Prevalence of SARS-CoV-2 Infection among Children and Adults in 15 US Communities, 2021

During January-August 2021, the Community Prevalence of SARS-CoV-2 Study used time/location sampling to recruit a cross-sectional, population-based cohort to estimate SARS-CoV-2 seroprevalence and nasal swab sample PCR positivity across 15 US communities. Survey-weighted estimates of SARS-CoV-2 infection and vaccine willingness among participants at each site were compared within demographic groups by using linear regression models with inverse variance weighting. Among 22,284 persons >2 months of age and older, median prevalence of infection (prior, active, or both) was 12.9% across sites and similar across age groups. Within each site, average prevalence of infection was 3 percentage points higher for Black than White persons and average vaccine willingness was 10 percentage points lower for Black than White persons and 7 percentage points lower for Black persons than for persons in other racial groups. The higher prevalence of SARS-CoV-2 infection among groups with lower vaccine willingness highlights the disparate effect of COVID-19 and its complications.

Tuberculosis care models for children and adolescents: a scoping review.

Objective: To map which tuberculosis care models are best suited for children and adolescents. Methods: We conducted a scoping review to assess the impact of decentralized, integrated and family-centred care on child and adolescent tuberculosis-related outcomes, describe approaches for these care models and identify key knowledge gaps. We searched seven literature databases on 5 February 2021 (updated 16 February 2022), searched the references of 18 published reviews and requested data from ongoing studies. We included studies from countries with a high tuberculosis burden that used a care model of interest and reported tuberculosis diagnostic, treatment or prevention outcomes for an age group < 20 years old. Findings: We identified 28 studies with a comparator group for the impact assessment and added 19 non-comparative studies to a qualitative analysis of care delivery approaches. Approaches included strengthening capacity in primary-level facilities, providing services in communities, screening for tuberculosis in other health services, co-locating tuberculosis and human immunodeficiency virus treatment, offering a choice of treatment location and providing social or economic support. Strengthening both decentralized diagnostic services and community linkages led to one-to-sevenfold increases in case detection across nine studies and improved prevention outcomes. We identified only five comparative studies on integrated or family-centred care, but 11 non-comparative studies reported successful treatment outcomes for at least 71% of children and adolescents. Conclusion: Strengthening decentralized services in facilities and communities can improve tuberculosis outcomes for children and adolescents. Further research is needed to identify optimal integrated and family-centred care approaches.

Assessing the Information-Motivation-Behavioral Skills Model to Predict Pre-exposure Prophylaxis Adherence Among Black Men Who have Sex with Men and Transgender Women in a Community Setting in New York City.

The Information-Motivation-Behavioral Skills (IMB) Model has been used to understand adherence to medications and intentions to uptake pre-exposure prophylaxis (PrEP) to prevent HIV infection. In the current study, the IMB Model was used to understand factors that predict adherence to PrEP among a community-based cohort of 204 Black men who have sex with men (MSM) and transgender women (TGW) using structural equation modeling. PrEP motivation was directly associated with PrEP behavioral skills (ß = 0.320, p = 0.009), and PrEP behavioral skills were directly associated with PrEP adherence (ß = 0.416, p = 0.001). PrEP knowledge and PrEP motivation were not associated with PrEP adherence, directly or indirectly. The analysis identified intervenable factors that predicted PrEP adherence. Screening for motivation and behavioral skills could be used to identify where additional support to improve PrEP adherence is needed, or whether to offer alternative PrEP modalities or delivery strategies.

RESUMEN: El Modelo de Información-Motivación-Habilidades Conductuales (IMB) ha sido utilizado para comprender la adherencia a los medicamentos y la intención de tomar la profilaxis pre-exposición (PrEP) para prevenir la infección por el VIH. En el estudio actual, se usó el modelo IMB para comprender los factores que predicen la adherencia a la PrEP entre una cohorte reclutada en la comunidad de 204 hombres que tienen sexo con hombres (HSH) y mujeres transgénero (TGW) de raza negra, usando modelos de ecuaciones estructurales. La motivación de adherir a la PrEP se asoció directamente con las habilidades conductuales de la PrEP adherencia (ß = 0.320, p = 0.009), y las habilidades conductuales de la PrEP adherencia se asociaron directamente con la adherencia a la PrEP (ß = 0.416, p = 0.001). El conocimiento de PrEP y la motivación de adherir a la PrEPno se asociaron con la adherencia a la PrEP, ni directa o indirectamente. El análisis identificó factores intervenibles que predijeron la adherencia a la PrEP. La evaluación de la motivación de adherir a la PrEP y las habilidades conductuales de la PrEP adherencia podría ser usado para identificar situaciones en que se necesita apoyo adicional para mejorar la adherencia a la PrEP, o si se deben ofrecer modalidades alternativas de recibir PrEP o estrategias alternativas para entregar PrEP.

