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.

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.

Core components of infection prevention and control programs at the facility level in Kazakhstan: key challenges and opportunities.

BACKGROUND: Kazakhstan is developing a National Roadmap to strengthen its Infection Prevention and Control (IPC), but until recently has lacked a country-wide facility-level assessment of IPC performance gaps. METHODS: In 2021, the World Health Organization (WHO)'s IPC Core Components and Minimal Requirements were assessed at 78 randomly selected hospitals across 17 administrative regions using adapted WHO tools. The study included site assessments, followed by structured interviews with 320 hospital staff, validation observations of IPC practices, and document reviews. RESULTS: All hospitals had at least one dedicated IPC staff member, 76% had IPC staff with any formal IPC training; 95% established an IPC committee and 54% had an annual IPC workplan; 92% had any IPC guidelines; 55% conducted any IPC monitoring in the past 12 months and shared the results with facility staff, but only 9% used monitoring data for improvements; 93% had access to a microbiological laboratory for HAI surveillance, but HAI surveillance with standardized definitions and systematic data collection was conducted in only one hospital. Adequate bed spacing of at least 1 m in all wards was maintained in 35% of hospitals; soap and paper towels were available at the hand hygiene stations in 62% and 38% of hospitals, respectively. CONCLUSIONS: Existing IPC programs, infrastructure, IPC staffing, workload and supplies present within hospitals in Kazakhstan allow for implementation of effective IPC. Development and dissemination of IPC guidelines based on the recommended WHO IPC core components, improved IPC training system, and implementation of systematic monitoring of IPC practices will be important first steps towards implementing targeted IPC improvement plans in facilities.

Social and structural determinants of health associated with police violence victimization: A latent class analysis of female sex workers who use drugs in Kazakhstan.

INTRODUCTION: Punitive legal environments remain a challenge to HIV prevention efforts in Central Asia, and female sex workers who use drugs are vulnerable to police violence. Little is known about the heterogeneity of police violence against female sex workers who use drugs and factors associated with HIV risk in Central Asia, despite the growing HIV epidemic. METHODS: We recruited a community-based sample of 255 female sex workers who use drugs in Almaty, Kazakhstan between February 2015 and May 2017. We used latent class analysis to differentiate women into distinct classes of police violence victimization, and multinomial logistic regression to identify individual-level health outcomes, HIV risk behaviors, and social and structural factors within the risk environment associated with class membership. RESULTS: A three-class model emerged: Low Victimization (51%), Discrimination and Extortion (15%), and Poly-Victimization (34%). Relative to Low Victimization, factors associated with Poly-Victimization included being positive for HIV and/or sexually-transmitted infections (STI) (aOR: 1.78 (95% CI: 1.01, 3.14)), prior tuberculosis diagnosis (2.73 (1.15, 6.50)), injection drug use (IDU) (2.00 (1.12, 3.58)), greater number of unsafe IDU behaviors (1.21 (1.08, 1.35)), homelessness (1.92 (1.06, 3.48)), greater drug use (1.22 (1.07, 1.39)) and sex work stigma (1.23 (1.06, 1.43)), greater number of sex work clients (2.40 (1.33, 4.31)), working for a boss/pimp (2.74 (1.16, 6.50)), client violence (2.99 (1.65, 5.42)), economic incentives for condomless sex (2.77 (1.42, 5.41)), accessing needle/syringe exchange programs (3.47 (1.42, 8.50)), recent arrest (2.99 (1.36, 6.55)) and detention (2.93 (1.62, 5.30)), and negative police perceptions (8.28 (4.20, 16.3)). Compared to Low Violence, Discrimination and Extortion was associated with lower odds of experiencing intimate partner violence (aOR= 0.26 (0.12, 0.59)), but no other significant associations with the risk environment upon adjusting for socio-demographic characteristics. CONCLUSION: Police violence against female sex workers who use drugs is pervasive in Kazakhstan. Patterns of police violence vary, with greater HIV susceptibility associated with a higher probability of experiencing multiple forms of police violence. Police sensitization workshops that integrate policing and harm reduction, and drug policy reforms that decriminalize drug use may help mitigate the HIV epidemic in Kazakhstan.

Acceptability of Community-Based Tuberculosis Preventive Treatment for People Living with HIV in Zimbabwe.

