High Incidence Rate of Computed Tomography-Measured Steatotic Liver Disease in Men With and Without HIV Infection.

INTRODUCTION: We determined steatotic liver disease (SLD) incidence in a prospective cohort of men with HIV (MWH) and men without HIV (MWOH). METHODS: Incident SLD was defined using paired noncontrast computed tomography scans performed during 2010-2013 and repeated during 2015-2017. RESULTS: Of 268 men, 173 MWH and 95 MWOH, 33 had incident SLD (11.1%, incidence rate 2.4 and 2.7/100 person-years for MWH and MWOH, respectively). Overall, higher abdominal visceral adipose tissue was independently associated with increased SLD risk. In MWH, increased visceral adipose tissue, insulin resistance, chronic hepatitis B, and cumulative etravirine use were associated with SLD. DISCUSSION: Metabolic factors, but not HIV, were associated with incident SLD. The high incidence rate suggests that SLD will continue to increase in PWH.

Renal outcomes in adults with HBV, HIV and HBV/HIV coinfection after 3 years of antiviral therapy in urban Tanzania.

BACKGROUND: An enhanced understanding of renal outcomes in persons with chronic HBV, HIV, and HBV/HIV coinfection is needed to mitigate chronic kidney disease in regions where HBV and HIV are endemic. OBJECTIVES: To investigate changes in estimated glomerular filtration rate (eGFR) in adults with HBV, HIV or HBV/HIV enrolled in a 3 year prospective cohort study of liver outcomes in Dar es Salaam, Tanzania and initiated on antiviral therapy. METHODS: We compared eGFR between and within groups over time using mixed-effects models. RESULTS: Four hundred and ninety-nine participants were included in the analysis (HBV: 164; HIV: 271; HBV/HIV: 64). Mean baseline eGFRs were 106.88, 106.03 and 107.18 mL/min/1.73 m2, respectively. From baseline to Year 3, mean eGFR declined by 4.3 mL/min/1.73 m2 (95% CI -9.3 to 0.7) and 3.7 (-7.8 to 0.5) in participants with HBV and HIV, respectively, and increased by 5.1 (-4.7 to 14.9) in those with HBV/HIV. In multivariable models, participants with HBV had lower eGFRs compared with those with HIV or HBV/HIV and, after adjusting for HBV DNA level and hepatitis B e antigen (HBeAg) status, significantly lower eGFRs than those with HBV/HIV at all follow-up visits. CONCLUSIONS: In this Tanzanian cohort, coinfection with HBV/HIV did not appear to exacerbate renal dysfunction compared with those with either infection alone. Although overall changes in eGFR were small, persons with HBV experienced lower eGFRs throughout follow-up despite their younger age and similar baseline values. Longer-term studies are needed to evaluate continuing changes in eGFR and contributions from infection duration and other comorbidities.

"I only seek treatment when I am ill": experiences of hypertension and diabetes care among adults living with HIV in urban Tanzania.

BACKGROUND: For adults living with HIV (ALHIV) and comorbidities, access to comprehensive healthcare services is crucial to achieving optimal health outcomes. This study aims to describe lived experiences, challenges, and coping strategies for accessing care for hypertension and/or diabetes (HTN/DM) in HIV care and treatment clinics (CTCs) and other healthcare settings. METHODOLOGY: We conducted a qualitative study that employed a phenomenological approach between January and April 2022 using a semi-structured interview guide in six HIV CTCs in Dar es Salaam, Tanzania. We purposively recruited 33 ALHIV with HTN (n = 16), DM (n = 10), and both (n = 7). Thematic content analysis was guided by the 5As framework of access to care. FINDINGS: The majority of the participants were females, between the ages of 54-73, and were recruited from regional referral hospitals. HIV CTCs at regional referral hospitals had more consistent provision of HTN screening services compared to those from district hospitals and health centers. Participants sought HTN/DM care at non-CTC health facilities due to the limited availability of such services at HIV CTCs. However, healthcare delivery for these conditions was perceived as unaccommodating and poorly coordinated. The need to attend multiple clinic appointments for the management of HTN/DM in addition to HIV care was perceived as frustrating, time-consuming, and financially burdensome. High costs of care and transportation, limited understanding of comorbidities, and the perceived complexity of HTN/DM care contributed to HTN/DM treatment discontinuity. As a means of coping, participants frequently monitored their own HTN/DM symptoms at home and utilized community pharmacies and dispensaries near their residences to check blood pressure and sugar levels and obtain medications. Participants expressed a preference for non-pharmaceutical approaches to comorbidity management such as lifestyle modification (preferred by young participants) and herbal therapies (preferred by older participants) because of concerns about side effects and perceived ineffectiveness of HTN/DM medications. Participants also preferred integrated care and focused patient education on multimorbidity management at HIV CTCs. CONCLUSION: Our findings highlight significant barriers to accessing HTN/DM care among ALHIV, mostly related to affordability, availability, and accessibility. Integration of NCD care into HIV CTCs, could greatly improve ALHIV health access and outcomes and align with patient preference.

