A DNA Methylation Signature from Buccal Swabs to Identify Tuberculosis Infection.

BACKGROUND: Tuberculosis (TB) is amongst the largest infectious causes of death worldwide and there is a need for a time- and resource-effective diagnostic method. In this novel and exploratory study, we show the potential of using buccal swabs to collect human DNA and investigate the DNA methylation (DNAm) signatures as a diagnostic tool for TB. METHODS: Buccal swabs were collected from pulmonary TB patients (n= 7), TB exposed (n= 7), and controls (n= 9) in Sweden. Using Illumina MethylationEPIC array the DNAm status was determined. RESULTS: We identified 5644 significant differentially methylated CpG sites between the patients and controls. Performing the analysis on a validation cohort of samples collected in Kenya and Peru (patients, n=26; exposed, n=9; control, n=10) confirmed the DNAm signature. We identified a TB consensus disease module, significantly enriched in TB-associated genes. Lastly, we used machine learning to identify a panel of seven CpG sites discriminative for TB and developed a TB classifier. In the validation cohort the classifier performed with an AUC of 0.94, sensitivity of 0.92, and specificity of 1. CONCLUSION: In summary, the result from this study shows clinical implications of using DNAm signatures from buccal swabs to explore new diagnostic strategies for TB.

Effects of Alcohol Use on Patient Retention in HIV Care in East Africa.

We sought to investigate the association between hazardous alcohol use and gaps in care for people living with HIV over a long-term follow-up period. Adults who had participated in our previously published Phase I study of hazardous alcohol use at HIV programs in Kenya and Uganda were eligible at their 42 to 48 month follow-up visit. Those who re-enrolled were followed for an additional ~ 12 months. Hazardous alcohol use behavior was measured using the Alcohol Use Disorders Identification Test (AUDIT) tool. Deidentified clinical data were used to assess gaps in care (defined as failure to return to clinic within 60 days after a missed visit). The proportion of patients experiencing a gap in care at a specific time point was based on a nonparametric moment-based estimator. A semiparametric Cox proportional hazard model was used to determine the association between hazardous alcohol use at enrollment in Phase I (AUDIT score ≥ 8) and gaps in care. Of the 731 study-eligible participants from Phase I, 5.5% had died, 10.1% were lost to follow-up, 39.5% transferred, 7.5% declined/not approached, and 37.3% were enrolled. Phase II participants were older, had less hazardous drinking and had a lower WHO clinical stage than those not re-enrolled. Hazardous drinking in the re-enrolled was associated with a Hazard Ratio (HR) of 1.88 [p-value = 0.016] for a gap in care. Thus, hazardous alcohol use at baseline was associated with an increased risk of experiencing a gap in care and presents an early target for intervention.

RESUMEN: Buscamos investigar la asociación entre el uso riesgoso de alcohol y retención en programas de VIH a largo plazo. Todo adulto que participó en nuestro estudio previamente publicado sobre el uso riesgoso de alcohol en programas de VIH en Kenia y Uganda era elegible a los 42 a 48 meses de seguimiento. Los adultos reinscritos en la fueron seguidos por ~ 12 meses adicionales. Usamos el "Alcohol Use Disorders Identification Test" (AUDIT) para medir uso de alcohol. Usamos datos clínicos anonimizados para evaluar interrupciones en cuidado (definido como falta de regresar a clínica 60 días después de faltar a una cita). Basamos la proporción de pacientes con una interrupción en cuidado clínico en un estimador momentáneo y no-paramétrico. Determinamos la asociación entre el uso riesgoso de alcohol al inicio de la primera fase (puntuación AUDIT ≥8) con retención en servicios clínicos usando un modelo de riesgo Cox semiparamétrico. De los 731 participantes elegibles, 5.5% habían muerto, 10.1% fueron perdidos a seguimiento clínico, 39.5% se transfirieron a otro programa, 7.5% declinaron participación o no fueron reclutados y 37.3% fueron reinscritos en la segunda fase. Los participantes reinscritos eran mayores, tenían menos uso riesgoso de alcohol y tenían VIH menos avanzado. El uso peligroso del alcohol se vio asociado con el riesgo de tener una interrupción en cuidado clínico [Proporción de Riesgo (Hazard Ratio, HR) PR=1.88, valor-p = 0.016]. Por lo tanto, el uso peligroso del alcohol incrementa el riesgo de perder seguimiento clínico y presenta una oportunidad para intervención.

