Randomized Trial of Dynamic Choice HIV Prevention at Antenatal and Postnatal Care Clinics in Rural Uganda and Kenya.

BACKGROUND: Pregnant and postpartum women in Sub-Saharan Africa are at high risk of HIV acquisition. We evaluated a person-centered dynamic choice intervention for HIV prevention (DCP) among women attending antenatal and postnatal care. SETTING: Rural Kenya and Uganda. METHODS: Women (aged 15 years or older) at risk of HIV acquisition seen at antenatal and postnatal care clinics were individually randomized to DCP vs. standard of care (SEARCH; NCT04810650). The DCP intervention included structured client choice of product (daily oral pre-exposure prophylaxis or postexposure prophylaxis), service location (clinic or out of facility), and HIV testing modality (self-test or provider-administered), with option to switch over time and person-centered care (phone access to clinician, structured barrier assessment and counseling, and provider training). The primary outcome was biomedical prevention coverage-proportion of 48-week follow-up with self-reported pre-exposure prophylaxis or postexposure prophylaxis use, compared between arms using targeted maximum likelihood estimation. RESULTS: Between April and July 2021, we enrolled 400 women (203 intervention and 197 control); 38% were pregnant, 52% were aged 15-24 years, and 94% reported no pre-exposure prophylaxis or postexposure prophylaxis use for ≥6 months before baseline. Among 384/400 participants (96%) with outcome ascertained, DCP increased biomedical prevention coverage 40% (95% CI: 34% to 47%; P < 0.001); the coverage was 70% in intervention vs. 29% in control. DCP also increased coverage during months at risk of HIV (81% in intervention, 43% in control; 38% absolute increase; 95% CI: 31% to 45%; P < 0.001). CONCLUSION: A person-centered dynamic choice intervention that provided flexibility in product, testing, and service location more than doubled biomedical HIV prevention coverage in a high-risk population already routinely offered access to biomedical prevention options.

Association between smoking and lack of HIV virological suppression in a cross-sectional study of persons with HIV on antiretroviral therapy in Uganda.

BACKGROUND: Smoking and alcohol use frequently co-occur and are the leading causes of preventable death in sub-Saharan Africa (SSA) and are common among people living with HIV (PLWH). While alcohol use has been shown to be associated with reduced adherence to antiretroviral treatment (ART), which may affect HIV viral suppression, the independent effect of smoking on HIV outcomes in SSA is unknown. We aimed to 1) describe the prevalence of current smoking and correlates of smoking; 2) assess the association of smoking with viral suppression, adjusting for level of alcohol use; 3) explore the relationship between smoking and CD4 cell count <350 cells/mm3, among participants who are virally suppressed. METHODS: We analyzed data from the Drinkers Intervention to Prevent Tuberculosis (DIPT) and the Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) studies conducted in Southwest Uganda. The studies enrolled PLWH who were on ART for at least 6 months and co-infected with latent tuberculosis and dominated with participants who had unhealthy alcohol use. Current smoking (prior 3 months) was assessed by self-report. Alcohol use was assessed using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C, modified for prior 3 months) and phosphatidylethanol (PEth), an alcohol biomarker. We used logistic regression to estimate the cross-sectional association between smoking and lack of virological suppression (≥40 copies/ml), adjusting for level of alcohol use and other covariates, and to examine the association between smoking and CD4 cell counts among PLWH with viral suppression. RESULTS: Of the 955 participants enrolled from 2017 to 2021 who had viral load (VL) results, 63% were men, median age was 40 years (interquartile range [IQR] 32-47), 63% engaged in high/very high-risk alcohol use (AUDIT-C≥6 or PEth≥200 ng/mL), and 22% reported smoking in the prior 3 months. Among 865 participants (91%) with viral suppression and available CD4 count, 11% had a CD4 cell count <350 cells/mm3. In unadjusted and adjusted analyses, there was no evidence of an association between smoking and lack of virological suppression nor between smoking and CD4 count among those with viral suppression. CONCLUSIONS: The prevalence of smoking was high among a study sample of PLWH in HIV care with latent TB in Southwest Uganda in which the majority of persons engaged in alcohol use. Although there was no evidence of an association between smoking and lack of virological suppression, the co-occurrence of smoking among PLWH who use alcohol underscores the need for targeted and integrated approaches to reduce their co-existence and improve health.

Mid-level managers' perspectives on implementing isoniazid preventive therapy for people living with HIV in Ugandan health districts: a qualitative study.

