Urine tenofovir testing for real-time PrEP adherence feedback: a qualitative study involving transgender women in Uganda.

INTRODUCTION: Adherence counselling with point-of-care (POC) drug-level feedback using a novel tenofovir assay may support pre-exposure prophylaxis (PrEP) adherence; however, perceptions of urine testing and its impact on adherence are not well studied. We qualitatively examined how POC tenofovir testing was experienced by transgender women (TGW) in Uganda. METHODS: Within a cluster randomized trial of peer-delivered HIV self-testing, self-sampling for sexually transmitted infections and PrEP among HIV-negative TGW showing overall low PrEP prevention-effective adherence (NCT04328025), we conducted a nested qualitative sub-study of the urine POC assay among a random sample of 30 TGW (August 2021-February 2022). TGW interviews explored: (1) experiences with POC urine tenofovir testing and (2) perceptions of PrEP adherence counselling with drug-level feedback. We used an inductive content analytic approach for analysis. RESULTS: Median age was 21 years (interquartile range 20-24), and 70% engaged in sex work. Four content categories describe how TGW experienced POC urine tenofovir testing: (1) Urine tenofovir testing was initially met with scepticism: Testing urine to detect PrEP initially induced anxiety, with some perceptions of being intrusive and unwarranted. With counselling, however, participants found POC testing acceptable and beneficial. (2) Alignment of urine test results and adherence behaviours: Drug-level feedback aligned with what TGW knew about their adherence. Concurrence between pill taking and tenofovir detection in urine reinforced confidence in test accuracy. (3) Interpretation of urine tenofovir results: TGW familiar with the interpretation of oral-fluid HIV self-tests knew that two lines on the test device signified positivity (presence of HIV). However, two lines on the urine test strip indicated a positive result for non-adherence (absence of tenofovir), causing confusion. Research nurses explained the difference in test interpretation to participants' satisfaction. (4) White coat dosing: Some TGW deliberately chose not to attend scheduled clinic appointments to avoid detecting their PrEP non-adherence during urine testing. They restarted PrEP before returning to clinic, a behaviour called "white coat dosing." CONCLUSIONS: Incorporating POC urine testing into routine PrEP adherence counselling was acceptable and potentially beneficial for TGW but required attention to context. Additional research is needed to identify effective strategies for optimizing adherence monitoring and counselling for this population.

Barriers to engagement in the care cascade for tuberculosis disease in India: A systematic review of quantitative studies.

BACKGROUND: India accounts for about one-quarter of people contracting tuberculosis (TB) disease annually and nearly one-third of TB deaths globally. Many Indians do not navigate all care cascade stages to receive TB treatment and achieve recurrence-free survival. Guided by a population/exposure/comparison/outcomes (PECO) framework, we report findings of a systematic review to identify factors contributing to unfavorable outcomes across each care cascade gap for TB disease in India. METHODS AND FINDINGS: We defined care cascade gaps as comprising people with confirmed or presumptive TB who did not: start the TB diagnostic workup (Gap 1), complete the workup (Gap 2), start treatment (Gap 3), achieve treatment success (Gap 4), or achieve TB recurrence-free survival (Gap 5). Three systematic searches of PubMed, Embase, and Web of Science from January 1, 2000 to August 14, 2023 were conducted. We identified articles evaluating factors associated with unfavorable outcomes for each gap (reported as adjusted odds, relative risk, or hazard ratios) and, among people experiencing unfavorable outcomes, reasons for these outcomes (reported as proportions), with specific quality or risk of bias criteria for each gap. Findings were organized into person-, family-, and society-, or health system-related factors, using a social-ecological framework. Factors associated with unfavorable outcomes across multiple cascade stages included: male sex, older age, poverty-related factors, lower symptom severity or duration, undernutrition, alcohol use, smoking, and distrust of (or dissatisfaction with) health services. People previously treated for TB were more likely to seek care and engage in the diagnostic workup (Gaps 1 and 2) but more likely to suffer pretreatment loss to follow-up (Gap 3) and unfavorable treatment outcomes (Gap 4), especially those who were lost to follow-up during their prior treatment. For individual care cascade gaps, multiple studies highlighted lack of TB knowledge and structural barriers (e.g., transportation challenges) as contributing to lack of care-seeking for TB symptoms (Gap 1, 14 studies); lack of access to diagnostics (e.g., X-ray), non-identification of eligible people for testing, and failure of providers to communicate concern for TB as contributing to non-completion of the diagnostic workup (Gap 2, 17 studies); stigma, poor recording of patient contact information by providers, and early death from diagnostic delays as contributing to pretreatment loss to follow-up (Gap 3, 15 studies); and lack of TB knowledge, stigma, depression, and medication adverse effects as contributing to unfavorable treatment outcomes (Gap 4, 86 studies). Medication nonadherence contributed to unfavorable treatment outcomes (Gap 4) and TB recurrence (Gap 5, 14 studies). Limitations include lack of meta-analyses due to the heterogeneity of findings and limited generalizability to some Indian regions, given the country's diverse population. CONCLUSIONS: This systematic review illuminates common patterns of risk that shape outcomes for Indians with TB, while highlighting knowledge gaps-particularly regarding TB care for children or in the private sector-to guide future research. Findings may inform targeting of support services to people with TB who have higher risk of poor outcomes and inform multicomponent interventions to close gaps in the care cascade.