Same-Day Antiretroviral Therapy Initiation as a Predictor of Loss to Follow-up and Viral Suppression Among People With Human Immunodeficiency Virus in Sub-Saharan Africa.

BACKGROUND: Treat-All guidelines recommend initiation of antiretroviral therapy (ART) for all people with HIV (PWH) on the day of diagnosis when possible, yet uncertainty exists about the impact of same-day ART initiation on subsequent care engagement. We examined the association of same-day ART initiation with loss to follow-up and viral suppression among patients in 11 sub-Saharan African countries. METHODS: We included ART-naive adult PWH from sites participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium who enrolled in care after Treat-All implementation and prior to January 2019. We used multivariable Cox regression to estimate the association between same-day ART initiation and loss to follow-up and Poisson regression to estimate the association between same-day ART initiation and 6-month viral suppression. RESULTS: Among 29 017 patients from 63 sites, 18 584 (64.0%) initiated ART on the day of enrollment. Same-day ART initiation was less likely among those with advanced HIV disease versus early-stage disease. Loss to follow-up was significantly lower among those initiating ART ≥1 day of enrollment, compared with same-day ART initiators (20.6% vs 27.7%; adjusted hazard ratio: .66; 95% CI .57-.76). No difference in viral suppression was observed by time to ART initiation (adjusted rate ratio: 1.00; 95% CI: .98-1.02). CONCLUSIONS: Patients initiating ART on the day of enrollment were more frequently lost to follow-up than those initiating later but were equally likely to be virally suppressed. Our findings support recent World Health Organization recommendations for providing tailored counseling and support to patients who accept an offer of same-day ART.

The Effect of HIV Treatment Interruption on Subsequent Immunological Response.

Recovery of CD4-positive T lymphocyte count after initiation of antiretroviral therapy (ART) has been thoroughly examined among people with human immunodeficiency virus infection. However, immunological response after restart of ART following care interruption is less well studied. We compared CD4 cell-count trends before disengagement from care and after ART reinitiation. Data were obtained from the East Africa International Epidemiology Databases to Evaluate AIDS (IeDEA) Collaboration (2001-2011; n = 62,534). CD4 cell-count trends before disengagement, during disengagement, and after ART reinitiation were simultaneously estimated through a linear mixed model with 2 subject-specific knots placed at the times of disengagement and treatment reinitiation. We also estimated CD4 trends conditional on the baseline CD4 value. A total of 10,961 patients returned to care after disengagement from care, with the median gap in care being 2.7 (interquartile range, 2.1-5.4) months. Our model showed that CD4 cell-count increases after ART reinitiation were much slower than those before disengagement. Assuming that disengagement from care occurred 12 months after ART initiation and a 3-month treatment gap, CD4 counts measured at 3 years since ART initiation would be lower by 36.5 cells/µL than those obtained under no disengagement. Given that poorer CD4 restoration is associated with increased mortality/morbidity, specific interventions targeted at better retention in care are urgently required.

Strain structure analysis of Mycobacterium tuberculosis circulating among HIV negative, positive and drug resistant TB patients attending chest clinics in Western Kenya.

BACKGROUND: Despite global tuberculosis (TB) interventions, the disease remains one of the major public health concerns. Kenya is ranked 15th among 22 high burden TB countries globally. METHODS: A cross-sectional study was conducted in Western Kenya, which comprises 10 counties. A multistage sampling method was used where a single sub-county was randomly selected followed by sampling two high volume health facility from each sub-county. Identification of spoligotype profiles and their family distribution and lineage level were achieved by comparison with SITVIT database. RESULTS: Lineage distribution pattern revealed that the most predominant lineage was CAS 220 (39.8%) followed by Beijing 128 (23.1%). The other lineages identified were T, LAM, H, X, S and MANU which were quantified as 87 (15.7%), 67 (12.1%), 16 (2.8%), 10 (1.8%), 8 (1.4%) and 5 (0.9%) respectively. CAS and Beijing strains were the most predominant lineage in both HIV negative and positive TB patients. The Beijing lineage was also the most predominant in resistant M. tuberculosis strains as compared to wild type. A total of 12 (2.0%) were orphaned M. tuberculosis strains which were spread across all the 10 counties of the study site. In multivariate logistic regression adjusting for potential cofounders three potential risk factors were significant. HIV status (OR = 1.52, CI = 0.29-3.68 and P value of 0.001), Alcohol use (OR = 0.59, CI = 0.43-3.12 and P-value =0.001) and cross border travel (OR = 0.61, CI = 0.49-3.87 and P value = 0.026). Most M. tuberculosis clinical isolates showed genetic clustering with multivariate logistic regression indicating three potential risk factors to clustering. HIV status (OR = 1.52, CI = 0.29-3.68 and P value of 0.001), Alcohol use (OR = 0.59, CI = 0.43-3.12 and P-value =0.001) and cross border travel (OR = 0.61, CI = 0.49-3.87 and P value = 0.026). CONCLUSION: There exist diverse strains of M. tuberculosis across the 10 counties of Western Kenya. Predominant distribution of clustered genotype points to the fact that most TB cases in this region are as a result of resent transmission other than activation of latent TB.

