Daily Pre-exposure Prophylaxis Research Articles

“I prefer to take pills when I plan to have sex”: Perceptions of on-demand versus daily oral pre-exposure prophylaxis among adolescents in Kampala, Uganda

There is limited information about the use of on-demand and daily pre-exposure prophylaxis (PrEP) among adolescents and young people (AYP) in sub-Saharan Africa. We explored perceptions of both regimens among 14- to 19-year-olds perceived to be at high risk of HIV infection in Kampala, Uganda, using qualitative data collection methods. Data were analysed by theme and interpreted based on constructs from the framework of acceptability. Although there were no noticeable gender differences in preferences for a particular regimen, acceptability of PrEP depended on individual AYP sexual behaviour at the time of the study. Those who perceived themselves to be at increased risk of acquiring HIV preferred using daily PrEP, citing the consistency that comes from taking a pill daily and which they considered to be efficacious and safe. AYP who had less frequent sex preferred on-demand PrEP because it would enable them to “plan for sex”. However, both groups perceived taking daily PrEP to be a burden, which was an impediment to acceptance of this form of PrEP. AYP anticipated that daily pill taking would be very stressful, requiring a lot of effort and would interrupt their daily routine. Therefore, while both on-demand and daily PrEP were acceptable and beneficial to these AYP, preferences for either regimen depended on self-perceived risk. Thus, oral PrEP use should be tailored to end-user preferences and risk profiles.

Usability and effectiveness of adherence monitoring of a mobile app designed to monitor and improve adherence to event-driven and daily HIV pre-exposure prophylaxis among men who have sex with men in Taiwan.

ObjectiveThe UPrEPU mobile app is a self-monitoring system to enable men who have sex with men to optimize their pre-exposure prophylaxis adherence for HIV prevention. The app was designed to accommodate a rather complicated event-driven dosing schedule. We aim to evaluate the usability of the UPrEPU app and its effectiveness in improving adherence monitoring.MethodsFrom May to October 2020, 35 participants were enrolled for the usability study and followed up for 4 months. Blood samples for the drug concentration in the dried blood spots were obtained once during the second to fourth follow-up visits. The effectiveness of adherence monitoring was analyzed using Cohen's kappa statistic to calculate the concordance between the average number of pills taken and drug concentration in the dried blood spots.ResultsOverall retention was 91.4% (32 participants) at the end of the study. Participants used the app for a mean of 29 days and made 2565 data entries in total, with an average of 76 data entries. The average systematic usability scale score for the app was 71.5, indicating acceptable usability. Slight agreement was reached between the dried blood spots measurement and the number of pills taken and recorded in the app (weighted kappa: 0.21).ConclusionsOur user-centered UPrEPU app demonstrated that it could accommodate both daily and event-driven dosing schedules for men who have sex with men clients with acceptable usability scores. We confirmed that complex behaviors such as different drug-dosing regimens that are contingent on sexual behaviors could be incorporated into the design of a mobile app.

