Enhancing HIV pre-exposure prophylaxis outcomes among Kenyan adolescent girls and young women with a novel pharmacy-based PrEP delivery platform: protocol for a cluster-randomized controlled trial.

BACKGROUND: In Kenya, 65% of sexually active unmarried women use modern contraceptives, a population at increased risk of HIV acquisition compared to other populations. Anchoring HIV prevention services, including pre-exposure prophylaxis (PrEP), to trusted contraceptive delivery settings offers opportunities to efficiently reach this important population. In Kenya, almost half (40%) of women accessing contraception services do so outside traditional healthcare facilities, such as retail pharmacies. Thus, integrating PrEP services into retail pharmacies may increase options for reaching adolescent girls and young women (AGYW) who could benefit from PrEP. Efforts are underway to define care pathways for pharmacy-delivered PrEP services in Kenya, including unsupported and supported models with nurse navigators. METHODS: The AGYW Pharmacy PrEP study is an unblinded 2-arm cluster-randomized controlled trial in Kisumu, Kenya. The objective is to determine the effect that unsupported versus supported pharmacy-delivered PrEP services has on PrEP initiation, persistence, and adherence among AGYW seeking contraception. Twenty retail pharmacies offering pharmacy provider-led PrEP delivery will be randomized 1:1 to either receive or not receive a nurse navigator to support PrEP delivery. Eligible AGYW (n = 1900 total, n = 950/arm) will be ≥ 15 years old, purchasing a method of contraception at the pharmacy. Trained pharmacy provider will offer eligible AGYW either daily oral PrEP or the monthly DPV vaginal ring. The primary trial outcomes are PrEP initiation (use of PrEP at 1 month), persistence (use of PrEP at 10 months), and adherence (quantified by levels of TFV or DPV in hair samples). Additionally, several secondary (STI incidence, PrEP method selection, predictors of PrEP adherence) and exploratory outcomes (HIV incidence, quality of care, contraceptive method mix) will be explored. DISCUSSION: We hypothesize pharmacy-delivered PrEP services supported with nurse navigator, versus delivered by pharmacy providers alone, will improve PrEP outcomes among AGYW seeking contraception. Our results will help policy makers better understand how to potentially implement this novel differentiated service model for PrEP and prime pharmacies for the delivery of new PrEP agents in the pipeline (e.g., long-acting injectables and multi-purpose technologies). The study was initiated on May 13, 2023, and is expected to be completed by February 2025. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05467306), with registration on July 20, 2022.

Intention and preference to use long-acting injectable PrEP among MSM in the Netherlands: a diffusion of innovation approach.

Long-acting injectable pre-exposure prophylaxis (LAI-PrEP) is efficacious in preventing HIV among men-who-have-sex-with-men (MSM) and will be soon available in Europe. This study investigated the intention and preference to use LAI-PrEP among MSM in the Netherlands by employing a diffusion of innovation approach. This study had a cross-sectional design nested within a cohort study established in 2017 to understand oral PrEP use among MSM. 309 MSM completed the survey on their awareness, interest, intention, and preference for LAI-PrEP in June 2022. Among them, 83% showed high/very-high interest in, and 63% showed high/very-high intention to use LAI-PrEP. A repeated innovator effect from the early adopters to LAI-PrEP was not observed. Early adopters did not show increased intention to use LAI-PrEP compared to other MSM subgroups, but neither did PrEP-naïve nor PrEP-discontinued MSM. However, among the 218 current oral PrEP users, suboptimal adherence was associated with preference for LAI-PrEP but not with intention to use it. In conclusion, our findings indicated that an effective, available, and affordable LAI-PrEP would be welcomed in the Netherlands, but that its introduction may not significantly expand PrEP coverage. However, the introduction of LAI-PrEP in the Netherlands could prove beneficial to MSM with suboptimal adherence to oral PrEP.

Factors Associated with PrEP Persistence and Loss of Follow-Up: A 5-Year Historic Cohort.

