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Objectives: To assess second‐line antiretroviral therapy (ART) virological failure and HIV drug resistance‐associated mutations (RAMs), in support of third‐line regimen planning in Asia. Methods: Adults > 18 years of age on second‐line ART for ≥ 6 months were eligible. Cross‐sectional data on HIV viral load (VL) and genotypic resistance testing were collected or testing was conducted between July 2015 and May 2017 at 12 Asia‐Pacific sites. Virological failure (VF) was defined as VL > 1000 copies/mL with a second VL > 1000 copies/mL within 3–6 months. FASTA files were submitted to Stanford University HIV Drug Resistance Database and RAMs were compared against the IAS‐USA 2019 mutations list. VF risk factors were analysed using logistic regression. Results: Of 1378 patients, 74% were male and 70% acquired HIV through heterosexual exposure. At second‐line switch, median [interquartile range (IQR)] age was 37 (32–42) years and median (IQR) CD4 count was 103 (43.5–229.5) cells/µL; 93% received regimens with boosted protease inhibitors (PIs). Median duration on second line was 3 years. Among 101 patients (7%) with VF, CD4 count > 200 cells/µL at switch [odds ratio (OR) = 0.36, 95% confidence interval (CI): 0.17–0.77 vs. CD4 ≤ 50) and HIV exposure through male–male sex (OR = 0.32, 95% CI: 0.17–0.64 vs. heterosexual) or injecting drug use (OR = 0.24, 95% CI: 0.12–0.49) were associated with reduced VF. Of 41 (41%) patients with resistance data, 80% had at least one RAM to nonnucleoside reverse transcriptase inhibitors (NNRTIs), 63% to NRTIs, and 35% to PIs. Of those with PI RAMs, 71% had two or more. Conclusions: There were low proportions with VF and significant RAMs in our cohort, reflecting the durability of current second‐line regimens. [ABSTRACT FROM AUTHOR]

Objectives: Early mortality among those still initiating antiretroviral therapy (ART) with advanced stages of HIV infection in resource‐limited settings remains high despite recommendations for universal HIV treatment. We investigated risk factors associated with early mortality in people living with HIV (PLHIV) starting ART at low CD4 levels in the Asia‐Pacific. Methods: PLHIV enrolled in the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD) who initiated ART with a CD4 count < 100 cells/μL between 2003 and 2018 were included in the study. Early mortality was defined as death within 1 year of ART initiation. PLHIV in follow‐up for > 1 year were censored at 12 months. Competing risk regression was used to analyse risk factors with loss to follow‐up as a competing risk. Results: A total of 1813 PLHIV were included in the study, of whom 74% were male. With 73 (4%) deaths, the overall first‐year mortality rate was 4.27 per 100 person‐years (PY). Thirty‐eight deaths (52%) were AIDS‐related, 10 (14%) were immune reconstituted inflammatory syndrome (IRIS)‐related, 13 (18%) were non‐AIDS‐related and 12 (16%) had an unknown cause. Risk factors included having a body mass index (BMI) < 18.5 [sub‐hazard ratio (SHR) 2.91; 95% confidence interval (CI) 1.60–5.32] compared to BMI 18.5–24.9, and alanine aminotransferase (ALT) ≥ 5 times its upper limit of normal (ULN) (SHR 6.14; 95% CI 1.62–23.20) compared to ALT < 5 times its ULN. A higher CD4 count (51–100 cells/μL: SHR 0.28; 95% CI 0.14–0.55; and > 100 cells/μL: SHR 0.12; 95% CI 0.05–0.26) was associated with reduced hazard for mortality compared to CD4 count ≤ 25 cells/μL. Conclusions: Fifty‐two per cent of early deaths were AIDS‐related. Efforts to initiate ART at CD4 counts > 50 cell/μL are associated with improved short‐term survival rates, even in those with late stages of HIV disease. [ABSTRACT FROM AUTHOR]

Objectives: Diabetes is a growing cause of morbidity and mortality in people living with HIV (PLHIV) receiving antiretroviral therapy (ART). We investigated the association between fasting plasma glucose (FPG) levels and mortality, and factors associated with FPG monitoring rates in Asia. Methods: Patients from the Therapeutics Research, Education, and AIDS Training in Asia (TREAT Asia) HIV Observational Database Low Intensity Transfer (TAHOD‐LITE) cohort were included in the present study if they had initiated ART. Competing risk and Poisson regression were used to analyse the association between FPG and mortality, and assess risk factors for FPG monitoring rates, respectively. FPG was categorized as diabetes (FPG ≥ 7.0 mmol/L), prediabetes (FPG 5.6–6.9 mmol/L) and normal FPG (FPG < 5.6 mmol/L). Results: In total, 33 232 patients were included in the analysis. Throughout follow‐up, 59% had no FPG test available. The incidence rate for diabetes was 13.7 per 1000 person‐years in the 4649 patients with normal FPG at ART initiation. Prediabetes [sub‐hazard ratio (sHR) 1.32; 95% confidence interval (CI) 1.07–1.64] and diabetes (sHR 1.90; 95% CI 1.52–2.38) were associated with mortality compared to those with normal FPG. FPG monitoring increased from 0.34 to 0.78 tests per person‐year from 2012 to 2016 (P < 0.001). Male sex [incidence rate ratio (IRR) 1.08; 95% CI 1.03–1.12], age > 50 years (IRR 1.14; 95% CI 1.09–1.19) compared to ≤ 40 years, and CD4 count ≥ 500 cells/μL (IRR 1.04; 95% CI 1.00–1.09) compared to < 200 cells/μL were associated with increased FPG monitoring. Conclusions: Diabetes and prediabetes were associated with mortality. FPG monitoring increased over time; however, less than half of our cohort had been tested. Greater resources should be allocated to FPG monitoring for early diabetic treatment and intervention and to optimize survival. [ABSTRACT FROM AUTHOR]