Oral PrEP uptake, adherence, and persistence during periconception periods among women in South Africa: an intervention study.

OBJECTIVE: We developed the Healthy Families-PrEP intervention to support HIV-prevention during periconception and pregnancy. We evaluated preexposure prophylaxis (PrEP) use with three objective measures. DESIGN: This single-arm intervention study enrolled women in KwaZulu-Natal, South Africa, who were HIV-uninfected, not pregnant, in a relationship with a partner with HIV or unknown-serostatus, and with pregnancy plans. PrEP was offered as part of a comprehensive HIV prevention intervention. Participants were followed for 12 months. METHODS: We evaluated periconception PrEP uptake and adherence using quarterly plasma tenofovir concentrations. We modeled factors associated with PrEP uptake and high plasma tenofovir (past day dosing). Patterns of use were analyzed using electronic pillcap data. Dried blood spots to measure intracellular tenofovir product (past 2 months dosing) were analyzed for a subset of women. RESULTS: Three hundred thirty women with median age 24 (IQR: 22-27) years enrolled. Partner HIV-serostatus was unknown by 96% ( N = 316); 60% (195) initiated PrEP. High plasma tenofovir concentrations were seen in 35, 25, 22, and 20% of samples at 3, 6, 9, and 12 months, respectively. Similar adherence was measured by pillcap and dried blood spots. In adjusted models, lower income, alcohol use, and higher HIV stigma were associated with high plasma tenofovir. Eleven HIV-seroconversions were observed (incidence rate: 4.04/100 person-years [95% confidence interval: 2.24-7.30]). None had detectable plasma tenofovir. CONCLUSION: The Healthy Families-PrEP intervention supported women in PrEP use. We observed high interest in periconception PrEP and over one-third adhered to PrEP in the first quarter; one-fifth were adherent over a year. High HIV incidence highlights the importance of strategies to reduce HIV incidence among periconception women. CLINICAL TRIAL NUMBER: NCT03194308.

Negative clinic experiences as a barrier to care for people with HIV and their impact on patient preferences for intervention support: a qualitative study in Cape Town, South Africa.

We conducted qualitative research among people with HIV (PWH) and care providers in Cape Town, South Africa to understand the impact of negative clinic experiences on adherence and support preferences. In-depth interviews were conducted with 41 patients with an unsuppressed viral load or a treatment gap, and focus group discussions with physicians, nurses, counselors, and community health workers. Questions addressed treatment history and adherence barriers, then participants evaluated evidence-based adherence interventions for potential scale up. Inductive analysis examined care experiences and corresponding preference for intervention options. More than half of PWH described negative experiences during clinic visits, including mistreatment by staff and clinic administration issues, and these statements were corroborated by providers. Those with negative experiences in care stated that fear of mistreatment led to nonadherence. Most patients with negative experiences preferred peer support groups or check-in texts to clinic-based interventions. We found that PWH's negative clinic experiences were a primary reason behind nonadherence and influenced preferences for support mechanisms. These findings emphasize the importance of HIV treatment adherence interventions at multiple levels both in and outside of the clinic, and providing more comprehensive training to providers to better serve PWH in adherence counseling, especially those who are most vulnerable..

