METHODS: Patients testing HBs antigen (Ag) or HCV antibody (Ab) positive within enrollment into TAHOD were considered HBV or HCV co-infected. Factors associated with HBV and/or HCV co-infection were assessed by logistic regression models. Factors associated with post-ART HIV immunological response (CD4 change after six months) and virological response (HIV RNA <400 copies/ml after 12 months) were also determined. Survival was assessed by the Kaplan-Meier method and log rank test.
RESULTS: A total of 7,455 subjects were recruited by December 2012. Of patients tested, 591/5656 (10.4%) were HBsAg positive, 794/5215 (15.2%) were HCVAb positive, and 88/4966 (1.8%) were positive for both markers. In multivariate analysis, HCV co-infection, age, route of HIV infection, baseline CD4 count, baseline HIV RNA, and HIV-1 subtype were associated with immunological recovery. Age, route of HIV infection, baseline CD4 count, baseline HIV RNA, ART regimen, prior ART and HIV-1 subtype, but not HBV or HCV co-infection, affected HIV RNA suppression. Risk factors affecting mortality included HCV co-infection, age, CDC stage, baseline CD4 count, baseline HIV RNA and prior mono/dual ART. Shortest survival was seen in subjects who were both HBV- and HCV-positive.
CONCLUSION: In this Asian cohort of HIV-infected patients, HCV co-infection, but not HBV co-infection, was associated with lower CD4 cell recovery after ART and increased mortality.
METHODS: In a regional HIV observational cohort in the Asia-Pacific region, patients with viral suppression (2 consecutive viral loads <400 copies/mL) and a CD4 count ≥200 cells per microliter who had CD4 testing 6 monthly were analyzed. Main study end points were occurrence of 1 CD4 count <200 cells per microliter (single CD4 <200) and 2 CD4 counts <200 cells per microliter within a 6-month period (confirmed CD4 <200). A comparison of time with single and confirmed CD4 <200 with biannual or annual CD4 assessment was performed by generating a hypothetical group comprising the same patients with annual CD4 testing by removing every second CD4 count.
RESULTS: Among 1538 patients, the rate of single CD4 <200 was 3.45/100 patient-years and of confirmed CD4 <200 was 0.77/100 patient-years. During 5 years of viral suppression, patients with baseline CD4 200-249 cells per microliter were significantly more likely to experience confirmed CD4 <200 compared with patients with higher baseline CD4 [hazard ratio, 55.47 (95% confidence interval: 7.36 to 418.20), P < 0.001 versus baseline CD4 ≥500 cells/μL]. Cumulative probabilities of confirmed CD4 <200 was also higher in patients with baseline CD4 200-249 cells per microliter compared with patients with higher baseline CD4. There was no significant difference in time to confirmed CD4 <200 between biannual and annual CD4 measurement (P = 0.336).
CONCLUSIONS: Annual CD4 monitoring in virally suppressed HIV patients with a baseline CD4 ≥250 cells per microliter may be sufficient for clinical management.
METHODS: Incidence of malignancy after cohort enrollment was evaluated. Factors associated with development of hematological and nonhematological malignancy were analyzed using competing risk regression and survival time using Kaplan-Meier.
