DESIGN: Death-related data were retrospectively and prospectively assessed in a longitudinal regional cohort study.
METHODS: Children under routine HIV care at sites in Cambodia, India, Indonesia, Malaysia, Thailand, and Vietnam between 2008 and 2017 were followed. Causes of death were reported and then independently and centrally reviewed. Predictors were compared using competing risks survival regression analyses.
RESULTS: Among 5918 children, 5523 (93%; 52% male) had ever been on combination antiretroviral therapy. Of 371 (6.3%) deaths, 312 (84%) occurred in those with a history of combination antiretroviral therapy (crude all-cause mortality 9.6 per 1000 person-years; total follow-up time 32 361 person-years). In this group, median age at death was 7.0 (2.9-13) years; median CD4 cell count was 73 (16-325) cells/μl. The most common underlying causes of death were pneumonia due to unspecified pathogens (17%), tuberculosis (16%), sepsis (8.0%), and AIDS (6.7%); 12% of causes were unknown. These clinical diagnoses were further grouped into AIDS-related infections (22%) and noninfections (5.8%), and non-AIDS-related infections (47%) and noninfections (11%); with 12% unknown, 2.2% not reviewed. Higher CD4 cell count and better weight-for-age z-score were protective against death.
CONCLUSION: Our standardized cause of death assessment provides robust data to inform regional resource allocation for pediatric diagnostic evaluations and prioritization of clinical interventions, and highlight the continued importance of opportunistic and nonopportunistic infections as causes of death in our cohort.
METHODS: Blips were defined as detectable VL (≥ 50 copies/mL) preceded and followed by undetectable VL (<50 copies/mL). Virological failure (VF) was defined as two consecutive VL ≥50 copies/ml. Cox proportional hazard models of time to first VF after entry, were developed.
RESULTS: 5040 patients (AHOD n = 2597 and TAHOD n = 2521) were included; 910 (18%) of patients experienced blips. 744 (21%) and 166 (11%) of high- and middle/low-income participants, respectively, experienced blips ever. 711 (14%) experienced blips prior to virological failure. 559 (16%) and 152 (10%) of high- and middle/low-income participants, respectively, experienced blips prior to virological failure. VL testing occurred at a median frequency of 175 and 91 days in middle/low- and high-income sites, respectively. Longer time to VF occurred in middle/low income sites, compared with high-income sites (adjusted hazards ratio (AHR) 0.41; p<0.001), adjusted for year of first cART, Hepatitis C co-infection, cART regimen, and prior blips. Prior blips were not a significant predictor of VF in univariate analysis (AHR 0.97, p = 0.82). Differing magnitudes of blips were not significant in univariate analyses as predictors of virological failure (p = 0.360 for blip 50-≤1000, p = 0.309 for blip 50-≤400 and p = 0.300 for blip 50-≤200). 209 of 866 (24%) patients were switched to an alternate regimen in the setting of a blip.
CONCLUSION: Despite a lower proportion of blips occurring in low/middle-income settings, no significant difference was found between settings. Nonetheless, a substantial number of participants were switched to alternative regimens in the setting of blips.
METHODS: HIV+ patients from the Australian HIV Observational Database (AHOD) and the TREAT Asia HIV Observational Database (TAHOD) meeting specific criteria were included. In these analyses Asian and Caucasian status were defined by cohort. Factors associated with a low CD4:CD8 ratio (cutoff <0.2) prior to ART commencement, and with achieving a normal CD4:CD8 ratio (>1) at 12 and 24 months post ART commencement were assessed using logistic regression.
RESULTS: There were 591 patients from AHOD and 2,620 patients from TAHOD who met the inclusion criteria. TAHOD patients had a significantly (P<0.001) lower odds of having a baseline (prior to ART initiation) CD4:CD8 ratio greater than 0.2. After 12 months of ART, AHOD patients were more than twice as likely to achieve a normal CD4:CD8 ratio compared to TAHOD patients (15% versus 6%). However, after adjustment for confounding factors there was no significant difference between cohorts in the odds of achieving a CD4:CD8 ratio >1 (P=0.475).
CONCLUSIONS: We found a significantly lower CD4:CD8 ratio prior to commencing ART in TAHOD compared to AHOD even after adjusting for confounders. However, after adjustment, there was no significant difference between the cohorts in odds of achieving normal ratio. Baseline CD4+ and CD8+ counts seem to be the main driver for this difference between these two populations.
METHODS: Prospectively collected longitudinal data from patients in Thailand, Hong Kong, Malaysia, Japan, Taiwan, and South Korea were provided for analysis. Covariates included demographics, hepatitis B and C coinfections, baseline CD4 T lymphocyte count, and plasma HIV-1 RNA levels. Clinical deterioration (a new diagnosis of Centers for Disease Control and Prevention category B/AIDS-defining illness or death) was assessed by proportional hazards models. Surrogate endpoints were 12-month change in CD4 cell count and virologic suppression post therapy, evaluated by linear and logistic regression, respectively.