859. Suboptimal Uptake, Retention, and Adherence of Daily Oral PrEP Among People with OUD Receiving HCV Treatment

BackgroundDaily oral pre-exposure prophylaxis (PrEP) with tenofovir/emtricitabine (TDF/FTC) effectively prevents HIV among people who use drugs (PWUD). Despite rising rates of HIV incidence and injection drug use, PrEP use remains low and limited research exists on PrEP adherence and retention in this population.MethodsBased in Washington, DC and Baltimore, the ANCHOR investigation evaluated a community-based model of care collocating hepatitis C (HCV) therapy, medication for opioid use disorder (OUD), and PrEP in people with chronic HCV, OUD, and drug use within 1 year. PrEP counseling was offered from HCV treatment Day 0 until Week 24 and subjects could start any time during this window. PrEP patients were followed for 48 weeks and assessed for adherence by self-report and dried blood spot analysis of TDF. ANCHOR PrEP study enrollment and participant retention along the PrEP continuum.Results198 participants enrolled in ANCHOR, of whom 185 (93%) were HIV-negative. 29 subjects (16% of HIV-negative group) initiated PrEP. 116 subjects (63%) met 2014 CDC criteria for PrEP initiation due to IDU (82, 44%), sex (9, 5%), or both (25, 14%). Those who initiated were more likely to meet both CDC sexual and IDU risk criteria than those who declined PrEP (P=0.006). Providers recommended PrEP to 94 subjects (51%), which was associated with uptake (P=0.02). While median treatment duration was 104 days (IQR 28, 276), only 8 subjects were retained through Week 48. The most common reason for discontinuation was side effects in 7 subjects or 24% of PrEP subgroup. Treatment interruptions occurred in one-third of the PrEP subgroup. Adherence of 4 to 7 pills per week was variable over time by self-report and declined by TDF analysis. No HIV seroconversions occurred. Demographic and epidemiological background of the ANCHOR study population. Total duration, in days, on PrEP in the ANCHOR study. Discontinued participants are grouped by reason for cessation of therapy.PrEP Adherence Adherence to PrEP by ANCHOR study timepoint, assessed via self-report (above) and dried bloodspot analysis of tenofovir level (below).ConclusionIn this cohort of people with OUD and HCV, 16% of subjects started PrEP. While clinical recommendation was associated with uptake, high rates of disruption and discontinuation, compounded by variable pill adherence, made daily oral TDF/FTC a suboptimal preventive strategy in this cohort. Emerging PrEP modalities like long-acting injectables have potential to address these barriers, but PWUD have been excluded from their research and development to date. Additional work to identify vulnerable individuals and to promote use, adherence, and retention will be critical in implementing PrEP more effectively in this key population.Disclosures Sarah Kattakuzhy, MD, Gilead Sciences (Scientific Research Study Investigator, Research Grant or Support) Elana S. Rosenthal, MD, Gilead Sciences (Research Grant or Support)Merck (Research Grant or Support)

Pregnant and breastfeeding women's prospective acceptability of two biomedical HIV prevention approaches in Sub Saharan Africa: A multisite qualitative analysis using the Theoretical Framework of Acceptability.

HIV infection during pregnancy and breastfeeding has implications for maternal health. Between May- November 2018, we explored prospective acceptability of two novel HIV Pre-exposure Prophylaxis (PrEP) products, oral pills and vaginal rings, through focus group discussions with 65 pregnant and breastfeeding women in Malawi, South Africa, Uganda, Zimbabwe. Qualitative analysis was completed, guided by the Theoretical Framework of Acceptability (TFA). First, a deductive thematic analysis was applied to relevant coded data, into the seven TFA constructs (Affective Attitude; Burden; Ethicality, Intervention Coherence; Opportunity Costs; Perceived Effectiveness; Self-efficacy). Next, an iterative analysis was completed to generate themes within each of the TFA constructs. Women's positive attitudes towards daily oral PrEP highlighted the familiarity of taking pills, understanding the purpose of taking pills, and the perception that it is an effective method to protect mothers and babies from HIV during pregnancy and breastfeeding. Women emphasized the ease of using the ring given its monthly duration that lowers burden on the user, its discreetness and invisibility once in place. The TFA analysis highlighted how acceptability of both methods could be enhanced by focusing on perceptions of the end users (i.e. the women) and not just the products themselves. This approach provided insights into how to refine the intervention materials and plans for implementation.

Fitting a vaccine into the HIV prevention landscape.

Fitting a vaccine into the HIV prevention landscape.

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.

Internet-Based HIV Self-Testing Among Men Who Have Sex With Men Through Pre-exposure Prophylaxis: 3-Month Prospective Cohort Analysis From China.