BACKGROUND: Isoniazid preventive therapy (IPT) works to prevent tuberculosis (TB) among people living with HIV (PLHIV), but uptake remains low in Sub-Saharan Africa. In this analysis, we sought to identify barriers mid-level managers face in scaling IPT in Uganda and the mechanisms by which the SEARCH-IPT trial intervention influenced their abilities to increase IPT uptake. METHODS: The SEARCH-IPT study was a cluster randomized trial conducted from 2017-2021. The SEARCH-IPT intervention created collaborative groups of district health managers, facilitated by local HIV and TB experts, and provided leadership and management training over 3-years to increase IPT uptake in Uganda. In this qualitative study we analyzed transcripts of annual Focus Group Discussions and Key Informant Interviews, from a subset of SEARCH-IPT participants from intervention and control groups, and participant observation field notes. We conducted the analysis using inductive and deductive coding (with a priori codes and those derived from analysis) and a framework approach for data synthesis. RESULTS: When discussing factors that enabled positive outcomes, intervention managers described feeling ownership over interventions, supported by the leadership and management training they received in the SEARCH-IPT study, and the importance of collaboration between districts facilitated by the intervention. In contrast, when discussing factors that impeded their ability to make changes, intervention and control managers described external funders setting agendas, lack of collaboration in meetings that operated with more of a 'top-down' approach, inadequate supplies and staffing, and lack of motivation among frontline providers. Intervention group managers mentioned redistribution of available stock within districts as well as between districts, reflecting efforts of the SEARCH-IPT intervention to promote between-district collaboration, whereas control group managers mentioned redistribution within their districts to maximize the use of available IPT stock. CONCLUSIONS: In Uganda, mid-level managers' perceptions of barriers to scaling IPT included limited power to set agendas and control over funding, inadequate resources, lack of motivation of frontline providers, and lack of political prioritization. We found that the SEARCH-IPT intervention supported managers to design and implement strategies to improve IPT uptake and collaborate between districts. This may have contributed to the overall intervention effect in increasing the uptake of IPT among PLHIV compared to standard practice. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03315962 , Registered 20 October 2017.

Community-Wide Universal Human Immunodeficiency Virus (HIV) Test and Treat Intervention Reduces Tuberculosis Transmission in Rural Uganda: A Cluster-Randomized Trial.

BACKGROUND: Human immunodeficiency virus (HIV) treatment reduces tuberculosis (TB) disease and mortality; however, the population-level impact of universal HIV-test-and-treat interventions on TB infection and transmission remain unclear. METHODS: In a sub-study nested in the SEARCH trial, a community cluster-randomized trial (NCT01864603), we assessed whether a universal HIV-test-and-treat intervention reduced population-level incident TB infection in rural Uganda. Intervention communities received annual, population-level HIV testing and patient-centered linkage. Control communities received population-level HIV testing at baseline and endline. We compared estimated incident TB infection by arms, defined by tuberculin skin test conversion in a cohort of persons aged 5 and older, adjusting for participation and predictors of infection, and accounting for clustering. RESULTS: Of the 32 trial communities, 9 were included, comprising 90 801 participants (43 127 intervention and 47 674 control). One-year cumulative incidence of TB infection was 16% in the intervention and 22% in the control; SEARCH reduced the population-level risk of incident TB infection by 27% (adjusted risk ratio = 0.73; 95% confidence interval [CI]: .57-.92, P = .005). In pre-specified analyses, the effect was largest among children aged 5-11 years and males. CONCLUSIONS: A universal HIV-test-and-treat intervention reduced incident TB infection, a marker of population-level TB transmission. Investments in community-level HIV interventions have broader population-level benefits, including TB reductions.

A Qualitative Exploration of Intimate Partner Violence Among HIV/TB Coinfected Persons With Problematic Alcohol Use Participating in an Incentive-Based Alcohol/Medication Adherence Intervention in Uganda During COVID-19.

In Uganda, four in ten women report experiencing intimate partner violence (IPV) in the past year. Salient drivers of IPV in sub-Saharan Africa include stress related to household finances, alcohol use, and partner infidelity. We conducted 42 interviews with participants (n = 32) in the Drinkers' Intervention to Prevent Tuberculosis (DIPT) study which included economic incentives, and their partners (n = 10) to understand how participating in DIPT during COVID-19 lockdown restrictions impacted relationship dynamics in intimate partnerships. Our findings highlight the need to develop policies to address root causes of IPV and to ensure continuity of IPV services in future pandemics. Policy and programming recommendations based on study results are presented.

Dynamic choice HIV prevention intervention at outpatient departments in rural Kenya and Uganda.