Acceptability and feasibility of long-term, real-time electronic adherence monitoring of HIV pre-exposure prophylaxis (PrEP) use among young women in Kenya: A mixed methods study.

Real-time electronic adherence monitoring involves "smart" pill boxes that record and monitor openings as a proxy for pill taking and may be useful in understanding and supporting PrEP use; however, acceptability and/or feasibility for PrEP users is uncertain. We sought to understand the experiences of using a real-time electronic adherence monitor for PrEP delivery among young women in Kisumu and Thika, Kenya. We used the Wisepill device to monitor PrEP use among 18-24-year-old women for two years. Half of the participants were randomized to also receive SMS adherence reminders (daily or as needed for missed doses). We assessed acceptability quantitatively and qualitatively according to the four constructs of Unified Theory of Acceptance and Use of Technology (UTAUT): performance expectancy, effort expectancy, social influence, and facilitating conditions. We assessed feasibility by monitor functionality during periods of PrEP use. We analyzed quantitative data descriptively and compared by site and over time; qualitative data were analyzed inductively and deductively. The median age was 21 years (IQR 19-22), median education was 12 years (IQR 10-13), 182 (53%) had disclosed PrEP use, and 55 (16%) reported recent intimate partner violence. Most participants reported high levels of usefulness and high interest in using the monitor with few problems or worries reported throughout follow-up. Feasibility was high overall with some differences by site (96% functional monitor days in Kisumu vs 88% in Thika). Few monitors were reported lost (N = 29; 8%) or dysfunctional (N = 11; 3%). In qualitative interviews, electronic monitoring was perceived as useful because it supported privacy, confidentiality, easy storage, and PrEP adherence. Effort was generally considered low. Participants expressed some concern for stigma from monitor and/or PrEP use. Facilitating conditions involved the monitor size, color, and battery life. Overall, real-time electronic adherence monitoring was a highly acceptable and feasible approach to understand PrEP adherence among young women in a sub-Saharan African setting.

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.

Pediatric Tuberculosis Infection Care Facilitators and Barriers: A Qualitative Study.

BACKGROUND: A total of 700 000 US children and adolescents are estimated to have latent tuberculosis (TB) infection. Identifying facilitators and barriers to engaging in TB infection care is critical to preventing pediatric TB disease. We explored families' and clinicians' perspectives on pediatric TB infection diagnosis and care. METHODS: We conducted individual interviews and small group discussions with primary care and subspecialty clinicians, and individual interviews with caregivers of children diagnosed with TB infection. We sought to elicit facilitators and barriers to TB infection care engagement. We used applied thematic analysis to elucidate themes relating to care engagement, and organized themes using a cascade-grounded pediatric TB infection care engagement framework. RESULTS: We enrolled 19 caregivers and 24 clinicians. Key themes pertaining to facilitators and barriers to care emerged that variably affected engagement at different steps of care. Clinic and health system themes included the application of risk identification strategies and communication of risk; care ecosystem accessibility; programs to reduce cost-related barriers; and medication adherence support. Patient- and family-level themes included TB knowledge and beliefs; trust in clinicians, tests, and medical institutions; behavioral skills; child development and parenting; and family resources. CONCLUSIONS: Risk identification, education techniques, trust, family resources, TB stigma, and care ecosystem accessibility enabled or impeded care cascade engagement. Our results delineate an integrated pediatric TB infection care engagement framework that can inform multilevel interventions to improve retention in the pediatric TB infection care cascade.

Social networks and HIV treatment adherence among people with HIV initiating treatment in rural Uganda and peri-urban South Africa.