Adapting and usability testing of the Kansas city cardiomyopathy questionnaire (KCCQ) in a heart failure clinic in Tanzania: the Swahili KCCQ.

BACKGROUND: The integration of patient-reported outcome measures (PROMS) into health care delivery systems is being increasingly recognized as an important component of quality, person-centered care, especially for chronic illnesses like congestive heart failure (CHF). However, while PROMS are increasingly being used to follow up CHF patients in high income countries, their use in sub-Saharan Africa is still limited. We adapted the Kansas City Cardiomyopathy Questionnaire (KCCQ-23), an internationally validated, CHF-specific PROM and tested its use in measuring outcomes in an outpatient CHF clinic at a cardiac referral hospital in Tanzania. METHODS: Adaptation of the KCCQ-23 included translation into Swahili by linguistic experts, in-depth cognitive debriefing in native Swahili-speaking CHF patients, and input from Tanzanian Cardiologists, PROMS experts, and the tool developer. Using a cross-sectional design, we tested the usability and observed the results of the translated KCCQ-23 in a convenience sample of 60 CHF patients attending outpatient clinic at the Jakaya Kikwete Cardiac Institute (JKCI) in Dar es Salaam. RESULTS: The survey was successfully completed by 59 (98.3%) of 60 enrolled participants. The mean (SD) age of participants was 54.9 (14.8) years (range 22-83), 30.5% were women and 72.2% had class 3 or 4 New York Heart Association (NYHA) symptoms at enrollment. The overall KCCQ-23 score was low, with a mean (SD) score of 21.7 (20.4) indicating generally very poor to poor patient reported outcomes in this population. The mean (SD) scores for the specific KCCQ-23 domains were 15.25 (24.2) for social limitation, 23.8 (27.4) for physical limitation, 27.1 (24.1) for quality of life and 40.7 (17.0) for self-efficacy. No socio-demographic or clinical characteristics were associated with their overall KCCQ-23 scores. Comparing the short version (KCCQ-12) with the full KCCQ-23 revealed excellent correlation between the two (r = 0.95; p < 0.0001). CONCLUSIONS: We successfully translated a validated tool, the Swahili KCCQ, for use in improving the care of patients with CHF in Tanzania and a broader population of Swahili-speaking patients. Both the Swahili KCCQ-12 and KCCQ-23 can be used, with similar outcomes. Work to expand the use of the tool in the clinic and other settings is planned.

Changes in liver stiffness after ART initiation in HIV-infected Nigerian adults with and without chronic HBV.

BACKGROUND: There are limited data from sub-Saharan Africa on long-term liver fibrosis changes in HIV- and HIV/HBV-infected individuals. OBJECTIVES: To assess the effects of ART on liver stiffness measurement (LSM) using transient elastography (TE) in HIV- and HIV/HBV-infected Nigerian adults and examine factors associated with fibrosis regression. METHODS: We included ART-naive HIV- and HIV/HBV-infected adults (≥18 years) enrolled in a prospective, longitudinal study of liver disease between July 2011 and February 2015 at Jos University Teaching Hospital HIV Care and Treatment Centre in Nigeria. Patients initiated ART and had TE at baseline and follow-up (year 3). LSM cut-offs for Metavir scores were 5.9, 7.6 and 9.4 kPa for moderate fibrosis, advanced fibrosis and cirrhosis, respectively. We used multivariable regression to identify factors associated with TE (≥1 Metavir) stage decline. RESULTS: A total of 106 HIV- and 71 HIV/HBV-infected patients [70.5% female and median age = 34 years (IQR = 29-42 years)] were studied. Baseline LSM and median LSM decline were significantly higher in HIV/HBV- versus HIV-infected patients; 41% of HIV/HBV-infected patients regressed ≥1 Metavir stage versus 17% of HIV-infected patients (P < 0.01); LSM scores at year 3 were not significantly different between HIV- and HIV/HBV-infected patients. In multivariable analyses, patients with baseline CD4+ T cells ≥200 (versus <200) cells/mm3 and lower BMIs were more likely to experience LSM stage decline. CONCLUSIONS: HBV coinfection does not attenuate LSM declines in HIV-infected patients after ART initiation despite being a risk factor for more advanced liver disease prior to therapy. The inverse association between BMI and TE stage decline needs further investigation.

Pattern of prevalent Hepatitis B virus genotypes in Zaria, Nigeria.