Provider attitudes about childhood tuberculosis prevention in Lesotho: a qualitative study.

BACKGROUND: The World Health Organization estimated that 1.12 million children developed tuberculosis (TB) in 2018, and at least 200,000 children died from TB. Implementation of effective child contact management is an important strategy to prevent childhood TB but these practices often are not prioritized or implemented, particularly in low- and middle-income countries. This study aimed to explore attitudes of healthcare providers toward TB prevention and perceived facilitators and challenges to child contact management in Lesotho, a high TB burden country. Qualitative data were collected via group and individual in-depth interviews with 12 healthcare providers at five health facilities in one district and analyzed using a thematic framework. RESULTS: Healthcare providers in our study were interested and committed to improve child TB contact management and identified facilitators and challenges to a successful childhood TB prevention program. Facilitators included: provider understanding of the importance of TB prevention and enhanced provider training on child TB contact management, with a particular focus on ruling out TB in children and addressing side effects. Challenges identified by providers were at multiple levels -- structural, clinic, and individual and included: [1] access to care, [2] supply-chain issues, [3] identification and screening of child contacts, and [4] adherence to isoniazid preventive therapy. CONCLUSIONS: Given the significant burden of TB morbidity and mortality in young children and the recent requirement by the WHO to report IPT initiation in child contacts, prioritization of child TB contact management is imperative and should include enhanced provider training on childhood TB and mentorship as well as strategies to eliminate challenges. Strategies that enable more efficient child TB contact management delivery include creating standardized tools that facilitate the implementation, tracking, and monitoring of child TB contact management coupled with guidance and mentorship from the district health management team. To tackle access to care challenges, we propose delivering intensive community health education, conducting community screening more efficiently using standardized tools, and facilitating access to services in the community.

Daily and Nondaily Oral Preexposure Prophylaxis in Men and Transgender Women Who Have Sex With Men: The Human Immunodeficiency Virus Prevention Trials Network 067/ADAPT Study.

Background: Nondaily dosing of oral preexposure prophylaxis (PrEP) may provide equivalent coverage of sex events compared with daily dosing. Methods: At-risk men and transgender women who have sex with men were randomly assigned to 1 of 3 dosing regimens: 1 tablet daily, 1 tablet twice weekly with a postsex dose (time-driven), or 1 tablet before and after sex (event-driven), and were followed for coverage of sex events with pre- and postsex dosing measured by weekly self-report, drug concentrations, and electronic drug monitoring. Results: From July 2012 to May 2014, 357 participants were randomized. In Bangkok, the coverage of sex events was 85% for the daily arm compared with 84% for the time-driven arm (P = .79) and 74% for the event-driven arm (P = .02). In Harlem, coverage was 66%, 47% (P = .01), and 52% (P = .01) for these groups. In Bangkok, PrEP medication concentrations in blood were consistent with use of ≥2 tablets per week in >95% of visits when sex was reported in the prior week, while in Harlem, such medication concentrations occurred in 48.5% in the daily arm, 30.9% in the time-driven arm, and 16.7% in the event-driven arm (P < .0001). Creatinine elevations were more common in the daily arm (P = .050), although they were not dose limiting. Conclusions: Daily dosing recommendations increased coverage and protective drug concentrations in the Harlem cohort, while daily and nondaily regimens led to comparably favorable outcomes in Bangkok, where participants had higher levels of education and employment. Clinical Trials Registration: NCT01327651.

Sex, PrEP, and Stigma: Experiences with HIV Pre-exposure Prophylaxis Among New York City MSM Participating in the HPTN 067/ADAPT Study.