BackgroundRoutine HIV testing accompanied with pre-exposure prophylaxis (PrEP) requires innovative support in a real-world setting.ObjectiveThis study aimed to determine the usage of HIV self-testing (HIVST) kits and their secondary distribution to partners among men who have sex with men (MSM) in China, who use PrEP, in an observational study between 2018 and 2019.MethodsIn 4 major cities in China, we prospectively followed-up MSM from the China Real-world oral PrEP demonstration study, which provides daily or on-demand PrEP for 12 months, to assess the usage and secondary distribution of HIVST on quarterly follow-ups. Half of the PrEP users were randomized to receive 2 HIVSTs per month in addition to quarterly facility-based HIV testing. We evaluated the feasibility of providing HIVST to PrEP users.ResultsWe recruited 939 MSM and randomized 471 to receive HIVST, among whom 235 (49.9%) were daily and 236 (50.1%) were on-demand PrEP users. At baseline, the median age was 29 years, 390 (82.0%) men had at least college-level education, and 119 (25.3%) had never undergone facility-based HIV testing before. Three months after PrEP initiation, 341 (74.5%) men had used the HIVST provided to them and found it very easy to use. Among them, 180 of 341 (52.8%) men had distributed the HIVST kits it to other MSM, and 132 (51.6%) among the 256 men who returned HIVST results reported that used it with their sexual partners at the onset of intercourse. Participants on daily PrEP were more likely to use HIVST (adjusted hazard ratio=1.3, 95% CI 1.0-1.6) and distribute HIVST kits (adjusted hazard ratio=1.3, 95% CI 1.1-1.7) than those using on-demand PrEP.ConclusionsMSM who used PrEP had a high rate of usage and secondary distribution of HIVST kits, especially among those on daily PrEP, which suggested high feasibility and necessity for HIVST after PrEP initiation. Assuming that fourth-generation HIVST kits are available, HIVST may be able to replace facility-based HIV testing to a certain extent.Trial RegistrationChinese Clinical Trial Registry ChiCTR1800020374; https://www.chictr.org.cn/showprojen.aspx?proj=32481International Registered Report Identifier (IRRID)RR2-10.1136/bmjopen-2019-036231

An interview with Dr. Mike Robertson on the development of novel drugs for HIV treatment in diverse populations

An interview with Dr. Mike Robertson on the development of novel drugs for HIV treatment in diverse populations

Long-term protection from HIV infection with oral HIV pre-exposure prophylaxis in gay and bisexual men: findings from the expanded and extended EPIC-NSW prospective implementation study.

Daily pre-exposure prophylaxis (PrEP) is effective in preventing HIV, but few long-term data are available on effectiveness and adherence in real-world settings. Here, we report trends in HIV incidence over 3 years in individuals at high risk who were prescribed PrEP in New South Wales (NSW), as well as adherence before the transition to subsidised PrEP. Expanded PrEP Implementation in Communities-New South Wales (EPIC-NSW) was a pragmatic, prospective, single-arm, implementation study of daily, oral PrEP in 31 sites (sexual health clinics, general practices, and a hospital) in NSW, Australia. Eligible participants were HIV-negative adults (aged ≥18 years) who were at high risk of HIV infection as defined in local PrEP guidelines. Participants were prescribed coformulated (once-daily, oral tablet) tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) as HIV PrEP and were followed up with HIV testing, sexually transmitted infection testing, and PrEP dispensing. Originally planned for 3700 participants followed for 1 year, the study was expanded so that all eligible participants in the state could obtain PrEP and extended until publicly subsidised PrEP became available in Australia. The primary outcome was new HIV infection among all participants who were dispensed PrEP at least once and had at least one follow-up HIV test result. Adherence was estimated by medication possession ratio (MPR), defined as the proportion of PrEP pills dispensed in 90 days, assuming daily dosing. This study is registered with ClinicalTrials.gov, NCT02870790. Between March 1, 2016, and April 30, 2018, we enrolled 9709 participants. 9596 participants were dispensed PrEP, of whom 9448 (98·3%) were gay or bisexual men. Participants were followed up until March 31, 2019, with at least one follow-up HIV test available in 9520 (99·2%) participants. Mean MPR declined from 0·93 to 0·64 from the first to the ninth quarter. There were 30 HIV seroconversions over 18 628 person-years, an incidence of 1·61 per 1000 person-years (95% CI 1·13-2·30). Being younger, living in a postcode with fewer gay men, reporting more risk behaviours at baseline, and having an MPR of less than 0·6 were each univariately associated with increased HIV incidence. In the final year of follow-up, when PrEP was mostly purchased rather than provided free by the study, HIV incidence remained low at 2·24 per 1000 person-years (1·46-3·44). HIV incidence remained low over up to 3 years of follow-up, including during a transition from study-provided to publicly subsidised PrEP. In a setting of affordable PrEP and associated health-care services, very low HIV incidence of 1 to 2 per 1000 person-years can be maintained in gay and bisexual men who were previously at high risk. New South Wales Ministry of Health, Australian Capital Territory Health Directorate, Gilead Sciences.