As Zimbabwe expands tuberculosis preventive treatment (TPT) for people living with HIV (PLHIV), the Ministry of Health and Child Care is considering making TPT more accessible to PLHIV via less-intensive differentiated service delivery models such as Community ART Refill Groups (CARGs). We designed a study to assess the feasibility and acceptability of integrating TPT into CARGs among key stakeholders, including CARG members, in Zimbabwe. We conducted 45 key informant interviews (KII) with policy makers, implementers, and CARG leaders; 16 focus group discussions (FGD) with 136 PLHIV in CARGs; and structured observations of 8 CARG meetings. KII and FGD were conducted in English and Shona. CARG observations were conducted using a structured checklist and time-motion data capture. Ninety six percent of participants supported TPT integration into CARGs and preferred multi-month TPT dispensing aligned with ART dispensing schedules. Participants noted that the existing CARG support systems could be used for TB symptom screening and TPT adherence monitoring/support. Other perceived advantages included convenience for PLHIV and decreased health facility provider workloads. Participants expressed concerns about possible medication stockouts and limited knowledge about TPT among CARG leaders but were confident that CARGs could effectively provide community-based TPT education, adherence monitoring/support, and TB symptom screening provided that CARG leaders received appropriate training and supervision. These results are consistent with findings from pilot projects in other African countries that are scaling up both differentiated service delivery for HIV and TPT and suggest that designing contextually appropriate approaches to integrating TPT into less-intensive HIV treatment models is an effective way to reach people who are established on ART but who may have missed out on access to TPT.

Enhanced Integration of TB Services in Reproductive Maternal Newborn and Child Health (RMNCH) Settings in Eswatini.

Tuberculosis (TB) primarily affects women during their reproductive years and contributes to maternal mortality and poor pregnancy outcomes. For pregnant women living with HIV (WLHIV), TB is the leading cause of non-obstetric maternal mortality, and pregnant WLHIV with TB are at increased risk of transmitting both TB and HIV to their infants. TB diagnosis among pregnant women, particularly WLHIV, remains challenging, and TB preventive treatment (TPT) coverage among pregnant WLHIV is limited. This project aimed to strengthen integrated TB and reproductive, maternal, neonatal and child health (RMNCH) services in Eswatini to improve screening and treatment for TB disease, TPT uptake and completion among women receiving RMNCH services. The project was conducted from April-December 2017 at four health facilities in Eswatini and introduced enhanced monitoring tools and on-site technical support in RMNCH services. We present data on TB case finding among women, and TPT coverage and completion among eligible WLHIV. A questionnaire (S1 Appendix) measured healthcare provider perspectives on the project after three months of project implementation, including feasibility of scaling-up integrated TB and RMNCH services. A total of 5,724 women (HIV-negative or WLHIV) were screened for active TB disease while attending RMNCH services; 53 (0.9%) were identified with presumptive TB, of whom 37 (70%) were evaluated for TB disease and 6 (0.1% of those screened) were diagnosed with TB. Among 1,950 WLHIV who screened negative for TB, 848 (43%) initiated TPT and 462 (54%) completed. Forty-three healthcare providers completed the questionnaire, and overall were highly supportive of integrated TB and RMNCH services. Integration of TB/HIV services in RMNCH settings was feasible and ensured high TB screening coverage among women of reproductive age, however, symptom screening identified few TB cases, and further studies should explore various screening algorithms and diagnostics that optimize case finding in this population. Interventions should focus on working with healthcare providers and patients to improve TPT initiation and completion rates.

Tuberculosis screening among ambulatory people living with HIV: a systematic review and individual participant data meta-analysis.