Timely initiation of and adherence to antiretroviral therapy (ART) is critical for improving HIV outcomes and reducing HIV transmissibility. Social networks, or the social relationships individuals have with each other, have been linked with positive health outcomes, but less is known about the extent to which social network composition and structure are associated with improved ART adherence among people living with HIV (PLWH). We conducted an ego-centric network study among 828 previously ART-naïve PLWH presenting for ART initiation at 11 clinics in Mbarara, Uganda (rural population) and Gugulethu, South Africa (peri-urban population). We collected social network data using name generator and name interpreter questions. ART adherence was monitored over 12 months using wireless monitors (Wisepill). Our primary outcome of interest was ART adherence during the 12-month follow-up period. We used generalized linear models to estimate the associations between network measures and ART adherence. PLWH at the Uganda site (compared with the South Africa site) were less isolated, had larger social networks, and had more social ties providing sufficient social support; they were also more likely to bridge different social groups whereby not all social ties were connected to each other. In Uganda, social isolation was associated with a 5.5 percentage point reduction in ART adherence (95% confidence interval [CI] -9.95 to -1.13; p = 0.014), while having more same gender social ties was associated with higher ART adherence (b = 0.13, 95% CI 0.02-0.25, p = 0.025). In South Africa, there was no association between social isolation and ART adherence, and having more friendship ties (vs. family ties) was associated with lower ART adherence (b = -2.20, 95% CI -3.56 to -0.84; p = 0.002). Identifying and supporting PLWH who are isolated may facilitate optimal adherence, but understanding how networks differentially affect ART adherence by country context is important.

Sexually transmitted infection (STI) knowledge and perceptions among people in HIV-sero-different partnerships in rural southwestern Uganda.

Globally, over one million people acquire curable sexually transmitted infections (STI) each day. Understanding how people think about STIs is key to building culturally appropriate STI prevention and treatment programs. We explored STI knowledge and perceptions in rural, southwestern Uganda to inform future interventions. From August 2020 to December 2020, we conducted individual in-depth interviews among adult men and women (≥18 years) with recent or current personal or partner pregnancy, a history of an STI diagnosis and treatment, and membership in an HIV-sero-different relationship. Interviews explored STI knowledge, perceptions, and barriers and facilitators to engaging in STI care. We used inductive and deductive approaches to generate a codebook guided by the healthcare literacy skills framework in a thematic analysis. Ten men with STI, five of their female partners, eighteen women with STI, and four of their male partners participated in individual in-depth interviews. The median age was 41 (range 27-50) for men and 29 (range 22-40) for women. Sixteen (43%) participants were with HIV. Significant themes include: 1) Participants obtained STI knowledge and information from the community (friends, family members, acquaintances) and medical professionals; 2) While participants knew STIs were transmitted sexually, they also believed transmission occurred via non-sexual mechanisms. 3) Participants associated different connotations and amounts of stigma with each STI, for example, participants reported that syphilis was passed down "genetically" from parent to child. 4) Participants reported uncertainty about whether STIs affected pregnancy outcomes and whether antenatal STI treatment was safe. The complicated nature of STIs has led to understandable confusion in settings without formal sexual healthcare education. Robust counseling and education prior to sexual debut will help allow men and women to understand the signs, symptoms, and treatments necessary for STI cure and to navigate often complicated and overburdened healthcare systems.

Effects of Maternal HIV Infection and Alcohol Use in Pregnancy on Birth Outcomes in Uganda.

Alcohol use and HIV infection are prevalent in sub-Saharan Africa (sSA), and both are associated with low birth weight. Yet, few studies have evaluated the combined effects of maternal HIV infection and alcohol use on birth outcomes. We analyzed data from a prospective cohort study of HIV-related placental changes in Ugandan women. We defined alcohol use as self-reported alcohol use within the last year, using the AUDIT questionnaire and used linear and logistic regression to measure associations between maternal alcohol use, HIV serostatus, and birth weight. In a subsample, we measured alcohol exposure using phosphatidylethanol (PEth) in neonatal heelstick dried blood spots to confirm maternal alcohol use. Of 352 participants, 176 (50%) were women with HIV (WHIV). Three of 176 (2%) HIVuninfected women and 17/176 (10%) of WHIV self-reported alcohol use (P = 0.002). Maternal HIV infection was associated with lower birth weight (ß = -0.12, 95% CI [-0.20, -0.02], P = 0.02), but self-reported alcohol use was not (ß = 0.06, 95% CI [-0.15, 0.26], P = 0.54), and the interaction between HIV serostatus and alcohol use was not significant (P = 0.13). Among the PEth subsample, neither HIV status nor PEthconfirmed alcohol use were associated with low birth weight. Maternal HIV infection was associated with lower birth weight, but alcohol use was not, and there was no significant interaction between maternal HIV infection and alcohol use. Alcohol use was more prevalent in WHIV and under-reporting was common. A larger study of the effects of laboratory-confirmed alcohol and HIV exposure on birth outcomes is warranted.