Health economics modeling of antiretroviral interventions amongst HIV serodiscordant couples

Antiretroviral treatment (ART) and pre-exposure prophylaxis (PrEP) for HIV-serodiscordant couples, effectively reduce mortality, transmission events and influence quality of life at the expense of increased costs. We aimed to evaluate health economics of antiretroviral-based strategies for HIV-serodiscordant couples in the China context. A deterministic model of HIV evolution and transmission within a cohort of serodiscordant couples was parameterized using the real-world database of Zhoukou city and published literature. We evaluated the mid-ART (a historical strategy, initiating ART with CD4 < 500 cells/mm3), early-ART (the current strategy, offering ART regardless of CD4 cell counts) and a hypothetical strategy (early-ART combined short-term daily PrEP) versus the late-ART (the baseline strategy, initiating ART with CD4 < 350 cells/mm3) offered by 2008 national guidelines. We estimated the incremental cost-effectiveness ratios (ICER) and incremental cost-utility ratios (ICUR) from a societal perspective, derived by clinical benefits and HIV-caused life quality respectively, and portrayed their changes over a 0–30 year’s timeframe. The model projections indicated that the antiretroviral-based interventions were more likely to obtain clinical benefits but difficult to improve quality of life, and cumulative ICER and ICUR were generally decreasing without achieving cost-saving. Scale-up access to ART for the HIV-positive among serodiscordant couples was easily fallen within the range of paying for incremental life-years and quality adjusted life years by the societal willingness. The hypothetical strategy had the potential to prevent most seroconversion events within marriages but required enormous upfront costs, thus it took a long time to reach established thresholds. The current strategy of early-ART is the most cost-effective. Clarifying the obstacles of high cost of PrEP and improving life quality for HIV-serodiscordant couples have emerged as an urgent requisition.

Awareness of HIV Preexposure Prophylaxis Among People at Risk for HIV: Results From the 2017-2019 National Survey of Family Growth.

Although daily preexposure prophylaxis (PrEP) is now widely accepted as a safe and effective method for reducing the risk of HIV in high-risk groups, uptake has been slow. The goal of this analysis was to identify factors associated with PrEP awareness among individuals at risk for HIV. This investigation analyzed data from the Centers for Disease Control and Prevention nationally representative survey, National Survey of Family Growth, for the years 2017 to 2019. Logistic regression was used to explore the relationship between PrEP awareness and demographics, HIV risk factors, and provider HIV risk screening. Only 37% of survey respondents with an increased risk of HIV were aware of PrEP. Several segments of the at-risk population had lower odds of being aware of PrEP, including heterosexual women, heterosexual men, individuals younger than 20 years, and individuals with lower levels of education. Those who participate in sex in exchange for money or drugs had significantly lower odds of being aware of PrEP. In comparison, PrEP awareness was significantly higher among nonheterosexual men and both men and women whose partners were HIV positive. Lastly, those who had been screened by a provider for HIV risk had significantly higher odds of being aware of PrEP. This research supports the need for policies and programs to increase awareness of PrEP, especially among certain segments of the population at increased risk for HIV.

Is event-driven PrEP dosing for HIV as effective as daily dosing?