RESULTS: Of 7455 patients, 107 patients (1%) developed a malignancy: 34 (0.5%) hematological [0.08 per 100 person-years (/100PY)] and 73 (1%) nonhematological (0.17/100PY). Of the hematological malignancies, non-Hodgkin lymphoma was predominant (n = 26, 76%): immunoblastic (n = 6, 18%), Burkitt (n = 5, 15%), diffuse large B-cell (n = 5, 15%), and unspecified (n = 10, 30%). Others include central nervous system lymphoma (n = 7, 21%) and myelodysplastic syndrome (n = 1, 3%). Nonhematological malignancies were mostly Kaposi sarcoma (n = 12, 16%) and cervical cancer (n = 10, 14%). Risk factors for hematological malignancy included age >50 vs. ≤30 years [subhazard ratio (SHR) = 6.48, 95% confidence interval (CI): 1.79 to 23.43] and being from a high-income vs. a lower-middle-income country (SHR = 3.97, 95% CI: 1.45 to 10.84). Risk was reduced with CD4 351-500 cells/µL (SHR = 0.20, 95% CI: 0.05 to 0.74) and CD4 >500 cells/µL (SHR = 0.14, 95% CI: 0.04 to 0.78), compared to CD4 ≤200 cells/µL. Similar risk factors were seen for nonhematological malignancy, with prior AIDS diagnosis showing a weak association. Patients diagnosed with a hematological malignancy had shorter survival time compared to patients diagnosed with a nonhematological malignancy.
CONCLUSIONS: Nonhematological malignancies were common but non-Hodgkin lymphoma was more predominant in our cohort. PLHIV from high-income countries were more likely to be diagnosed, indicating a potential underdiagnosis of cancer in low-income settings.
METHODS: Patients from TREAT Asia HIV Observational Database (September 2015 data transfer) aged 18 years and older with a CD4 count <50 cells/mm at ART initiation were included. The effect of macrolide prophylaxis on HIV-associated mortality or AIDS-defining conditions (as a combined outcome) and HIV-associated mortality alone were evaluated using competing risk regression. Sensitivity analysis was conducted in patients with a CD4 <100 cells/mm at ART initiation.
RESULTS: Of 1345 eligible patients, 10.6% received macrolide prophylaxis. The rate of the combined outcome was 7.35 [95% confidence interval (CI): 6.04 to 8.95] per 100 patient-years, whereas the rate of HIV-associated mortality was 3.14 (95% CI: 2.35 to 4.19) per 100 patient-years. Macrolide use was associated with a significantly decreased risk of HIV-associated mortality (hazard ratio 0.10, 95% CI: 0.01 to 0.80, P = 0.031) but not with the combined outcome (hazard ratio 0.86, 95% CI: 0.32 to 2.229, P = 0.764). Sensitivity analyses showed consistent results among patients with a CD4 <100 cells/mm at ART initiation.
CONCLUSIONS: Macrolide prophylaxis is associated with improved survival among Asian HIV-infected patients with low CD4 cell counts and on ART. This study suggests the increased usage and coverage of macrolide prophylaxis among people living with HIV in Asia.
METHODS: Analyses were based on patients recruited to the TREAT Asia HIV Observational Database (TAHOD), consisting of 21 sites in 12 countries. Patients on triple antiretroviral therapy (ART) were included if they were alive, without previous CVD, and had data on CVD risk factors. Annual new CVD events for 2019-2028 were estimated with the D:A:D equation, accounting for age- and sex-adjusted mortality. Modelled intervention scenarios were treatment of high total cholesterol, low high-density lipoprotein cholesterol (HDL) or high blood pressure, abacavir or lopinavir substitution, and smoking cessation.
RESULTS: Of 3,703 included patients, 69% were male, median age was 46 (IQR 40-53) years and median time since ART initiation was 9.8 years (IQR 7.5-14.1). Cohort incidence rates of CVD were projected to increase from 730 per 100,000 person-years (pys) in 2019 to 1,432 per 100,000 pys in 2028. In the modelled intervention scenarios, most events can be avoided by smoking cessation, abacavir substitution, lopinavir substitution, decreasing total cholesterol, treating high blood pressure and increasing HDL.
CONCLUSIONS: Our projections suggest a doubling of CVD incidence rates in Asian HIV-positive adults in our cohort. An increase in CVD can be expected in any ageing population, however, according to our models, this can be close to averted by interventions. Thus, there is an urgent need for risk screening and integration of HIV and CVD programmes to reduce the future CVD burden.