BACKGROUND: Hepatitis B virus (HBV) is hyperendemic in Nigeria. Available literature reveal genotype E as being predominant in West Africa. This study aimed at identifying the current pattern and prevalent genotypes of HBV in Zaria, Nigeria. MATERIALS AND METHODS: Four millilitre of blood was collected in ethylenediaminetetraacetic acid-container from each of 165 HBV surface antigen-positive participants recruited purposively from the gastroenterology clinic from May to August, 2017. Plasma was separated and frozen at -20°C till analysis. Multiplex-nested polymerase chain reaction using type-specific primers was used to identify the various HBV genotypes. RESULTS: Median (and interquartile range) age of the participants was 31.0 (25.5-39.0) years, with males constituting 107 (64.8%). Majority (83.6%) of the samples analysed were HBV-DNA-positive with 82.6% of the HBV-DNA-positive samples being mixed genotype infections. Irrespective of mode of occurrence, five HBV genotypes were identified with HBV/E (97.1%) being the most predominant, followed by HBV/B (82.6%), HBV/A (24.6%), then HBV/C (17.4%), while HBV/D (0.7%) was the least prevalent. CONCLUSION: In most (99.1%) of the mixed-infection were a combination of genotype E, the predominant genotype, with other genotypes predominantly genotype B. HBV genotypes E, B, A, C and D are the prevalent genotypes in Zaria, Nigeria, as they occur in single genotype and in mixed-genotypes pattern.

Time Requirements for Acquisition of Hepatitis C Virus Therapy in HIV/HCV Coinfected Patients.

Background: The process of obtaining approval for hepatitis C virus (HCV) treatment may be time consuming and complicated due to prior authorizations and the need to appeal denials. Pharmacists are poised to play a critical role in the acquisition and management of oral direct acting antivirals (DAAs) for the treatment of HCV infection; however, the time expended in this activity requires assessment. Objective: The objective of this study was to assess time expenditures by pharmacists to acquire DAAs for HCV therapy. Methods: Patients were enrolled in the Northwestern University Viral Hepatitis Registry, a prospective, observational cohort of ambulatory, adult patients living with human immunodeficiency virus (HIV) coinfected with chronic hepatitis B and/or C virus, and recruited since 2013 from the Infectious Disease Center at Northwestern Memorial Hospital, Chicago, IL. Patients were included in the current study if they were referred to the pharmacist for HCV DAA acquisition, drug-drug interaction management, and adherence counseling between February 1, 2014, and April 30, 2015. Patient demographics, virus-specific characteristics, and time required to secure HCV DAA treatment, counsel patients, and follow-up therapy were collected. Results: Among 54 HIV/HCV coinfected patients referred for treatment, all eventually received approval for DAA therapy. However, 87% (n = 47) required prior authorization. Pharmacists dedicated 2.1 hours/patient (interquartile range 1.5-2.8 hours; range 0.75-6.5 hours) to manage DAA therapy. Conclusion: Successful acquisition of HCV DAA therapy relied heavily on pharmacist effort, reflecting the vital role that pharmacists play in this process. Dedicated resources for medication access should be considered to ensure timely DAA acquisition.

Switching to second-line ART in relation to mortality in a large Tanzanian HIV cohort.

Objectives: In a large cohort of HIV-infected Tanzanians, we assessed: (i) rates of first-line treatment failure and switches to second-line ART; (ii) the effect of switching to second-line ART on death and loss to follow-up; and (iii) treatment outcomes on second-line ART by regimen. Methods: HIV-1-infected adults (≥15 years) initiated on first-line ART between November 2004 and September 2012, and who remained on initial therapy for at least 24 weeks before switching, were studied. Survival analyses were conducted to examine the effect of second-line ART on mortality and loss to follow-up in: (i) the whole cohort; (ii) all patients eligible for second-line ART by immunological failure (IF) and/or virological failure (VF) criteria; and (iii) patients eligible by VF criteria. Results: In total, 47 296 HIV-infected patients [mean age 37.5 (SD 9.5) years, CD4 175 (SD 158) cells/mm 3 , 71% female] were included in the analyses. Of these, 1760 (3.7%) patients switched to second-line ART (incidence rate = 1.7/100 person-years). Higher rates of mortality were observed in switchers versus non-switchers in all patients and patients with ART failure using IF/VF criteria. Switching only protected against mortality in patients with ART failure defined virologically and with the highest level of adherence [switching versus non-switching; >95% adherence; adjusted HR = 0.50 (95% CI = 0.26-0.93); P = 0.03]. Conclusions: Switching patients to second-line ART may only be beneficial in a select group of patients who are virologically monitored and demonstrate good adherence. Our data emphasize the need for routine viral load monitoring and aggressive adherence interventions in HIV programmes in sub-Saharan Africa.