Viral Load Status Before Switching to Dolutegravir-Containing Antiretroviral Therapy and Associations With Human Immunodeficiency Virus Treatment Outcomes in Sub-Saharan Africa.

BACKGROUND: Dolutegravir is being rolled out globally as part of preferred antiretroviral therapy (ART) regimens, including among treatment-experienced patients. The role of viral load (VL) testing before switching patients already on ART to a dolutegravir-containing regimen is less clear in real-world settings. METHODS: We included patients from the International epidemiology Databases to Evaluate AIDS consortium who switched from a nevirapine- or efavirenz-containing regimen to one with dolutegravir. We used multivariable cause-specific hazards regression to estimate the association of the most recent VL test in the 12 months before switching with subsequent outcomes. RESULTS: We included 36 393 patients at 37 sites in 5 countries (Democratic Republic of the Congo, Kenya, Rwanda, Tanzania, Uganda) who switched to dolutegravir from July 2017 through February 2020, with a median follow-up of approximately 11 months. Compared with those who switched with a VL <200 copies/mL, patients without a recent VL test or with a preswitch VL ≥1000 copies/mL had significantly increased hazards of an incident VL ≥1000 copies/mL (adjusted hazard ratio [aHR], 2.89; 95% confidence interval [CI], 1.99-4.19 and aHR, 6.60; 95% CI, 4.36-9.99, respectively) and pulmonary tuberculosis or a World Health Organization clinical stage 4 event (aHR, 4.78; 95% CI, 2.77-8.24 and aHR, 13.97; 95% CI, 6.62-29.50, respectively). CONCLUSIONS: A VL test before switching to dolutegravir may help identify patients who need additional clinical monitoring and/or adherence support. Further surveillance of patients who switched to dolutegravir with an unknown or unsuppressed VL is needed.

The Causal Effect of Tracing by Peer Health Workers on Return to Clinic Among Patients Who Were Lost to Follow-up From Antiretroviral Therapy in Eastern Africa: A "Natural Experiment" Arising From Surveillance of Lost Patients.

BACKGROUND.: The effect of tracing human immunodeficiency virus (HIV)-infected patients who are lost to follow-up (LTFU) on reengagement has not been rigorously assessed. We carried out an ex post analysis of a surveillance study in which LTFU patients were randomly selected for tracing to identify the effect of tracing on reengagement. METHODS.: We evaluated HIV-infected adults on antiretroviral therapy who were LTFU (>90 days late for last visit) at 14 clinics in Uganda, Kenya, and Tanzania. A random sample of LTFU patients was selected for tracing by peer health workers. We assessed the effect of selection for tracing using Kaplan-Meier estimates of reengagement among all patients as well as the subset of LTFU patients who were alive, contacted in person by the tracer, and out of care. RESULTS.: Of 5781 eligible patients, 991 (17%) were randomly selected for tracing. One year after selection for tracing, 13.3% (95% confidence interval [CI], 11.1%-15.3%) of those selected for tracing returned compared with 10.0% (95% CI, 9.1%-10.8%) of those not randomly selected, an adjusted risk difference of 3.0% (95% CI, .7%-5.3%). Among patients found to be alive, personally contacted, and out of care, tracing increased the absolute probability of return at 1 year by 22% (95% CI, 7.1%-36.2%). The effect of tracing on rate of return to clinic decayed with a half-life of 7.0 days after tracing (95% CI, 2.6 %-12.9%). CONCLUSIONS.: Tracing interventions increase reengagement, but developing methods for targeting LTFU patients most likely to benefit can make this practice more efficient.

