My Way: development and preliminary evaluation of a novel delivery system for PrEP and other sexual health needs of young women in Western Kenya.

INTRODUCTION: Young women in sub-Saharan Africa are a priority population for HIV prevention, yet challenges with adherence and persistence to HIV pre-exposure prophylaxis (PrEP) are common. This study involved the development and pilot testing of My Way-a novel delivery system for PrEP and co-packaged sexual health services. METHODS: My Way was developed in Kisumu, Kenya through a user-centred design process (2020). The intervention involves peer-delivery and support for HIV testing and PrEP use, self-collected vaginal swabs for sexually transmitted infection (STI) testing, pregnancy testing, oral contraceptive pills, self-injectable medroxyprogesterone and/or condoms. My Way was assessed among 16- to 24-year-old sexually active women in a randomized controlled trial versus standard of care (SoC; 2021-2022). Use of PrEP and other sexual health services were tracked at 1, 3 and 6 months for feasibility. Acceptability was determined by questionnaire. The effect of the intervention on tenofovir diphosphate (TFV-DP) levels was assessed by chi-square test (primary outcome); other predictors were explored with regression analysis. RESULTS: Among 150 women, the median age was 22 years and the median number of sexual partners was 2. Moderate/severe depression was common (60%). In the intervention arm, peers made 88% (198/225) of possible kit deliveries (177 with PrEP) and 49 STIs were diagnosed. In the SoC arm, 24% (55/225) of expected clinic visits occurred (53 with PrEP); no STI testing was performed. TVF-DP was detected in 16 participants at 6 months: 16% (12/75) in the intervention arm versus 5% (4/75) in the SoC arm (p = 0.03). Persistence among those with ongoing HIV prevention needs (i.e. prevention-effective persistence) was 18% (12/67) versus 7% (4/56; p = 0.08). No women acquired HIV. The intervention was significantly associated with detectable TFV-DP (OR 3.5, 1.1-11.4; p = 0.04); moderate/severe depression trended towards an association with TFV-DP (OR 0.2, 0.03-1.6; p = 0.13). CONCLUSIONS: My Way is a promising delivery system for PrEP and other sexual health services among young women in Western Kenya. We found high feasibility and acceptability. PrEP use was modest, but higher with My Way compared to SoC. Long-acting PrEP formulations may overcome important barriers to PrEP use and should be explored in combination with the My Way delivery model.

Electronic Antiretroviral Therapy Adherence Monitors and Associated Interventions Improve Adolescent-Caregiver Relationships and Self-Efficacy Among Adolescents and Young Adults with HIV in Uganda.

Many adolescents and young adults with HIV (AYWH) struggle with antiretroviral therapy (ART) adherence and experience poorer outcomes than adults. Relevant factors include forgetfulness and poor self-efficacy related to their evolving neurobiology. We qualitatively explored experiences of AYWH-caregivers dyads using real-time ART adherence monitors and associated reminder functions in the home setting. As part of an implementation science-oriented study, AYWH used the Wisepill adherence monitor for 3 months. AYWH could also opt for short message service (SMS) self-reminders, a self-selected social supporter for delayed or missed doses, or an alarm reminder. We conducted in-depth interviews with randomly selected AYWH-caregiver dyads regarding their experience using the monitor. Qualitative data were analyzed using inductive content analysis. We completed 15 AYWH-caregiver dyad interviews. Of the AYWH, 67% were female, mean age was 16 years, 56% lived with their biological mother, and 86% were virologically suppressed. AYWH and their caregivers generally found the adherence monitors acceptable, though some had privacy concerns. AYWH felt the monitors helped them take charge of their medication, largely through the real-time alarm and SMS reminders; this took the burden of adherence reminders away from the caregivers, improving strained AYWH-caregiver relationships. Two adolescents reported rebound poor adherence after monitor withdrawal. ART adherence monitors and associated tools were largely acceptable to AYWH and their caregivers in home settings. The intervention helped improve AYWH self-efficacy and alleviated burden from some AYWH-caregiver relationships. Rebound poor adherence suggests the need for on-going support and/or other means to achieve intrinsic mechanisms for sustained adherence. Clinical Trial Registration number: NCT03825952.