PROBABLY, although there are no head-to-head trials comparing the 2 dosing regimens. Event-driven pre-exposure prophylaxis (PrEP) dosing reduces HIV conversion by 86% compared to placebo (strength of recommendation [SOR]: B, large randomized controlled trial [RCT]). Daily PrEP reduces HIV conversion by 44% to 86% (SOR: B, based on open-label RCTs).Event-driven PrEP regimens may be associated with lower adherence when compared with daily PrEP regimens (average of 70% for event-driven PrEP vs average of 92% for daily PrEP) (SOR: B, based on open-label and cohort trials). Event-driven PrEP regimens have lower medication costs, and they are associated with no difference in the rate of sexually transmitted infections (STIs) (SOR: B, based on prospective cohort studies). Patients may prefer them to daily regimens (75% choose event driven PrEP vs 25% choose daily PrEP) (SOR: BB, based on the preponderance of prospective cohort studies with conflicting results).

HIV pre-exposure prophylaxis for men who have sex with men in west Africa: a multicountry demonstration study

HIV pre-exposure prophylaxis (PrEP) data in men who have sex with men (MSM) in west Africa are essential to guide its large-scale implementation. We assessed the uptake of event-driven and daily PrEP, HIV incidence, and changes over time in sexual behaviours and prevalence of bacterial sexually transmitted infections (STIs) in MSM in Burkina Faso, Côte d'Ivoire, Mali, and Togo. We did a prospective cohort study from Nov 20, 2017, to April 14, 2020, in four community-based clinics in Abidjan (Côte d'Ivoire), Bamako (Mali), Lomé (Togo), and Ouagadougou (Burkina Faso). Participants were MSM aged 18 years or older at substantial risk of HIV infection. Participants could choose between event-driven (2+1+1 dosing) and daily oral PrEP (tenofovir disoproxil fumarate 300 mg plus emtricitabine 200 mg), switch regimen, and discontinue or restart PrEP. We compared HIV incidence in this study with that of the same cohort before the availability of PrEP (CohMSM). Statistical analysis included the Kaplan-Meier method and mixed-effects regression models. This study is registered with ClinicalTrials.gov, NCT03459157. We followed up 598 participants for a total of 743·6 person-years. At enrolment, 445 (74%) of 598 participants chose event-driven PrEP and 153 (26%) of 598 chose daily PrEP. 60 (13%) of 445 and 65 (42%) of 153 participants switched PrEP regimen at least once (p<0·0001). 159 participants (27%) were lost to follow-up. Overall HIV incidence was 2·3 per 100 person-years (95% CI 1·3-3·7; adjusted incidence rate ratio 0·21, 95% CI 0·12-0·36 compared with CohMSM). Adherence was optimal in 802 (41%) of 1946 measures with event-driven PrEP and in 394 (71%) of 554 measures with daily PrEP (p<0·0001). Coverage of sex acts with PrEP only and PrEP and condom decreased during follow-up (p=0·039 if PrEP only; p=0·0025 if PrEP and condom). The frequency of condomless anal sex remained stable (p=0·96). The number of male sexual partners (p<0·0001) and number of sex acts with casual male partners (p=0·0014 for 1-4 sex acts in previous 4 weeks; p=0·030 for ≥5 sex acts) decreased. The prevalence of gonorrhoea, chlamydia, and syphilis remained stable. PrEP availability helped prevent HIV infection and did not lead to an increase in risky sexual behaviours or other STIs. PrEP should be urgently implemented in west Africa. Retention in care and PrEP adherence require special attention to ensure PrEP reaches its full prevention potential. ANRS and Expertise France. For the French translation of the abstract see Supplementary Materials section.

Salient Constructs for the Development of Shared Decision-Making Tools for HIV Pre-Exposure Prophylaxis Uptake and Regimen Choice: Behaviors, Behavioral Skills, and Beliefs.