Hepatitis B virus sequencing and liver fibrosis evaluation in HIV/HBV co-infected Nigerians.

OBJECTIVES: Molecular characteristics of hepatitis B virus (HBV), such as genotype and genomic mutations, may contribute to liver-related morbidity and mortality. The association of these characteristics with liver fibrosis severity in sub-Saharan Africa is uncertain. We aimed to characterise molecular HBV features in human immunodeficiency virus (HIV)/HBV co-infected Nigerians and evaluate associations between these characteristics and liver fibrosis severity before and after antiretroviral therapy (ART) initiation. METHODS: HIV/HBV co-infected Nigerians underwent liver fibrosis estimation by transient elastography (TE) prior to and 36 months after ART initiation. Basal core promoter/precore (BCP/PC) and preS1/preS2/S regions of HBV were sequenced from baseline plasma samples. We evaluated associations between HBV mutations and liver fibrosis severity by univariate and multivariable regression. RESULTS: At baseline, 94 patients underwent TE with median liver stiffness of 6.4 (IQR 4.7-8.7) kPa. Patients were predominantly infected with HBV genotype E (45/46) and HBe-antigen negative (75/94, 79.8%). We identified BCP A1762T/G1764A in 15/35 (43%), PC G1896A in 20/35 (57%), 'a' determinant mutations in 12/45 (26.7%) and preS2 deletions in 6/16 (37.5%). PreS2 mutations were associated with advanced fibrosis in multivariable analysis. At follow-up, median liver stiffness was 5.2 (IQR 4.1-6.6) kPa. No HBV molecular characteristics were associated with lack of fibrosis regression, although HIV virologic control, body mass index (BMI) and baseline CD4+ T-cell count were associated with a decline in fibrosis stage. CONCLUSION: Frequent BCP/PC and preS1/preS2/S mutations were found in ART-naïve HIV/HBV co-infected Nigerians. Median liver stiffness declined after initiation of ART, regardless of pre-ART HBV mutational pattern or virologic characteristics.

High rates of hepatitis C virus (HCV) cure using direct-acting antivirals in HIV/HCV-coinfected patients: a real-world perspective.

OBJECTIVES: There are few data on the real-world experience of FDA-approved oral hepatitis C virus (HCV) direct-acting antiviral (DAA) drug combinations in HIV/HCV-coinfected patients. We evaluated the safety and efficacy of DAA therapies in a cohort of HIV/HCV patients in a large urban clinic in Chicago. METHODS: HIV/HCV-coinfected adults (≥18 years) enrolled in the Northwestern University Viral Hepatitis Registry between January 2013 and June 2015 were analysed. Treated patients received one of the following DAA combinations: sofosbuvir/ledipasvir, sofosbuvir/ribavirin, sofosbuvir/simeprevir or paritaprevir/ritonavir/ombitasvir/dasabuvir ±â€Šribavirin. The primary outcome was sustained virological response at 12 weeks after DAA completion (SVR12). RESULTS: Seventy-seven HIV/HCV patients were evaluated for DAA therapy. Most patients were male (62/77, 81%) and infected with HCV genotype 1 (67/77, 87%). Some 32/77 (42%) were cirrhotic and 29/77 (38%) had received prior treatment with an IFN-containing regimen. DAA therapy was more likely to be started in Caucasians than persons of other ethnicities (P = 0.01). The overall SVR12 rate was 92% in 52 patients who completed therapy and had follow-up by the end of the study: sofosbuvir/simeprevir, 32/33 (97%); sofosbuvir/ribavirin, 4/7 (57%); sofosbuvir/ledipasvir, 11/11 (100%); and paritaprevir/ritonavir/ombitasvir/dasabuvir, 1/1 (100%). Four patients relapsed after therapy with sofosbuvir/simeprevir (n = 1) or sofosbuvir/ribavirin (n = 3). Adverse events were uncommon and did not result in DAA treatment interruption or discontinuation. CONCLUSIONS: The HCV DAA combinations of sofosbuvir/ledipasvir and sofosbuvir/simeprevir were highly effective and well tolerated in this diverse population of HIV/HCV-coinfected patients, many of whom had advanced liver disease. HIV coinfection should not be considered a barrier to successful HCV treatment with DAAs.

HIV virological failure and drug resistance in a cohort of Tanzanian HIV-infected adults.