OBJECTIVE: HIV Pre-Exposure Prophylaxis (PrEP) has been used in France since 2016. Its effectiveness is no longer to be demonstrated. However, follow-up and adherence remain the main pitfalls. The main objective of this study was to identify factors associated with persistence or loss of PrEP follow-up. DESIGN: An historic cohort of PrEP users was compiled from the database of consultations in the Indre-et-Loire dedicated sexual health centers (CeGIDD) from June 2016 to June 2021. METHODS: Kaplan-Meier curves were performed to compare the group of persistent PrEP users to the discontinuation group. Factors associated with PrEP discontinuation were identified using Cox modelling, considering time-dependent variables. Final variables included in the model were selected based on the Akaike Information Criterion (AIC) and clinical relevance. RESULTS: Over the period, 568 PrEP users were included in the cohort. Median follow-up was 2.3 years. A quarter of users were lost to follow-up within 3 months after PrEP initiation. Sexual risk reduction AIDS community-based support (HR = 0.65[0.42;0.99]), being in a couple (HR = 0.51[0.38;0.68]), and history of syphilis (HR = 0.57[0.40;0.81]) were significantly associated with persistence of follow-up. Remote consultations (HR = 2.74[1.63;4.61]), chemsex practices (HR = 2.01[1.29;3.14]), and side effects (HR=1.72[1.03;2.88]) were significantly associated with a loss of follow-up. CONCLUSION: These results suggest that more sexual risk reduction AIDS community-based counseling could be a key, necessary for supporting PrEP users in their follow-up pathway. Indeed, AIDS community-based support could be used to build a basis for developing safe pathways. Remote consultations could represent a response to the issue of access to PrEP. To create a significant impact on global HIV incidence, the PrEP offer must be extended, and at-risk PrEP users supported to maintain PrEP use.

Challenges recruiting and retaining people at risk for HIV who use methamphetamine in a randomized PrEP adherence trial in Seattle, WA.

BACKGROUND: Methamphetamine is associated with increased HIV risk and suboptimal adherence to pre-exposure prophylaxis (PrEP). Interventions to support PrEP adherence for people who use methamphetamine are needed. METHODS: We evaluated peer navigation to support adherence among people initiating PrEP who use methamphetamine. The HIV Prevention in Methamphetamine Users (HMU!) study enrolled participants from May 2018-January 2022 in Seattle, WA, and followed them for 6 months. Surveys collected sociodemographic, drug use, and sexual behavior data at enrollment, month 3, and month 6. Dried blood spots (DBS) were collected at months 1, 3, and 6 to measure PrEP adherence. RESULTS: We enrolled 21 participants of a target sample of 40, of whom 20 were prescribed PrEP. Nine participants (43%) received peer navigation and 12 (57%) received standard of care or text messaging. At baseline, most participants reported at least weekly methamphetamine use (17, 81%) and condomless receptive anal intercourse (CRAI) (16, 76%). One-third reported CRAI with a partner with HIV. Among those who provided a DBS, 78% and 50% had results commensurate with ≥4 pills/week at the month 3 and 6 visit, respectively. More than half of those prescribed PrEP completed a month 6 visit (11, 55%). Retention was not associated with peer support compared to standard of care or text messaging (p = .20). CONCLUSIONS: We enrolled half our target sample size despite extensive recruitment efforts. As expected, participants had challenges with PrEP adherence and persistence. While peer navigation interventions should be studied further, additional interventions are likely needed to support PrEP uptake, adherence, and persistence among people who use methamphetamine.

Cascade analysis of awareness, willingness, uptake and adherence with regard to PrEP among young men who have sex with men (YMSM) in China: A comparison between students and non-students.

INTRODUCTION: In China, young men who have sex with men (YMSM) are one of the groups most at risk of HIV/AIDS. The uptake of pre-exposure prophylaxis (PrEP) among YMSM has not been well documented. A cascade analysis of awareness, willingness, use and adherence with regard to PrEP was conducted separately among YMSM students and non-students. METHODS: From 20 October to 30 December 2021, all adolescents aged 16-24 years were selected for the study from among MSM recruited from 31 provincial administrative regions in mainland China. Participants were included in a cross-sectional study of awareness, willingness, use and adherence with regard to PrEP among YMSM. Logistic regression modelling was used to identify factors associated with the four outcomes. RESULTS: Among 1014 student and 866 non-student YMSMs, respectively, 88.07% and 81.64% had heard of PrEP; 58.16% and 50.35% were willing to use PrEP; 7.59% and 7.62% had used PrEP; and 3.16% and 3.58% had adhered to PrEP. Among students, those living in high-risk areas and pilot cities and those who had engaged in commercial sex and group sex had a positive effect on PrEP use, and the same trends were found among non-students living in high-risk areas and pilot cities and those who had engaged in group sex. 'Daily oral' and 'flexible' PrEP use positively influenced adherence among both groups. CONCLUSIONS: A differentiation strategy of PrEP promotion should be implemented among YMSM. Material support for students, such as financial resources, should increase, while non-students should increase their level of perception of HIV risk.

Low daily oral PrEP adherence and low validity of self-report in a randomized trial among PWID in Ukraine.