The HPTN 067/Alternative Dosing to Augment Pre-Exposure Prophylaxis Pill Taking (ADAPT) study evaluated daily and non-daily dosing schedules for oral pre-exposure prophylaxis (PrEP) to prevent HIV. A qualitative sub-study including focus groups and in-depth interviews was conducted among men who have sex with men participating in New York City to understand their experience with PrEP and study dosing schedules. The 37 sub-study participants were 68% black, 11% white, and 8% Asian; 27% were of Hispanic/Latino ethnicity. Mean age was 34 years. Themes resulting from qualitative analysis include: PrEP is a significant advance for HIV prevention; non-daily dosing of PrEP is congruent with HIV risk; and pervasive stigma connected to HIV and risk behavior is a barrier to PrEP adherence, especially for non-daily dosing schedules. The findings underscore how PrEP intersects with other HIV prevention practices and highlight the need to understand and address multidimensional stigma related to PrEP use.

Limited awareness of pre-exposure prophylaxis among black men who have sex with men and transgender women in New York city.

Awareness of Pre-exposure prophylaxis (PrEP) was assessed among a cohort of substance-using black men who have sex with men and transgender women (MSM/TGW) participating in the STAR Study, which recruited black MSM/TGW in New York City for HIV testing and linked HIV-infected individuals into care from July 2012 to April 2015. Sociodemographic, psychosocial, known HIV risk factors, and PrEP awareness were assessed among participants. Multivariable logistic regression was conducted to assess factors associated with PrEP awareness. Of 1673 participants, median age was 43 years and 25% were under age 30. Most participants (85.8%) reported having insufficient income for basic necessities at least occasionally, 54.8% were homeless, and 71.3% were unemployed. Awareness of PrEP was reported among 18.2% of participants. PrEP awareness was associated with younger age (adjusted odds ratio [aOR] 0.87, per 5 years), gay identity (aOR 2.46), higher education (aOR 1.70), more frequent past HIV testing (aOR 3.18), less HIV stigma (aOR 0.61), less hazardous/harmful alcohol use (aOR 0.61), and more sexual partners (aOR 1.04, per additional partner in past 30 days). In this substance-using black MSM/TGW cohort with high rates of poverty and homelessness, PrEP awareness was low. This study demonstrates the need for targeted dissemination of PrEP information to key populations to increase awareness and ultimately improve uptake and utilization of PrEP.

A Qualitative Evaluation of the Acceptability of an Interactive Voice Response System to Enhance Adherence to Isoniazid Preventive Therapy Among People Living with HIV in Ethiopia.

Interactive voice response (IVR) is increasingly used to monitor and promote medication adherence. In 2014, we evaluated patient acceptability toward IVR as part of the ENRICH Study, aimed to enhance adherence to isoniazid preventive therapy for tuberculosis prevention among HIV-positive adults in Ethiopia. Qualitative interviews were completed with 30 participants exposed to 2867 IVR calls, of which 24 % were completely answered. Individualized IVR options, treatment education, and time and cost savings facilitated IVR utilization, whereas poor IVR instruction, network and power malfunctions, one-way communication with providers, and delayed clinic follow-up inhibited utilization. IVR acceptability was complicated by HIV confidentiality, mobile phone access and literacy, and patient-provider trust. Incomplete calls likely reminded patients to take medication but were less likely to capture adherence or side effect data. Simple, automated systems that deliver health messages and triage clinic visits appear to be acceptable in this resource-limited setting.

Prevalence, patterns, and correlates of HIV disclosure among TB-HIV patients initiating antiretroviral therapy in Lesotho.