OBJECTIVES: There are few data on ART failure rates and drug resistance from Tanzania, where there is a wide diversity of non-B HIV subtypes. We assessed rates and predictors of virological failure in HIV-infected Tanzanians and describe drug resistance patterns in a subgroup of these patients. METHODS: ART-naive, HIV-1-infected adults enrolled in a randomized controlled trial between November 2006 and 2008 and on ≥24 weeks of first-line NNRTI-containing ART were included. Population-based genotyping of HIV-1 protease and reverse transcriptase was performed on stored plasma from patients with virological failure (viral load >1000 copies/mL at ≥24 weeks of ART) and at baseline, where available. RESULTS: A total of 2403 patients [median (IQR) age 37 (32-43) years; 70% female] were studied. The median (IQR) baseline CD4+ T cell count was 128 (62-190) cells/µL. Predominant HIV subtypes were A, C and D (92.2%). The overall rate of virological failure was 14.9% (95% CI 13.2%-16.1%). In adjusted analyses, significant predictors of virological failure were lower CD4+ T cell count (P = 0.01) and non-adherence to ART (P < 0.01). Drug resistance mutations were present in 87/115 samples (75.7%); the most common were M184V/I (52.2%) and K103N (35%). Thymidine analogue mutations were uncommon (5.2%). The prevalence of mutations in 45 samples pre-ART was 22%. CONCLUSIONS: High levels of early ART failure and drug resistance were observed among Tanzanian HIV-1-infected adults enrolled in a well-monitored study. Initiating treatment early and ensuring optimal adherence are vital for the success and durability of first-line ART in these settings.

Preparedness of HIV care and treatment clinics for the management of concomitant non-communicable diseases: a cross-sectional survey.

BACKGROUND: In Sub-Saharan Africa, epidemiological studies have reported an increasing burden of non-communicable diseases (NCD) among people living with HIV. NCD management can be feasibly integrated into HIV care; however, clinic readiness to provide NCD services in these settings should first be assessed and gaps in care identified. METHODS: A cross-sectional survey conducted in July 2013 assessed the resources available for NCD care at 14 HIV clinics in Dar es Salaam, Tanzania. Survey items related to staff training, protocols, and resources for cardiovascular disease risk factor screening, management, and patient education. RESULTS: 43 % of clinics reported treating patients with hypertension; however, only 21 % had a protocol for NCD management. ECHO International Health standards for essential clinical equipment were used to measure clinic readiness; 36 % met the standard for blood pressure cuffs, 14 % for glucometers. Available laboratory tests for NCD included blood glucose (88 %), urine dipsticks (78 %), and lipid panel (57 %). 21 % had a healthcare worker with NCD training. All facilities provided some form of patient education, but only 14 % included diabetes, 57 % tobacco cessation, and 64 % weight management. CONCLUSIONS: A number of gaps were identified in this sample of HIV clinics that currently limit the ability of Tanzanian healthcare workers to diagnose and manage NCD in the context of HIV care. Integrated NCD and HIV care may be successfully achieved in these settings with basic measures incorporated into existing infrastructures at minimal added expense, i.e., improving access to basic functioning equipment, introducing standardized treatment guidelines, and improving healthcare worker education.

Nucleoside reverse transcriptase inhibitor resistance mutations associated with first-line stavudine-containing antiretroviral therapy: programmatic implications for countries phasing out stavudine.

BACKGROUND: The World Health Organization Antiretroviral Treatment Guidelines recommend phasing-out stavudine because of its risk of long-term toxicity. There are two mutational pathways of stavudine resistance with different implications for zidovudine and tenofovir cross-resistance, the primary candidates for replacing stavudine. However, because resistance testing is rarely available in resource-limited settings, it is critical to identify the cross-resistance patterns associated with first-line stavudine failure. METHODS: We analyzed HIV-1 resistance mutations following first-line stavudine failure from 35 publications comprising 1,825 individuals. We also assessed the influence of concomitant nevirapine vs. efavirenz, therapy duration, and HIV-1 subtype on the proportions of mutations associated with zidovudine vs. tenofovir cross-resistance. RESULTS: Mutations with preferential zidovudine activity, K65R or K70E, occurred in 5.3% of individuals. Mutations with preferential tenofovir activity, ≥ two thymidine analog mutations (TAMs) or Q151M, occurred in 22% of individuals. Nevirapine increased the risk of TAMs, K65R, and Q151M. Longer therapy increased the risk of TAMs and Q151M but not K65R. Subtype C and CRF01_AE increased the risk of K65R, but only CRF01_AE increased the risk of K65R without Q151M. CONCLUSIONS: Regardless of concomitant nevirapine vs. efavirenz, therapy duration, or subtype, tenofovir was more likely than zidovudine to retain antiviral activity following first-line d4T therapy.

Prevalence and Risk Factors for Renal Insufficiency among Adults Living with HIV in Tanzania: Results from a Cross-Sectional Study in 2020-2021.