Trends in hepatitis B virus testing practices and management in HIV clinics across sub-Saharan Africa.

BACKGROUND: Approximately 8% of HIV-infected individuals are co-infected with hepatitis B virus (HBV) in sub-Saharan Africa (SSA). Knowledge of HBV status is important to guide optimal selection of antiretroviral therapy (ART) and monitor/prevent liver-related complications. We describe changes in testing practices and management of HBV infection over a 3-year period in HIV clinics across SSA. METHODS: A medical chart review was conducted in large urban HIV treatment centers in Côte d'Ivoire (3 sites), Benin, Burkina Faso, Cameroon, Kenya, Senegal, South Africa, Togo, Uganda and Zambia (1 site each). Of the patients who started ART between 2010 and 2012, 100 per year were randomly selected from each clinic. Demographic, clinical and laboratory information as well as individual treatment histories were collected using a standardized questionnaire. We examined changes over time in the proportion of patients screened for HBV infection (HBV surface antigen [HBsAg]-positivity), identified predictors of HBV testing using logistic regression, and assessed the proportion of patients initiating a tenofovir (TDF)-containing ART regimen. RESULTS: Overall, 3579 charts of patients initiating ART (64.4% female, median age 37 years) were reviewed in 12 clinics. The proportion of patients screened for HBsAg increased from 17.8% in 2010 to 24.4% in 2012 overall, and ranged from 0.7% in Kenya to 96% in South Africa. In multivariable analyses, age and region were associated with HBsAg screening. Among 759 individuals tested, 88 (11.6%; 95% confidence interval [CI] 9.4-14.1) were HBV-infected, of whom 71 (80.7%) received a TDF-containing ART regimen. HBsAg-positive individuals were twice as likely to receive a TDF-containing first-line ART regimen compared to HBsAg-negative patients (80.7% vs. 40.3%, p < 0.001). The proportion of patients on TDF-containing ART increased from 57.9% in 2010 to 90.2% in 2012 in HIV/HBV-co-infected patients (Chi-2 test for trend: p = 0.01). Only 114 (5.0%) patients were screened for anti-HCV antibodies and one of them (0.9%, 95% CI 0.02-4.79) had a confirmed HCV infection. CONCLUSIONS: The systematic screening for HBV infection in HIV-positive patients before ART initiation was limited in most African countries and its uptake varied widely across clinics. Overall, the prescription of TDF increased over time, with 90% of HIV/HBV-coinfected patients receiving this drug in 2012.

Retention in Care and Patient-Reported Reasons for Undocumented Transfer or Stopping Care Among HIV-Infected Patients on Antiretroviral Therapy in Eastern Africa: Application of a Sampling-Based Approach.

BACKGROUND: Improving the implementation of the global response to human immunodeficiency virus requires understanding retention after starting antiretroviral therapy (ART), but loss to follow-up undermines assessment of the magnitude of and reasons for stopping care. METHODS: We evaluated adults starting ART over 2.5 years in 14 clinics in Uganda, Tanzania, and Kenya. We traced a random sample of patients lost to follow-up and incorporated updated information in weighted competing risks estimates of retention. Reasons for nonreturn were surveyed. RESULTS: Among 18 081 patients, 3150 (18%) were lost to follow-up and 579 (18%) were traced. Of 497 (86%) with ascertained vital status, 340 (69%) were alive and, in 278 (82%) cases, updated care status was obtained. Among all patients initiating ART, weighted estimates incorporating tracing outcomes found that 2 years after ART, 69% were in care at their original clinic, 14% transferred (4% official and 10% unofficial), 6% were alive but out of care, 6% died in care (<60 days after last visit), and 6% died out of care (≥ 60 days after last visit). Among lost patients found in care elsewhere, structural barriers (eg, transportation) were most prevalent (65%), followed by clinic-based (eg, waiting times) (33%) and psychosocial (eg, stigma) (27%). Among patients not in care elsewhere, psychosocial barriers were most prevalent (76%), followed by structural (51%) and clinic based (15%). CONCLUSIONS: Accounting for outcomes among those lost to follow-up yields a more informative assessment of retention. Structural barriers contribute most to silent transfers, whereas psychological and social barriers tend to result in longer-term care discontinuation.

Task Shifting and Skin Punch for the Histologic Diagnosis of Kaposi's Sarcoma in Sub-Saharan Africa: A Public Health Solution to a Public Health Problem.