Disclosure of HIV-positive status has important implications for patient outcomes and preventing HIV transmission, but has been understudied in TB-HIV patients. We assessed disclosure patterns and correlates of non-disclosure among adult TB-HIV patients initiating ART enrolled in the START Study, a mixed-methods cluster-randomized trial conducted in Lesotho, which evaluated a combination intervention package (CIP) versus standard of care. Interviewer-administered questionnaire data were analyzed to describe patterns of disclosure. Patient-related factors were assessed for association with non-disclosure to anyone other than a health-care provider and primary partners using generalized linear mixed models. Among 371 participants, 95% had disclosed their HIV diagnosis to someone other than a health-care provider, most commonly a spouse/primary partner (76%). Age, TB knowledge, not planning to disclose TB status, greater perceived TB stigma, and CIP were associated with non-disclosure in unadjusted models (p < .1). In adjusted models, all point estimates were similar and greater TB knowledge (adjusted odds ratio [aOR] 0.59, 95% confidence interval [CI] 0.39-0.90) and CIP (aOR 0.20, 95% CI 0.05-0.79) remained statistically significant. Among 220 participants with a primary partner, 76% had disclosed to that partner. Significant correlates of partner non-disclosure (p < .1) in unadjusted analyses included being female, married/cohabitating, electricity at home, not knowing if partner was HIV-positive, and TB knowledge. Adjusted point estimates were largely similar, and being married/cohabitating (aOR 0.03, 95% CI 0.01-0.12), having electricity at home (aOR 0.38, 95% CI 0.17-0.85) and greater TB knowledge (aOR 0.76, 95% CI 0.59-0.98) remained significant. In conclusion, although nearly all participants reported disclosing their HIV status to someone other than a health-care provider at ART initiation, nearly a quarter of participants with a primary partner had not disclosed to their partner. Additional efforts to support HIV disclosure (e.g., counseling) may be needed for TB-HIV patients, particularly for women and those unaware of their partners' status.

Interferon-γ release assays and tuberculin skin testing for diagnosis of latent tuberculosis infection in healthcare workers in the United States.

RATIONALE: IFN-γ release assays (IGRAs) are alternatives to tuberculin skin testing (TST) for diagnosis of latent tuberculosis infection. Limited data suggest IGRAs may not perform well for serial testing of healthcare workers (HCWs). OBJECTIVES: Determine the performance characteristics of IGRAs versus TST for serial testing of HCWs. METHODS: A longitudinal study involving 2,563 HCWs undergoing occupational tuberculosis screening at four healthcare institutions in the United States, where the average tuberculosis case rate ranged from 4 to 9 per 100,000 persons. QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB (T-SPOT), and TST were performed at baseline and every 6 months for 18 months between February 2008 and March 2011. MEASUREMENTS AND MAIN RESULTS: A total of 2,418 HCWs completed baseline testing, which was positive for 125 (5.2%) by TST, 118 (4.9%) by QFT-GIT, and 144 (6.0%) by T-SPOT. A baseline positive TST with negative IGRAs was associated with bacillus Calmette-Guérin (BCG) vaccination (odds ratio: 25.1 [95% confidence interval: 15.5, 40.5] vs. no BCG). Proportions of participants with test conversion during the study period were 138 of 2,263 (6.1%) for QFT-GIT, 177 of 2,137 (8.3%) for T-SPOT, and 21 of 2,293 (0.9%) for TST (P < 0.001 for QFT-GIT vs. TST and for T-SPOT vs. TST; P = 0.005 for QFT-GIT vs. T-SPOT). Of the QFT-GIT and T-SPOT converters, 81 of 106 (76.4%) and 91 of 118 (77.1%), respectively, were negative when retested 6 months later. There was negative/positive discordance for 15 of 170 (8.8%) participants by QFT-GIT and for 19 of 151 (12.6%) by T-SPOT when blood was drawn 2 weeks later. CONCLUSIONS: Most conversions among HCWs in low TB incidence settings appear to be false positives, and these occurred six to nine times more frequently with IGRAs than TST; repeat testing of apparent converters is warranted.

Treatment practices, outcomes, and costs of multidrug-resistant and extensively drug-resistant tuberculosis, United States, 2005-2007.

To describe factors associated with multidrug-resistant (MDR), including extensively-drug-resistant (XDR), tuberculosis (TB) in the United States, we abstracted inpatient, laboratory, and public health clinic records of a sample of MDR TB patients reported to the Centers for Disease Control and Prevention from California, New York City, and Texas during 2005-2007. At initial diagnosis, MDR TB was detected in 94% of 130 MDR TB patients and XDR TB in 80% of 5 XDR TB patients. Mutually exclusive resistance was 4% XDR, 17% pre-XDR, 24% total first-line resistance, 43% isoniazid/rifampin/rifabutin-plus-other resistance, and 13% isoniazid/rifampin/rifabutin-only resistance. Nearly three-quarters of patients were hospitalized, 78% completed treatment, and 9% died during treatment. Direct costs, mostly covered by the public sector, averaged $134,000 per MDR TB and $430,000 per XDR TB patient; in comparison, estimated cost per non-MDR TB patient is $17,000. Drug resistance was extensive, care was complex, treatment completion rates were high, and treatment was expensive.