OBJECTIVE: HIV prevention service delivery models that offer product choices, and the option to change preferences over time, may increase prevention coverage. Outpatient departments in sub-Saharan Africa diagnose a high proportion of new HIV infections, but are an understudied entry point to biomedical prevention. DESIGN: Individually randomized trial of dynamic choice HIV prevention (DCP) intervention vs. standard-of-care (SOC) among individuals with current/anticipated HIV exposure risk at outpatient departments in rural Kenya and Uganda (SEARCH; NCT04810650). METHODS: Our DCP intervention included 1) product choice (oral preexposure prophylaxis [PrEP] or postexposure prophylaxis [PEP]) with an option to switch over time, 2) HIV provider- or self-testing, 3) service location choice (community vs. clinic-based), and 4) provider training on patient-centered care. Primary outcome was proportion of follow-up covered by PrEP/PEP over 48 weeks assessed via self-report. RESULTS: We enrolled 403 participants (61% women; median 27 years, IQR 22-37). In the DCP arm, 86% ever chose PrEP, 15% ever chose PEP over 48 weeks; selection of HIV self-testing increased from 26 to 51% and of out-of-facility visits from 8 to 52%. Among 376 of 403 (93%) with outcomes ascertained, time covered by PrEP/PEP was higher in DCP (47.5%) vs. SOC (18.3%); difference = 29.2% (95% confidence interval: 22.7-35.7; P  < 0.001). Effects were similar among women and men (28.2 and 31.0% higher coverage in DCP, respectively) and larger during periods of self-reported HIV risk (DCP 64.9% vs. SOC 26.3%; difference = 38.6%; 95% confidence interval: 31.0-46.2; P  < 0.001). CONCLUSION: A dynamic choice HIV prevention intervention resulted in two-fold greater time covered by biomedical prevention products compared to SOC in general outpatient departments in eastern Africa.

Randomized Trial of a "Dynamic Choice" Patient-Centered Care Intervention for Mobile Persons With HIV in East Africa.

BACKGROUND: Persons with HIV (PWH) with high mobility face obstacles to HIV care engagement and viral suppression. We sought to understand whether a patient-centered intervention for mobile PWH would improve viral suppression and retention in care, and if so, which subgroups would benefit most. METHODS: In a randomized trial, we evaluated the effect of an intervention designed to address barriers to care among mobile (≥2 weeks out of community in previous year) PWH with viral nonsuppression or recent missed visits in Kenya and Uganda (NCT04810650). The intervention included dynamic choice of a "travel pack" (emergency antiretroviral therapy [ART] supply, discrete ART packaging, and travel checklist), multimonth and offsite refills, facilitated transfer to out-of-community clinics, and hotline access to a mobility coordinator. The primary outcome was viral suppression (<400 copies/mL) at 48 weeks. Secondary outcomes included retention in care and ART possession. RESULTS: From April 2021 to July 2022, 201 participants were enrolled and randomized (102 intervention, 99 control): 109 (54%) were female participants and 101 (50%) from Kenya; median age was 37 years (interquartile range: 29-43). At 48 weeks, there was no significant difference in viral suppression in intervention (85%) vs. control (86%). The intervention improved retention in care (risk ratio: 1.06[1.02-1.1]; P < 0.001) and ART possession (risk ratio: 1.07[1.03-1.11]; P < 0.001), with larger effect sizes among persons with baseline nonsuppression and high mobility (≥2 weeks out of community in previous 3 months). CONCLUSIONS: Mobile PWH-centered care should be considered for high-risk mobile populations, including nonsuppressed and highly mobile PWH, to improve retention in care and sustain viral suppression over time. TRIAL REGISTRATION: NCT04810650.

A community-based dynamic choice model for HIV prevention improves PrEP and PEP coverage in rural Uganda and Kenya: a cluster randomized trial.