Fueled by HIV, sub-Saharan Africa has the highest incidence of Kaposi's sarcoma (KS) in the world. Despite this, KS diagnosis in the region is based mostly on clinical grounds. Where biopsy is available, it has traditionally been excisional and performed by surgeons, resulting in multiple appointments, follow-up visits for suture removal, and substantial costs. We hypothesized that a simpler approach - skin punch biopsy - would make histologic diagnosis more accessible. To address this, we provided training and equipment for skin punch biopsy of suspected KS to three HIV clinics in East Africa. The procedure consisted of local anesthesia followed by a disposable cylindrical punch blade to obtain specimens. Hemostasis is facilitated by Gelfoam®. Patients removed the dressing after 4 days. From 2007 to 2013, 2,799 biopsies were performed. Although originally targeted to be used by physicians, biopsies were performed predominantly by nurses (62%), followed by physicians (15%), clinical officers (12%) and technicians (11%). There were no reports of recurrent bleeding or infection. After minimal training and provision of inexpensive equipment (USD 3.06 per biopsy), HIV clinics in East Africa can integrate same-day skin punch biopsy for suspected KS. Task shifting from physician to non-physician greatly increases access. Skin punch biopsy should be part of any HIV clinic's essential procedures. This example of task shifting may also be applicable to the diagnosis of other cancers (e.g., breast) in resource-limited settings.

Modeling the HIV Cascade of Care Using Routinely Collected Clinical Data to Guide Programmatic Interventions and Policy Decisions.

BACKGROUND: The HIV care cascade is a framework to examine effectiveness of HIV programs and progress toward global targets to end the epidemic but has been conceptualized as a unidirectional process that ignores cyclical care patterns. We present a dynamic cascade that accounts for patient "churn" and apply novel analytic techniques to readily available clinical data to robustly estimate program outcomes and efficiently assess progress toward global targets. METHODS: Data were assessed for 35,649 people living with HIV and receiving care at 78 clinics in East Africa between 2014 and 2020. Patients were aged ≥15 years and had ≥1 viral load measurements. We used multi-state models to estimate the probability of being in 1 of 5 states of a dynamic HIV cascade: (1) in HIV care but not on antiretroviral therapy (ART), (2) on ART, (3) virally suppressed, (4) in a gap-in-care, and (5) deceased and compared these among subgroups. To assess progress toward global targets, we summed those probabilities across patients and generated population-level proportions of patients on ART and virally suppressed in mid-2020. RESULTS: One year after enrollment, 2.8% of patients had not initiated ART, 86.7% were receiving ART, 57.4% were virally suppressed, 10.2% were disengaged from care, and 0.3% had died. At 5 years, the proportion on ART remained steady but viral suppression increased to 77.2%. Of those aged 15-25, >20% had disengaged from care and <60% were virally suppressed. In mid-2020, 90.1% of the cohort was on ART, 90.7% of whom had suppressed virus. CONCLUSIONS: Novel analytic approaches can characterize patient movement through a dynamic HIV cascade and, importantly, by capitalizing on readily available data from clinical cohorts, offer an efficient approach to estimate population-level proportions of patients on ART and virally suppressed. Significant progress toward global targets was observed in our cohort but challenges remain among younger patients.

Tuberculosis Is Associated with Chronic Hypoxemia among Kenyan Adults (CHAKA): A Case-Control Study.

Rationale: Data on risk factors for chronic hypoxemia in low- and middle-income countries are lacking. Objectives: We aimed to quantify the association between potential risk factors and chronic hypoxemia among adults hospitalized in Kenya. Methods: A hospital-based, case-control study was conducted at Moi Teaching and Referral Hospital in Eldoret, Kenya. Adult inpatients were screened on admission and enrolled in a 1:2 case-to-control ratio. Cases were patients with chronic hypoxemia, defined as resting oxygen saturation as measured by pulse oximetry (SpO2) ⩽ 88% on admission and either 1-month postdischarge SpO2 ⩽ 88% or, if they died before follow-up, documented SpO2 ⩽ 88% in the 6 months before enrollment. Control subjects were randomly selected, stratified by sex, among nonhypoxemic inpatients. Data were collected using questionnaires and structured chart review. Regression was used to assess the associations between chronic hypoxemia and age, sex, smoking status, biomass fuel use, elevation, and self-reported history of tuberculosis and human immunodeficiency virus diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) are reported. Results: We enrolled 108 chronically hypoxemic cases and 240 nonhypoxemic control subjects into our Chronic Hypoxemia among Kenyan Adults (CHAKA) cohort. In multivariable analysis, compared with control subjects, chronically hypoxemic cases had significantly higher odds of older age (OR, 1.2 per 5-year increase [95% CI, 1.1-1.3]), female sex (OR, 3.6 [95% CI, 1.8-7.2]), current or former tobacco use (OR, 4.7 [95% CI, 2.3-9.6]), and prior tuberculosis (OR, 11.8 [95% CI, 4.7-29.6]) but no increase in the odds of human immunodeficiency virus diagnosis and biomass fuel use. Conclusions: These findings highlight the potential impact of prior tuberculosis on chronic lung disease in Kenya and the need for further studies on posttuberculosis lung disease.