RESULTS: Of 1105 patients, 1036 (93.8%) infected with CRF01_AE or subtype B were eligible for inclusion in clinical deterioration analyses and contributed 1546.7 person-years of follow-up (median: 413 days, interquartile range: 169-672 days). Patients >40 years demonstrated smaller immunological increases (P = 0.002) and higher risk of clinical deterioration (hazard ratio = 2.17; P = 0.008). Patients with baseline CD4 cell counts >200 cells per microliter had lower risk of clinical deterioration (hazard ratio = 0.373; P = 0.003). A total of 532 patients (48.1% of eligible) had CD4 counts available at baseline and 12 months post therapy for inclusion in immunolgic analyses. Patients infected with subtype B had larger increases in CD4 counts at 12 months (P = 0.024). A total of 530 patients (48.0% of eligible) were included in virological analyses with no differences in response found between genotypes.
CONCLUSIONS: Results suggest that patients infected with CRF01_AE have reduced immunologic response to therapy at 12 months, compared with subtype B-infected counterparts. Clinical deterioration was associated with low baseline CD4 counts and older age. The lack of differences in virologic outcomes suggests that all patients have opportunities for virological suppression.
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: 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: Long-term LTFU was defined as LTFU occurring after 5 years on ART. LTFU was defined as (1) patients not seen in the previous 12 months; and (2) patients not seen in the previous 6 months. Factors associated with LTFU were analysed using competing risk regression.
RESULTS: Under the 12-month definition, the LTFU rate was 2.0 per 100 person-years (PY) [95% confidence interval (CI) 1.8-2.2 among 4889 patients included in the study. LTFU was associated with age > 50 years [sub-hazard ratio (SHR) 1.64; 95% CI 1.17-2.31] compared with 31-40 years, viral load ≥ 1000 copies/mL (SHR 1.86; 95% CI 1.16-2.97) compared with viral load < 1000 copies/mL, and hepatitis C coinfection (SHR 1.48; 95% CI 1.06-2.05). LTFU was less likely to occur in females, in individuals with higher CD4 counts, in those with self-reported adherence ≥ 95%, and in those living in high-income countries. The 6-month LTFU definition produced an incidence rate of 3.2 per 100 PY (95% CI 2.9-3.4 and had similar associations but with greater risks of LTFU for ART initiation in later years (2006-2009: SHR 2.38; 95% CI 1.93-2.94; and 2010-2011: SHR 4.26; 95% CI 3.17-5.73) compared with 2003-2005.
CONCLUSIONS: The long-term LTFU rate in our cohort was low, with older age being associated with LTFU. The increased risk of LTFU with later years of ART initiation in the 6-month analysis, but not the 12-month analysis, implies that there was a possible move towards longer HIV clinic scheduling in Asia.
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: 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: 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: This cross-sectional study recruited adult PWH during routine follow-up at five HIV clinical sites in the Asia-Pacific region. Participants were screened for depression using Patient Health Questionnaire-9 and SU using Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). Quality of life (QoL) was assessed with WHOQOL-HIV BREF and functional ability with World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). Factors associated with mean QoL and disability scores were analysed using linear regression.
RESULTS: Of 864 PWH enrolled, 753 screened positive for depression or SU. The median (interquartile range, IQR) age was 38 (31-47) years and 97% were on ART. Overall mean WHOQOL-HIV BREF and WHODAS scores indicated greater impairment with increasing depressive symptom severity and SU risk. In multivariate analysis, PWH reporting previous trauma/stress (difference = 2.7, 95% confidence interval [CI] 1.5-3.9, P
METHODS: We did a cohort analysis of TB cases in SECOND-LINE. TB cases included any clinical or laboratory-confirmed diagnoses and/or commencement of treatment for TB after randomization. Baseline factors associated with TB were analyzed using Cox regression stratified by site.
RESULTS: TB cases occurred at sites in Argentina, India, Malaysia, Nigeria, South Africa, and Thailand, in a cohort of 355 of the 541 SECOND-LINE participants. Overall, 20 cases of TB occurred, an incidence rate of 3.4 per 100 person-years (95% CI: 2.1 to 5.1). Increased TB risk was associated with a low CD4+-cell count (≤200 cells/μL), high viral load (>200 copies/mL), low platelet count (<150 ×109/L), and low total serum cholesterol (≤4.5 mmol/L) at baseline. An increased risk of death was associated with TB, adjusted for CD4, platelets, and cholesterol. A low CD4+-cell count was significantly associated with incident TB, mortality, other AIDS diagnoses, and virologic failure.