Guidelines for tuberculosis screening and preventive treatment among pregnant and breastfeeding women living with HIV in PEPFAR-supported countries.

BACKGROUND: Tuberculosis (TB) preventive treatment (TPT) is recommended by the World Health Organization (WHO) for persons living with HIV, including pregnant and breastfeeding women. Given the President's Emergency Plan for AIDS Relief (PEPFAR)'s investment in TPT services for persons living with HIV as a strategy to prevent TB as well as uncertainty in guidelines and policy regarding use of TPT during pregnancy and the postpartum period, we conducted a review of current relevant national guidelines among PEPFAR-supported countries. METHODS: Our review included 44/49 PEPFAR-supported countries to determine if TB screening and TPT are recommended specifically for pregnant and breastfeeding women living with HIV (WLHIV). National guidelines reviewed and abstracted included TB, HIV, prevention of vertical HIV transmission, TPT, and any other relevant guidelines. We abstracted information regarding TB screening, including screening tools and frequency; and TPT, including timing, regimen, frequency, and laboratory monitoring. RESULTS: Of 44 PEPFAR-supported countries for which guidelines were reviewed, 66% were high TB incidence countries; 41% were classified by WHO as high TB burden countries, and 43% as high HIV-associated TB burden countries. We found that 64% (n = 28) of countries included TB screening recommendations for pregnant WLHIV in their national guidelines, and most (n = 35, 80%) countries recommend TPT for pregnant WLHIV. Fewer countries included recommendations for breastfeeding as compared to pregnant WLHIV, with only 32% (n = 14) mentioning TB screening and 45% (n = 20) specifically recommending TPT for this population; most of these recommend isoniazid-based TPT regimens for pregnant and breastfeeding WLHIV. However, several countries also recommend isoniazid combined with rifampicin (3RH) or rifapentine (3HP). CONCLUSIONS: Despite progress in the number of PEPFAR-supported countries that specifically include TB screening and TPT recommendations for pregnant and breastfeeding WLHIV in their national guidelines, many PEPFAR-supported countries still do not include specific screening and TPT recommendations for pregnant and breastfeeding WLHIV.

Isoniazid preventive therapy completion between July-September 2019: A comparison across HIV differentiated service delivery models in Uganda.

BACKGROUND: Tuberculosis (TB) remains the leading cause of death among people living with HIV (PLHIV). To prevent TB among PLHIV, the Ugandan national guidelines recommend Isoniazid Preventive Therapy (IPT) across differentiated service delivery (DSD) models, an effective way of delivering ART. DSD models include Community Drug Distribution Point (CDDP), Community Client-led ART Delivery (CCLAD), Facility-Based Individual Management (FBIM), Facility-Based Group (FBG), and Fast Track Drug Refill (FTDR). Little is known about the impact of delivering IPT through DSD. METHODS: We reviewed medical records of PLHIV who initiated IPT between June-September 2019 at TASO Soroti (TS), Katakwi Hospital (KH) and Soroti Regional Referral Hospital (SRRH). We defined IPT completion as completing a course of isoniazid within 6-9 months. We utilized a modified Poisson regression to compare IPT completion across DSD models and determine factors associated with IPT completion in each DSD model. RESULTS: Data from 2968 PLHIV were reviewed (SRRH: 50.2%, TS: 25.8%, KH: 24.0%); females: 60.7%; first-line ART: 91.7%; and Integrase Strand Transfer Inhibitor (INSTI)-based regimen: 61.9%. At IPT initiation, the median age and duration on ART were 41.5 (interquartile range [IQR]; 32.3-50.2) and 6.0 (IQR: 3.7-8.6) years, respectively. IPT completion overall was 92.8% (95%CI: 91.8-93.7%); highest in CDDP (98.1%, 95%CI: 95.0-99.3%) and lowest in FBG (85.8%, 95%CI: 79.0-90.7%). Compared to FBIM, IPT completion was significantly higher in CDDP (adjusted rate ratio [aRR] = 1.15, 95%CI: 1.09-1.22) and CCLAD (aRR = 1.09, 95% CI 1.02-1.16). In facility-based models, IPT completion differed between sites (p<0.001). IPT completion increased with age for FBIM and CCLAD and was lower among female participants in the CCLAD (aRR = 0.82, 95%CI 0.67-0.97). CONCLUSION: IPT completion was high overall but highest in community-based models. Our findings provide evidence that supports integration of IPT within DSD models for ART delivery in Uganda and similar settings.