Metabolic causes of liver disease among adults living with HIV from low- and middle-income countries: a cross-sectional study.

INTRODUCTION: Liver disease is a leading cause of morbidity and mortality among persons living with HIV (PLHIV). While chronic viral hepatitis has been extensively studied in low- and middle-income countries (LMICs), there is limited information about the burden of metabolic disorders on liver disease in PLHIV. METHODS: We conducted a cross-sectional analysis of baseline data collected between October 2020 and July 2022 from the IeDEA-Sentinel Research Network, a prospective cohort enrolling PLHIV ≥40 years on antiretroviral treatment (ART) for ≥6 months from eight clinics in Asia, Americas, and central, East, southern and West Africa. Clinical assessments, laboratory testing on fasting blood samples and liver stiffness measurement (LSM)/controlled attenuation parameter (CAP) by vibration-controlled transient elastography were performed. Multivariable logistic regression models assessed factors associated with liver fibrosis (LSM ≥7.1 kPa) and steatosis (CAP ≥248 dB/m). Population attributable fraction (PAF) of each variable associated with significant liver fibrosis was estimated using Levin's formula. RESULTS: Overall, 2120 PLHIV (56% female, median age 50 [interquartile range: 45-56] years) were included. The prevalence of obesity was 19%, 12% had type 2 diabetes mellitus (T2DM), 29% had hypertension and 53% had dyslipidaemia. The overall prevalence of liver fibrosis and steatosis was 7.6% (95% confidence interval [CI] 6.1-8.4) and 28.4% (95% CI 26.5-30.7), respectively, with regional variability. Male sex at birth (odds ratio [OR] 1.62, CI 1.10-2.40), overweight/obesity (OR = 2.50, 95% CI 1.69-3.75), T2DM (OR 2.26, 95% CI 1.46-3.47) and prolonged exposure to didanosine (OR 3.13, 95% CI 1.46-6.49) were associated with liver fibrosis. Overweight/obesity and T2DM accounted for 42% and 11% of the PAF for liver fibrosis, while HBsAg and anti-HCV accounted for 3% and 1%, respectively. Factors associated with steatosis included overweight/obesity (OR 4.25, 95% CI 3.29-5.51), T2DM (OR 2.06, 95% CI 1.47-2.88), prolonged exposure to stavudine (OR 1.69, 95% CI 1.27-2.26) and dyslipidaemia (OR 1.68, 95% CI 1.31-2.16). CONCLUSIONS: Metabolic disorders were significant risk factors for liver disease among PLHIV in LMICs. Early recognition of metabolic disorders risk factors might be helpful to guide clinical and lifestyle interventions. Further prospective studies are needed to determine the causative natures of these findings.

The Tuberculosis Sentinel Research Network (TB-SRN) of the International epidemiology Databases to Evaluate AIDS (IeDEA): protocol for a prospective cohort study in Africa, Southeast Asia and Latin America.