"Yes, I'm reminded, but it doesn't mean I'm taking them": Experiences with Short Message Service Reminder Use in Real-time Monitoring of HIV PrEP among Young Women in Kenya.

Adherence to oral pre-exposure prophylaxis (PrEP) is challenging, and cellular technology offers a promising opportunity for support. However, a recent randomized controlled trial found that SMS reminders did not improve PrEP adherence. We used qualitative methods to explore the trial participants' experiences with the SMS intervention. We conducted serial in-depth interviews with 54 young Kenyan women, using inductive and deductive content analysis . Initially, SMS reminders were highly acceptable. Participants expressed enthusiasm with receiving the reminders because of the coded nature of the SMS reminders; they also helped in 'habit forming' with daily adherence. However, overtime, participants reported growing concerns about privacy, self-efficacy, and responsibility and SMS fatigue. Participants also reported other challenges, including phone loss, poor telephone network, and lack of electricity. Further research to explore if SMS reminders in alternative formats or with different frequency is needed, in addition to identification of alternate adherence support strategies.

Multi-level Factors Driving Pre-exposure Prophylaxis Non-initiation Among Young Women at High Risk for HIV in Kenya.

Few studies have focused on understanding pre-exposure prophylaxis (PrEP) non-initiation among young, high-risk women in sub-Saharan Africa. This study aimed to qualitatively explore why young women in Kenya at high-risk for HIV chose not to enroll in a PrEP adherence trial. We performed 40 semi-structured interviews with young high-risk women assessing concerns about PrEP and/or study participation. We also assessed community-level factors influencing decision-making around PrEP through 10 focus groups involving peers, young men, caregivers, and community leaders. Our qualitative data reflect the complexity of navigating barriers preventing PrEP initiation in settings where taking PrEP may be perceived as immoral behavior. Framed within the context of risk perception, the decision to start PrEP may run counter to the potential risk of losing support from one's community. Our findings suggest that approaches addressing social norms, while de-medicalizing HIV prevention services, are needed to further increase PrEP uptake among young Kenyan women.

Implementation of Electronic Adherence Monitors and Associated Interventions for Routine HIV Antiretroviral Therapy in Uganda: Promising Findings.

Background: High, sustained adherence is critical for achieving the individual and public health benefits of HIV antiretroviral therapy (ART). Electronic monitors provide detailed adherence information and can enable real-time interventions; however, their use to date has largely been confined to research. This pilot study (NCT03825952) sought to understand feasibility and acceptability a relatively low-cost version of this technology and associated interventions for routine ART delivery in sub-Saharan Africa. Methods: We provided two ART clinics in rural, southwestern Uganda with electronic adherence monitors for data-informed counseling as well as optional SMS messages to clients and/or social supporters (daily or triggered by missed or delayed doses) and/or an alarm. Clinic and ART client experiences were observed for 3 months per client, including time and motion studies. Qualitative interviews among clients, clinicians, and healthcare administrators were informed by the Consolidated Framework for Implementation Research. Results: Fifty-one ART clients were enrolled; 57% were male and the median age was 34 years. Choice of associated intervention varied among participants. The median number of visits during follow-up was two per client. Counselors reviewed the adherence data with 90% of clients at least once; 67% reviewed data at all visits. Average adherence was 94%; four clients had adherence gaps >1 week. Acceptability was high; all but one client found the monitor "very useful" and all found SMS "very useful." Clinic visits among clients with the intervention lasted 4 min longer on average than those in standard care. The monitors and daily SMS generally functioned well, although excess SMS were triggered, primarily due to cellular network delays. Overall, participants felt the technology improved adherence, clinic experiences, and clinician-client relationships. Few worried about stigma and privacy. Cost was a concern for implementation, particularly at scale. Conclusion: We successfully implemented a relatively low-cost electronic ART adherence monitor and associated interventions for routine care in rural Uganda. Feasibility and acceptability were generally high, and individuals were identified who could benefit from adherence support. Future work should involve longitudinal follow-up of diverse populations, clinical outcomes, and detailed cost-effectiveness analysis to help drive policy decisions around the uptake of this technology for routine clinical care. Clinical Trial Registration: identifier: NCT03825952.