BACKGROUND: The efficacy of daily oral pre-exposure prophylaxis (PrEP) in preventing HIV transmission among people who inject drugs (PWID) was demonstrated over a decade ago. However, only a few studies among PWID have since measured PrEP adherence using laboratory markers. METHODS: In this trial, we randomized recently injecting PWID in Kyiv, Ukraine, to receive daily oral TDF/FTC with or without SMS reminders. Enrollment and PrEP initiation took place at an HIV clinic. Subsequent visits at months 1, 3, and 6 were conducted at a community harm reduction center and included a structured interview, adherence counseling, PrEP dispensing, and dried blood spot collection. PrEP adherence was assessed using standard self-reported measures and TDF/FTC biomarkers. RESULTS: A total of 199 PWID (99 SMS, 100 No-SMS) were enrolled, of whom 24 % were women, with a median age of 37. At month 6, 79.4 % (158/199) of participants were retained, with 84 % (133/158) reporting opioid injection and 20 % (31/158) reporting stimulant injection in the past 30 days. 77 % (122/158) reported taking >95 % of PrEP doses in the past month, and 87 % reported taking the last dose within 2 days. Tenofovir diphosphate was detected in 17 % (28/158) of participants, and emtricitabine triphosphate was detected in 25 % (40/158). Only 3 % (5/158) had metabolite levels indicative of consistent PrEP uptake at 4+ doses per week. There was no association between the SMS intervention and TDF/FTC metabolite detection. CONCLUSION: Adherence to daily oral PrEP among actively injecting PWID, without daily supervision or incentives, was extremely low, despite supportive counseling and SMS reminders. We also observed a high rate of discordance between self-report and classification by a validated biomarker of adherence. Given the scarcity of evidence and emerging data suggesting low oral PrEP adherence among PWID, additional implementation studies with TDF/FTC biomarkers are needed to study whether a sufficient level of adherence to daily PrEP is attainable among PWID, especially as long-acting injectable PrEP offers a promising alternative.

Examining the Role of Autonomy Support, Goal Setting, and Care Coordination Quality on HIV PrEP Adherence in Black Men Who Have Sex with Men: HPTN 073.

Autonomy support is a concept that is derived from self-determination theory. Autonomy refers to the freedom to act as one chooses. The current study aimed to examine if autonomy support was associated with dried blood spot validated pre-exposure prophylaxis (PrEP) adherence, and whether the association was mediated by PrEP adherence goal setting and progress toward PrEP adherence goals. Our sample was drawn from Black men who have sex with men (MSM) from across three cities (Chapel Hill, NC; Los Angeles, CA; and Washington, DC) in the United States between February 2013 and September 2014. We used logistic regression to evaluate associations between study variables and path analysis to test mediation effects. Participants were, on average, 28 [standard deviation (SD) = 1.12] years old and 25% were unemployed. We found that MSM who experienced high autonomy support were more likely to adhere to PrEP [odds ratio (OR) = 1.17; 95% confidence interval: 1.00-1.38]. MSM who set PrEP adherence goals were more likely to adhere to PrEP. Moreover, MSM who reported making progress toward their goals were also more likely to adhere to PrEP. Finally, client perception of coordination quality enhanced the magnitude of the association between goal setting and goal progress and the effect size of goal progress on PrEP adherence. Autonomy support, goal setting, goal monitoring/evaluation, and care coordination quality influenced PrEP adherence among Black MSM. Our findings indicate that while it is important to set goals for PrEP adherence, goal setting may need to be accompanied by progress monitoring to achieve the maximal effect.

A Text Messaging-Based Support Intervention to Enhance Pre-exposure Prophylaxis for HIV Prevention Adherence During Pregnancy and Breastfeeding: Protocol for a Randomized Controlled Trial.

