Antiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce ...the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings.
Between November 5, 2012, and January 5, 2015, we enrolled and followed 1,013 heterosexual HIV-1-serodiscordant couples in Kenya and Uganda in a prospective implementation study. ART and PrEP were offered through a pragmatic strategy, with ART promoted for all couples and PrEP offered until 6 mo after ART initiation by the HIV-1 infected partner, permitting time to achieve virologic suppression. One thousand thirteen couples were enrolled, 78% of partnerships initiated ART, and 97% used PrEP, during a median follow-up of 0.9 years. Objective measures of adherence to both prevention strategies demonstrated high use (≥85%). Given the low HIV-1 incidence observed in the study, an additional analysis was added to compare observed incidence to incidence estimated under a simulated counterfactual model constructed using data from a prior prospective study of HIV-1-serodiscordant couples. Counterfactual simulations predicted 39.7 HIV-1 infections would be expected in the population at an incidence of 5.2 per 100 person-years (95% CI 3.7-6.9). However, only two incident HIV-1 infections were observed, at an incidence of 0.2 per 100 person-years (95% CI 0.0-0.9, p < 0.0001 versus predicted). The use of a non-concurrent comparison of HIV-1 incidence is a potential limitation of this approach; however, it would not have been ethical to enroll a contemporaneous population not provided access to ART and PrEP.
Integrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of <0.5% per year compared to an expected incidence of >5% per year.
BACKGROUND:For HIV-serodiscordant couples, integrated delivery of antiretroviral therapy (ART) for HIV-positive partners and time-limited pre-exposure prophylaxis (PrEP) for negative partners ...virtually eliminates HIV transmission. Standardized messaging, sensitive to the barriers and motivators to HIV treatment and prevention, is needed for widespread scale-up of this approach.
METHODS:Within the Partners Demonstration Project, a prospective interventional project among 1013 serodiscordant couples in Kenya and Uganda, we offered ART to eligible HIV-positive partners and PrEP to HIV-negative partners before ART initiation and through the HIV-positive partnerʼs first 6 months of ART use. We conducted individual and group discussions with counseling staff to elicit the health communication framework and key messages about ART and PrEP that were delivered to couples.
RESULTS:Counseling sessions for serodiscordant couples about PrEP and ART included discussions of HIV serodiscordance, PrEP and ART initiation and integrated use, and PrEP discontinuation. ART messages emphasized daily, lifelong use for treatment and prevention, adherence, viral suppression, resistance, side effects, and safety of ART during pregnancy. PrEP messages emphasized daily dosing, time-limited PrEP use until the HIV-positive partner sustained 6 months of high adherence to ART, adherence, safety during conception, side effects, and other risks for HIV.
CONCLUSIONS:Counseling messages for HIV-serodiscordant couples are integral to the delivery of time-limited PrEP as a “bridge” to ART-driven viral suppression. Their incorporation into programmatic scale-up will maximize intervention impact on the global epidemic.
: Pre-exposure prophylaxis (PrEP) can provide high protection against HIV infection and is a recommended intervention for HIV-negative persons with substantial HIV risk. Demonstration projects ...conducted in diverse settings worldwide illustrate practical examples of how PrEP can be delivered. This manuscript presents estimates of effectiveness and patterns of PrEP use within a two-year demonstration project of PrEP for HIV-negative members of heterosexual HIV serodiscordant couples in East Africa.
: The PrEP delivery model integrated PrEP into HIV treatment services, prioritizing PrEP use for HIV-negative partners within serodiscordant couples before and during the first 6 months after the partner living with HIV initiated antiretroviral therapy (ART). We measured PrEP uptake through pharmacy records and adherence to PrEP through medication event monitoring system (MEMS) bottle caps and quantification of tenofovir in plasma among a random sample of participants. We estimated HIV infections prevented using a counterfactual cohort simulated from the placebo arm of a previous PrEP clinical trial.
: We enrolled 1,010 HIV serodiscordant couples that were naïve to ART and PrEP. Ninety-seven percent of HIV-negative partners initiated PrEP. Objective measures suggest high adherence: 71% of HIV-negative participants took ≥80% of expected doses, as recorded via MEMS, and 81% of plasma samples had tenofovir detected. Four incident HIV infections were observed (incidence rate=0.24 per 100 person-years), a 95% reduction (95% CI 86-98%, p<0.0001) in HIV incidence, relative to estimated HIV incidence for the population in the absence of PrEP integrated into HIV treatment services.
: PrEP uptake and adherence were high and incident HIV was rare in this PrEP demonstration project for African HIV-negative individuals whose partners were known to be living with HIV. Delivery of PrEP to HIV-negative partners within HIV serodiscordant couples was feasible and should be prioritized for wide-scale implementation.
COVID-19-related lockdowns and other public health measures may have differentially affected the quality of life (QOL) of older people with and without human immunodeficiency virus (HIV) in rural ...Uganda.