INTRODUCTION: Tuberculosis (TB) is a leading infectious cause of death globally. It is the most common opportunistic infection in people living with HIV, and the most common cause of their morbidity and mortality. Following TB treatment, surviving individuals may be at risk for post-TB lung disease. The TB Sentinel Research Network (TB-SRN) provides a platform for coordinated observational TB research within the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. METHODS AND ANALYSIS: This prospective, observational cohort study will assess treatment and post-treatment outcomes of pulmonary TB (microbiologically confirmed or clinically diagnosed) among 2600 people aged ≥15 years, with and without HIV coinfection, consecutively enrolled at 16 sites in 11 countries, across 6 of IeDEA's global regions. Data regarding clinical and sociodemographic factors, mental health, health-related quality of life, pulmonary function, and laboratory and radiographic findings will be collected using standardised questionnaires and data collection tools, beginning from the initiation of TB treatment and through 12 months after the end of treatment. Data will be aggregated for proposed analyses. ETHICS AND DISSEMINATION: Ethics approval was obtained at all implementing study sites, including the Vanderbilt University Medical Center Human Research Protections Programme. Participants will provide informed consent; for minors, this includes both adolescent assent and the consent of their parent or primary caregiver. Protections for vulnerable groups are included, in alignment with local standards and considerations at sites. Procedures for requesting use and analysis of TB-SRN data are publicly available. Findings from TB-SRN analyses will be shared with national TB programmes to inform TB programming and policy, and disseminated at regional and global conferences and other venues.

A case report of a 16-year-old male with extrapulmonary tuberculosis presenting as multiloculated mediastinal, pleural, and paravertebral fluid collections with chest pain, Eldoret, Kenya.

Key Clinical Message: Extrapulmonary TB presenting as multiloculated pleural fluid collections is rare in persons less than 18 years of age, but it can occur. High index of suspicion is important in establishing early diagnosis and treatment to reduce morbidity and mortality. Abstract: We present a case report of an immunocompetent African young man who presented with persistent chest pain and fever, and was diagnosed with extrapulmonary tuberculosis (EPTB) following chest CT scan, pleural biopsy histopathology examination, and Ziehl-Neelsen (ZN) staining, and pleural fluid Gene Xpert studies.

Asthma, Airflow Obstruction, and Eosinophilic Airway Inflammation Prevalence in Western Kenya: A Population-Based Cross-Sectional Study.

Objectives: Determine the prevalence of airway disease (e.g., asthma, airflow obstruction, and eosinophilic airway inflammation) in Kenya, as well as related correlates of airway disease and health-related quality of life. Methods: A three-stage, cluster-randomized cross-sectional study in Uasin Gishu County, Kenya was conducted. Individuals 12 years and older completed questionnaires (including St. George's Respiratory Questionnaire for COPD, SGRQ-C), spirometry, and fractional exhaled nitric oxide (FeNO) testing. Prevalence ratios with 95% confidence intervals (CIs) were calculated. Multivariable models were used to assess correlates of airflow obstruction and high FeNO. Results: Three hundred ninety-two participants completed questionnaires, 369 completed FeNO testing, and 305 completed spirometry. Mean age was 37.5 years; 64% were women. The prevalence of asthma, airflow obstruction on spirometry, and eosinophilic airway inflammation was 21.7%, 12.3% and 15.7% respectively in the population. Women had significantly higher SGRQ-C scores compared to men (15.0 vs. 7.7). Wheezing or whistling in the last year and SGRQ-C scores were strongly associated with FeNO levels >50 ppb after adjusting for age, gender, BMI, and tobacco use. Conclusion: Airway disease is a significant health problem in Kenya affecting a young population who lack a significant tobacco use history.

Preswitch Regimens Influence the Rate of Weight Gain After Switch to Tenofovir Disoproxil Fumarate, Lamivudine, and Dolutegravir (TLD): Study From an East African Cohort.

Background: Switching from non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens to dolutegravir (DTG) has been associated with greater weight gain. Methods: We conducted our analysis using a longitudinal cohort of people with HIV (PWH) in Western Kenya. We evaluated changes in the rate of weight gain among treatment-experienced, virally suppressed PWH who switched from NNRTI to tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD). We modeled the weights pre- and postswitch using a 2-phase model with linear trend preswitch and an inverted exponential function postswitch. We estimated an 18-month excess weight gain by comparing the projected weight with that expected using the preswitch rate. Results: A total of 18 662 individuals were included in our analysis, with 55% switching from efavirenz (EFV) and 45% from nevirapine (NVP). Of the studied individuals, 51% were female, and the median age and body mass index (BMI) were 51 years and 22 kg/m2, respectively. For the overall population, the rate of weight gain increased from 0.47 kg/year preswitch to 0.77 kg/year, with higher increases for females (0.57 kg/year to 0.96 kg/year) than males (0.34 kg/year to 0.62 kg/year). The rate of weight gain for individuals switching from EFV-based regimens significantly increased from 0.57 kg/year preswitch to 1.11 kg/year postswitch but remained stable at 0.35 kg/year preswitch vs 0.32 kg/year postswitch for individuals switching from NVP-based regimens. Conclusions: Switching from NNRTI-based regimens to TLD is associated with a modest increase in the rate of weight gain, with the preswitch NNRTI being the key determinant of the amount of weight gain experienced postswitch.