Patient-provider experiences with chronic non-communicable disease care during COVID-19 lockdowns in rural Uganda: A qualitative analysis.

Non-communicable diseases (NCDs) are a growing health burden in Sub-Saharan Africa and especially Uganda, where they account for over one third of all deaths. During the COVID-19 pandemic, public health control measures such as societal "lockdowns" had a significant impact on longitudinal NCD care though no studies have looked at the lived experience around NCD care during the pandemic. Our objective was to understand the experience of NCD care for both patients and providers in southwestern Uganda during the COVID-19 pandemic. We conducted in-depth, in-person qualitative interviews with 20 patients living with hypertension, diabetes, and/or cardiac disease purposefully selected from the outpatient clinics at Mbarara Regional Referral Hospital and 11 healthcare providers from public health facilities in Mbarara, southwestern Uganda. We analyzed transcripts according to conventional content analysis. We identified four major themes that emerged from the interviews; (1) difficulty accessing medication; (2) food insecurity; (3) barriers to the delivery of NCD clinical care and (4) alternative forms of care. Pre-existing challenges with NCD care were exacerbated during COVID-19 lockdown periods and care was severely disrupted, leading to worsened patient health and even death. The barriers to care were exacerbations of underlying systemic problems with NCD care delivery that require targeted interventions. Future work should leverage digital health interventions, de-centralizing NCD care, improving follow-up, providing social supports to NCD patients, and rectifying supply chain issues.

The feasibility, acceptability, and preliminary impact of real-time monitors and SMS on tuberculosis medication adherence in southwestern Uganda: Findings from a mixed methods pilot randomized controlled trial.

We conducted a pilot randomized controlled trial among patients initiating treatment for drug-sensitive tuberculosis (TB). Participants received real-time electronic adherence monitors and were randomized (1:1:1) to: (i) daily SMS (reminders to TB patients and notifications to social supporters sent daily for 3 months, then triggered by late or missed dosing for 3 months); (ii) weekly SMS (reminders to TB patients and notifications to social supporters sent weekly for 3 months, then triggered by late or missed dosing for 3 months); or (iii) control (no SMS). Feasibility was mainly verified by the technical function of the intervention at Month 6. The primary outcome was percent adherence as ascertained by the real time monitor. Quantitative feasibility/acceptability data were summarized descriptively. Percentage adherence and adherence patterns were assessed and compared by linear regression models. Qualitative acceptability data was collected through interviews and analyzed using content analysis. Among 63 participants, the median age was 35 years, 75% had no regular income, and 84% were living with HIV. Feasibility was demonstrated as most of the daily [1913/2395 (80%)] and weekly [631/872 (72%)] SMS reminders to TB patients were sent successfully. Also, most of the daily [1577/2395 (66%)] and weekly [740/872 (85%)] SMS notifications to social supporters and adherence data (96%) were sent successfully. Challenges included TB status disclosure, and financial constraints. All patients perceived the intervention to be useful in reminding and motivating them to take medication. Median adherence (IQR) in the daily SMS, weekly SMS, and control arms was 96.1% (84.8, 98.0), 92.5% (80.6, 96.3), and 92.2% (56.3, 97.8), respectively; however, differences between the intervention and control arms were not statistically significant. Real-time monitoring linked to SMS was feasible and acceptable and may have improved TB medication adherence. Larger studies are needed to further assess impact on adherence and clinical outcomes. Trial registration. ClinicalTrials.gov registration number: NCT03800888. https://ichgcp.net/clinical-trials-registry/NCT03800888.