BACKGROUND: Cisgender women in Kenya are at elevated risk of HIV acquisition during pregnancy and post partum. Acute HIV infection during pregnancy and breastfeeding accounts for approximately one-third of all vertical HIV transmissions. The World Health Organization recommends offering oral tenofovir-based pre-exposure prophylaxis (PrEP) to pregnant and postpartum women who are HIV negative but at substantial and ongoing risk for HIV acquisition. PrEP delivery for pregnant and postpartum women is expanding within routine maternal child health clinics in Kenya. However, approximately half of pregnant women discontinue PrEP within 30 days of initiation. Therefore, it is crucial to develop PrEP adherence strategies that enhance support for adherence when peripartum events and health issues pose challenges to sustaining PrEP adherence. OBJECTIVE: We are conducting a randomized controlled trial to determine the effect of a bidirectional communication platform named Mobile Solutions for Women's and Children's Health (mWACh), which utilizes two-way SMS text messaging between patients and remote nurses to support PrEP adherence and address maternal health concerns in real time during the peripartum period. METHODS: The mWACh-PrEP study is a randomized trial designed to support PrEP adherence during the peripartum period by comparing mWACh-PrEP to the standard of care (ie, in-clinic adherence counseling) among women who are HIV negative and initiating PrEP. Purposive sampling was used to select 5 facilities offering PrEP in antenatal clinics in Kisumu and Siaya Counties, and block randomization will be used to divide participants into groups. Participants in the intervention arm will receive a customized messaging curriculum via SMS text messages targeted toward their particular perinatal stage. The primary outcome, PrEP adherence at 6 months post partum, will be evaluated using a log-binomial regression model, adjusting for imbalanced baseline characteristics. Based on a previous study of directly observed dosing conditions, we will use a hair tenofovir concentration cutoff of 0.038 ng/mg (corresponding to 7 doses/week) as the primary adherence outcome measured at 6 months post partum (binary outcome). Qualitative interviews and cost-effective analyses will be conducted to understand the feasibility, acceptability, and economic impact of the intervention. RESULTS: Enrollment began in March 2022 and is projected to continue until July 2023, with follow-up through March 2024. The study results are expected to be reported in 2025. CONCLUSIONS: This trial will provide insights into using mobile health to enhance PrEP adherence among pregnant and postpartum mothers. Additionally, the findings will have implications for the use of mobile health technology to improve adherence to other daily medications during the peripartum period. TRIAL REGISTRATION: ClinicalTrials.gov NCT04472884; https://clinicaltrials.gov/ct2/show/NCT04472884. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41170.

Influences on PrEP Uptake and Adherence Among South African Women During Periconception and Pregnancy: A Qualitative Analysis.

Pre-exposure prophylaxis (PrEP) is highly effective for HIV prevention, yet PrEP delivery to women in periconception and pregnancy has lagged. We report qualitative research from a study evaluating PrEP use as part of safer conception care for 330 South African women. Fifty-two semi-structured interviews were conducted with 25 study participants to identify influences on PrEP adherence. Influences were: (1) changing proximity to male partners; (2) COVID-19 lockdown; (3) mobile lifestyle; (4) PrEP-related stigma; (5) disclosure of PrEP use; and (6) pregnancy and motherhood. Data also revealed important contextual information shaping adherence influences for women, including: (a) not living with partners, (b) partners as drivers of pregnancy intention, and (c) feeling at high risk for HIV. Disclosure of PrEP use, addressing stigma, strategies for traveling with pills, and counseling on prevention effective adherence are promising components of PrEP-inclusive HIV prevention interventions for South African women who are pregnant or planning pregnancy.

PrEP Use and Adherence among Transgender Persons in Chicago, IL (SHIPP Study, 2014-2018, USA).

Few studies investigating daily oral preexposure prophylaxis (PrEP) focus on transgender persons. The Sustainable Health Center Implementation PrEP Pilot (SHIPP) Study included a large observational cohort of transgender persons with implications for PrEP in the United States. We examined data from SHIPP's observational cohort and its Medication Adherence Substudy (MAS) to understand adherence among transgender participants in Chicago, IL. We assessed adherence by the proportion of days covered (PDC) for PrEP medication prescriptions, self-reported interview data, and concentrations of intracellular tenofovir diphosphate (TFV-DP) in dried blood spot (DBS) samples. Between 2014 and 2018, there were 510 transgender participants, 349 (68.4%) transgender women and 152 (29.8%) transgender men. Forty-five of these participants were enrolled in the MAS, 31 (68.9%) transgender women and 9 (20.0%) transgender men. By the 3-month follow up, 100% of MAS participants who completed an interview reported taking 4 or more doses of PrEP in the previous week. At 6, 9, and 12 months, taking 4 or more doses in the past week was reported by 81.0%, 94.1%, and 83.3% of participants, respectively. Results from TFV-DP DBS indicated that fewer participants reached the same level of adherence (4 or more doses/week) at clinical visits compared to self-report and even fewer participants reached this level of adherence based on the calculated PDC. Among participants who remained on PrEP throughout the study, DBS adherence levels declined after the first three months. There remains a critical need to develop strategies to address barriers and interventions that support PrEP adherence among transgender people.

Substance Use and Adherence to HIV Pre-Exposure Prophylaxis in Studies Enrolling Men Who Have Sex with Men and Transgender Women: A Systematic Review.