The availability of multiple pre-exposure prophylaxis (PrEP) regimens creates a preference-sensitive choice for individuals weighing alternative HIV prevention strategies. Investigating factors that are associated with PrEP uptake and regimen choice are key to developing tools to support that decision. A cross-sectional survey was offered to 536 participants in a PrEP demonstration project for gay, bisexual, and other men who have sex with men across 3 cities in China, of which 412 completed surveys and were included in the analysis. We conducted bivariable analyses followed by multi-variable logistic regressions to examine factors associated with overall PrEP uptake and PrEP regimen choice. Among the 412 participants, 36.9% were daily PrEP users, 28.4% were event-driven users, and 34.7% were non-PrEP users. Higher levels of education, lower PrEP use stigma, and higher perceived benefits of PrEP were associated with greater PrEP uptake. More frequent sex, higher PrEP adherence self-efficacy, higher endorsement of the belief in elevated efficacy of daily over on-demand PrEP, and lower endorsement of a desire for a PrEP method that is only taken when needed led to greater odds of choosing the daily PrEP regimen. As multiple HIV prevention modalities become available, there is a greater need for a shared decision-making approach to support this preference-sensitive choice of HIV prevention method. Our findings suggest salient constructs to inform the development of shared decision-making tools to support regimen choice.

Facilitators and barriers of 2-1-1 HIV pre-exposure prophylaxis.

An alternative strategy for men who have sex with men (MSM) experiencing challenges with daily HIV pre-exposure prophylaxis (PrEP) includes 2-1-1 dosing. Understanding 2-1-1 PrEP facilitators and barriers, especially during the SARS-CoV-2 pandemic, may guide researchers and healthcare providers in future studies and clinical preparedness. We conducted a national cross-sectional study of MSM in the US who had taken 2-1-1 PrEP to examine facilitators and barriers of this on-demand PrEP dosing option. With the shelter-in-place orders in March 2020, this study was adapted to include questions on how the SARS-CoV-2 pandemic affected participants’ PrEP use. A total of 140 individuals participated in the survey, 106 of which completed questions pertaining to the SARS-CoV-2 pandemic. The most common reasons for switching from once-daily to 2-1-1 PrEP included having sex less frequently (63.6%) and wanting to take fewer pills (46.4%). Participants reported high medication adherence based on each component of 2-1-1 PrEP dosing (>84%). The most common barriers with 2-1-1 PrEP dosing included unplanned sexual encounters resulting in missing the double-dose pre-sex (43.6%) and trouble remembering doses post-sex (29.3%). Facilitators of the 2-1-1 PrEP dosing strategy included reductions in sexual encounters (63.6%), preference to take fewer pills (46.4%), need to reduce cost (22.1%), and desire to reduce side effects (19.3%). Challenges to receiving PrEP services during the pandemic included obtaining laboratory testing (25.5%) and PrEP refills (either receipt of a refill authorization from a healthcare provider or processing of a refill from the pharmacy) (18.9%). 2-1-1 PrEP is an effective HIV prevention method; therefore, understanding facilitators and barriers of this dosing strategy can result in continuous provision of HIV prevention efforts, particularly during a pandemic.

Acceptability of daily pre-exposure prophylaxis among adolescent men who have sex with men, travestis and transgender women in Brazil: A qualitative study.