With improved survival, adults living with HIV (ALHIV) are increasingly likely to experience age-related and HIV-related comorbidities, including renal insufficiency. Other risk factors for renal insufficiency (high blood pressure (BP), obesity, diabetes, and dyslipidemia) are also growing more common among ALHIV. To determine the prevalence of renal insufficiency (defined as an eGFR < 60 mL/min/1.73 m2) and factors associated with reduced eGFR, we conducted a cross-sectional study at six HIV clinics in Dar-es-Salaam, Tanzania. We applied multivariable (MV) ordinal logistic regression models to identify factors associated with reduced eGFR and examined the interaction of age with BP levels. Among the 450 ALHIV on ART analyzed [26% males; median age 43 (IQR: 18-72) years; 89% on tenofovir-containing ART; 88% HIV viral load ≤50 copies/mL], 34 (7.5%) had renal insufficiency. Prevalence was higher among males (12%) vs. females (6%), p = 0.03; ALHIV ≥50 (21%) vs. <50 years (2.5%), p < 0.001; those with high [≥130/80 mmHg (15%)] vs. normal [<120/80 mmHg (4%)] BP, p < 0.01 and those with dyslipidemia (10%) vs. those without (4.5%), p < 0.03. After adjusting for covariates, age (in years) was the only covariate with a statistically significant association with reduced eGFR (OR = 1.09 (1.07-1.12), p < 0.001). No significant interaction between age and BP was found. Interventions to increase routine screening for renal insufficiency, especially among older ALHIV, and improve BP control are critical to reducing kidney disease-related morbidity and mortality.

Effect of high-dose multivitamin supplements on alanine aminotransferase elevations among adults living with HIV on antiretroviral therapy in Tanzania.

BACKGROUND: HIV infection can cause malabsorption and rapid utilization of nutrients. A randomized trial of multivitamin supplementation among people living with HIV/AIDS (PLWHA) initiating antiretroviral therapy (ART) in Tanzania was stopped early due to increased alanine aminotransferase (ALT) concentrations in the multiple recommended dietary allowances (RDA) multivitamin group. We conducted detailed analysis to assess the effect of multivitamins on ALT elevations and evaluate whether subgroups of PLWHA have greater hepatotoxicity risks associated with the use of high-dose multivitamins. METHODS: We utilized data from a randomized, double-blind trial conducted in 2006-2009 that assessed the effect of high-dose multivitamins that contained vitamin B complex, vitamin C, and vitamin E at multiple RDA as compared to standard-dose multivitamins containing single RDAs among adults initiating ART in Tanzania. We evaluated the effect of high-dose multivitamins on incident mild/moderate ALT elevations > 40 IU/L, persistent ALT elevations > 40 IU/L (2 + clinic visits), and severe ALT elevations > 200IU/L using Cox proportional hazard models. We then evaluated effect modification by patient characteristics to determine if subgroups of PLWHA experienced different magnitudes of risk for ALT elevations associated with high-dose multivitamins. RESULTS: High-dose multivitamins increased the risk of incident mild/moderate ALT elevations > 40 IU/mL as compared to standard-dose multivitamins (hazard ratio (HR): 1.41; 95%CI: 1.26,1.58) as well as incident sustained mild/moderate ALT elevations (HR: 1.19; 95%CI: 1.04,1.36), but there was no overall effect on severe ALT elevations (HR: 1.44; 95% CI: 0.91,2.28). There was no evidence that the effect of high-dose multivitamins on any or sustained mild/moderate ALT elevations was modified by any patient characteristic. However, CD4 T-cell count was found to modify the effect of high-dose multivitamins on severe ALT elevations (p-value for interaction:0.01). Among participants with a baseline CD4 T-cell count ≤ 100 cells/µL, individuals receiving high-dose multivitamins had 3.74 times (95%CI: 1.52-9.17) the risk of incident severe ALT elevations compared to standard-dose multivitamins, while participants with CD4 T-cell counts > 100 cells/µL, appeared to have no effect of high-dose multivitamins on severe ALT elevations (HR:0.92; 95% CI: 0.50,1.67). CONCLUSIONS: High-dose RDA multivitamin supplementation increased the incidence of any mild to moderate ALT elevations among adults starting ART in Tanzania and the magnitude of the risk does not appear to differ by patient characteristics. However, immunocompromised PLWHA with CD4 T-cell counts < 100 cells/µL may experience greater risk of severe ALT elevations associated with the use of high-dose multivitamins. Although the study findings offer significant insights, it is essential to take into account limitations imposed by newer cART regimes.

Patients' and Care Providers' Reported Barriers and Suggestions for Improving HIV Viral Load Testing in Tanzania: A Qualitative Study in Dar es Salaam.