METHODS: Treatment modification was defined as a change of two antiretrovirals, a drug class change or treatment interruption (TI), all for >14 days. We assessed factors associated with CD4 changes and undetectable viral load (UVL <1,000 copies/ml) at 1 year after second-line failure using linear and logistic regression, respectively. Survival time was analysed using competing risk regression.
RESULTS: Of the 328 patients who failed second-line ART in our cohorts, 208 (63%) had a subsequent treatment modification. Compared with those who continued the failing regimen, the average CD4 cell increase was higher in patients who had a modification without TI (difference =77.5, 95% CI 35.3, 119.7) while no difference was observed among those with TI (difference =-5.3, 95% CI -67.3, 56.8). Compared with those who continued the failing regimen, the odds of achieving UVL was lower in patients with TI (OR=0.18, 95% CI 0.06, 0.60) and similar among those who had a modification without TI (OR=1.97, 95% CI 0.95, 4.10), with proportions of UVL 60%, 22% and 75%, respectively. Survival time was not affected by treatment modifications.
CONCLUSIONS: CD4 cell improvements were observed in those who had treatment modification without TI compared with those on the failing regimen. When no other options are available, maintaining the same failing ART combination provided better VL control than interrupting treatment.
SETTINGS: A validation study among people living with HIV(PLHIV) aged ≥18 years among the cohorts in the Asia-Pacific region.
METHODS: PLHIV with baseline eGFR>60 mL/min/1.73m were included for validation of the D:A:D CKD full version and the short version without cardiovascular risk factors. Those with <3 eGFR measurements from baseline or previous exposure to potentially nephrotoxic antiretrovirals were excluded. Kaplan-Meier methods were used to estimate the probability of CKD development. Area Under the Receiver Operating Characteristics (AUROC) was also used to validate the risk score.
RESULTS: We included 5,701 participants in full model(median 8.1 [IQR 4.8-10.9] years follow-up) and 9,791 in short model validation(median 4.9 [IQR 2.5-7.3] years follow-up). The crude incidence rate of CKD was 8.1 (95%CI 7.3-8.9) per 1,000 person-years(PYS) in the full model cohort and 10.5 (95%CI 9.6-11.4) per 1,000 PYS in the short model cohort. The progression rates for CKD at 10 years in the full model cohort were 2.7%, 8.9% and 26.1% for low-, medium- and high-risk groups, and 3.5%, 11.7% and 32.4% in the short model cohort. The AUROC for the full and short risk score was 0.81 (95%CI 0.79-0.83) and 0.83 (95%CI 0.81-0.85), respectively.
CONCLUSION: The D:A:D CKD full- and short-risk score performed well in predicting CKD events among Asian PLHIV. These risk prediction models may be useful to assist clinicians in identifying individuals at high risk of developing CKD.
METHODS: Patients initiating cART between 2006 and 2013 were included. TI was defined as stopping cART for >1 day. Treatment failure was defined as confirmed virological, immunological or clinical failure. Time to treatment failure during cART was analysed using Cox regression, not including periods off treatment. Covariables with P < 0.10 in univariable analyses were included in multivariable analyses, where P < 0.05 was considered statistically significant.
RESULTS: Of 4549 patients from 13 countries in Asia, 3176 (69.8%) were male and the median age was 34 years. A total of 111 (2.4%) had TIs due to AEs and 135 (3.0%) had TIs for other reasons. Median interruption times were 22 days for AE and 148 days for non-AE TIs. In multivariable analyses, interruptions >30 days were associated with failure (31-180 days HR = 2.66, 95%CI (1.70-4.16); 181-365 days HR = 6.22, 95%CI (3.26-11.86); and >365 days HR = 9.10, 95% CI (4.27-19.38), all P < 0.001, compared to 0-14 days). Reasons for previous TI were not statistically significant (P = 0.158).
CONCLUSIONS: Duration of interruptions of more than 30 days was the key factor associated with large increases in subsequent risk of treatment failure. If TI is unavoidable, its duration should be minimised to reduce the risk of failure after treatment resumption.