INTRODUCTION: Optimizing HIV prevention may require structured approaches for providing client-centred choices as well as community-based entry points and delivery. We evaluated the effect of a dynamic choice model for HIV prevention, delivered by community health workers (CHWs) with clinician support, on the use of biomedical prevention among persons at risk of HIV in rural East Africa. METHODS: We conducted a cluster randomized trial among persons (≥15 years) with current or anticipated HIV risk in 16 villages in Uganda and Kenya (SEARCH; NCT04810650). The intervention was a client-centred HIV prevention model, including (1) structured client choice of product (pre-exposure prophylaxis [PrEP] or post-exposure prophylaxis [PEP]), service location (clinic or out-of-clinic) and HIV testing modality (self-test or rapid test), with the ability to switch over time; (2) a structured assessment of patient barriers and development of a personalized support plan; and (3) phone access to a clinician 24/7. The intervention was delivered by CHWs and supported by clinicians who oversaw PrEP and PEP initiation and monitoring. Participants in control villages were referred to local health facilities for HIV prevention services, delivered by Ministry of Health staff. The primary outcome was biomedical prevention coverage: a proportion of 48-week follow-up with self-reported PrEP or PEP use. RESULTS: From May to July 2021, we enrolled 429 people (212 intervention; 217 control): 57% women and 35% aged 15-24 years. Among intervention participants, 58% chose PrEP and 58% chose PEP at least once over follow-up; self-testing increased from 52% (baseline) to 71% (week 48); ≥98% chose out-of-facility service delivery. Among 413 (96%) participants with the primary outcome ascertained, average biomedical prevention coverage was 28.0% in the intervention versus 0.5% in the control: a difference of 27.5% (95% CI: 23.0-31.9%, p<0.001). Impact was larger during periods of self-reported HIV risk: 36.6% coverage in intervention versus 0.9% in control, a difference of 35.7% (95% CI: 27.5-43.9, p<0.001). Intervention effects were seen across subgroups defined by sex, age group and alcohol use. CONCLUSIONS: A client-centred dynamic choice HIV prevention intervention, including the option to switch between products and CHW-based delivery in the community, increased biomedical prevention coverage by 27.5%. However, substantial person-time at risk of HIV remained uncovered.

Effect of a brief alcohol counselling intervention on HIV viral suppression and alcohol use among persons with HIV and unhealthy alcohol use in Uganda and Kenya: a randomized controlled trial.

INTRODUCTION: Unhealthy alcohol use significantly contributes to viral non-suppression among persons with HIV (PWH). It is unknown whether brief behavioural interventions to reduce alcohol use can improve viral suppression among PWH with unhealthy alcohol use in sub-Saharan Africa (SSA). METHODS: As part of the SEARCH study (NCT04810650), we conducted an individually randomized trial in Kenya and Uganda of a brief, skills-based alcohol intervention among PWH with self-reported unhealthy alcohol use (Alcohol Use Disorders Identification Test-Consumption [AUDIT-C], prior 3 months, ≥3/female; ≥4/male) and at risk of viral non-suppression, defined as either recent HIV viral non-suppression (≥400 copies/ml), missed visits, out of care or new diagnosis. The intervention included baseline and 3-month in-person counselling sessions with interim booster phone calls every 3 weeks. The primary outcome was HIV viral suppression (<400 copies/ml) at 24 weeks, and the secondary outcome was unhealthy alcohol use, defined by AUDIT-C or phosphatidylethanol (PEth), an alcohol biomarker, ≥50 ng/ml at 24 weeks. RESULTS: Between April and September 2021, 401 persons (198 intervention, 203 control) were enrolled from HIV clinics in Uganda (58%) and Kenya (27%) and alcohol-serving venues in Kenya (15%). At baseline, 60% were virally suppressed. Viral suppression did not differ between arms at 24 weeks: suppression was 83% in intervention and 82% in control arms (RR: 1.01, 95% CI: 0.93-1.1). Among PWH with baseline viral non-suppression, 24-week suppression was 73% in intervention and 64% in control arms (RR 1.15, 95% CI: 0.93-1.43). Unhealthy alcohol use declined from 98% at baseline to 73% in intervention and 84% in control arms at 24 weeks (RR: 0.86, 95% CI: 0.79-0.94). Effects on unhealthy alcohol use were stronger among women (RR 0.70, 95% CI: 0.56-0.88) than men (RR 0.93, 95% CI: 0.85-1.01) and among participants with a baseline PEth⩽200 ng/ml (RR 0.68, 95% CI: 0.53-0.87) versus >200 ng/ml (RR 0.97, 95% CI: 0.92-1.02). CONCLUSIONS: In a randomized trial of 401 PWH with unhealthy alcohol use and risk for viral non-suppression, a brief alcohol intervention reduced unhealthy alcohol use but did not affect viral suppression at 24 weeks. Brief alcohol interventions have the potential to improve the health of PWH in SSA by reducing alcohol use, a significant driver of HIV-associated co-morbidities.

Financial incentives for reduced alcohol use and increased isoniazid adherence during tuberculosis preventive therapy among people with HIV in Uganda: an open-label, factorial randomised controlled trial.