Adolescents face socio-structural, personal and programmatic barriers to HIV prevention services, highlighting the importance of understanding knowledge and acceptability as essential aspects to promote their broader access to pre-exposure prophylaxis (PrEP). We analyzed the acceptability of PrEP among adolescent men who have sex with men (MSM), travestis and transgender women (TGW). A qualitative investigation was conducted as part of the formative research of the PrEP15-19 study, an ongoing demonstration study that analyzes the effectiveness of daily PrEP among adolescent MSM, travestis and TGW aged 15-19 in three Brazilian cities. A total of 37 semi-structured interviews and 6 focus groups were conducted. Building from thematic analysis focusing on participants' sexual encounters, perceptions about PrEP efficacy, and vulnerability contexts, we analyzed prospective acceptability of PrEP. Knowledge about PrEP was incipient and characterized by adolescents' frequent doubts about its prescription and efficacy. The 'ideal' use of PrEP appeared together with consistent condom use, especially in casual sex. PrEP use was also mentioned as depending on increased learning about prevention management over time. Main barriers to PrEP use included the incorporation of a daily medication into participants' routine and its impact on their social lives, especially related to stigma. Concerns over short- and long-term side effects were also reported as barriers to PrEP use. TGW and travestis contrasted using PrEP with the precarity of their life conditions, and some expressed a critical vision about PrEP by associating it with pharmaceuticalization and trans necropolitics. Participants' low knowledge and acceptability of PrEP are circumscribed by a rigid perception of condom as the ideal prevention method and the context of their sexual relations. Prospective acceptability highlights that the successful uptake of PrEP depends on overcoming barriers of access to health services and confronting transphobia and homophobia as part of care.

Imperfect adherence in real life: a prevention-effective perspective on adherence to daily and event-driven HIV pre-exposure prophylaxis among men who have sex with men - a prospective cohort study in Taiwan.

IntroductionBoth daily and event‐driven (ED) pre‐exposure prophylaxis (PrEP) have been demonstrated to be highly effective among men who have sex with men (MSM). Prevention‐effective adherence proposes that PrEP adherence should be aligned with the risk of HIV, which could be applied to both daily and ED PrEP adherence measurement. The objective of this study was to describe the relationship between the use of PrEP and sex events among the MSM PrEP users and identify factors associated with adherence among daily and ED MSM PrEP users.MethodsA multicentre, observational, prospective cohort study was conducted at three hospital‐based clinics in three urban cities of Taiwan from January 2018 to December 2019. MSM ages 18 years or older – at high risk of HIV acquisition and taking PrEP during the study period – were included in the analysis. MSM PrEP users were allowed to choose between daily and ED PrEP based on their preference. Data on sociodemographic characteristics, mental health, sexual behaviours, substance use and PrEP‐taking behaviours were collected at each visit.ResultsA total of 374 MSM were included in the analysis with 1,054 visits. More than half (56%) of the PrEP users chose ED at the baseline and 150 regimen switches were reported by 21% of the participants. There was only one seroconversion documented during the study period. Most (84.2%) of the MSM PrEP users were able to adhere to PrEP during the most recent anal intercourse in the past one month. Among ED PrEP users with suboptimal adherence, the majority (81.9%) missed the pre‐coital dose. In the multivariable analysis, we found that participants who switched from daily to an ED dosing regimen were associated with poorer adherence to PrEP.ConclusionsA high level of PrEP adherence was observed among the majority of MSM in a real‐world setting. On the other hand, Taiwanese MSM switching from daily to ED dosing regimens were less likely to adhere to PrEP, suggesting that novel approaches focusing on a dosing switch would be necessary for MSM to improve their adherence to PrEP.

Tenofovir Alafenamide for HIV Prevention: Review of the Proceedings from the Gates Foundation Long-Acting TAF Product Development Meeting.

The ability to successfully develop a safe and effective vaccine for the prevention of HIV infection has proven challenging. Consequently, alternative approaches to HIV infection prevention have been pursued, and there have been a number of successes with differing levels of efficacy. At present, only two oral preexposure prophylaxis (PrEP) products are available, Truvada and Descovy. Descovy is a newer product not yet indicated in individuals at risk of HIV-1 infection from receptive vaginal sex, because it still needs to be evaluated in this population. A topical dapivirine vaginal ring is currently under regulatory review, and a long-acting (LA) injectable cabotegravir product shows strong promise. Although demonstrably effective, daily oral PrEP presents adherence challenges for many users, particularly adolescent girls and young women, key target populations. This limitation has triggered development efforts in LA HIV prevention options. This article reviews efforts supported by the Bill & Melinda Gates Foundation, as well as similar work by other groups, to identify and develop optimal LA HIV prevention products. Specifically, this article is a summary review of a meeting convened by the foundation in early 2020 that focused on the development of LA products designed for extended delivery of tenofovir alafenamide (TAF) for HIV prevention. The review broadly serves as technical guidance for preclinical development of LA HIV prevention products. The meeting examined the technical feasibility of multiple delivery technologies, in vivo pharmacokinetics, and safety of subcutaneous (SC) delivery of TAF in animal models. Ultimately, the foundation concluded that there are technologies available for long-term delivery of TAF. However, because of potentially limited efficacy and possible toxicity issues with SC delivery, the foundation will not continue investing in the development of LA, SC delivery of TAF products for HIV prevention.