METHODS: Treatment modification was defined as a change of two antiretrovirals, a drug class change or treatment interruption (TI), all for >14 days. We assessed factors associated with CD4 changes and undetectable viral load (UVL <1,000 copies/ml) at 1 year after second-line failure using linear and logistic regression, respectively. Survival time was analysed using competing risk regression.
RESULTS: Of the 328 patients who failed second-line ART in our cohorts, 208 (63%) had a subsequent treatment modification. Compared with those who continued the failing regimen, the average CD4 cell increase was higher in patients who had a modification without TI (difference =77.5, 95% CI 35.3, 119.7) while no difference was observed among those with TI (difference =-5.3, 95% CI -67.3, 56.8). Compared with those who continued the failing regimen, the odds of achieving UVL was lower in patients with TI (OR=0.18, 95% CI 0.06, 0.60) and similar among those who had a modification without TI (OR=1.97, 95% CI 0.95, 4.10), with proportions of UVL 60%, 22% and 75%, respectively. Survival time was not affected by treatment modifications.
CONCLUSIONS: CD4 cell improvements were observed in those who had treatment modification without TI compared with those on the failing regimen. When no other options are available, maintaining the same failing ART combination provided better VL control than interrupting treatment.
METHODS: We investigated HIV treatment outcomes among people who acquired HIV via injecting drug use in the TREAT Asia HIV Observational Database (TAHOD) between January 2003 and March 2019. Trends in CD4 count and viral suppression (VS, HIV viral load <1000 copies/mL) were assessed. Factors associated with mean CD4 changes were analysed using repeated measures linear regression, and combined AIDS event and mortality were analysed using survival analysis.
RESULTS: Of 622 PWID from 12 countries in the Asia-Pacific, 93% were male and the median age at ART initiation was 31 years (IQR, 28 to 34). The median pre-ART CD4 count was 71 cells/µL. CD4 counts increased over time, with a mean difference of 401 (95% CI, 372 to 457) cells/µL at year-10 (n = 78). Higher follow-up HIV viral load and pre-ART CD4 counts were associated with smaller increases in CD4 counts. Among 361 PWID with ≥1 viral load after six months on ART, proportions with VS were 82%, 88% and 93% at 2-, 5- and 10-years following ART initiation. There were 52 new AIDS-defining events and 50 deaths during 3347 person-years of follow-up (PYS) (incidence 3.05/100 PYS, 95% CI, 2.51 to 3.70). Previous AIDS or TB diagnosis, lower current CD4 count and adherence <95% were associated with combined new AIDS-defining event and death.
CONCLUSIONS: Despite improved outcomes over time, our findings highlight the need for rapid ART initiation and adherence support among PWID within Asian settings.
METHODS: HIV-infected adults enrolled in the TREAT Asia HIV Observational Database were eligible if they had an HIV RNA measurement documented at the time of ART initiation. The dataset was randomly split into a derivation data set (75% of patients) and a validation data set (25%). Factors associated with pre-treatment HIV RNA <100,000 copies/mL were evaluated by logistic regression adjusted for study site. A prediction model and prediction scores were created.
RESULTS: A total of 2592 patients were enrolled for the analysis. Median [interquartile range (IQR)] age was 35.8 (29.9-42.5) years; CD4 count was 147 (50-248) cells/mm3; and pre-treatment HIV RNA was 100,000 (34,045-301,075) copies/mL. Factors associated with pre-treatment HIV RNA <100,000 copies/mL were age <30 years [OR 1.40 vs. 41-50 years; 95% confidence interval (CI) 1.10-1.80, p = 0.01], body mass index >30 kg/m2(OR 2.4 vs. <18.5 kg/m2; 95% CI 1.1-5.1, p = 0.02), anemia (OR 1.70; 95% CI 1.40-2.10, p 350 cells/mm3(OR 3.9 vs. <100 cells/mm3; 95% CI 2.0-4.1, p 2000 cells/mm3(OR 1.7 vs. <1000 cells/mm3; 95% CI 1.3-2.3, p 25 yielded the sensitivity of 46.7%, specificity of 79.1%, positive predictive value of 67.7%, and negative predictive value of 61.2% for prediction of pre-treatment HIV RNA <100,000 copies/mL among derivation patients.