BACKGROUND: Alcohol use is common among people with HIV and is a risk factor for tuberculosis disease and non-adherence to isoniazid preventive therapy (IPT). Few interventions exist to reduce alcohol use and increase IPT adherence in sub-Saharan Africa. The aim of this study was to test the hypothesis that financial incentives conditional on point-of-care negative urine alcohol biomarker testing and positive urine isoniazid testing would reduce alcohol use and increase isoniazid adherence, respectively, in people with HIV who have latent tuberculosis infection and hazardous alcohol use. METHODS: We conducted an open-label, 2×2 factorial randomised controlled trial in Uganda. Eligible for the study were non-pregnant HIV-positive adults (aged ≥18 years) prescribed antiretroviral therapy for at least 6 months, with current heavy alcohol use confirmed by urine ethyl glucuronide (biomarker of recent alcohol use) and a positive Alcohol Use Disorders Identification Test-Consumption (AUDIT-C; ≥3 for women, ≥4 for men) for the past 3 months' drinking, no history of active tuberculosis, tuberculosis treatment, or tuberculosis preventive therapy, and a positive tuberculin skin test. We randomly assigned participants (1:1:1:1) initiating 6 months of IPT to: no incentives (group 1); or incentives for recent alcohol abstinence (group 2), isoniazid adherence (group 3), or both (group 4). Escalating incentives were contingent on monthly point-of-care urine tests negative for ethyl glucuronide (groups 2 and 4), or positive on IsoScreen (biomarker of recent isoniazid use; groups 3 and 4). The primary alcohol outcome was non-hazardous use by self-report (AUDIT-C <3 for women, <4 for men) and phosphatidylethanol (PEth; past-month alcohol biomarker) <35 ng/mL at 3 months and 6 months. The primary isoniazid adherence outcome was more than 90% bottle opening of days prescribed. We performed intention-to-treat analyses. This trial is registered with ClinicalTrials.gov (NCT03492216), and is complete. FINDINGS: From April 16, 2018, to Aug 2, 2021, 5508 people were screened, of whom 680 were randomly assigned: 169 to group 1, 169 to group 2, 170 to group 3, and 172 to group 4. The median age of participants was 39 years (IQR 32-47), 470 (69%) were male, 598 (90%) of 663 had HIV RNA viral loads of less than 40 copies per mL, median AUDIT-C score was 6 (IQR 4-8), and median PEth was 252 ng/mL (IQR 87-579). Among 636 participants who completed the trial with alcohol use endpoint measures (group 1: 152, group 2: 159, group 3: 161, group 4: 164), non-hazardous alcohol use was more likely in the groups with incentives for alcohol abstinence (groups 2 and 4) versus no alcohol incentives (groups 1 and 3): 57 (17·6%) of 323 versus 31 (9·9%) of 313, respectively; adjusted risk difference (aRD) 7·6% (95% CI 2·7 to 12·5, p=0·0025). Among 656 participants who completed the trial with isoniazid adherence endpoint measures (group 1: 158, group 2: 163, group 3: 168, group 4: 167), incentives for isoniazid adherence did not increase adherence: 244 (72·8%) of 335 in the isoniazid incentive groups (groups 3 and 4) versus 234 (72·9%) of 321 in the no isoniazid incentive groups (groups 1 and 2); aRD -0·2% (95% CI -7·0 to 6·5, p=0·94). Overall, 53 (8%) of 680 participants discontinued isoniazid due to grade 3 or higher adverse events. There was no significant association between randomisation group and hepatotoxicity resulting in isoniazid discontinuation, after adjusting for sex and site. INTERPRETATION: Escalating financial incentives contingent on recent alcohol abstinence led to significantly lower biomarker-confirmed alcohol use versus control, but incentives for recent isoniazid adherence did not lead to changes in adherence. The alcohol intervention was efficacious despite less intensive frequency of incentives and clinic visits than traditional programmes for substance use, suggesting that pragmatic modifications of contingency management for resource-limited settings can have efficacy and that further evaluation of implementation is merited. FUNDING: National Institute on Alcohol Abuse and Alcoholism. TRANSLATION: For the Runyankole translation of the abstract see Supplementary Materials section.

Geographical, social, and political contexts of tuberculosis control and intervention, as reported by mid-level health managers in Uganda: 'The activity around town'.

Training district-level health officers and other mid-level health system managers revealed multiple contextual factors across political, administrative, and social axes affecting tuberculosis (TB) and TB control in Uganda. Individual relationships between local health, political, and media leaders affect efforts to inform the public and provide services, yet greater administrative coordination between national-level logistics, implementing partner funding, and local needs is required. Social challenges to TB control include high population mobility, local industries, poverty with high-density living and social venues, and misinformation about TB. Capitalizing on implementation knowledge and sharing data can overcome social geographic challenges to TB-prevention planning through strategic healthcare capacity-building at the district level.

Uptake of a patient-centred dynamic choice model for HIV prevention in rural Kenya and Uganda: SEARCH SAPPHIRE study.