Acceptability of interferon-gamma release assays among healthcare workers who receive routine employee tuberculosis testing.

BACKGROUND: Healthcare workers (HCWs) undergo annual testing for latent tuberculosis infection (LTBI). OBJECTIVE: Compare acceptability of tuberculin skin test (TST) and interferon-gamma release assay (IGRA) among HCWs. METHODS: HCWs at four medical centers in the US were administered an acceptability questionnaire including a brief objective description of both tests and eliciting attitudes regarding TST and IGRAs, confidence in results, and likelihood of taking LTBI treatment. RESULTS: Of 406 participants, 75% had never heard of IGRAs. IGRAs were preferred to TST. Belief in accuracy of hypothetical positive results of TST or IGRA and willingness to accept LTBI treatment were similar across tests. When presented with hypothetical discordant results, HCWs expressed more confidence in IGRAs. Perceived accuracy of results was the most important factor in test preferences. CONCLUSIONS: Although HCWs preferred and indicated more confidence in IGRAs, the likelihood that HCWs would believe LTBI diagnosis and initiate treatment based on positive results was similar for TST and IGRAs.

Integrating 3HP-based tuberculosis preventive treatment into Zimbabwe's Fast Track HIV treatment model: experiences from a pilot study.

INTRODUCTION: Tuberculosis (TB) causes one-third of HIV-related deaths worldwide, making TB preventive treatment (TPT) a critical element of HIV programmes. Approximately 16% of people living with HIV (PLHIV) on antiretrovirals in Zimbabwe are enrolled in the Fast Track (FT) differentiated service delivery model, which includes multi-month dispensing of antiretrovirals and quarterly health facility (HF) visits. We assessed the feasibility and acceptability of utilizing FT to deliver 3HP (3 months of once-weekly rifapentine and isoniazid) for TPT by aligning TPT and HIV visits, providing multi-month dispensing of 3HP, and using phone-based monitoring and adherence support. METHODS: We recruited a purposive sample of 50 PLHIV enrolled in FT at a high-volume HF in urban Zimbabwe. At enrolment, participants provided written informed consent, completed a baseline survey, and received counselling, education and a 3-month supply of 3HP. A study nurse mentor called participants at weeks 2, 4 and 8 to monitor and support adherence and side effects. When participants returned for their routine 3-month FT visit, they completed another survey, and study staff conducted a structured medical record review. In-depth interviews were conducted with providers who participated in the pilot. RESULTS: Participants were enrolled between April and June 2021 and followed through September 2021. Median age = 32 years (IQR 24,41), 50% female, median time in FT 1.8 years (IQR 0.8,2.7). Forty-eight participants (96%) completed 3HP in 13 weeks; one completed in 16 weeks, and one stopped due to jaundice. Most participants (94%) reported "always" or "almost always" taking 3HP correctly. All reported they were very satisfied with the counselling, education, support and quality of care they received from providers and FT service efficiency. Almost all (98%) said they would recommend it to other PLHIV. Challenges reported included pill burden (12%) and tolerability (24%), but none had difficulty with phone-based counselling or wished for additional HF-based visits. DISCUSSION: Using FT to deliver 3HP was feasible and acceptable. Some reported tolerability challenges but 98% completed 3HP, and all appreciated the efficiency of aligning TPT and HIV HF visits, multi-month dispensing and phone-based counselling. CONCLUSIONS: Scaling up this approach could expand TPT coverage in Zimbabwe.

Paediatric tuberculosis preventive treatment preferences among HIV-positive children, caregivers and healthcare providers in Eswatini: a discrete choice experiment.