CONCLUSION: A model prediction for pre-treatment HIV RNA <100,000 copies/mL produced an area under the ROC curve of 0.70. A larger sample size for prediction model development as well as for model validation is warranted.
METHODS: Patients enrolled in the TREAT Asia HIV Observational Database cohort and on cART for more than six months were analysed. Comorbidities included hypertension, diabetes, dyslipidaemia and impaired renal function. Treatment outcomes of patients ≥50 years of age with comorbidities were compared with those <50 years and those ≥50 years without comorbidities. We analysed 5411 patients with virological failure and 5621 with immunologic failure. Our failure outcomes were defined to be in-line with the World Health Organization 2016 guidelines. Cox regression analysis was used to analyse time to first virological and immunological failure.
RESULTS: The incidence of virologic failure was 7.72/100 person-years. Virological failure was less likely in patients with better adherence and higher CD4 count at cART initiation. Those acquiring HIV through intravenous drug use were more likely to have virological failure compared to those infected through heterosexual contact. On univariate analysis, patients aged <50 years without comorbidities were more likely to experience virological failure than those aged ≥50 years with comorbidities (hazard ratio 1.75, 95% confidence interval (CI) 1.31 to 2.33, p
METHODS: Participants enrolled in a regional Asian HIV-infected cohort with weight and height measurements at ART initiation were eligible for inclusion in the analysis. Factors associated with weight changes and incident MetS (according to the International Diabetic Federation (IDF) definition) were analysed using linear mixed models and Cox regression, respectively. Competing-risk regression models were used to investigate the association of MetS with all-cause mortality.
RESULTS: Among 4931 people living with HIV (PLWH), 66% were male. At ART initiation, the median age was 34 [interquartile range (IQR) 29-41] years, and the median (IQR) weight and body mass index (BMI) were 55 (48-63) kg and 20.5 (18.4-22.9) kg/m2 , respectively. At 1, 2 and 3 years of ART, overall mean (± standard deviation) weight gain was 2.2 (±5.3), 3.0 (±6.2) and 3.7 (±6.5) kg, respectively. Participants with baseline CD4 count ≤ 200 cells/µL [weight difference (diff) = 2.2 kg; 95% confidence interval (CI) 1.9-2.5 kg] and baseline HIV RNA ≥ 100 000 HIV-1 RNA copies/mL (diff = 0.6 kg; 95% CI 0.2-1.0 kg), and those starting with integrase strand transfer inhibitor (INSTI)-based ART (diff = 2.1 kg; 95% CI 0.7-3.5 kg vs. nonnucleoside reverse transcriptase inhibitors) had greater weight gain. After exclusion of those with abnormal baseline levels of MetS components, 295/3503 had incident MetS [1.18 (95% CI 1.05-1.32)/100 person-years (PY)]. The mortality rate was 0.7 (95% CI 0.6-0.8)/100 PY. MetS was not significantly associated with all-cause mortality in the adjusted model (P = 0.236).
CONCLUSIONS: Weight gain after ART initiation was significantly higher among those initiating ART with lower CD4 count, higher HIV RNA and an INSTI-based regimen after controlling for baseline BMI. Greater efforts to identify and manage MetS among PLWH are needed.