INTRODUCTION: Person-centred HIV prevention delivery models that offer structured choices in product, testing and visit location may increase coverage. However, data are lacking on the actual uptake of choices among persons at risk of HIV in southern Africa. In an ongoing randomized study (SEARCH; NCT04810650) in rural East Africa, we evaluated the uptake of choices made when offered in a person-centred, dynamic choice model for HIV prevention. METHODS: Using the PRECEDE framework, we developed a persont-centred, Dynamic Choice HIV Prevention (DCP) intervention for persons at risk of HIV in three settings in rural Kenya and Uganda: antenatal clinic (ANC), outpatient department (OPD) and in the community. Components include: provider training on product choice (predisposing); flexibility and responsiveness to client desires and choices (pre-exposure prophylaxis [PrEP]/post-exposure prophylaxis [PEP], clinic vs. off-site visits and self- or clinician-based HIV testing) (enabling); and client and staff feedback (reinforcing). All clients received a structured assessment of barriers with personalized plans to address them, mobile phone access to clinicians (24 hours/7 days/week) and integrated reproductive health services. In this interim analysis, we describe the uptake of choices of product, location and testing during the first 24 weeks of follow-up (April 2021-March 2022). RESULTS: A total of 612 (203 ANC, 197 OPD and 212 community) participants were randomized to the person-centred DCP intervention. We delivered the DCP intervention in all three settings with diverse populations: ANC: 39% pregnant; median age: 24 years; OPD: 39% male, median age 27 years; and community: 42% male, median age: 29 years. Baseline choice of PrEP was highest in ANC (98%) vs. OPD (84%) and community (40%); whereas the proportion of adults selecting PEP was higher in the community (46%) vs. OPD (8%) and ANC (1%). Personal preference for off-site visits increased over time (65% at week 24 vs. 35% at baseline). Interest in alternative HIV testing modalities grew over time (38% baseline self-testing vs. 58% at week 24). CONCLUSIONS: A person-centred model incorporating structured choice in biomedical prevention and care delivery options in settings with demographically diverse groups, in rural Kenya and Uganda, was responsive to varying personal preferences over time in HIV prevention programmes.

Efficacy of alcohol reduction interventions among people with HIV as evaluated by self-report and a phosphatidylethanol (PEth) outcome: protocol for a systematic review and individual participant data meta-analysis.

INTRODUCTION: Unhealthy alcohol use is associated with a range of adverse outcomes among people with HIV (PWH). Testing the efficacy and promoting the availability of effective interventions to address unhealthy alcohol use among PWH is thus a priority. Alcohol use outcomes in intervention studies are often measured by self-report alone, which can lead to spurious results due to information biases (eg, social desirability). Measuring alcohol outcomes objectively through biomarkers, such as phosphatidylethanol (PEth), in addition to self-report has potential to improve the validity of intervention studies. This protocol outlines the methods for a systematic review and individual participant data meta-analysis that will estimate the efficacy of interventions to reduce alcohol use as measured by a combined categorical self-report/PEth variable among PWH and compare these estimates to those generated when alcohol is measured by self-report or PEth alone. METHODS AND ANALYSIS: We will include randomised controlled trials that: (A) tested an alcohol intervention (behavioural and/or pharmacological), (B) enrolled participants 15 years or older with HIV; (C) included both PEth and self-report measurements, (D) completed data collection by 31 August 2023. We will contact principal investigators of eligible studies to inquire about their willingness to contribute data. The primary outcome variable will be a combined self-report/PEth alcohol categorical variable. Secondary outcomes will include PEth alone, self-report alone and HIV viral suppression. We will use a two-step meta-analysis and random effects modelling to estimate pooled treatment effects; I2 will be calculated to evaluate heterogeneity. Secondary and sensitivity analyses will explore treatment effects in adjusted models and within subgroups. Funnel plots will be used to explore publication bias. ETHICS AND DISSEMINATION: The study will be conducted with deidentified data from completed randomised controlled trials and will be considered exempt from additional ethical approval. Results will be disseminated through peer-reviewed publications and international scientific meetings. PROSPERO REGISTRATION NUMBER: CRD42022373640.

Universal HIV Testing and Treatment With Patient-Centered Care Improves ART Uptake and Viral Suppression Among Adults Reporting Hazardous Alcohol Use in Uganda and Kenya.