"I felt special!": a qualitative study of peer-delivered HIV self-tests, STI self-sampling kits and PrEP for transgender women in Uganda.

INTRODUCTION: Peer delivery is a client-centred approach that could maximize the coverage and impact of HIV services for transgender women (TGW). We conducted qualitative interviews to examine how peer-delivered HIV self-testing (HIVST), sexually transmitted infection self-sampling (STISS) and oral pre-exposure prophylaxis (PrEP) influenced prevention choices among TGW and their intimate partners in Uganda. METHODS: Within a cluster randomized trial of peer-delivered HIVST, STISS and PrEP among HIV-negative TGW (NCT04328025), we conducted 55 qualitative interviews with 30 TGW, 15 intimate partners and 10 TGW peers (August 2021-February 2022). TGW interviews explored: (1) HIV self-test and PrEP experiences; (2) HIVST with intimate partners; and (3) descriptions of self-sampling for STI testing. Partner interviews covered: (1) experiences with HIVST; (2) disclosure of HIV status to intimate partner; and (3) descriptions of sexual behaviours after testing. Peer interview topics included: (1) intervention delivery experiences; and (2) recommendations for peer-delivered HIV prevention services to TGW, including psychological support and coping strategies. Qualitative data were analysed using an inductive content analytic approach. RESULTS: Peer-delivered combination prevention was valued by this group of TGW and their partners. (1) Peer services extended beyond delivering HIV/STI kits and PrEP refills to caring for individual health and wellbeing by providing stigma coping strategies. Peer psychosocial support empowered research participants to become "HIVST ambassadors," teach non-study TGW about self-testing and PrEP, and encourage linkage to care. (2) HIVST with intimate partners and mutual disclosure of HIV status strengthened partnered relationships. PrEP use after both partners tested HIV negative implied infidelity. (3) Self-sampling enabled TGW to take control of their STI testing and avoid the embarrassment of exposing their bodies. Privacy and confidentiality motivated the uptake of STI testing and treatment. CONCLUSIONS: In this sample of TGW from Uganda, peer delivery of HIVST, STISS and PrEP refills benefitted individual prevention efforts and extended to a new linkage of TGW not engaged in care. Integrating peer services into differentiated PrEP delivery could increase HIV/STI test coverage and PrEP use in this vulnerable population.

Model-based predictions of protective HIV pre-exposure prophylaxis adherence levels in cisgender women.

Most human immunodeficiency virus (HIV) infections occur in cisgender women in resource-limited settings. In women, self-protection with emtricitabine/tenofovir disoproxil fumarate pre-exposure prophylaxis (FTC/TDF-PrEP) constitutes a major pillar of HIV prevention. However, clinical trials in women had inconsistent outcomes, sparking uncertainty about adherence requirements and reluctance in evaluating on-demand regimens. We analyzed data from published FTC/TDF-PrEP trials to establish efficacy ranges in cisgender women. In a 'bottom-up' approach, we modeled hypotheses in the context of risk-group-specific, adherence-efficacy profiles and challenged those hypotheses with clinical data. We found that different clinical outcomes were related to the proportion of women taking the product, allowing coherent interpretation of the data. Our analysis showed that 90% protection was achieved when women took some product. We found that hypotheses of putative male/female differences were either not impactful or statistically inconsistent with clinical data. We propose that differing clinical outcomes could arise from pill-taking behavior rather than biological factors driving specific adherence requirements in cisgender women.

Adherence to daily, oral TDF/FTC PrEP during periconception among HIV-exposed South African women.

