Viral hepatitis and diabetes among people living with HIV in low- and high-income countries

Liver disease has emerged as a significant non-AIDS-related health concern impacting the survival rates of people living with HIV (PLHIV). This has been found attributed to infectious diseases such as hepatitis C (HCV) and hepatitis B (HBV), which are found in high prevalence in the Asia-Pacific region. Among non-infectious diseases, diabetes is a concern because of its link to other metabolic comorbidities including liver disease. Despite the availability of advanced treatment and management options for HBV, HCV, and diabetes, their prevalence remains high among PLHIV. The aim of this thesis was to investigate the continued burden of HCV and HBV co-infection and diabetes that lead to liver disease among PLHIV. Analyses included data routinely collected from two large TREAT Asia adult observational HIV cohorts (TAHOD: 2003-2020 and TAHOD-LITE: 2010-2019) involving 12 countries from Asia-Pacific, and the RESPOND consortium (2012-2019) which includes 19 HIV cohorts from Europe and Australia. Viral hepatitis was found to be a factor associated with early death in the Asia-Pacific. The hepatitis cascade of care identified that 30% of patients did not have subsequent pre-treatment viral load testing or initiate treatment after diagnosis and there was a low frequency of nucleic acid testing prior to and after treatment. Further investigation on testing rates found higher HCV RNA testing rates and shorter time to first positive HCV RNA test in more recent calendar years and in higher income countries highlighting poor accessibility to HCV RNA testing in lower-middle income countries (LMICs). Furthermore, liver function test measurements had a targeted testing approach rather than routine. In addition to viral hepatitis, diabetes was found to be associated with liver cirrhosis. Investigation of diabetes as an outcome found both high body mass index (BMI) and current use of integrase strand transfer inhibitors (INSTIs) to increase the risk of diabetes. Greater efforts are needed to improve linkage to viral hepatitis treatment and access to affordable testing for screening and monitoring treatment response in the Asia-Pacific. As more PLHIV are now transitioning to INSTIs, a better understanding of the relationship between INSTI and diabetes is vital in the management of diabetes to prevent advanced liver 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

Association of VASP Polymorphisms and Infectious Disease Burden in Global Populations and Identification of Candidate Resistance Haplotypes in Sub-Saharan Africa

Enteric pathogens employ numerous strategies to breach the intestinal epithelial barrier. One critical target of these pathogens is the host cell cytoskeleton. Pathogens may induce cytoskeletal remodeling to disrupt tight junctions and increase the permeability of the epithelium to gain access to underlying tissue. Alternatively, the cytoskeletal machinery may be directly co-opted to facilitate the attachment, invasion, or intracellular motility of these pathogens. The vasodilator-stimulated phosphoprotein (VASP) is a processive actin polymerase that induces membrane remodeling through the polymerization of actin cytoskeletal filaments. Interestingly, VASP is regulated by a variety of pathogens to induce cytoskeletal remodeling in host cells. If VASP is indeed a conversed target of pathogens, it is plausible that evolutionary pressure on host cells would select for genetic variants of VASP to inhibit the ability of pathogens to co-opt VASP function. To investigate this possibility, we determined the minor allele (MAF) frequency of all single nucleotide polymorphisms (SNPS) in VASP across 26 global populations. A heatmap was constructed to represent the minor allele frequency of \u3e400 SNPs and revealed increased minor allele frequency in Sub-Saharan African populations, that exhibit disproportionally high burdens of infectious disease compared with global populations. Next, linkage disequilibrium (LD) analysis was conducted on SNPS with increased MAF in Sub-Saharan African populations and likely to impact VASP function. SNPs found to be in linkage disequilibrium were then employed to reconstruct VASP haplotype

Trends in mortality among ART-treated HIV-infected adults in the Asia-Pacific region between 1999 and 2017:results from the TREAT Asia HIV Observational Database (TAHOD) and Australian HIV Observational Database (AHOD) of IeDEA Asia-Pacific