The Quality of Life and Aging with HIV in Rural Uganda study enrolled people with and without HIV aged over 49 from October 2020 to October 2021. We collected data on COVID-19-related stressors (behavior changes, concerns, interruptions in health care, income, and food) and the participants' QOL. We used linear regression to estimate the associations between COVID-19-related stressors and QOL, adjusting for demographic characteristics, mental and physical health, and time before vs after the lockdown during the second COVID-19 wave in Uganda. Interaction between HIV and COVID-19-related stressors evaluated effect modification.
We analyzed complete data from 562 participants. Mean age was 58 (standard deviation (SD) = 7); 265 (47%) participants were female, 386 (69%) were married, 279 (50%) had HIV, and 400 (71%) were farmers. Those making ≥5 COVID-19-related behavior changes compared to those making ≤2 had worse general QOL (estimated linear regression coefficient (b) = - 4.77; 95% confidence interval (CI) = -6.61, -2.94) and health-related QOL (b = -4.60; 95% CI = -8.69, -0.51). Having access to sufficient food after the start of the COVID-19 pandemic (b = 3.10, 95% CI = 1.54, 4.66) and being interviewed after the start of the second lockdown (b = 2.79, 95% CI = 1.30, 4.28) were associated with better general QOL. Having HIV was associated with better health-related QOL (b = 5.67, 95% CI = 2.91,8.42). HIV was not associated with, nor did it modify the association of COVID-19-related stressors with general QOL.
In the context of the COVID-19 pandemic in an HIV-endemic, low-resource setting, there was reduced QOL among older Ugandans making multiple COVID-19 related behavioral changes. Nonetheless, good QOL during the second COVID-19 wave may suggest resilience among older Ugandans.
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.
Introduction
: Pre-exposure prophylaxis (PrEP) can provide high protection against HIV infection and is a recommended intervention for HIV-negative persons with substantial HIV risk, such as ...individuals with a partner living with HIV. Demonstration projects of PrEP have been conducted in diverse settings worldwide to illustrate practical examples of how PrEP can be delivered.
Methods
: We evaluated delivery of PrEP for HIV-negative partners within heterosexual HIV serodiscordant couples in an open-label demonstration project in East Africa. The delivery model integrated PrEP into HIV treatment services, prioritizing PrEP for HIV-negative partners within serodiscordant couples prior to and during the first 6 months after the partner living with HIV initiated antiretroviral therapy (ART). We measured adherence to PrEP through medication event monitoring system (MEMS) bottle caps and quantification of tenofovir in plasma among a random sample of participants. We estimated HIV infections prevented using a counterfactual cohort simulated from the placebo arm of a previous PrEP clinical trial.
Results
: We enrolled 1,010 HIV serodiscordant couples that were naïve to ART and PrEP. Ninety-seven percent (97%) of HIV-negative partners initiated PrEP, and when PrEP was dispensed, objective measures suggest high adherence: 71% of HIV-negative participants took ≥80% of expected doses, as recorded via MEMS, and 81% of plasma samples had tenofovir detected. A total of 4 incident HIV infections were observed (incidence rate=0.24 per 100 person-years), a 95% reduction (95% CI 86-98%, p<0.0001) in HIV incidence, relative to estimated HIV incidence for the population in the absence of PrEP integrated into HIV treatment services.
Conclusions
: PrEP uptake and adherence were high and incident HIV was rare in this PrEP demonstration project for African HIV-negative individuals whose partners were known to be living with HIV. Delivery of PrEP to HIV-negative partners within HIV serodiscordant couples was feasible and should be prioritized for wide-scale implementation.
For HIV-1 serodiscordant couples, HIV-1 exposure and risk of transmission is heightened during pregnancy attempts, but safer conception strategies can reduce risk. As safer conception programs are ...scaled up, understanding couples' preferences and experiences can be useful for programmatic recommendations. We followed 1013 high-risk, heterosexual HIV-1 serodiscordant couples from Kenya and Uganda for two years in an open-label delivery study of integrated pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART), the Partners Demonstration Project. We used descriptive statistics to describe the cohort and multivariate logistic regression to characterize women who reported use of a safer conception strategy by their first annual visit. 66% (569/859) of women in the study were HIV-infected and 73% (627/859) desired children in the future. At the first annual visit, 59% of women recognized PrEP, 58% ART, 50% timed condomless sex, 23% self-insemination, and fewer than 10% recognized male circumcision, STI treatment, artificial insemination, and sperm washing as safer conception strategies. Among those recognizing these strategies and desiring pregnancy, 37% reported using PrEP, 14% ART, and 30% timed condomless sex. Women who reported discussing their fertility desires with their male partners were more likely to report having used at least one strategy for safer conception (adjusted odds ratio = 1.91, 95% confidence interval:1.26-2.89). Recognition of use of safer conception strategies among women who expressed fertility desires was low, with ARV-based strategies and self-insemination the more commonly recognized and used strategies. Programs supporting HIV-1 serodiscordant couples can provide opportunities for couples to talk about their fertility desires and foster communication around safer conception practices.
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.
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.
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.
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.
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.
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.
ClinicalTrials.gov NCT03825952; https://clinicaltrials.gov/ct2/show/NCT03825952.
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