METHODS: We investigated serum creatinine (S-Cr) monitoring rates before and during ART and the incidence and prevalence of renal dysfunction after starting TDF by using data from a regional cohort of HIV-infected individuals in the Asia-Pacific. Time to renal dysfunction was defined as time from TDF initiation to the decline in estimated glomerular filtration rate (eGFR) to <60 ml/min/1.73m2 with >30% reduction from baseline using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or the decision to stop TDF for reported TDF-nephrotoxicity. Predictors of S-Cr monitoring rates were assessed by Poisson regression and risk factors for developing renal dysfunction were assessed by Cox regression.
RESULTS: Among 2,425 patients who received TDF, S-Cr monitoring rates increased from 1.01 to 1.84 per person per year after starting TDF (incidence rate ratio 1.68, 95%CI 1.62-1.74, p <0.001). Renal dysfunction on TDF occurred in 103 patients over 5,368 person-years of TDF use (4.2%; incidence 1.75 per 100 person-years). Risk factors for developing renal dysfunction included older age (>50 vs. ≤30, hazard ratio [HR] 5.39, 95%CI 2.52-11.50, p <0.001; and using PI-based regimen (HR 1.93, 95%CI 1.22-3.07, p = 0.005). Having an eGFR prior to TDF (pre-TDF eGFR) of ≥60 ml/min/1.73m2 showed a protective effect (HR 0.38, 95%CI, 0.17-0.85, p = 0.018).
CONCLUSIONS: Renal dysfunction on commencing TDF use was not common, however, older age, lower baseline eGFR and PI-based ART were associated with higher risk of renal dysfunction during TDF use in adult HIV-infected individuals in the Asia-Pacific region.
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 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) 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.
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: 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: The Strategic Timing of AntiRetroviral Treatment (START) trial, as previously reported, randomly assigned 4684 ART-naive HIV-positive adults with CD4+ counts .500 cells/mm3 to immediate treatment initiation after random assignment (n = 2325) or deferred treatment (n= 2359). In 2015, a 57% lower risk of the primary end point (AIDS, SNA, or death) for the immediate group was reported, and the deferred group was offered ART. This article reports the follow-up that continued to December 31, 2021. Cox proportional-hazards models were used to compare hazard ratios for the primary end point from randomization through December 31, 2015, versus January 1, 2016, through December 31, 2021.
RESULTS: Through December 31, 2015, approximately 7 months after the cutoff date from the previous report, the median CD4+ count was 648 and 460 cells/mm3 in the immediate and deferred groups, respectively, at treatment initiation. The percentage of follow-up time spent taking ART was 95% and 36% for the immediate and deferred groups, respectively, and the time-averaged CD4+ difference was 199 cells/mm3. After January 1, 2016, the percentage of follow-up time on treatment was 97.2% and 94.1% for the immediate and deferred groups, respectively, and the CD4+ count difference was 155 cells/mm3. After January 1, 2016, a total of 89 immediate and 113 deferred group participants experienced a primary end point (hazard ratio of 0.79 [95% confidence interval, 0.60 to 1.04] versus hazard ratio of 0.47 [95% confidence interval, 0.34 to 0.65; P<0.001]) before 2016 (P=0.02 for hazard ratio difference).
CONCLUSIONS: Among adults with CD4+ counts >500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
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.
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: This 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 (<18.5 kg/m2 ), normal (18.5-22.9 kg/m2 ), overweight (23-24.9 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.
RESULTS: A 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] = 1.79; 95% confidence interval [CI] 1.31-2.44; p 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.
METHODS: The study population consisted of HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD). Individuals were included in this analysis if they started combination antiretroviral treatment (cART) after 2002, were being treated at a centre that documented a median rate of viral load monitoring ≥0.8 tests/patient/year among TAHOD enrolees, and experienced a minor or major treatment substitution while on virally suppressive cART. The primary endpoint to evaluate outcomes was clinical or virological failure (VF), followed by an ART class change. Clinical failure was defined as death or an AIDS diagnosis. VF was defined as confirmed viral load measurements ≥400 copies/mL followed by an ART class change within six months. Minor regimen substitutions were defined as within-class changes and major regimen substitutions were defined as changes to a drug class. The patterns of substitutions and rate of clinical or VF after substitutions were analyzed.
RESULTS: Of 3994 adults who started ART after 2002, 3119 (78.1%) had at least one period of virological suppression. Among these, 1170 (37.5%) underwent a minor regimen substitution, and 296 (9.5%) underwent a major regimen substitution during suppression. The rates of clinical or VF were 1.48/100 person years (95% CI 1.14 to 1.91) in the minor substitution group, 2.85/100 person years (95% CI 1.88 to 4.33) in the major substitution group and 2.53/100 person years (95% CI 2.20 to 2.92) among patients that did not undergo a treatment substitution.
CONCLUSIONS: The rate of clinical or VF was low in both major and minor substitution groups, showing that regimen substitution is generally effective in non-clinical trial settings in Asian countries.
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: 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: Data linkages with the national death registry or national HIV database were conducted in 2020 on all PLHIV who met LTFU criteria while enrolled in care at participating HIV clinical sites. LTFU was defined as having no documented clinical contact in the previous year, excluding transfers and deaths. Survival time was analyzed using the Cox regression, stratified by site.
RESULTS: Data linkages were performed for 489 PLHIV who had been LTFU at sites in Malaysia (n = 2) and Thailand (n = 4). There were 151 (31%) deaths after being LTFU; the mortality rate was 4.89 per 100 person-years. Risk factors for mortality after being LTFU were older age [41-50 years: hazard ratio (HR) = 1.99, 95% confidence interval (CI): 1.08 to 3.68; and older than 50 years: HR = 4.93, 95% CI: 2.63 to 9.22; vs. age 30 years or younger]; receiving NRTI + PI (HR = 1.87, 95% CI: 1.22 to 2.85 vs. NRTI + NNRTI); positive hepatitis C antibody (HR = 2.25, 95% CI: 1.40 to 3.62); and having previous AIDS illness (HR = 1.45, 95% CI: 1.03 to 2.05). An improved survival was seen with a higher CD4 count (CD4 351-500 cells/µL: HR = 0.40, 95%CI: 0.21-0.76; and CD4 >500 cells/µL: HR = 0.43, 95%CI: 0.25-0.75; vs. CD4 ≤200 cells/µL).
CONCLUSIONS: Almost one-third of PLHIV who were LTFU in this cohort had died while out of care, emphasizing the importance of efforts to reengage PLHIV after they have been LTFU and ensure they have access to ongoing ART.
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: 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: 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.