Background: Daily, oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) as pre-exposure prophylaxis (PrEP) reduces HIV acquisition for African women. Adherence is key to efficacy and patterns of adherence can be highly variable in real-world settings. Using group-based trajectory modeling (GBTM), we sought to identify distinct patterns of periconception PrEP adherence and evaluate potential baseline predictors of such adherence trajectories. Methods: We conducted a single-arm longitudinal study for women aged 18-35 years living in Durban, South Africa with personal or partner plans for pregnancy with a partner with HIV or of unknown serostatus. Participants were offered safer conception counseling, including daily oral PrEP; women who initiated PrEP were given a bottle with an electronic pillcap that recorded when device opens. Weekly adherence to daily PrEP was modeled using GBTM with a censored normal outcome distribution as a function of weeks since PrEP initiation. The number and functional form of the adherence trajectory groups were primarily selected based on Bayesian information criteria (BIC) and confirmed by mean estimated probabilities of group membership. A multivariable version of the selected model assessed baseline predictors of membership in adherence trajectory groups. Results: Overall mean (95% CI) adherence to PrEP was 63% (60%, 67%). We identified four groups of women with distinct patterns of adherence: (1) high (i.e., ≥6 doses per week) steady adherence throughout follow-up (22% of PrEP initiators); (2) moderate (i.e., 4-5 doses per week), but steady adherence (31%); (3) initially high, but consistently declining adherence (21%); and (4) initially moderate adherence, followed by a rapid decline and subsequent rebound (26%). In multivariable-adjusted analyses, older age was associated with membership in the high, steady adherence group as compared to the group identified with an adherence trajectory of initially high, then decline, and finally a rebound. Conclusions: GBTM is useful for exploring potential heterogeneity in longitudinal patterns of medication adherence. Although a large proportion of women in this study achieved high levels of adherence by electronic pillcap initially, far fewer women maintained these levels consistently. Knowledge of different adherence trajectories could be used to develop targeted strategies for optimizing HIV prevention during periconception.

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.

A user-centred implementation strategy for tuberculosis contact investigation in Uganda: protocol for a stepped-wedge, cluster-randomised trial.

BACKGROUND: Tuberculosis(TB) is among the leading causes of infectious death worldwide. Contact investigation is an evidence-based, World Health Organisation-endorsed intervention for timely TB diagnosis, treatment, and prevention but has not been widely and effectively implemented. METHODS: We are conducting a stepped-wedge, cluster-randomised, hybrid Type III implementation-effectiveness trial comparing a user-centred to a standard strategy for implementing TB contact investigation in 12 healthcare facilities in Uganda. The user-centred strategy consists of several client-focused components including (1) a TB-education booklet, (2) a contact-identification algorithm, (3) an instructional sputum-collection video, and (4) a community-health-rider service to transport clients, CHWs, and sputum samples, along with several healthcare-worker-focused components, including (1) collaborative improvement meetings, (2) regular audit-and-feedback reports, and (3) a digital group-chat application designed to develop a community of practice. Sites will cross-over from the standard to the user-centred strategy in six, eight-week transition steps following a randomly determined site-pairing scheme and timeline. The primary implementation outcome is the proportion of symptomatic close contacts completing TB evaluation within 60 days of TB treatment initiation by the index person with TB. The primary clinical effectiveness outcomes are the proportion of contacts diagnosed with and initiating active TB disease treatment and the proportion initiating TB preventative therapy within 60 days. We will assess outcomes from routine source documents using intention-to-treat analyses. We will also conduct nested mixed-methods studies of implementation fidelity and context and perform cost-effectiveness and impact modelling. The Makerere School of Public Health IRB(#554), the Uganda National Council for Science and Technology(#HS1720ES), and the Yale Institutional Review Board(#2000023199) approved the study and waived informed consent for the main trial implementation-effectiveness outcomes. We will submit results for publication in peer-reviewed journals and disseminate findings to local policymakers and representatives of affected communities. DISCUSSION: This pragmatic, quasi-experimental implementation trial will inform efforts to find and prevent undiagnosed persons with TB in high-burden settings using contact investigation. It will also help assess the suitability of human-centred design and communities of practice for tailoring implementation strategies and sustaining evidence-based interventions in low-and-middle-income countries. TRIAL REGISTRATION: The trial was registered(ClinicalTrials.gov Identifier NCT05640648) on 16 November 2022, after the trial launch on 7 March 2022.

Area-Based Sociodemographic Factors Associated with Latent Tuberculosis Infection in a Low-Prevalence Setting.