OBJECTIVE: Isoniazid preventive therapy initiation and completion rates are suboptimal among children. Shorter tuberculosis (TB) preventive treatment (TPT) regimens have demonstrated safety and efficacy in children and may improve adherence but are not widely used in high TB burden countries. Understanding preferences regarding TPT regimens' characteristics and service delivery models is key to designing services to improve TPT initiation and completion rates. We examined paediatric TPT preferences in Eswatini, a high TB burden country. DESIGN: We conducted a sequential mixed-methods study utilising qualitative methods to inform the design of a discrete choice experiment (DCE) among HIV-positive children, caregivers and healthcare providers (HCP). Drug regimen and service delivery characteristics included pill size and formulation, dosing frequency, medication taste, treatment duration and visit frequency, visit cost, clinic wait time, and clinic operating hours. An unlabelled, binary choice design was used; data were analysed using fixed and mixed effects logistic regression models, with stratified models for children, caregivers and HCP. SETTING: The study was conducted in 20 healthcare facilities providing TB/HIV care in Manzini, Eswatini, from November 2018 to December 2019. PARTICIPANTS: Ninety-one stakeholders completed in-depth interviews to inform the DCE design; 150 children 10-14 years, 150 caregivers and 150 HCP completed the DCE. RESULTS: Despite some heterogeneity, the results were fairly consistent among participants, with palatability of medications viewed as the most important TPT attribute; fewer and smaller pills were also preferred. Additionally, shorter waiting times and cost of visit were found to be significant drivers of choices. CONCLUSION: Palatable medication, smaller/fewer pills, low visit costs and shorter clinic wait times are important factors when designing TPT services for children and should be considered as new paediatric TPT regimens in Eswatini are rolled out. More research is needed to determine the extent to which preferences drive TPT initiation, adherence and completion rates.

Improving child tuberculosis contact identification and screening in Lesotho: Results from a mixed-methods cluster-randomized implementation science study.

BACKGROUND: Child tuberculosis (TB) contact management is recommended for preventing TB in children but its implementation is suboptimal in high TB/HIV-burden settings. The PREVENT Study was a mixed-methods, clustered-randomized implementation study that evaluated the effectiveness and acceptability of a community-based intervention (CBI) to improve child TB contact management in Lesotho, a high TB burden country. METHODS: Ten health facilities were randomized to CBI or standard of care (SOC). CBI holistically addressed the complex provider-, patient-, and caregiver-related barriers to prevention of childhood TB. Routine TB program data were abstracted from TB registers and cards for all adult TB patients aged >18 years registered during the study period, and their child contacts. Primary outcome was yield (number) of child contacts identified and screened per adult TB patient. Generalized linear mixed models tested for differences between study arms. CBI acceptability was assessed via semi-structured in-depth interviews with a purposively selected sample of 20 healthcare providers and 28 caregivers. Qualitative data were used to explain and confirm quantitative results. We used thematic analysis to analyze the data. RESULTS: From 01/2017-06/2018, 973 adult TB patients were recorded, 490 at CBI and 483 at SOC health facilities; 64% male, 68% HIV-positive. At CBI and SOC health facilities, 216 and 164 child contacts were identified, respectively (p = 0.16). Screening proportions (94% vs. 62%, p = 0.13) were similar; contact yield per TB case (0.40 vs. 0.20, p = 0.08) was higher at CBI than SOC health facilities, respectively. CBI was acceptable to caregivers and healthcare providers. CONCLUSION: Identification and screening for TB child contacts were similar across study arms but yield was marginally higher at CBI compared with SOC health facilities. CBI scale-up may enhance the ability to reach and engage child TB contacts, contributing to efforts to improve TB prevention among children.

Hazardous alcohol use, antiretroviral therapy receipt, and viral suppression in people living with HIV who inject drugs in the United States, India, Russia, and Vietnam.

OBJECTIVES: In high-income countries, hazardous alcohol use is associated with reduced receipt of antiretroviral therapy (ART) and viral suppression among people living with HIV (PLHIV) who inject drugs. These associations are less understood in lower middle-income countries (LMIC) and upper middle-income countries. DESIGN: We examined associations between hazardous alcohol use, ART receipt, and viral suppression among PLHIV who reported current or former injection drug use. Participants were from nine studies in the United States (high-income country), India (LMIC), Russia (upper middle-income country), and Vietnam (LMIC). METHODS: Hazardous alcohol use was measured via Alcohol Use Disorders Identification Test. Outcomes were HIV viral suppression (viral load of <1000 RNA copies/ml) and self-reported ART receipt. Logistic regression assessed associations between hazardous alcohol use and both outcome variables, controlling for age and sex, among participants with current and former injection drug use. RESULTS: Among 2790 participants, 16% were women, mean age was 37.1 ±â€Š9.5 years. Mean Alcohol Use Disorders Identification Test scores were 4.6 ±â€Š8.1 (women) and 6.2 ±â€Š8.3 (men); 42% reported ART receipt; 40% had viral suppression. Hazardous alcohol use was significantly associated with reduced ART receipt in India (adjusted odds ratio = 0.59, 95% confidence interval: 0.45-0.77, P < 0.001); and lower rates of viral suppression in Vietnam (adjusted odds ratio = 0.51, 95% confidence interval: 0.31-0.82, P = 0.006). CONCLUSION: Associations between hazardous alcohol use, ART receipt, and viral suppression varied across settings and were strongest in LMICs. Addressing hazardous alcohol use holds promise for improving HIV continuum of care outcomes among PLHIV who inject drugs. Specific impact and intervention needs may differ by setting.