BACKGROUND: The WHO-recommended tuberculosis screening and diagnostic algorithm in ambulatory people living with HIV is a four-symptom screen (known as the WHO-recommended four symptom screen [W4SS]) followed by a WHO-recommended molecular rapid diagnostic test (eg Xpert MTB/RIF [hereafter referred to as Xpert]) if W4SS is positive. To inform updated WHO guidelines, we aimed to assess the diagnostic accuracy of alternative screening tests and strategies for tuberculosis in this population. METHODS: In this systematic review and individual participant data meta-analysis, we updated a search of PubMed (MEDLINE), Embase, the Cochrane Library, and conference abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to Aug 2, 2019. We screened the reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional, observational studies and randomised trials among adult and adolescent (age ≥10 years) ambulatory people living with HIV, irrespective of signs and symptoms of tuberculosis. We extracted study-level data using a standardised data extraction form, and we requested individual participant data from study authors. We aimed to compare the W4SS with alternative screening tests and strategies and the WHO-recommended algorithm (ie, W4SS followed by Xpert) with Xpert for all in terms of diagnostic accuracy (sensitivity and specificity), overall and in key subgroups (eg, by antiretroviral therapy [ART] status). The reference standard was culture. This study is registered with PROSPERO, CRD42020155895. FINDINGS: We identified 25 studies, and obtained data from 22 studies (including 15 666 participants; 4347 [27·7%] of 15 663 participants with data were on ART). W4SS sensitivity was 82% (95% CI 72-89) and specificity was 42% (29-57). C-reactive protein (≥10 mg/L) had similar sensitivity to (77% [61-88]), but higher specificity (74% [61-83]; n=3571) than, W4SS. Cough (lasting ≥2 weeks), haemoglobin (<10 g/dL), body-mass index (<18·5 kg/m2), and lymphadenopathy had high specificities (80-90%) but low sensitivities (29-43%). The WHO-recommended algorithm had a sensitivity of 58% (50-66) and a specificity of 99% (98-100); Xpert for all had a sensitivity of 68% (57-76) and a specificity of 99% (98-99). In the one study that assessed both, the sensitivity of sputum Xpert Ultra was higher than sputum Xpert (73% [62-81] vs 57% [47-67]) and specificities were similar (98% [96-98] vs 99% [98-100]). Among outpatients on ART (4309 [99·1%] of 4347 people on ART), W4SS sensitivity was 53% (35-71) and specificity was 71% (51-85). In this population, a parallel strategy (two tests done at the same time) of W4SS with any chest x-ray abnormality had higher sensitivity (89% [70-97]) and lower specificity (33% [17-54]; n=2670) than W4SS alone; at a tuberculosis prevalence of 5%, this strategy would require 379 more rapid diagnostic tests per 1000 people living with HIV than W4SS but detect 18 more tuberculosis cases. Among outpatients not on ART (11 160 [71·8%] of 15 541 outpatients), W4SS sensitivity was 85% (76-91) and specificity was 37% (25-51). C-reactive protein (≥10 mg/L) alone had a similar sensitivity to (83% [79-86]), but higher specificity (67% [60-73]; n=3187) than, W4SS and a sequential strategy (both test positive) of W4SS then C-reactive protein (≥5 mg/L) had a similar sensitivity to (84% [75-90]), but higher specificity than (64% [57-71]; n=3187), W4SS alone; at 10% tuberculosis prevalence, these strategies would require 272 and 244 fewer rapid diagnostic tests per 1000 people living with HIV than W4SS but miss two and one more tuberculosis cases, respectively. INTERPRETATION: C-reactive protein reduces the need for further rapid diagnostic tests without compromising sensitivity and has been included in the updated WHO tuberculosis screening guidelines. However, C-reactive protein data were scarce for outpatients on ART, necessitating future research regarding the utility of C-reactive protein in this group. Chest x-ray can be useful in outpatients on ART when combined with W4SS. The WHO-recommended algorithm has suboptimal sensitivity; Xpert for all offers slight sensitivity gains and would have major resource implications. FUNDING: World Health Organization.

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.

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.

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.

Increasing partner HIV testing and linkage to care in TB settings: findings from an implementation study in Pwani, Tanzania.