OBJECTIVES: Determine whether patient-centered, streamlined HIV care achieves higher antiretroviral therapy (ART) uptake and viral suppression than the standard treatment model for people with HIV (PWH) reporting hazardous alcohol use. DESIGN: Community cluster-randomized trial. METHODS: The Sustainable East Africa Research in Community Health trial (NCT01864603) compared an intervention of annual population HIV testing, universal ART, and patient-centered care with a control of baseline population testing with ART by country standard in 32 Kenyan and Ugandan communities. Adults (15 years or older) completed a baseline Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) and were classified as no/nonhazardous (AUDIT-C 0-2 women/0-3 men) or hazardous alcohol use (≥3 women/≥4 men). We compared year 3 ART uptake and viral suppression of PWH reporting hazardous use between intervention and control arms. We compared alcohol use as a predictor of year 3 ART uptake and viral suppression among PWH, by arm. RESULTS: Of 11,070 PWH with AUDIT-C measured, 1723 (16%) reported any alcohol use and 893 (8%) reported hazardous use. Among PWH reporting hazardous use, the intervention arm had higher ART uptake (96%) and suppression (87%) compared with control (74%, adjusted risk ratio [aRR] = 1.28, 95% CI: 1.19 to 1.38; and 72%, aRR = 1.20, 95% CI: 1.10 to 1.31, respectively). Within arm, hazardous alcohol use predicted lower ART uptake in control (aRR = 0.86, 95% CI: 0.78 to 0.96), but not intervention (aRR = 1.02, 95% CI: 1.00 to 1.04); use was not predictive of suppression in either arm. CONCLUSIONS: The Sustainable East Africa Research in Community Health intervention improved ART uptake and viral suppression among PWH reporting hazardous alcohol use and eliminated gaps in ART uptake between PWH with hazardous and no/nonhazardous use. Patient-centered HIV care may decrease barriers to HIV care for PWH with hazardous alcohol use.

Effects of a COVID-19 Public Health Lockdown on Drinking and Health Behavior Among Persons with HIV and with Unhealthy Alcohol use in Uganda.

To better understand the impact of Uganda's initial COVID-19 lockdown on alcohol use, we conducted a cross-sectional survey (August 2020-September 2021) among persons with HIV (PWH) with unhealthy alcohol use (but not receiving an alcohol intervention), enrolled in a trial of incentives to reduce alcohol use and improve isoniazid preventive therapy. We examined associations between bar-based drinking and decreased alcohol use, and decreased alcohol use and health outcomes (antiretroviral therapy [ART] access, ART adherence, missed clinic visits, psychological stress and intimate partner violence), during lockdown. Of 178 adults surveyed whose data was analyzed, (67% male, median age: 40), 82% reported bar-based drinking at trial enrollment; 76% reported decreased alcohol use during lockdown. In a multivariate analysis, bar-based drinking was not associated with greater decreases in alcohol use during lockdown compared to non-bar-based drinking (OR = 0.81, 95% CI: 0.31-2.11), adjusting for age and sex. There was a significant association between decreased alcohol use and increased stress during lockdown (adjusted ß = 2.09, 95% CI: 1.07-3.11, P < 0.010), but not other health outcomes.

Field assessment of BinaxNOW antigen tests as COVID-19 treatment entry point at a community testing site in San Francisco during evolving omicron surges.

COVID-19 oral treatments require initiation within 5 days of symptom onset. Although antigen tests are less sensitive than RT-PCR, rapid results could facilitate entry to treatment. We collected anterior nasal swabs for BinaxNOW and RT-PCR testing and clinical data at a walk-up, community site in San Francisco, California between January and June 2022. SARS-CoV-2 genomic sequences were generated from positive samples and classified according to subtype and variant. Monte Carlo simulations were conducted to estimate the expected proportion of SARS-CoV-2 infected persons who would have been diagnosed within 5 days of symptom onset using RT-PCR versus BinaxNOW testing. Among 25,309 persons tested with BinaxNOW, 2,799 had concomitant RT-PCR. 1137/2799 (40.6%) were SARS-CoV-2 RT-PCR positive. We identified waves of predominant omicron BA.1, BA.2, BA.2.12, BA.4, and BA.5 among 720 sequenced samples. Among 1,137 RT-PCR positive samples, 788/1137 (69%) were detected by BinaxNOW; 94% (669/711) of those with Ct value <30 were detected by BinaxNOW. BinaxNOW detection was consistent over lineages. In analyses to evaluate entry to treatment, BinaxNOW detected 81.7% (361/442, 95% CI: 77-85%) of persons with COVID-19 within 5 days of symptom onset. In comparison, RT-PCR (24-hour turnaround) detected 84.2% (372/442, 95% CI: 80-87%) and RT-PCR (48-hour turnaround) detected 67.0% (296/442, 95% CI: 62-71%) of persons with COVID-19 within 5 days of symptom onset. BinaxNOW detected high viral load from anterior nasal swabs consistently across omicron sublineages emerging between January and June of 2022. Simulations support BinaxNOW as an entry point for COVID-19 treatment in a community field setting.