Understanding Pre-Exposure Prophylaxis Adherence in Young Women in Kenya.

OBJECTIVE: To present detailed analyses of long-term pre-exposure prophylaxis (PrEP) use and associated behaviors and perceptions among young Kenyan women. DESIGN: Prospective, observational cohort. METHODS: The Monitoring PrEP among Young Adult women Study involved 18 to 24-year-old women at high HIV risk initiating PrEP in Kisumu and Thika, Kenya. Visits for PrEP counseling and dispensing, HIV testing, and socio-behavioral data collection occurred at Month 1 and quarterly for 2 years. PrEP adherence was measured with pharmacy refill and real-time electronic monitoring, plus tenofovir diphosphate levels in 15% of participants. HIV risk behavior and perception were assessed by self-report in weekly short message service surveys from Months 6-24. Predictors of adherence were assessed with multivariable logistic regression analysis. RESULTS: Three hundred forty-eight women (median age 21, VOICE risk score 7) were followed for 617 person-years. Pharmacy refills steadily declined from 100% (Month 0-1) to 54% (Months 22-24). Average electronically monitored adherence similarly declined from 65% (Month 0-1) to 15% (Months 22-24). Electronically monitored adherence had moderately high concordance with tenofovir diphosphate levels (67%). High average adherence (5+ doses/week) was seen at 385/1898 (20%) participant-visits and associated with low baseline VOICE risk score, >1 current sexual partner, ≤1-hour travel time to clinic, and the Kisumu site. short message service-reported behavior and risk perception were not associated with adherence. Four women acquired HIV (incidence 0.7/100 person-years). CONCLUSIONS: PrEP adherence was modest and declined over time. HIV risk was inconsistently associated with adherence; clinic access and site-level factors were also relevant. Relatively low HIV incidence suggests participants may have achieved protection through multiple strategies.

Pre-exposure Prophylaxis Uptake, Adherence, and Persistence: A Narrative Review of Interventions in the U.S.

Since 2012, HIV pre-exposure prophylaxis (PrEP) has been available to prevent HIV transmission; yet, uptake, adherence, and persistence to PrEP have been suboptimal. This narrative review examines the latest interventions and programs to improve all 3 stages of PrEP adherence and reviews ongoing studies to promote effective PrEP use. From 2017 to 2020, a total of 20 studies analyzed different individual- and structural-level approaches to increase PrEP adherence, including behavior change interventions, technology-based interventions (e.g., short message service messages and mobile applications), and alternate delivery strategies (e.g., pharmacy-based PrEP, integration with other services, and home delivery). Most published interventions involved men who have sex with men, although 3 assessed women (2 transgender, 1 cisgender). Randomized, controlled data support 3 behavioral change interventions and 1 technology-based intervention. Alternate delivery strategies seem promising, although more robust study designs are generally needed. In addition, data on the alignment of ongoing HIV risk and PrEP persistence (i.e., prevention-effective adherence) were limited. The authors also identified 20 ongoing studies that are promoting PrEP adherence. Future work should be inclusive of all at-risk groups in the U.S., including African American and Latinx heterosexual populations and people who inject drugs. Proven and promising approaches may work well in combination and may also need to be adapted with the introduction of long-acting pre-exposure prophylaxis formulations. Collectively, this body of work indicates considerable progress toward understanding the role PrEP adherence will play in Ending the HIV Epidemic in the U.S. that will be bolstered by the outcomes of ongoing trials.