Objectives: With aging of the HIV‐positive population, cardiovascular disease (CVD) increasingly contributes to morbidity and mortality. We investigated CVD‐related and other causes of death (CODs) and factors associated with CVD in a multi‐country Asian HIV‐positive cohort. Methods: Patient data from 2003–2017 were obtained from the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD). We included patients on antiretroviral therapy (ART) with > 1 day of follow‐up. Cumulative incidences were plotted for CVD‐related, AIDS‐related, non‐AIDS‐related, and unknown CODs, and any CVD (i.e. fatal and nonfatal). Competing risk regression was used to assess risk factors of any CVD. Results: Of 8069 patients with a median follow‐up of 7.3 years [interquartile range (IQR) 4.4–10.7 years], 378 patients died [incidence rate (IR) 6.2 per 1000 person‐years (PY)], and this total included 22 CVD‐related deaths (IR 0.36 per 1000 PY). Factors significantly associated with any CVD event (IR 2.2 per 1000 PY) were older age [sub‐hazard ratio (sHR) 2.21; 95% confidence interval (CI) 1.36–3.58 for age 41–50 years; sHR 5.52; 95% CI 3.43–8.91 for ≥ 51 years, compared with < 40 years], high blood pressure (sHR 1.62; 95% CI 1.04–2.52), high total cholesterol (sHR 1.89; 95% CI 1.27–2.82), high triglycerides (sHR 1.55; 95% CI 1.02–2.37) and high body mass index (BMI) (sHR 1.66; 95% CI 1.12–2.46). CVD crude IRs were lower in the later ART initiation period and in lower middle‐ and upper middle‐income countries. Conclusions: The development of fatal and nonfatal CVD events in our cohort was associated with older age, and treatable risk factors such as high blood pressure, triglycerides, total cholesterol and BMI. Lower CVD event rates in middle‐income countries may indicate under‐diagnosis of CVD in Asian‐Pacific resource‐limited settings. [ABSTRACT FROM AUTHOR]

Objectives The aim of the study was to assess the prevalence and characteristics associated with current smoking in an Asian HIV-positive cohort, to calculate the predictive risks of cardiovascular disease ( CVD), coronary heart disease ( CHD) and myocardial infarction ( MI), and to identify the impact that simulated interventions may have. Methods Logistic regression analysis was used to distinguish associated current smoking characteristics. Five-year predictive risks of CVD, CHD and MI and the impact of simulated interventions were calculated utilizing the Data Collection on Adverse Effects of Anti- HIV Drugs Study (D:A:D) algorithm. Results Smoking status data were collected from 4274 participants and 1496 of these had sufficient data for simulated intervention calculations. Current smoking prevalence in these two groups was similar (23.2% vs. 19.9%, respectively). Characteristics associated with current smoking included age > 50 years compared with 30-39 years [odds ratio ( OR) 0.65; 95% confidence interval ( CI) 0.51-0.83], HIV exposure through injecting drug use compared with heterosexual exposure ( OR 3.03; 95% CI 2.25-4.07), and receiving antiretroviral therapy ( ART) at study sites in Singapore, South Korea, Malaysia, Japan and Vietnam in comparison to Thailand (all OR > 2). Women were less likely to smoke than men ( OR 0.11; 95% CI 0.08-0.14). In simulated interventions, smoking cessation demonstrated the greatest impact in reducing CVD and CHD risk and closely approximated the impact of switching from abacavir to an alternate antiretroviral in the reduction of 5-year MI risk. Conclusions Multiple interventions could reduce CVD, CHD and MI risk in Asian HIV-positive patients, with smoking cessation potentially being the most influential. [ABSTRACT FROM AUTHOR]

Objectives We evaluated the effect of the time interval between the initiation of antiretroviral therapy ( ART) and the initiation of tuberculosis ( TB) treatment on clinical outcomes in HIV/ TB-coinfected patients in an Asian regional cohort. Methods Adult HIV/ TB-coinfected patients in an observational HIV-infected cohort database who had a known date of ART initiation and a history of TB treatment were eligible for study inclusion. The time interval between the initiation of ART and the initiation of TB treatment was categorized as follows: TB diagnosed while on ART, ART initiated ≤ 90 days after initiation of TB treatment ('early ART'), ART initiated > 90 days after initiation of TB treatment ('delayed ART'), and ART not started. Outcomes were assessed using survival analyses. Results A total of 768 HIV/ TB-coinfected patients were included in this study. The median CD4 T-cell count at TB diagnosis was 100 [interquartile range ( IQR) 40-208] cells/μL. Treatment outcomes were not significantly different between the groups with early ART and delayed ART initiation. Kaplan− Meier analysis indicated that mortality was highest for those diagnosed with TB while on ART (3.77 deaths per 100 person-years), and the prognoses of other groups were not different (in deaths per 100 person-years: 2.12 for early ART, 1.46 for delayed ART, and 2.94 for ART not started). In a multivariate model, the interval between ART initiation and TB therapy initiation did not significantly impact all-cause mortality. Conclusions A negative impact of delayed ART in patients coinfected with TB was not observed in this observational cohort of moderately to severely immunosuppressed patients. The broader impact of earlier ART initiation in actual clinical practice should be monitored more closely. [ABSTRACT FROM AUTHOR]