Optimal adherence to pre-exposure prophylaxis (PrEP) is critical, but challenging. Men who have sex with men and transgender women have high rates of HIV incidence and substance use. Substance use is associated with reduced adherence to other medications, but associations between substance use and adherence to PrEP are less clear. Thus, the current review 1) systematically evaluates the measurement of substance use and PrEP adherence in studies examining both and 2) summarizes reported findings. Peer-reviewed articles published between 2010 - April 2021 examining associations between substance use and PrEP adherence were reviewed. Fifty studies met inclusion criteria. Assessment of substance use (i.e., mostly via self-reports at baseline) and PrEP adherence (i.e., often via tenofovir diphosphate [TFV-DP] concentration levels at follow-up) varied considerably across studies. Many studies used categorical variables (e.g., substance use: yes/no). Studies using TFV-DP levels defined adherence consistently (i.e., TFV-DP ≥ 700 fmol/punch), with slight variations. Qualitative studies (n = 10) indicated that substance use (mainly alcohol) is related to poorer PrEP adherence. While quantitative findings to date are equivocal for alcohol, there is a pattern of findings linking stimulant use with poorer PrEP adherence. This review reveals four methodological gaps, which can be addressed in future research by: 1) use of uniform benchmarks for substance use measures, 2) prospective assessment for substance use, 3) use of continuous outcome variables wherever possible, and 4) more extensive consideration of potential confounders. Addressing these methodological gaps may help us reach more definitive conclusions regarding associations between substance use and PrEP adherence.

Using Behavioral Economics to Support PrEP Adherence for HIV Prevention.

PURPOSE OF REVIEW: We explored different behavioral economics (BE) mechanisms through which pre-exposure prophylaxis (PrEP) initiation and adherence could be impacted and examined recent work using BE principles to further HIV prevention efforts. We also generated new intervention ideas based on existing HIV testing and ART adherence literature. RECENT FINDINGS: There is limited work that uses BE principles to design interventions to increase PrEP initiation and adherence, mostly involving financial incentives. The recent works highlighted involve financial incentives and demonstrate that key populations are open to accepting monetary incentives to increase PrEP initiation and improve adherence. However, there are mixed results on the long-term impacts of using incentives to modify behavior. While there are a few ongoing studies that utilize BE principles to increase PrEP use, there is need to develop studies that test these concepts, to promote PrEP initiation and adherence. We suggest methods of exploring non-incentives-based ideas to increase PrEP use in key populations.

The Influencing Factors of HIV-Preventive Behavior Based on Health Belief Model among HIV-Negative MSMs in Western China: A Structural Equation Modeling Analysis.

(1) Background: Men who have sex with other men (MSMs) are at high risk of being infected by the human immunodeficiency virus (HIV) in western China. Pre-exposure prophylaxis (PrEP) is an efficient way to prevent HIV transmission. However, adherence is the most vital determinant factor affecting PrEP effectiveness. We conducted a study based on the Health Belief Model to explore factors that predict adherence to PrEP among a cohort of 689 MSMs in western China. (2) Methods: We assessed perceived susceptibility, severity, benefits, barriers, self-efficacy, cues to action, and HIV-preventive behavior through a cross-sectional survey. (3) Results: PrEP self-efficacy was directly associated with PrEP behaviors (ß = 0.221, p < 0.001), cues to action were directly associated with PrEP behaviors (ß = 0.112, p < 0.001), perceived benefits were directly associated with PrEP behaviors (ß = 0.101, p < 0.001), and perceived susceptibility was directly associated with PrEP behaviors (ß = 0.117, p = 0.043). (4) Conclusion: Medication self-efficacy, perceived susceptibility, and cue to action structures are predictors of the MSMs' HIV-preventive behavior in western China. These results will provide theoretical plans for promoting PrEP adherence in MSMs.

Prospective study of oral pre-exposure prophylaxis initiation and adherence among young women in KwaZulu-Natal, South Africa.