METHODS: We used data from the TREAT Asia HIV Observational Database. Patients were included if they started antiretroviral therapy during or after 2003, had a serum creatinine measurement at antiretroviral therapy initiation (baseline), and had at least 2 follow-up creatinine measurements taken ≥3 months apart. Patients with a baseline estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 were excluded. Chronic kidney disease was defined as 2 consecutive eGFR values ≤60 mL/min/1.73 m2 taken ≥3 months apart. Generalized estimating equations were used to identify factors associated with eGFR change. Competing risk regression adjusted for study site, age and sex, and cumulative incidence plots were used to evaluate factors associated with chronic kidney disease (CKD).
RESULTS: Of 2547 patients eligible for this analysis, tenofovir was being used by 703 (27.6%) at baseline. Tenofovir use, high baseline eGFR, advanced HIV disease stage, and low nadir CD4 were associated with a decrease in eGFR during follow-up. Chronic kidney disease occurred at a rate of 3.4 per 1000 patient/years. Factors associated with CKD were tenofovir use, old age, low baseline eGFR, low nadir CD4, and protease inhibitor use.
CONCLUSIONS: There is an urgent need to enhance renal monitoring and management capacity among at-risk groups in Asia and improve access to less nephrotoxic antiretrovirals.
METHODS: PLHIV from a regional observational cohort without DM prior to antiretroviral therapy (ART) initiation were included in the analysis. DM was defined as having a fasting blood glucose ≥126 mg/dL, glycated haemoglobin ≥6.5%, a two-hour plasma glucose ≥200 mg/dL, or a random plasma glucose ≥200 mg/dL. A Cox regression model, stratified by site, was used to identify risk factors associated with DM.
RESULTS AND DISCUSSION: Of the 1927 participants included, 127 were diagnosed with DM after ART initiation. Median follow-up time from ART initiation to DM diagnosis was 5.9 years (interquartile range (IQR): 2.8 to 8.9 years). The crude incidence rate of DM was 1.08 per 100 person-years (100 PYS), 95% confidence interval (CI) (0.9 to 1.3). In the multivariate analysis, later years of follow-up (2011 to 2013: HR = 2.34, 95% CI 1.14 to 4.79, p = 0.02; and 2014 to 2017: HR = 7.20, 95% CI 3.27 to 15.87, p 50 years: HR = 4.19, 95% CI 2.12 to 8.28, p 30 kg/m2 (HR = 4.3, 95% CI 1.53 to 12.09, p = 0.006) compared to BMI <18.5 kg/m2 , and high blood pressure (HR = 2.05, 95% CI 1.16 to 3.63, p = 0.013) compared to those without high blood pressure, were associated with developing DM. The hazard was reduced for females (HR = 0.47, 95% CI 0.28 to 0.80, p = 0.006).
CONCLUSIONS: Type 2 DM in HIV-infected Asians was associated with later years of follow-up, high blood pressure, obesity and older age. This highlights the importance of monitoring and routine screening for non-communicable diseases including DM as PLHIV age.
METHODS: Adults living with HIV enrolled in a regional observational cohort in Asia who had initiated combination antiretroviral therapy (cART) were included in the analysis. Factors associated with new TB diagnoses after cohort entry and survival after cART initiation were analysed using Cox regression, stratified by site.
RESULTS: A total of 7355 patients from 12 countries enrolled into the cohort between 2003 and 2016 were included in the study. There were 368 reported cases of TB after cohort entry with an incidence rate of 0.99 per 100 person-years (/100 pys). Multivariate analyses adjusted for viral load (VL), CD4 count, body mass index (BMI) and cART duration showed that CTX reduced the hazard for new TB infection by 28% (HR 0.72, 95% CI l 0.56, 0.93). Mortality after cART initiation was 0.85/100 pys, with a median follow-up time of 4.63 years. Predictors of survival included age, female sex, hepatitis C co-infection, TB diagnosis, HIV VL, CD4 count and BMI.
CONCLUSIONS: CTX was associated with a reduction in the hazard for new TB infection but did not impact survival in our Asian cohort. The potential preventive effect of CTX against TB during periods of severe immunosuppression should be further explored.