Couples HIV testing for tuberculosis (TB) patients and their partners may be an effective means to identify HIV-positive persons and strengthen linkage to HIV care. We evaluated an intervention to increase HIV testing and linkage to care (LTC) of newly diagnosed persons and re-linkage for TB/HIV patients in Pwani, Tanzania. In 2014, 12 TB settings within two regional clusters participated; each cluster included ≥1 referral hospital, health center, and directly observed therapy center. Three months after introducing tools to record HIV service delivery, TB clinic staff and peer education volunteers in Cluster 1 received training on HIV partner testing and linkage/re-linkage, and staff in the second cluster received training 3 months thereafter. Twelve months after tools were introduced, clinic records were abstracted to assess changes in couples HIV testing, LTC, and re-linkage. Staff interviews assessed the feasibility and acceptability of the service delivery model. HIV prevalence was high among TB patients during the study period (44.9%; 508/1132), as well as among others who received HIV testing (19.8%; 253/1288). Compared to pre-implementation, couples HIV testing increased in both clusters from 1.8% to 35.2%. Documented LTC increased (from 5.7% to 50.0%) following the introduction of the tools. Additional increases in LTC (from 57.9% to 79.3%) and re-linkage (from 32.9% to 53.7%) followed Cluster 1 training, but no additional increases after Cluster 2 training. Staff perceived little burden associated with service delivery. This study demonstrated a feasible, low-burden approach to expand couples HIV testing and linkage of HIV-positive persons to care. TB settings in sub-Saharan Africa serve populations at disproportionate risk for HIV infection and should be considered key venues to expand access to effective HIV prevention strategies for both patients and their partners. HIV services in TB settings should include HIV testing, condom distribution, and linkage to appropriate additional services.

The PREVENT study to evaluate the effectiveness and acceptability of a community-based intervention to prevent childhood tuberculosis in Lesotho: study protocol for a cluster randomized controlled trial.

BACKGROUND: Effective, evidence-based interventions to prevent childhood tuberculosis (TB) in high TB/HIV-burden, resource-limited settings are urgently needed. There is limited implementation of evidence-based contact management strategies, including isoniazid preventive therapy (IPT), for child contacts of TB cases in Lesotho. METHODS/DESIGN: This mixed-methods implementation science study utilizes a two-arm cluster-randomized trial design with randomization at the health facility level. The study aims to evaluate the effectiveness and acceptability of a combination community-based intervention (CBI) versus standard of care (SOC) for the management of child TB contacts. The study includes three phases: (I) exploratory phase; (II) intervention implementation and testing phase; (III) post-intervention explanatory phase. Healthcare provider interviews to inform intervention refinement (phase I) were completed in December 2015. In phase II, 10 health facilities were randomized to deliver the CBI or SOC, with stratification by facility type (i.e., hospital vs. health center). CBI holistically addresses the complex provider-related, patient-related, and caregiver-related barriers to prevention of childhood TB through nurse training and mentorship; health education for caregivers and patients by village health workers; adherence support using text messaging and village health workers; and multidisciplinary team meetings, where programmatic data are reviewed and challenges and solutions are discussed. SOC sites follow country guidelines for child TB contact management. Routine TB program data will be abstracted for all adult TB cases newly registered during the study period and their child contacts from TB registers and cards. The anticipated sample size is 1080 child contacts. Primary outcomes are yield (number) of child contacts, including children < 5 years of age and HIV-positive children < 15 years of age; IPT initiation; and IPT completion. Secondary outcomes include HIV testing; yield of active prevalent TB among child contacts; and acceptability and utilization of CBI components. Intervention implementation began in February 2016 and is ongoing. Post-intervention interviews with healthcare providers and caregivers (phase III) commenced in February 2017. DISCUSSION: The PREVENT study tests the effectiveness and acceptability of a novel combination CBI for child TB contact management in Lesotho. If effective, CBI will have important implications for addressing childhood TB in Lesotho and elsewhere. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02662829 . Registered on 15 January 2016.

Reaching the end of the line: Operational issues with implementing phone-based unannounced pill counts in resource-limited settings.

INTRODUCTION: Accurate measurement of adherence is necessary to ensure that therapeutic outcomes can be attributed to the recommended treatment. Phone-based unannounced pill counts were shown to be feasible and reliable measures of adherence in developed settings; and have been further used as part of medication adherence interventions. However, it is not clear whether this method can be implemented successfully in resource-limited settings, where cellular network and mobile phone coverage may be low. Our objective is to describe operational issues surrounding the use of phone-based unannounced pill counts in Lesotho and Ethiopia. METHODS: Phone-based monthly unannounced pill counts, using an adaptation of a standardized protocol from previous US-based studies, were utilized to measure anti-TB and antiretroviral medication adherence in two implementation science studies in resource-limited settings, START (Lesotho) and ENRICH (Ethiopia). RESULTS: In START, 19.6% of calls were completed, with 71.9% of participants reached at least once; majority of failed call attempts were due to phones not being available (54.8%) or because participants were away from the pills (32.7%). In ENRICH, 33.5% of calls were completed, with 86.7% of participants reached at least once; the main reasons for failed call attempts were phones being switched off (31.5%), participants not answering (27.3%), participants' discomfort speaking on the phone (15.4%), and network problems (13.2%). Structural, facility-level, participant-level, and data collection challenges were encountered in these settings. DISCUSSION: Phone-based unannounced pill counts were found to be challenging, and response rates suboptimal. While some of these challenges were specific to local contexts, most of them are generalizable to resource-limited settings. In a research study context, a possible solution to ease operational challenges may be to focus phone-based unannounced pill count efforts on a randomly selected sample from participants who are provided with study phones and rigorously ensure that call attempts are made for these participants.