Effect of SMS reminders on PrEP adherence in young Kenyan women (MPYA study): a randomised controlled trial.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is highly effective for preventing HIV acquisition. However, adherence among young women (aged 18-24 years) has been challenging. SMS reminders have been shown to improve adherence to antiretroviral therapy in some contexts, including in combination with real-time adherence monitoring. We aimed to determine the effect of SMS reminders on PrEP adherence among young women in Kenya over a 2-year period. METHODS: The monitoring PrEP among young adult women (MPYA) study was an open label randomised controlled trial involving young adult women at high risk of HIV in Thika and Kisumu, Kenya. Participants were recruited from colleges, vocational institutions, informal settlements, and community-based organisations supporting young women. Women had to be aged 18-24 years and at high risk of HIV acquisition (defined as a VOICE risk score of 5 or higher, or being in a serodiscordant relationship). Study staff randomly assigned participants (1:1) to receive either SMS reminders (SMS reminder group) or no reminders (no SMS reminder group). Study group assignment was known to trial staff but masked to investigators. Reminders were initially sent daily and participants could switch to as-needed reminders (ie, sent only if they missed opening the monitor as expected) after 1 month. Study visits occurred at 1 month, 3 months, and then quarterly (ie, every 3 months). The primary outcome was PrEP adherence over 24 months measured with a real-time electronic monitor and assessed by negative binomial models adjusted for the study site and quarter among participants who collected PrEP. This trial is registered with ClinicalTrials.gov, NCT02915367. FINDINGS: Of 642 women initially approached, 348 eligible women were enrolled between Dec 21, 2016, and Feb 5, 2018. Participants were randomly assigned to either the SMS reminder group (n=173) or the no SMS reminder group (n=175). The median age was 21 years (IQR 19-22) and 228 (66%) of the 348 participants reported condomless sex in the month before baseline. 24 (14%) of the 173 participants assigned to receive daily SMS reminders later opted for as-needed reminders. 69 291 (97%) of 71 791 SMS reminders were sent as planned. Among participants collecting PrEP (thus potentially suggesting a desire for HIV protection), electronically monitored adherence averaged 26·8% over 24 months and was similar by study group (27·0% with SMS, 26·6% without SMS, adjusted incidence rate ratio 1·16 [95% CI 0·93-1·45], p=0·19). There were no serious adverse events related to trial participation; five social harms occurred in each study group, primarily related to PrEP use. INTERPRETATION: SMS reminders were ineffective in promoting PrEP adherence among young Kenyan women. Given the overall low adherence in the trial, additional interventions are needed to support PrEP use in this population. FUNDING: US National Institute of Mental Health.

Dynamic Perceived HIV Risk and Sexual Behaviors Among Young Women Enrolled in a PrEP Trial in Kenya: A Qualitative Study.