Area-based sociodemographic markers, such as census tract foreign-born population, have been used to identify individuals and communities with a high risk for tuberculosis (TB) infection in the United States. However, these markers have not been evaluated as independent risk factors for TB infection in children. We evaluated associations between census tract poverty, crowding, foreign-born population, and the CDC's Social Vulnerability Index (CDC-SVI) ranking and TB infection in a population of children tested for TB infection in Boston, Massachusetts. After adjustment for age, crowding, and foreign-born percentage, increasing census tract poverty was associated with increased odds of TB infection (adjusted odds ratio [aOR] per 10% increase in population proportion living in poverty: 1.20 [95% CI, 1.04-1.40]; P = 0.01), although this association was attenuated after further adjustment for preferred language. In separate models, increasing CDC-SVI ranking was associated with increased odds of TB infection, including after adjustment for age and language preference (aOR per 10-point increase in CDC-SVI rank: 1.08 [95% CI, 1.02-1.15]; P = 0.01). Our findings suggest area-based sociodemographic factors may be valuable for characterizing TB infection risk and defining the social ecology of pediatric TB infection in low-burden settings.

Evaluating disparities in code status designation among patients admitted with COVID-19 at a quaternary care center early in the pandemic.

The COVID-19 pandemic has highlighted disparities in outcomes by social determinants to health. It is unclear how much end-of-life discussions and a patient's decision about code status ("do not resuscitate," do not resuscitate, or "comfort measures only," [CMO] orders) might contribute to in hospital disparities in care, especially given know racial inequities in end-of-life care. Here, we looked at factors associated with code status orders at the end of hospitalization for patients with COVID-19. We conducted a retrospective chart review of all patients who presented to the Emergency Department of a large quaternary hospital between 8 March and 3 June 2020. We used logistic regression modeling to quantify the degree to which social determinants of health, including race, ethnicity, area deprivation index (ADI), English as a primary language, homelessness, and illicit substance use might impact the likelihood of a particular code status at the end-of a patient's hospitalization, while controlling for disease severity. Among social determinants to health, only white race (odds ratio [OR] 2.0; P = .03) and higher ADI (OR 1.2; P = .03) were associated with having a do not resuscitate or a CMO order. Additionally, we found that patients with white race (OR 2.9; P = .02) were more likely to carry a CMO order. Patient race and ADI were associated with different code status orders at the end of hospitalization. Differences in code status might have contributed to disparities in COVID-19 outcomes early in the pandemic, though further investigations are warranted.

Sexually Transmitted Infection Point-of-Care Testing in Resource-Limited Settings: A Narrative Review Guided by an Implementation Framework.

ABSTRACT: Most sexually transmitted infections (STIs) are acquired in resource-limited settings (RLSs) where laboratory diagnostic access is limited. Advancements in point-of-care testing (POC) technology have the potential to bring STI testing to many RLSs. We define POC as performed near the patient and with results readily available to inform clinical practice. The World Health Organization Special Programme for Research and Training in Tropical Diseases further outlines desirable POC characteristics with the REASSURED criteria.Despite advantages related to immediate test-and-treat care, integrating POC into RLS health care systems can present challenges that preclude reliance on these tests. In 2018, we incorporated molecular near-POC for chlamydia, gonorrhea, and trichomoniasis and SDBioline treponemal immunochromatographic testing confirmed by rapid plasma reagin for syphilis diagnosis at the Mbarara University of Science and Technology Research Laboratory in rural southwestern Uganda. We describe our experiences with STI POC as a case example to guide a narrative review of the field using the Consolidated Framework for Implementation Research as a conceptual framework.Although POC and near-POC are described as easy to use, the challenges of limited person-power, health care processes, limited infrastructure/resources, high costs, and quality control obstacles can impede the impact of these tests. Increased investment in operators, training, and infrastructure, restructuring health care systems to accommodate increased POC access, and optimizing costs are all crucial to the successful implementation of STI POC in RLS. Expanded STI POC in RLS will increase access to accurate diagnoses, appropriate treatment, and engagement in partner notification, treatment, and prevention efforts.