PrEP (or not) based on criteria from guidelines from Europe, Korea, South Africa, Taiwan, the United Kingdom, United States and the World Health Organization. To compare guideline performance, we calculated sensitivity, specificity, Youden’s Index (YI), Matthew’s Correlation Coefficient (MCC), F1 scores and diagnostic odds ratios. For each guideline, performance measures were compared to random allocation of PrEP by randomly selecting a proportion of participants equal to the proportion indicated.ResultsThere were 287 (17∙3%) incident HIV seroconversions among 1663 MSM. The number of men indicated for PrEP from different guidelines ranged from 556 (33∙4%) to 1569 (94∙2%). Compared to random allocation, sensitivity of algorithms to predict seroconversion ranged from slightly worse (−4∙7%) to 30∙2% better than random. However, in absolute terms, none of the sensitivity values increased by more than 11% when compared to random allocation. For all guidelines, specificity was not meaningfully better than random allocation. No guidelines had high binary classification performance measures.ConclusionsThe performance of international indication guidelines in this sample was only slightly better than random allocation. Using such guidelines to screen out MSM self‐identifying as interested in PrEP could lead to misallocation of resources and to good candidates for PrEP being denied access. For settings in which international guidelines perform poorly, alternative indication approaches should be considered.     

Provider perspectives on service delivery modifications to maintain access to HIV pre‐exposure prophylaxis during the COVID‐19 pandemic: qualitative results from a PrEP implementation project in Kenya

IntroductionHIV pre‐exposure prophylaxis (PrEP) is an essential prevention strategy being scaled up for priority populations in Kenya, including for HIV serodiscordant couples. The COVID‐19 pandemic posed challenges to PrEP rollout. We conducted a qualitative study of PrEP providers to understand how clinics adjusted PrEP delivery during the COVID‐19 pandemic.MethodsSince 2017, the Partners Scale‐Up Project has integrated PrEP into 25 HIV clinics in Central and Western Kenya. We conducted qualitative interviews with 40 purposively sampled clinic personnel. We interviewed personnel once during the first pandemic wave (May–Aug 2020) and again after some decline in COVID‐19 rates (Nov–Jan 2021). We analysed data using inductive memo‐writing and summarized data by themes along the PrEP delivery cascade, guided by the Framework for Reporting Adaptation and Modifications (FRAME).ResultsWe interviewed 27 clinical officers, five nurses, four health records and information officers, and four counsellors from Central (n = 20) and Western (n = 20) Kenya. About half (n = 19) were female, with a median age of 32 (IQR: 29–34) and 2.3 years of experience delivering PrEP (IQR: 2–3). All participants reported clinic changes in PrEP demand creation and service delivery during the pandemic. Modifications occurred during PrEP implementation and sustainment phases, were partly reactive to the pandemic and also facilitated by interim Ministry of Health guidance on PrEP delivery during COVID, and were made by PrEP delivery teams, clients and clinic managers. Commonly reported modifications included dispensing multiple‐month PrEP refills, intensifying phone‐based client engagement and collaborating with other HIV clinics to ensure that clients with prolonged stays in other regions could continue to access PrEP. Some clinics also adopted practices to streamline visits, such as within clinical‐room PrEP dispensing, pre‐packing PrEP and task‐shifting. Most providers liked these changes and hoped they would continue after the pandemic subsides.ConclusionsCOVID‐19 served as a catalyst for PrEP delivery innovations in Kenya. HIV clinics successfully and rapidly adapted their PrEP demand creation, refill and retention strategies to promote PrEP uptake and effective use. These modified implementation strategies highlight opportunities to streamline the delivery of PrEP, as well as other HIV and chronic care services, and strengthen engagement with populations post‐pandemic.     