Patient perceptions of facilitators and barriers to reducing hazardous alcohol use among people living with HIV in East Africa.

BACKGROUND: Hazardous alcohol use among people living with HIV is associated with poor outcomes and increased morbidity and mortality. Understanding the hazardous drinking experiences of people living with HIV is needed to reduce their alcohol use. METHODS: We conducted 60 interviews among people living with HIV in East Africa with hazardous drinking histories. Interviews and Alcohol Use Disorder Identification Test (AUDIT) scores were conducted 41 - 60 months after their baseline assessment of alcohol use to identify facilitators and barriers to reduced alcohol use over time. RESULTS: People living with HIV who stopped or reduced hazardous drinking were primarily motivated by their HIV condition and desire for longevity. Facilitators of reduced drinking included health care workers' recommendations to reduce drinking (despite little counseling and no referrals) and social support. In those continuing to drink at hazardous levels, barriers to reduced drinking were stress, social environment, alcohol accessibility and alcohol dependency. CONCLUSIONS: Interventions that capacity-build professional and lay health care workers with the skills and resources to decrease problematic alcohol use, along with alcohol cessation in peer support structures, should be explored.

Effects of the COVID-19 pandemic on late postpartum women living with HIV in Kenya.

Although an estimated 1.4 million women living with HIV (WHIV) are pregnant each year globally, data describing the effects of the COVID-19 pandemic on postpartum women in low- and middle-income countries (LMICs) are limited. To address this gap, we conducted phone surveys among 170 WHIV ≥18 years and 18-24 months postpartum enrolled in HIV care at the Academic Model Providing Access to Healthcare in western Kenya, and assessed the effects of the pandemic across health, social and economic domains. We found that 47% of WHIV experienced income loss and 71% experienced food insecurity during the pandemic. The majority (96%) of women reported having adequate access to antiretroviral treatment and only 3% reported difficulties refilling medications, suggesting that the program's strategies to maintain HIV service delivery during the early phase of the pandemic were effective. However, 21% of WHIV screened positive for depression and 8% for anxiety disorder, indicating the need for interventions to address the mental health needs of this population. Given the scale and duration of the pandemic, HIV programs in LMICs should work with governments and non-governmental organizations to provide targeted support to WHIV at highest risk of food and income insecurity and their associated adverse health outcomes.

Weight Gain Among Treatment-Naïve Persons With HIV Receiving Dolutegravir in Kenya.

BACKGROUND: Several recent studies have linked integrase strand transfer inhibitors (INSTI) with increased weight gain. SETTING: The effects of sex on weight gain with dolutegravir (DTG)-based antiretroviral therapy (ART) among treatment-naïve participants in a lower-income, sub-Saharan population with high rates of pre-ART underweight and tuberculosis (TB) coinfection are unknown. METHODS: Our analysis included treatment-naïve participants in Kenya and starting their first treatment regimen between January 1, 2015, and September 30, 2018. Participants were grouped into 2 cohorts based on the initial treatment regimen [DTG vs. nonnucleoside reverse transcriptase inhibitors (NNRTI)]. We modelled weight changes over time using a multivariable nonlinear mixed-effect model, with participant as a random effect. Logistic regression models were constructed to evaluate the association between different variables with extreme increase in body mass index (≥10% increase). RESULTS: Seventeen thousand forty-four participants met our inclusion criteria. Sixty-two percent of participants were women, 6% were receiving active TB therapy, and 97% were on NNRTI-based regimens. Participants starting DTG-based regimens were more likely to gain weight when compared with participants starting NNRTI-based regimens. Female participants starting DTG-based regimens experienced the highest weight gain compared with other participants (mean gain of 6.1 kgs at 18 months). Female participants receiving DTG-based regimens, along with participants with lower CD4 cell counts, underweight at baseline, and those receiving active TB therapy were also at higher risk for extreme body mass index increase. CONCLUSIONS: Our study in a lower-income sub-Saharan African population confirms higher weight gain with DTG-based regimens compared with traditional ART for treatment-naïve patients.