Offering a choice of daily and event-driven preexposure prophylaxis for men who have sex with men in the Netherlands: a cost-effectiveness analysis.

To assess the cost-effectiveness of a preexposure prophylaxis (PrEP) programme offering a choice of daily and event-driven PrEP for men who have sex with men (MSM) in the Netherlands. We used an agent-based transmission model and an economic model to simulate a programme offering only daily PrEP and a programme offering daily and event-driven PrEP. Use of PrEP medication and preference for daily versus event-driven PrEP were estimated from the Amsterdam PrEP Demonstration Project (AMPrEP). We calculated costs, quality-adjusted life-years (QALY), and incremental cost-effectiveness ratios (ICER), over 2018-2027. An ICER less than €20 000 per QALY gained was considered cost-effective. Using AMPrEP data, we estimated that 27% of PrEP users chose event-driven PrEP with a median of 12 pills per month; daily PrEP users used a median of 30 pills per month. With PrEP, 3740 HIV infections were averted and 1482 QALYs were gained over 2018-2027, compared to the scenario without PrEP. The probability of the PrEP programme being cost-effective (compared to not having a PrEP programme) increased from 91% with daily PrEP to 94% with a choice of daily and event-driven PrEP. The probability of being cost-saving increased from 42% with only daily PrEP to 48% with choice of daily and event-driven PrEP. A daily PrEP programme for MSM would be cost-effective. Providing a choice of daily and event-driven PrEP can result in savings and is more likely to be cost-effective and cost-saving, compared to a programme offering only daily PrEP.

Influences on Early Discontinuation and Persistence of Daily Oral PrEP Use Among Kenyan Adolescent Girls and Young Women: A Qualitative Evaluation From a PrEP Implementation Program.

Discontinuation of daily oral pre-exposure prophylaxis (PrEP) is frequent among adolescent girls and young women (AGYW) in African settings. We explored factors influencing early PrEP discontinuation and persistence among Kenyan AGYW who accepted PrEP within a programmatic setting. We conducted in-depth interviews with AGYW (aged 15-24 years) who accepted PrEP from 4 maternal child health (MCH) and family planning (FP) clinics. AGYW were identified by nurses at routine clinic visits and purposively sampled based on 4 categories: (1) accepted PrEP pills, but never initiated PrEP use (eg, never swallowed PrEP pills), (2) discontinued PrEP <1 month after initiation, (3) discontinued PrEP within 1-3 months, and (4) persisted with PrEP use >3 months. Informed by the Stages of Change Model, thematic analysis characterized key influences on PrEP discontinuation/persistence. We conducted 93 in-depth interviews with AGYW who accepted pills. Median age was 22 years, 71% were married; 89% were from MCH, and 11% were from FP clinics. Early PrEP use was positively influenced by encouragement from close confidants and effective concealment of PrEP pill-taking when necessary to avoid stigma or negative reactions from partners. Pregnancy helped conceal PrEP use because pill-taking is normalized during pregnancy, but concealment became more difficult postpartum. AGYW found keeping up with daily PrEP pill-taking challenging, and many noted only episodic periods of the HIV risk. Frequently testing HIV-negative reassured AGYW that PrEP was working and motivated persistence. As PrEP programs scale-up in MCH/FP, it is increasingly important to enhance protection-effective PrEP use through approaches tailored to AGYW, with special considerations during pregnancy and postpartum.