The study explores barriers and suggestions for improving viral load testing (VLT) uptake in Tanzania, revealing that only 58% of patients receive VLT annually, contrary to the Tanzanian National Guidelines toward the 95-95-95 UNAIDS targets. Twelve individual interviews and three patient-focus groups were conducted as part of a qualitative study conducted in six human immunodeficiency virus (HIV) clinics in Dar es Salaam to identify potential suggestions for access enhancement, as well as barriers to VLT uptake. Using King's theory of goal attainment, we found that missing appointments was the primary individual barrier to VLT uptake, along with limited knowledge among individuals living with HIV. Participants also face system-level barriers, such as a lack of integrated care and evening service availability. The study suggests that, despite challenges, there is potential for improvement in the uptake and quality of VLT services in Tanzanian public health facilities through a holistic approach.

Patients' and care providers' reported barriers and suggestions for improving HIV viral load testing in Tanzania: A qualitative study in Dar es SalaamThe study investigates barriers and potential suggestions to improve viral load testing (VLT) uptake in Tanzania, highlighting that only 58% of patients receive VLT annually, contrary to the Tanzanian national guidelines. A qualitative study in six HIV clinics in Dar es Salaam involved 12 in-depth interviews and three patient-focused group discussions to identify facilitators and barriers to VLT uptake, using King's goal attainment theory. Missing appointments is the main barrier to VLT uptake, attributed to distance from care and high transport costs. Healthcare providers and patients also face systemic and structural barriers, such as a lack of integrated care and evening service availability. Patients suggest effective communication, service extension, and knowledge sharing to improve VLT uptake. The study suggests that, despite challenges, there is potential for improvement in the uptake and quality of VLT services in Tanzanian public health facilities through a holistic approach.

The prevalence of metabolic syndrome and associated factors among adults on antiretroviral therapy in Dar es Salaam, Tanzania.

Background: Adults living with HIV (ALHIV) are at increased risk of developing metabolic syndrome (MetS). Several factors are associated with an increase in MetS in these individuals, including certain antiretroviral therapies (ART). There is limited data on the prevalence of MetS among ALHIV in sub-Saharan Africa following scale up of newer integrase inhibitor-containing ART regimens. Objective: We assessed the prevalence and correlates of MetS among ALHIV patients receiving tenofovir, lamivudine, and dolutegravir (TLD) in Tanzania. Methods: We conducted a retrospective cross-sectional analysis of ALHIV aged ≥18 enrolled in a cardiovascular health study at six HIV Care and Treatment Clinics from 11/2020-1/2021 in Dar es Salaam, Tanzania. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III). Descriptive statistics were used to summarize the results, and logistic regression was used to assess demographic, behavioral, and HIV-related risk factors associated with MetS. Covariates with a p-value <0.2 at the univariate level were included in the multivariate model. Results: Three hundred and eighty nine participants were included in the analysis. The mean age (SD) was 43 years (±11) years, and 286 (73.5%) were female. The prevalence of MetS in this population was 21%. In univariate analysis, MetS components that were significantly higher among women vs. men included abdominal obesity (27.3% vs. 4.9%), reduced HDL (77.9% vs. 53.4%), and elevated glucose (18.5% vs. 14.6%), all p< 0.05. Age≥ 50 yrs [AOR 3.25; (95% CI 1.80-5.84), p < 0.01] and BMI [AOR 0.16; (95% CI 0.09-0.30), P ≤0.01] were both associated with an increased odds of MetS in multivariate analyses. Conclusion: MetS. is prevalent among Tanzanian ALHIV on TLD. Routine screening for MetS and healthy lifestyle promotion, particularly among women and those aging, should be a priority to prevent against cardiovascular disease. Further studies are needed to monitor the long-term impact of these newer ART regimens on MetS and CVD.

Generalized and COVID related anxiety as risk factors for health outcomes among adolescents with HIV during COVID-19 in Tanzania.

The COVID-19 pandemic and associated prevention strategies caused widespread interruptions to care and treatment for people living with HIV. Adolescents living with HIV (AWHIV) were particularly vulnerable to poor mental and physical health during COVID-19. We assessed the burden of generalized and COVID-19-related anxiety and associations with adherence to HIV care and treatment and viral load suppression (VLS) among AWHIV during the peak of the COVID-19 pandemic in Tanzania. Methods: This cross-sectional study was conducted among AWHIV aged 15-19 years attending 10 clinics in Dar es Salaam from April 2022-February 2023. Study participants completed a self-administered questionnaire including Generalized Anxiety Disorder (GAD), COVID-19-related anxiety, and other psychosocial and physical health and support measures. HIV visit adherence, viral load and sociodemographic data were abstracted from patient health records.Analysis:: Multivariable (MV) quasibinomial and logistic regression models examined associations of Generalized and COVID-19-related anxiety with visit adherence and HIV virologic suppression (HIV VL < 50 copies/mL). Data were analyzed using R software. Results: 658 AWHIV (52% male) were included in this analysis. Most (86%) had been on antiretroviral treatment (ART) for at least four years, 55% attended at least 75% of their scheduled clinic visits, and 78% were HIV virologically suppressed. The median GAD and COVID-19-related anxiety scores were 2 (IQR: 0-5, and 26 (IQR: 13-43; respectively. Only 2% scored moderate-severe generalized anxiety (score 10-21). We found no significant associations between COVID-19-related anxiety or GAD and visit adherence. Higher GAD was inversely associated with VLS (adjusted odds ratio (AOR): 0.89 (95% CI 0.81, 0.98)). Female gender and higher quality of physical life were significantly associated with VLS. Conclusion: Low levels of generalized and COVID-19 related anxiety were reported among Tanzanian AWHIV. Integrating screening and management of generalized anxiety screening into HIV care for AWHIV could improve VLS among this population.