DISCUSSION: The risk of TB remains elevated in PLHIV in the setting of second-line HIV therapy in TB endemic regions. TB was associated with a greater risk of death. Finding that low CD4+ T-cell count was significantly associated with poor outcomes in this population supports the value of CD4+ monitoring in HIV clinical management.
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.
METHODS: HIV-positive patients enrolled in the TREAT Asia HIV Observational Database who had used second-line ART for ≥6 months were included. ART use and rates and predictors of second-line treatment failure were evaluated.
RESULTS: There were 302 eligible patients. Most were male (76.5%) and exposed to HIV via heterosexual contact (71.5%). Median age at second-line initiation was 39.2 years, median CD4 cell count was 146 cells per cubic millimeter, and median HIV viral load was 16,224 copies per milliliter. Patients started second-line ART before 2007 (n = 105), 2007-2010 (n = 147) and after 2010 (n = 50). Ritonavir-boosted lopinavir and atazanavir accounted for the majority of protease inhibitor use after 2006. Median follow-up time on second-line therapy was 2.3 years. The rates of treatment failure and mortality per 100 patient/years were 8.8 (95% confidence interval: 7.1 to 10.9) and 1.1 (95% confidence interval: 0.6 to 1.9), respectively. Older age, high baseline viral load, and use of a protease inhibitor other than lopinavir or atazanavir were associated with a significantly shorter time to second-line failure.
CONCLUSIONS: Increased access to viral load monitoring to facilitate early detection of first-line ART failure and subsequent treatment switch is important for maximizing the durability of second-line therapy in Asia. Although second-line ART is highly effective in the region, the reported rate of failure emphasizes the need for third-line ART in a small portion of patients.
METHODS: A retrospective review of all the neonates and infants (<1 year) was conducted from the CAF registry for CAF treatment. The CAF type (proximal or distal), size, treatment method, and follow-up angiography were reviewed to assess outcomes and coronary remodeling.
RESULTS: Forty-eight patients were included from 20 centers. Of these, 30 were proximal and 18 had distal CAF; 39 were large, 7 medium, and 2 had small CAF. The median age and weight was 0.16 years (0.01-1) and 4.2 kg (1.7-10.6). Heart failure was noted in 28 of 48 (58%) patients. Transcatheter closure was performed in 24, surgical closure in 18, and 6 were observed medically. Procedural success was 92% and 94 % for transcatheter closure and surgical closure, respectively. Follow-up data were obtained in 34 of 48 (70%) at a median of 2.9 (0.1-18) years. Angiography to assess remodeling was available in 20 of 48 (41%). I. Optimal remodeling (n=10, 7 proximal and 3 distal CAF). II. Suboptimal remodeling (n=7) included (A) symptomatic coronary thrombosis (n=2, distal CAF), (B) asymptomatic coronary thrombosis (n=3, 1 proximal and 2 distal CAF), and (C) partial thrombosis with residual cul-de-sac (n=1, proximal CAF) and vessel irregularity with stenosis (n=1, distal CAF). Finally, (III) persistent coronary artery dilation (n=4). Antiplatelets and anticoagulation were used in 31 and 7 patients post-closure, respectively. Overall, 7 of 10 (70%) with proximal CAF had optimal remodeling, but 5 of 11 (45%) with distal CAF had suboptimal remodeling. Only 1 of 7 patients with suboptimal remodeling were on anticoagulation.
CONCLUSIONS: Neonates/infants with hemodynamically significant CAF can be treated by transcatheter or surgical closure with excellent procedural success. Patients with distal CAF are at higher risk for suboptimal remodeling. Postclosure anticoagulation and follow-up coronary anatomic evaluation are warranted.
Methods: Sixteen LMIC sites included in the International Epidemiology Databases to Evaluate AIDS - Asia-Pacific network were surveyed.
Results: Sites were mostly (81%) based in urban public referral hospitals. Half had protocols to assess tobacco and alcohol use. Protocols for assessing physical inactivity and obesity were in place at 31% and 38% of sites, respectively. Most sites provided educational material on ASCVD risk factors (between 56% and 75% depending on risk factors). A total of 94% reported performing routine screening for hypertension, 100% for hyperlipidaemia and 88% for diabetes. Routine ASCVD risk assessment was reported by 94% of sites. Protocols for the management of hypertension, hyperlipidaemia, diabetes, high ASCVD risk and chronic ischaemic stroke were in place at 50%, 69%, 56%, 19% and 38% of sites, respectively. Blood pressure monitoring was free for patients at 69% of sites; however, most required patients to pay some or all the costs for other ASCVD-related procedures. Medications available in the clinic or within the same facility included angiotensin-converting enzyme inhibitors (81%), statins (94%) and sulphonylureas (94%).
Conclusion: The consistent availability of clinical screening, diagnostic testing and procedures and the availability of ASCVD medications in the Asian LMIC clinics surveyed are strengths that should be leveraged to improve the implementation of cardiovascular care protocols.