PrEP use and HIV seroconversion rates in adolescent girls and young women from Kenya and South Africa: the POWER demonstration project

IntroductionHIV incidence remains high among African adolescent girls and young women (AGYW). The primary objective of this study is to assess pre‐exposure prophylaxis (PrEP) initiation, use, persistence and HIV acquisition among African AGYW offered PrEP in order to inform PrEP scale‐up.MethodsPOWER was a prospective implementation science evaluation of PrEP delivery for sexually active HIV‐negative AGYW ages 16–25 in family planning clinics in Kisumu, Kenya and youth and primary healthcare clinics in Cape Town and Johannesburg, South Africa. Follow‐up visits occurred at month 1 and quarterly for up to 36 months. PrEP users were defined based on the month 1 refill. PrEP persistence through month 6 was assessed using Kaplan–Meier survival analysis among AGYW with a month 1 visit, defining non‐persistence as an ≥15 day gap in PrEP availability for daily dosing. PrEP execution was evaluated in a subset with PrEP supply from the prior visit sufficient for daily dosing by measuring blood tenofovir diphosphate (TFV‐DP) levels.ResultsFrom June 2017 to September 2020, 2550 AGYW were enrolled (1000 in Kisumu, 787 in Cape Town and 763 in Johannesburg). Median age was 21 years, 66% had a sexual partner of unknown HIV status, and 29% had chlamydia and 10% gonorrhoea. Overall, 2397 (94%) initiated PrEP and 749 (31%) had a refill at 1 month. Of AGYW who could reach 6 months of post‐PrEP initiation follow‐up, 128/646 (20%) persisted with PrEP for 6 months and an additional 92/646 (14%) had a gap and restarted PrEP. TFV‐DP levels indicated that 47% (91/193) took an average of ≥4 doses/week. Sixteen HIV seroconversions were observed (incidence 2.2 per 100 person‐years, 95% CI 1.2, 3.5); 13 (81%) seroconverters either did not have PrEP dispensed in the study interval prior to seroconversion or TFV‐DP levels indicated <4 doses/week in the prior 6 weeks.ConclusionsIn this study of PrEP integration with primary care and reproductive health services for African AGYW, demand for PrEP was high. Although PrEP use decreased in the first months, an important fraction used PrEP through 6 months.  Strategies are needed to simplify PrEP delivery, support adherence and offer long‐acting PrEP options to improve persistence and HIV protection.     

Incremental costs of integrated PrEP provision and effective use counselling in community‐based platforms for adolescent girls and young women in South Africa: an observational study

IntroductionAdolescent girls and young women (AGYW) are a priority population for pre‐exposure prophylaxis (PrEP), a highly effective HIV prevention method. However, effective PrEP use among AGYW has been low. Interventions to support PrEP effective use may improve pill‐taking. Affordability of PrEP programs depends on their cost. We, therefore, evaluated the cost of community‐based PrEP with effective use counselling.MethodsCost data from a randomized controlled trial were used to evaluate the cost of PrEP provision with effective use counselling offered to AGYW through community‐based HIV testing platforms between November 2018 and November 2019. AGYW were randomized to receive (1) group‐based community health club effective use counselling, (2) individualized effective use counselling or (3) community‐based PrEP dispensary. Task shifting of effective use counselling from nurses to trained lay counsellors was implemented in groups 1 and 2. Personnel costs were estimated from time‐and‐motion observations and staff interviews. Expenditure and ingredients‐based approaches were used to estimate costs for medical and non‐medical supplies.ResultsIn total, 603 AGYW initiated PrEP and accrued a total of 1280 months on PrEP. Average cost per person‐month on PrEP with group‐based community health club, individualized effective use counselling and community‐based PrEP dispensary under the Department of Health scenario were similar and high (USD $55.32, $55.65 and $55.46, respectively) due to low PrEP client volume observed in the clinical trial. Increasing client volume (scaled Department of Health scenario) reduced cost per‐person month estimates to USD $15.48, $26.40 and $13.99, respectively.ConclusionsAs designed, individualized effective use counselling increased the cost of standard‐of‐care PrEP delivery by 89%, group‐based community health effective use counselling increased the cost of standard‐of‐care PrEP delivery by 11%. These estimates can inform cost‐effectiveness and budget impact analysis for PrEP provision with effective use counselling services.     

Uptake and outcomes of a novel community‐based HIV post‐exposure prophylaxis (PEP) programme in rural Kenya and Uganda