Surveillance Metrics and History of the COVID-19 Pandemic in Central Asia: Updated Epidemiological Assessment.

BACKGROUND: This study updates the COVID-19 pandemic surveillance in Central Asia we conducted during the first year of the pandemic by providing 2 additional years of data for the region. The historical context provided through additional data can inform regional preparedness and early responses to infectious outbreaks of either the SARS-CoV-2 virus or future pathogens in Central Asia. OBJECTIVE: First, we aim to measure whether there was an expansion or contraction in the pandemic in Central Asia when the World Health Organization (WHO) declared the end of the public health emergency for the COVID-19 pandemic on May 5, 2023. Second, we use dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Third, we aim to provide historical context for the course of the pandemic in Central Asia. METHODS: Traditional surveillance metrics, including counts and rates of COVID-19 transmissions and deaths, and enhanced surveillance indicators, including speed, acceleration, jerk, and persistence, were used to measure shifts in the pandemic. To identify the appearance and duration of variants of concern, we used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID). We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a 1-sided t test to determine whether regional speed was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data across the sample period. RESULTS: Speed for the region had remained below the outbreak threshold for 7 months by the time of the WHO declaration. Acceleration and jerk were also low and stable. Although the 1- and 7-day persistence coefficients remained statistically significant, the coefficients were relatively small in magnitude (0.125 and 0.347, respectively). Furthermore, the shift parameters for either of the 2 most recent weeks around May 5, 2023, were both significant and negative, meaning the clustering effect of new COVID-19 cases became even smaller in the 2 weeks around the WHO declaration. From December 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t test of speed equal to 10 became entirely insignificant for the first time in March 2023. CONCLUSIONS: Although COVID-19 continues to circulate in Central Asia, the rate of transmission remained well below the threshold of an outbreak for 7 months ahead of the WHO declaration. COVID-19 appeared to be endemic in the region and no longer reached the threshold of a pandemic. Both standard and enhanced surveillance metrics suggest the pandemic had ended by the time of the WHO declaration.

South Asia's COVID-19 History and Surveillance: Updated Epidemiological Assessment.

BACKGROUND: This study updates our findings from the COVID-19 pandemic surveillance we first conducted in South Asia in 2020 with 2 additional years of data for the region. We assess whether COVID-19 had transitioned from pandemic to endemic at the point the World Health Organization (WHO) ended the public health emergency status for COVID-19 on May 5, 2023. OBJECTIVE: First, we aim to measure whether there was an expansion or contraction in the pandemic in South Asia around the WHO declaration. Second, we use dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Third, we aim to provide historical context for the course of the pandemic in South Asia. METHODS: In addition to updating the traditional surveillance data and dynamic panel estimates from our original study, this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a 1-sided t test to determine whether regional weekly speed or transmission rate per 100,000 population was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data across the sample period. RESULTS: Speed for the region had remained below the outbreak threshold for over a year by the time of the WHO declaration. Acceleration and jerk were also low and stable. While the 1-day persistence coefficients remained statistically significant and positive (1.168), the 7-day persistence coefficient was negative (-0.185), suggesting limited cluster effects in which cases on a given day predict cases 7 days forward. Furthermore, the shift parameters for either of the 2 most recent weeks around May 5, 2023, did not indicate any overall change in the persistence measure around the time of the WHO declaration. From December of 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t test of speed equal to 10 was statistically insignificant across the entire pandemic. CONCLUSIONS: While COVID-19 continued to circulate in South Asia, the rate of transmission had remained below the outbreak threshold for well over a year ahead of the WHO declaration. COVID-19 is endemic in the region and no longer reaches the threshold of the pandemic definition. Both standard and enhanced surveillance metrics confirm that the pandemic had ended by the time of the WHO declaration. Prevention policies should be a focus ahead of future pandemics. On that point, policy should emphasize an epidemiological task force with widespread testing and a contact-tracing system.