INTRODUCTION: Oral tenofovir disoproxil fumarate/emtricitabine pre-exposure prophylaxis (PrEP), introduced into South Africa (SA) in 2016, has increasingly become part of HIV prevention standard of care. Given the urgent need for increased HIV prevention efforts for young women in SA, we conducted an implementation study to explore oral PrEP initiation and adherence, and the impact of oral PrEP on HIV incidence in this group. METHODS: This prospective cohort study (CAPRISA 082) was conducted at two sites (urban and rural) in KwaZulu-Natal, between March 2016 and February 2018. HIV-negative, sexually active women, aged 18-30 years, were enrolled and followed for approximately 10 months. Oral PrEP was offered as part of a comprehensive HIV prevention package. Adherence to oral PrEP was measured using pill counts and tenofovir-diphosphate (TFV-DP) levels. Characteristics of oral PrEP initiators versus non-initiators were compared using risk ratios. HIV incidence rates were measured using Poisson regression. RESULTS: Of 425 women enrolled, 262 (62%) initiated oral PrEP. Uptake was significantly higher at the rural site compared to the urban site (78% [n = 203/259] vs. 36% [n = 59/166], respectively, p-value<0.001). Approximately 25% and 50% had stopped using oral PrEP by 3 and 12 months post-initiation, respectively. Median pill count adherence was 90% (interquartile range: 81-97%); however, TFV-DP was only detected in 13% of samples tested, that is 56/431 samples from 97 (37%) participants who initiated oral PrEP. In total, 11 women seroconverted yielding an HIV incidence rate of 2.81 per 100 person-years (95% confidence interval: 1.40-5.03). Nine of 11 seroconverters had initiated oral PrEP; however, all showed drug levels equivalent to taking one to zero tablets per week. Among women who initiated oral PrEP, >50% had discontinued using oral PrEP by study end, with side effects, such as diarrhoea, nausea, headaches and rash, being the most frequent reason for discontinuation. CONCLUSIONS: Despite moderate oral PrEP initiation and high pill count adherence, adherence as measured by TFV-DP levels was low and early discontinuation was high. The overall HIV incidence rate was high underscoring the critical need to address barriers to oral PrEP initiation, adherence and continued use, as well as expanding HIV prevention options for young women.

A Mobile Phone App to Support Adherence to Daily HIV Pre-exposure Prophylaxis Engagement Among Young Men Who Have Sex With Men and Transgender Women Aged 15 to 19 Years in Thailand: Pilot Randomized Controlled Trial.

BACKGROUND: Widespread smartphone use provides opportunities for mobile health HIV prevention strategies among at-risk populations. OBJECTIVE: This study aims to investigate engagement in a theory-based (information-motivation-behavioral skills model) mobile phone app developed to support HIV pre-exposure prophylaxis (PrEP) adherence among Thai young men who have sex with men (YMSM) and young transgender women (YTGW) in Bangkok, Thailand. METHODS: A randomized controlled trial was conducted among HIV-negative YMSM and YTGW aged 15-19 years initiating daily oral PrEP. Participants were randomized to receive either youth-friendly PrEP services (YFS) for 6 months, including monthly contact with site staff (clinic visits or telephone follow-up) and staff consultation access, or YFS plus use of a PrEP adherence support app (YFS+APP). The target population focus group discussion findings and the information-motivation-behavioral skills model informed app development. App features were based on the 3Rs-risk assessment of self-HIV acquisition risk, reminders to take PrEP, and rewards as redeemable points. Dried blood spots quantifying of tenofovir diphosphate were collected at months 3 and 6 to assess PrEP adherence. Tenofovir diphosphate ≥350-699 fmol/punch was classified as fair adherence and ≥700 fmol/punch as good adherence. Data analysis on app use paradata and exit interviews were conducted on the YFS+APP arm after 6 months of follow-up. RESULTS: Between March 2018 and June 2019, 200 participants with a median age of 18 (IQR 17-19) years were enrolled. Overall, 74% (148/200) were YMSM; 87% (87/100) of participants who received YFS+APP logged in to the app and performed weekly HIV acquisition risk assessments (log-in and risk assessment [LRA]). The median duration between the first and last log-in was 3.5 (IQR 1.6-5.6) months, with a median frequency of 6 LRAs (IQR 2-10). Moreover, 22% (22/100) of the participants in the YFS+APP arm were frequent users (LRA≥10) during the 6-month follow-up period. YMSM were 9.3 (95% CI 1.2-74.3) times more likely to be frequent app users than YTGW (P=.04). Frequent app users had higher proportions (12%-16%) of PrEP adherence at both months 3 and 6 compared with infrequent users (LRA<10) and the YFS arm, although this did not reach statistical significance. Of the 100 participants in the YFS+APP arm, 23 (23%) were interviewed. The risk assessment function is perceived as the most useful app feature. Further aesthetic adaptations and a more comprehensive rewards system were suggested by the interviewees. CONCLUSIONS: Higher rates of PrEP adherence among frequent app users were observed; however, this was not statistically significant. A short app use duration of 3 months suggests that they may be useful in establishing habits in taking daily PrEP, but not long-term adherence. Further studies on the specific mechanisms of mobile phone apps that influence health behaviors are needed. TRIAL REGISTRATION: ClinicalTrials.gov NCT03778892; https://clinicaltrials.gov/ct2/show/NCT03778892.