IntroductionAntiretroviral‐based HIV prevention, including pre‐exposure prophylaxis (PrEP), is expanding in generalized epidemic settings, but additional prevention options are needed for individuals with periodic, high‐risk sexual exposures. Non‐occupational post‐exposure prophylaxis (PEP) is recommended in global guidelines. However, in Africa, awareness of and access to PEP for sexual exposures are limited. We assessed feasibility, acceptability, uptake and adherence in a pilot study of a patient‐centred PEP programme with options for facility‐ or community‐based service delivery.MethodsAfter population‐level HIV testing with universal access to PrEP for persons at elevated HIV risk (SEARCH Trial:{"type":"clinical-trial","attrs":{"text":"NCT01864603","term_id":"NCT01864603"}}NCT01864603), we conducted a pilot PEP study in five rural communities in Kenya and Uganda between December 2018 and May 2019. We assessed barriers to PEP in the population and implemented an intervention to address these barriers, building on existing in‐country PEP protocols. We used community leaders for sensitization. Test kits and medications were acquired through the Ministry of Health supply chain and healthcare providers based at the Ministry of Health clinics were trained on PEP delivery. Additional intervention components were (a)PEP availability seven days/week, (b)PEP hotline staffed by providers and (c)option for out‐of‐facility medication delivery. We assessed implementation using the Proctor framework and measured seroconversions via repeat HIV testing. Successful “PEP completion” was defined as self‐reported adherence over four weeks of therapy with post‐PEP HIV testing.ResultsCommunity leaders were able to sensitize and mobilize for PEP. The Ministry of Health supplied test kits and PEP medications; after training, healthcare providers delivered the 28‐day regimen with high completion rates. Among 124 persons who sought PEP, 66% were female, 24% were ≤25 years and 42% were fisherfolk. Of these, 20% reported exposure with a serodifferent partner, 72% with a new or existing relationship and 7% from transactional sex. 12% of all visits were conducted at out‐of‐facility community‐based sites; 35% of participants had ≥1 out‐of‐facility visit. No serious adverse events were reported. Overall, 85% met the definition of PEP completion. There were no HIV seroconversions.ConclusionsAmong individuals with elevated‐risk exposures in rural East African communities, patient‐centred PEP was feasible, acceptable and provides a promising addition to the current prevention toolkit.     

A qualitative exploration to understand barriers and facilitators to daily oral PrEP uptake and sustained adherence among HIV‐negative women planning for or with pregnancy in rural Southwestern Uganda

IntroductionAntiretroviral pre‐exposure prophylaxis (PrEP) may reduce periconception and pregnancy HIV incidence among women in settings, where gender power imbalances limit HIV testing, engagement in care and HIV viral suppression. We conducted qualitative interviews to understand factors influencing periconception and pregnancy PrEP uptake and use in a cohort of women (Trial registration: {"type":"clinical-trial","attrs":{"text":"NCT03832530","term_id":"NCT03832530"}}NCT03832530) offered safer conception counselling in rural Southwestern Uganda, where PrEP uptake was high.MethodsBetween March 2018 and January 2019, in‐depth interviews informed by conceptual frameworks for periconception risk reduction and PrEP adherence were conducted with 37 women including those with ≥80% and <80% adherence to PrEP doses measured by electronic pill cap, those who never initiated PrEP, and seven of their male partners. Content and dyadic analyses were conducted to identify emergent challenges and facilitators of PrEP use within individual and couple narratives.ResultsThe median age for women was 33 years (IQR 28, 35), 97% felt likely to acquire HIV and 89% initiated PrEP. Individual‐level barriers included unwillingness to take daily pills while healthy, side effects and alcohol use. Women overcame these barriers through personal desires to have control over their HIV serostatus, produce HIV‐negative children and prevent HIV transmission within partnerships. Couple‐level barriers included nondisclosure, mistrust and gender‐based violence; facilitators included shared goals and perceived HIV protection, which improved communication, sexual intimacy and emotional support within partnerships through a self‐controlled method. Community‐level barriers included multi‐level stigma related to HIV, ARVs/PrEP and serodifference; facilitators included active peer, family or healthcare provider support as women aspired to safely meet socio‐cultural expectations to conceive and preserve serodifferent relationships. Confidence in PrEP effectiveness was promoted by positive peer experiences with PrEP and ongoing HIV testing.ConclusionsMulti‐level forms of HIV‐, serodifference‐ and disclosure‐related stigma, side effects, pill burden, alcohol use, relationship dynamics, social, professional and partnership support towards adaptation and HIV risk reduction influence PrEP uptake and adherence among HIV‐negative women with plans for pregnancy in rural Southwestern Uganda. Confidence in PrEP, individually controlled HIV prevention and improved partnership communication and intimacy promoted PrEP adherence. Supporting individuals to overcome context‐specific barriers to PrEP use may be an important approach to improving uptake and prolonged use.