Background: In Kenya and elsewhere in sub-Saharan Africa, young women are disproportionately affected by the HIV epidemic compared to young men. The extent to which young women's self-perceptions about risk of HIV acquisition influence their sexual behaviors and use of HIV prevention methods remains unclear. We therefore conducted a qualitative study to explore these issues among young women enrolled in a pre-exposure prophylaxis (PrEP) trial. Methods: From January 2017 to January 2020, we conducted serial semi-structured in-depth interviews 50 purposively selected young women (18-24 years old) who were participating in the MPYA (Monitoring PrEP for Young Adult women) study-a randomized controlled trial in Thika and Kisumu, Kenya, assessing the impact of SMS reminders on PrEP adherence. Interviews were conducted at three time points (~1 week, 3, and 12 months after initiating PrEP). We used an inductive, content analytic approach to identify key themes related to risk perceptions, sexual behavior, and use of HIV prevention tools. Results: Around the time of enrollment, most of the 50 women interviewed reported being at high risk of HIV because of their own sexual behaviors, such as inconsistent condom use, multiple sexual partners, and transactional sex. Additionally, high risk perception was based on the behavior of their partners, such as refusing to use condoms and being unsure of their partner's HIV status. Young women's perceived risk of HIV acquisition was a key motivator for PrEP initiation and continuation. During PrEP use, participants reported feeling protected and at less risk compared to peers who were not taking PrEP. Some reported no longer using condoms because they were confident that PrEP provided enough protection. Over time, many young women reported reducing risky sexual behaviors because of the regular counseling and HIV testing they received as part of their PrEP services. This lowered risk perception was in most cases accompanied by discontinuation of PrEP. Conclusions: HIV risk perception among young women in Kenya was dynamic and influenced their use of PrEP and condoms over time, suggesting an often-deliberate approach to HIV prevention and sexual health.

Factors Affecting the Implementation of Electronic Antiretroviral Therapy Adherence Monitoring and Associated Interventions for Routine HIV Care in Uganda: Qualitative Study.

BACKGROUND: High, sustained adherence to HIV antiretroviral therapy (ART) is critical for achieving viral suppression, which in turn leads to important individual health benefits and reduced secondary viral transmission. Electronic adherence monitors record a date-and-time stamp with each opening as a proxy for pill-taking behavior. These monitors can be combined with interventions (eg, data-informed adherence counseling, SMS-based adherence support, and/or alarms) and have been shown to improve adherence in multiple settings. Their use, however, has largely been limited to the research context. OBJECTIVE: The goal of the research was to use the Consolidated Framework for Implementation Research (CFIR) to understand factors relevant for implementing a low-cost electronic adherence monitor and associated interventions for routine HIV clinical care in Uganda. METHODS: We conducted in-depth qualitative interviews with health care administrators, clinicians, and ART clients about likes and dislikes of the features and functions of electronic adherence monitors and associated interventions, their potential to influence HIV care, suggestions on how to measure their value, and recommendations for their use in routine care. We used an inductive, content analysis approach to understand participant perspectives, identifying aspects of CFIR most relevant to technology implementation in this setting. RESULTS: We interviewed 34 health care administrators/clinicians and 15 ART clients. Participants largely saw the monitors and associated interventions as favorable and beneficial for supporting adherence and improving clinical outcomes through efficient, differentiated care. Relevant outside factors included structural determinants of health, international norms around supporting adherence, and limited funding that necessitates careful assessment of costs and benefits. Within the clinic, the adherence data were felt likely to improve the quality of counseling and thereby morale, as well as increase the efficiency of care delivery. Existing infrastructure and care expenditures and the need for proper training were other noted considerations. At the individual level, the desire for good health and a welcomed pressure to adhere favored uptake of the monitors, although some participants were concerned with clients not using the monitors as planned and the influence of poverty, stigma, and need for privacy. Finally, participants felt that decisions around the implementation process would have to come from the Ministry of Health and other funders and would be influenced by sustainability of the technology and the target population for its use. Coordination across the health care system would be important for implementation. CONCLUSIONS: Low-cost electronic adherence monitoring combined with data-informed counseling, SMS-based support, and/or alarms have potential for use in routine HIV care in Uganda. Key metrics of successful implementation will include their impact on efficiency of care delivery and clinical outcomes with careful attention paid to factors such as stigma and cost. Further theory-driven implementation science efforts will be needed to move promising technology from research into clinical care. TRIAL REGISTRATION: ClinicalTrials.gov NCT03825952; https://clinicaltrials.gov/ct2/show/NCT03825952.

Technological methods to measure adherence to antiretroviral therapy and preexposure prophylaxis.