The ENRICH Study to evaluate the effectiveness of a combination intervention package to improve isoniazid preventive therapy initiation, adherence and completion among people living with HIV in Ethiopia: rationale and design of a mixed methods cluster randomized trial.

BACKGROUND: Isoniazid preventive therapy (IPT) prevents tuberculosis among HIV-positive individuals, however implementation is suboptimal. Implementation science studies are needed to identify interventions to address this evidence-to-program gap. OBJECTIVE: The ENRICH Study is a mixed methods cluster randomized trial aimed at evaluating the effectiveness and acceptability of a combination intervention package (CIP) to improve IPT implementation in Ethiopia. DESIGN: Ten health centers were randomized to receive the CIP or standard of care. The CIP includes: nurse training and mentorship using a clinical algorithm, tool to identify IPT-eligible family members, and data review at multidisciplinary team meetings; patient transport reimbursement; and adherence support using peer educators and interactive voice response messages. Routine data were abstracted for all newly-enrolled IPT-eligible HIV-positive patients; anticipated sample size was 1400 individuals. A measurement cohort of patients initiating IPT was recruited; target enrollment was 500 individuals, to be followed for the duration of IPT (6-9 months). Inclusion criteria were: HIV-positive; initiated IPT; age ≥18; Amharic-, Oromiffa-, Harari-, or Somali-speaking; and capable of informed consent. Three groups were recruited from CIP health centers for in-depth interviews: IPT initiators; IPT non-initiators; and health care providers. Primary outcomes are: IPT initiation; and IPT completion. Secondary outcomes include: retention; adherence; change in CD4+ count; adverse events; and acceptability. Follow-up is complete. DISCUSSION: The ENRICH Study evaluates a CIP targeting barriers to IPT implementation. If the CIP is found effective and acceptable, this study has the potential to inform TB prevention strategies for HIV patients in resource-limited countries in sub-Saharan Africa.

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.

Using mHealth for HIV/TB Treatment Support in Lesotho: Enhancing Patient-Provider Communication in the START Study.

BACKGROUND: mHealth is a promising means of supporting adherence to treatment. The Start TB patients on ART and Retain on Treatment (START) study included real-time adherence support using short-text messaging service (SMS) text messaging and trained village health workers (VHWs). We describe the use and acceptability of mHealth by patients with HIV/tuberculosis and health care providers. METHODS: Patients and treatment supporters received automated, coded medication and appointment reminders at their preferred time and frequency, using their own phones, and $3.70 in monthly airtime. Facility-based VHWs were trained to log patient information and text message preferences into a mobile application and were given a password-protected mobile phone and airtime to communicate with community-based VHWs. The use of mHealth tools was analyzed from process data over the study course. Acceptability was evaluated during monthly follow-up interviews with all participants and during qualitative interviews with a subset of 30 patients and 30 health care providers at intervention sites. Use and acceptability were contextualized by monthly adherence data. FINDINGS: From April 2013 to August 2015, the automated SMS system successfully delivered 39,528 messages to 835 individuals, including 633 patients and 202 treatment supporters. Uptake of the SMS intervention was high, with 92.1% of 713 eligible patients choosing to receive SMS messages. Patient and provider interviews yielded insight into barriers and facilitators to mHealth utilization. The intervention improved the quality of health communication between patients, treatment supporters, and providers. HIV-related stigma and technical challenges were identified as potential barriers. CONCLUSIONS: The mHealth intervention for HIV/tuberculosis treatment support in Lesotho was found to be a low-tech, user-friendly intervention, which was acceptable to patients and health care providers.

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.