Introduction: AIDS-related deaths in people living with HIV/AIDS have been decreasing in number since the introduction of combination antiretroviral treatment (cART). However, data on recent causes of death in the Asia-Pacific region are limited. Hence, we analysed and compared AIDS-related and non-AIDS–related mortality in high- and low-income settings in the region. Methods: Patients from the TREAT Asia HIV Observational Database (TAHOD) and Australian HIV Observational Database (AHOD) receiving cART between 1999 and 2017 were included. Causes of death verification were based on review of the standardized Cause of Death (CoDe) form designed by the D:A:D group. Cohorts were grouped as AHOD (all high-income sites), TAHOD-high (high/upper-middle income countries) and TAHOD-low (lower-middle income countries). TAHOD sites were split into high/upper-middle income and lower-middle income country settings based on World Bank classifications. Competing risk regression was used to analyse factors associated with AIDS and non-AIDS–related mortality. Results: Of 10,386 patients, 522 died; 187 from AIDS-related and 335 from non-AIDS–related causes. The overall incidence rate of deaths during follow-up was 0.28 per 100 person-years (/100 PYS) for AIDS and 0.51/100 PYS for non-AIDS. Analysis indicated that the incidence rate of non-AIDS mortality decreased from 0.78/100 PYS to 0.37/100 PYS from year groups 2003 to 2007 to 2013 to 2017 (p < 0.001). Similarly, incidence rates of AIDS-related deaths decreased from 0.51/100 PYS to 0.09/100 PYS from year groups 2003 to 2007 to 2013 to 2017 (p < 0.001). More recent years of follow-up were associated with reduced hazard for non-AIDS mortality (2008 to 2012: aSHR (adjusted sub-hazard ratio) 0.72, 95% confidence interval (CI) 0.54 to 0.96, p = 0.027; 2013 to 2017: aSHR 0.64, 95% CI 0.47 to 0.87, p = 0.004) compared to years 2003 to 2007. The AHOD cohort had almost twice the hazard of non-AIDS mortality compared to TAHOD-low (lower-middle income sites) (aSHR 1.72, 95% CI, 1.20 to 2.46, p = 0.003); there were no differences between cohorts for AIDS-related mortality (p = 0.834). Conclusion: AIDS and non-AIDS–related mortality rates have decreased over the past years in the Asia-Pacific region. There is a greater risk for non-AIDS–associated deaths in the AHOD cohort compared to lower-middle income settings in TAHOD. © 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society

BMI as a predictor of high fasting blood glucose among people living with HIV in the Asia‐Pacific region

BackgroundNon-Asian body mass index (BMI) classifications are commonly used as a risk factor for high fasting blood glucose (FBG). We investigated the incidence and factors associated with high FBG among people living with HIV in the Asia-Pacific region, using a World Health Organization BMI classification specific to Asian populations.MethodsThis study included people living with HIV enrolled in a longitudinal cohort study from 2003 to 2019, receiving antiretroviral therapy (ART), and without prior tuberculosis. BMI at ART initiation was categorized using Asian BMI classifications: underweight (&lt;18.5&nbsp;kg/m2 ), normal (18.5-22.9&nbsp;kg/m2 ), overweight (23-24.9&nbsp;kg/m2 ), and obese (≥25 kg/m2 ). High FBG was defined as a single post-ART FBG measurement ≥126 mg/dL. Factors associated with high FBG were analyzed using Cox regression models stratified by site.ResultsA total of 3939 people living with HIV (63% male) were included. In total, 50% had a BMI in the normal weight range, 23% were underweight, 13% were overweight, and 14% were obese. Median age at ART initiation was 34 years (interquartile range 29-41). Overall, 8% had a high FBG, with an incidence rate of 1.14 per 100 person-years. Factors associated with an increased hazard of high FBG included being obese (≥25 kg/m2 ) compared with normal weight (hazard ratio [HR]&nbsp;=&nbsp;1.79; 95% confidence interval [CI] 1.31-2.44; p &lt; 0.001) and older age compared with those aged ≤30 years (31-40 years: HR&nbsp;=&nbsp;1.47; 95% CI 1.08-2.01; 41-50 years: HR&nbsp;=&nbsp;2.03; 95% CI 1.42-2.90; ≥51 years: HR&nbsp;=&nbsp;3.19; 95% CI 2.17-4.69; p &lt; 0.001).ConclusionPeople living with HIV with BMI &gt;25 kg/m2 were at increased risk of high FBG. This indicates that regular assessments should be performed in those with high BMI, irrespective of the classification used

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

International audienceIntroduction 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