PURPOSE OF REVIEW: The WHO's Consolidated Guidelines (2016) call for research on improved methods to proactively monitor adherence and identify those individuals who have the greatest needs for adherence support. This review aims to elucidate the latest technologies available to measure adherence to HIV antiretroviral therapy and preexposure prophylaxis against HIV infection and present their utility in various settings and populations. RECENT FINDINGS: Within the last few years, advances have been made in the features of existing technology to measure adherence (real-time electronic adherence measurements), additional approaches have been developed (digital medicine systems) and improved (short message service surveys), and point of care testing for pharmacokinetic measures are under development. SUMMARY: Technology advances in adherence measurement are promising for improved accuracy and, in some cases, the ability to intervene with adherence challenges in real time. This progress will greatly further our understanding of adherence behavior, as well as the ability to effectively link interventions with individuals who need them, thus maximizing the clinical and public health benefits of both antiretroviral therapy and preexposure prophylaxis.

Mortality in the First 3 Months on Antiretroviral Therapy Among HIV-Positive Adults in Low- and Middle-income Countries: A Meta-analysis.

Previous meta-analyses reported mortality estimates of 12-month post-antiretroviral therapy (ART) initiation; however, 40%-60% of deaths occur in the first 3 months on ART, a more sensitive measure of averted deaths through early ART initiation. To determine whether early mortality is dropping as treatment thresholds have increased, we reviewed studies of 3 months on ART initiation in low- to middle-income countries. Studies of 3-month mortality from January 2003 to April 2016 were searched in 5 databases. Articles were included that reported 3-month mortality from a low- to middle-income country; nontrial setting and participants were ≥15. We assessed overall mortality and stratified by year using random effects models. Among 58 included studies, although not significant, pooled estimates show a decline in mortality when comparing studies whose enrollment of patients ended before 2010 (7.0%; 95% CI: 6.0 to 8.0) with the studies during or after 2010 (4.0%; 95% CI: 3.0 to 5.0). To continue to reduce early HIV-related mortality at the population level, intensified efforts to increase demand for ART through active testing and facilitated referral should be a priority. Continued financial investments by multinational partners and the implementation of creative interventions to mitigate multidimensional complex barriers of accessing care and treatment for HIV are needed.

A meta-analysis assessing all-cause mortality in HIV-exposed uninfected compared with HIV-unexposed uninfected infants and children.

OBJECTIVE: Conduct a meta-analysis examining differential all-cause mortality rates between HIV-exposed uninfected (HEU) infants and children as compared with their HIV-unexposed uninfected (HUU) counterparts. DESIGN: Meta-analysis summarizing the difference in mortality between HEU and HUU infants and children. Reviewed studies comparing children in the two groups for all-cause mortality, in any setting, from 1994 to 2016 from six databases. METHODS: Meta-analyses were done estimating overall mortality comparing the two groups, stratified by duration of follow-up time from birth (0-12, 12-24 and >24 months) and by year enrollment ended in each study: less than 2002 compared with at least 2002, when single-dose nevirapine for prevention of mother-to-child transmission (PMTCT) commenced in low-income and middle-income countries. RESULTS: Included 22 studies, for a total of 29 212 study participants [n = 8840 (30.3%) HEU; n = 20 372 (37.7%) HUU]. Random effects models showed HEU had a more than 70% increased risk of mortality vs. HUU. Stratifying by age showed that HEU vs. HUU had a significant 60-70% increased risk of death at every age strata. There was a significant 70% increase in the risk of mortality between groups before the implementation of PMTCT, which remained after 2002 [risk ratio: 1.46; 95% confidence interval (CI): 1.14-1.87], when the availability of PMTCT services was widespread, suggesting that prenatal antiretroviral therapy, and healthier mothers, does not fully eliminate this increased risk in mortality. CONCLUSION: We show a consistent increase risk of mortality for HEU vs. HUU infants and children. Longitudinal research is needed to elucidate underlying mechanisms, such as maternal and infant health status and breast feeding practices, which may help explain these differences in mortality.