The effect of PrEP uptake and adherence on the spread of HIV in the presence of casual and long-term partnerships.

A model with both casual and long-term partnerships is considered with respect to the impact of a pre-exposure prophylaxis (PrEP) on the spread of HIV. We consider the effect of the effectiveness of PrEP, the rate that susceptible individuals choose to take PrEP, and compliance with the daily dose of the pre-exposure prophylaxis. The rate of infection in long-term partnerships is computed using a linearized expected value as a means for including the nonlocal effects of long-term partnerships while maintaining computational feasibility. The reproduction numbers for models with casual partnerships, long-term partnerships, and a combination of both are analytically computed and global stability of both disease-free and endemic equilibria is shown. Sensitivity and PRCC analysis results suggest that increasing the compliance among the current PrEP users is a more effective strategy in the fight against the HIV epidemic than increased coverage with poor compliance. Furthermore, an analysis of the reproduction number shows that models with either casual or monogamous long-term partnerships can reach the desired $ R_0 < 1 $ threshold for high enough levels of compliance and uptake, however, a model with both casual and monogamous long-term partnerships will require additional interventions. Methods highlighted in this manuscript are applicable to other incurable diseases or diseases with imperfect vaccines effected by long-term partnerships.

Multilevel Barriers to HIV PrEP Uptake and Adherence Among Black and Hispanic/Latinx Transgender Women in Southern California.

Black and Hispanic/Latinx transgender women in the United States (U.S.) are disproportionately affected by HIV. Pre-exposure prophylaxis (PrEP) reduces risk of HIV infection but PrEP uptake remains low among Black and Hispanic/Latinx transgender women. Between July 2018 and August 2019, we conducted individual interviews with 30 Black and Hispanic/Latinx transgender women who were prescribed PrEP through a PrEP demonstration project and 10 healthcare providers who provide PrEP services to transgender women in Los Angeles and San Diego, California. The interviews assessed general attitudes, experiences, and beliefs about PrEP as well as individual-, interpersonal-, community-, and structural-level barriers to PrEP uptake and adherence. PrEP adherence was assessed by collecting quantitative intracellular tenofovir-diphosphate (TFV-DP) levels in retrospect on batched, banked dried blood spot (DBS) samples. We utilized qualitative content analysis to identify themes from the interviews. Findings indicated the presence of individual-level barriers including cost concerns, mental health issues, substance use, and concerns about PrEP side effects including hormone interaction. Interpersonal-level barriers included the influence of intimate/romantic partners and the impact of patient-provider communication. Community-level barriers consisted of experiencing stigma and negative community opinions about PrEP use as well as having negative experiences in healthcare settings. Structural-level barriers included unreliable transportation, employment, and housing insecurity. Interventions aiming to increase PrEP uptake and adherence among Black and Hispanic/Latinx transgender women in the U.S. should employ a multilevel approach to addressing the needs of transgender women, especially the structural barriers that have greatly limited the use of PrEP.

RESUMEN: Las mujeres transexuales negras e hispanas/latinx en los Estados Unidos (EE. UU.) se ven afectadas de manera desproporcionada por el VIH. La profilaxis previa a la exposición (PrEP) reduce el riesgo de infección por VIH, pero la aceptación sigue siendo baja entre las mujeres transgénero negras e hispanas/latinx. Entre julio de 2018 y agosto de 2019, realizamos entrevistas individuales con 30 mujeres transgénero negras e hispanas/latinx a las que se les recetó PrEP a través de un proyecto de demostración de PrEP y a 10 proveedores de atención médica que brindan servicios de PrEP a mujeres transgénero en Los Ángeles y San Diego, California. Las entrevistas evaluaron las actitudes, experiencias y creencias generales sobre PrEP, así como las barreras a nivel individual, interpersonal, comunitario y estructural para la aceptación y la adherencia. La adherencia a PrEP se evaluó mediante la recolección de niveles intracelulares cuantitativos de difosfato de tenofovir (TFV-DP) en retrospectiva en muestras de manchas de sangre seca (DBS) acumuladas y almacenadas. Utilizamos análisis de contenido cualitativo para identificar temas de las entrevistas. Los hallazgos indicaron la presencia de barreras a nivel individual, incluidas preocupaciones de costos, problemas de salud mental, uso de sustancias y preocupaciones sobre los efectos secundarios de PrEP, incluida la interacción hormonal. Las barreras a nivel interpersonal incluyeron la influencia de las parejas íntimas/románticas y el impacto de la comunicación entre el paciente y el proveedor. Las barreras a nivel de la comunidad consistieron en experimentar estigma y opiniones negativas de la comunidad sobre el uso de PrEP, así como tener experiencias negativas en entornos de atención médica. Las barreras a nivel estructural incluían transporte poco confiable, así como inseguridad en el empleo y la vivienda. Las intervenciones destinadas a aumentar la aceptación y el cumplimiento de PrEP entre las mujeres transgénero negras e hispanas/latinx en los EE. UU. deben emplear un enfoque multinivel para abordar las necesidades de las mujeres transgénero, especialmente las barreras estructurales que han limitado en gran medida el uso de PrEP.