Determinants of alcohol use among people living with HIV initiating isoniazid preventive therapy in Ethiopia.

BACKGROUND: Hepatotoxicity, an adverse effect of isoniazid preventative therapy (IPT), is exacerbated by alcohol consumption. Although the WHO recommends IPT for people living with HIV (PLHIV), it is contraindicated in regular alcohol users. The objective of this study was to identify the prevalence and determinants of alcohol use among PLHIV initiating IPT in Ethiopia. METHODS: Baseline data (July 2013-May 2015) from 316 participants in the Enhance Initiation and Retention in IPT Care for HIV (ENRICH) study were used to assess the prevalence of alcohol use. Multinomial logistic regression was used to identify determinants of non-hazardous and hazardous alcohol use, compared to no alcohol use. RESULTS: Overall, 41.8% of participants reported alcohol use, of which 45.5% reported hazardous use. Compared to non-alcohol users, hazardous users were younger (adjusted odds ratio [AOR]: 1.06; 95% confidence interval [95% CI]: 1.02, 1.11), more likely to be male (AOR: 6.40; 95% CI: 3.17, 12.93), Orthodox (AOR: 3.96; 95% CI: 1.74, 9.00), have larger support networks (AOR: 3.82; 95% CI: 1.61, 9.06), and report greater amount (AOR: 14.80; 95% CI: 5.76, 38.02) and frequency (AOR: 5.91; 95% CI: 2.75, 12.67) of khat use. CONCLUSIONS: Alcohol use was prevalent in this population, and current WHO guidelines would exclude a substantial proportion of the population from receiving IPT. PLHIV in this region would benefit from routine screening for alcohol and khat use, and from substance use education and counseling while receiving IPT until it can be determined whether alcohol users can safely receive IPT.

Factors Associated With Sex-Related Pre-exposure Prophylaxis Adherence Among Men Who Have Sex With Men in New York City in HPTN 067.

BACKGROUND: HPTN 067 assessed the feasibility of daily and non-daily dosing of open-label emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)-based pre-exposure prophylaxis (PrEP). METHODS: Factors associated with sex-related PrEP adherence were assessed among men who have sex with men (MSM) randomized to one of 3 PrEP dosing arms in HPTN 067 in New York City. Sex-related PrEP adherence was defined per protocol as at least 1 PrEP tablet taken within 4 days pre-sex and at least 1 additional PrEP tablet taken within 24 hours post-sex, assessed via electronic drug monitoring and weekly interviews. Demographic data and behavioral measures were evaluated for association with sex-related PrEP adherence. Logistic regression for clustered data was used to estimate the unadjusted and adjusted odds ratios. RESULTS: Of 176 randomized MSM participants, 59% were Black, 10% White, 25% Hispanic, and 6% other; median age was 31 years. In the multivariable analyses, higher sex-related PrEP adherence was significantly associated with daily dosing arm, older age, employment, and higher PrEP adherence behavioral skills. Lower sex-related PrEP adherence was significantly associated with identifying as Black or Hispanic (compared with White), opiate use, and reporting "I forgot" as an adherence barrier. CONCLUSIONS: This analysis identified populations of MSM who might benefit from additional support to optimize PrEP adherence, including those who are younger, unemployed, or opiate users. MSM with lower PrEP behavioral skills may benefit from targeted interventions. Further study is needed to assess racial and ethnic disparities in PrEP adherence, which may reflect broader social and economic inequalities not captured in this study.