Two-Stage TMLE to reduce bias and improve efficiency in cluster randomized trials.

Cluster randomized trials (CRTs) randomly assign an intervention to groups of individuals (e.g., clinics or communities) and measure outcomes on individuals in those groups. While offering many advantages, this experimental design introduces challenges that are only partially addressed by existing analytic approaches. First, outcomes are often missing for some individuals within clusters. Failing to appropriately adjust for differential outcome measurement can result in biased estimates and inference. Second, CRTs often randomize limited numbers of clusters, resulting in chance imbalances on baseline outcome predictors between arms. Failing to adaptively adjust for these imbalances and other predictive covariates can result in efficiency losses. To address these methodological gaps, we propose and evaluate a novel two-stage targeted minimum loss-based estimator to adjust for baseline covariates in a manner that optimizes precision, after controlling for baseline and postbaseline causes of missing outcomes. Finite sample simulations illustrate that our approach can nearly eliminate bias due to differential outcome measurement, while existing CRT estimators yield misleading results and inferences. Application to real data from the SEARCH community randomized trial demonstrates the gains in efficiency afforded through adaptive adjustment for baseline covariates, after controlling for missingness on individual-level outcomes.

The Association Between Social Network Characteristics and Tuberculosis Infection Among Adults in 9 Rural Ugandan Communities.

BACKGROUND: Social network analysis can elucidate tuberculosis transmission dynamics outside the home and may inform novel network-based case-finding strategies. METHODS: We assessed the association between social network characteristics and prevalent tuberculosis infection among residents (aged ≥15 years) of 9 rural communities in Eastern Uganda. Social contacts named during a census were used to create community-specific nonhousehold social networks. We evaluated whether social network structure and characteristics of first-degree contacts (sex, human immunodeficiency virus [HIV] status, tuberculosis infection) were associated with revalent tuberculosis infection (positive tuberculin skin test [TST] result) after adjusting for individual-level risk factors (age, sex, HIV status, tuberculosis contact, wealth, occupation, and Bacillus Calmette-Guérin [BCG] vaccination) with targeted maximum likelihood estimation. RESULTS: Among 3 335 residents sampled for TST, 32% had a positive TST results and 4% reported a tuberculosis contact. The social network contained 15 328 first-degree contacts. Persons with the most network centrality (top 10%) (adjusted risk ratio, 1.3 [95% confidence interval, 1.1-1.1]) and the most (top 10%) male contacts (1.5 [1.3-1.9]) had a higher risk of prevalent tuberculosis, than those in the remaining 90%. People with ≥1 contact with HIV (adjusted risk ratio, 1.3 [95% confidence interval, 1.1-1.6]) and ≥2 contacts with tuberculosis infection were more likely to have tuberculosis themselves (2.6 [ 95% confidence interval: 2.2-2.9]). CONCLUSIONS: Social networks with higher centrality, more men, contacts with HIV, and tuberculosis infection were positively associated with tuberculosis infection. Tuberculosis transmission within measurable social networks may explain prevalent tuberculosis not associated with a household contact. Further study on network-informed tuberculosis case finding interventions is warranted.

Feasibility and preliminary effectiveness of integrating HIV prevention into an adolescent empowerment and livelihood intervention at youth clubs in rural Uganda.

The uptake of HIV prevention services is lower among youth than adults in sub-Saharan Africa. Existing youth livelihood trainings offer a potential entry point to HIV prevention services. We determined feasibility and preliminary effectiveness of integrating HIV prevention into youth clubs implementing an empowerment and livelihood for adolescents (ELA) intervention in rural Uganda. Staff conducted community mobilization for youth (15-24 years) over one month. Clubs met (3×/week) over six months, with local peer mentors trained to teach life-skills and sexual/reproductive health education. We integrated mentor-led education on HIV prevention, including pre- and post-exposure prophylaxis (PrEP/PEP). Clubs offered on-site HIV testing, a field trip to a local clinic and PrEP referrals after one month and six months. Surveys were conducted at baseline and six months. Forty-two participants (24 adolescent girls/young women (AGYW) and 18 adolescent boys/young men (ABYM)) joined the clubs. At baseline, no participants accepted referral for PrEP, whereas 5/18 (28%) sexually active, HIV-negative AGYW requested PrEP referral at follow-up. One ABYM requested PEP referral. Integration of HIV prevention services into an established ELA curriculum at mentor-led youth clubs in rural Uganda was feasible. PrEP uptake increased among sexually active AGYW. Evaluation of this approach for HIV prevention among youth merits further study.