Youth-friendly services and a mobile phone application to promote adherence to pre-exposure prophylaxis among adolescent men who have sex with men and transgender women at-risk for HIV in Thailand: a randomized control trial.

INTRODUCTION: Strategies are needed to curb the increasing HIV incidence in young men who have sex with men (YMSM) and transgender women (YTGW) worldwide. We assessed the impact of youth-friendly services (YFS) and a mobile phone application (app) on adherence to pre-exposure prophylaxis (PrEP) in YMSM and YTGW in Thailand. METHODS: A randomized control trial was conducted in YMSM and YTGW aged 15 to 19 years. Participants were provided daily oral tenofovir disoproxil fumerate/emtricitabine (TDF/FTC), condoms and randomized to receive either YFS or YFS plus a PrEP app (YFS + APP), whose features included self-assessment of HIV acquisition risk, point rewards and reminders for PrEP and clinic appointments. Clinic visits occurred at zero, one, three and six months and telephone contact at two, four and five months. HIV testing was performed at every clinic visit. PrEP adherence was evaluated with intracellular tenofovir diphosphate (TFV-DP) concentrations in dried blood spot (DBS) samples at months 3 and 6. The primary endpoint assessed was "PrEP adherence" defined as TFV-DP DBS concentrations ≥700 fmol/punch (equivalent to ≥4 doses of TDF/week). RESULTS: Between March 2018 and June 2019, 489 adolescents were screened at three centres in Bangkok. Twenty-seven (6%) adolescents tested positive for HIV and 200 (41%) adolescents participated in the study. Of these, 147 were YMSM (74%) and 53 YTGW (26%). At baseline, median age was 18 years (IQR 17 to 19), 66% reported inconsistent condom use in the past month. Sexually transmitted infection prevalence was 23%. Retention at six months was 73%. In the YFS + APP arm, median app use duration was three months (IQR 1 to 5). PrEP adherence at month 3 was 51% in YFS and 54% in YFS + APP (p-value 0.64) and at month 6 was 44% in YFS and 49% in YFS + APP (p-value 0.54). No HIV seroconversions occurred during 75 person years of follow-up. CONCLUSIONS: Youth-friendly PrEP services enabled good adherence among half of adolescent PrEP users. However, the mobile phone application tested did not provide additional PrEP adherence benefit in this randomized trial. Adolescent risk behaviours are dynamic and require adaptive programmes that focus on "prevention-effective adherence."

PrEP Nonadherence, White Coat Dosing, and HIV Risk Among a Cohort of MSM.

Among a cohort of men who have sex with men in a pre-exposure prophylaxis (PrEP) adherence trial, syphilis requiring treatment was associated with white coat dosing (increased PrEP adherence immediately preceding study visits) when compared with participants with optimal drug concentrations. The findings highlight the need for identifying and reducing barriers to PrEP adherence.

Assessing determinants of pre-exposure prophylaxis (PrEP) adherence among a sample of rural Midwestern men who have sex with men (MSM).

Pre-exposure prophylaxis (PrEP) efficacy in preventing HIV among gay, bisexual, and other men who have sex with men (MSM) is dependent upon adherence. Little is known about the PrEP adherence experiences among MSM who live in rural areas of the US. This qualitative study was informed by a modified version of Straussian Grounded Theory. Thirty-four 34 rural Midwestern MSM participated in telephone interviews that assessed their PrEP adherence factors. Overall, participants adhered to the PrEP regimen, ranging from missing none to a couple of doses per month. Participants had high self-efficacy (competence) and self-reliance (autonomy) in taking PrEP daily. Participants incorporated PrEP into their already existing routines. Participants were motivated to adhere to prevent HIV acquisition and be financially responsible. All participants mentioned their PrEP provider discussed the importance of adherence with PrEP's effectiveness, but future patient-provider PrEP adherence communication varied among participants. Future PrEP adherence interventions should address counseling strategies that leverage these constructs to support pill taking. Future research should explore patient-provider conversations surrounding PrEP adherence to inform provider- and patient-level interventions.