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Background: Having 90% of patients on antiretroviral therapy (ART) and achieving an undetectable viral load (VL) is 1 of the 90: 90: 90 by 2020 targets. In this global analysis, we investigated the proportions of adult and paediatric patients with VL suppression in the first 3 years after ART initiation. Methods: Patients from the IeDEA cohorts who initiated ART between 2010 and 2014 were included. Proportions with VL suppression (<1000 copies/ mL) were estimated using (1) strict intention to treat (ITT)-loss to follow-up (LTFU) and dead patients counted as having detectable VL; and (2) modified ITT-LTFU and dead patients were excluded. Logistic regression was used to identify predictors of viral suppression at 1 year after ART initiation using modified ITT. Results: A total of 35,561 adults from 38 sites/16 countries and 2601 children from 18 sites/6 countries were included. When comparing strict with modified ITT methods, the proportion achieving VL suppression at 3 years from ART initiation changed from 45.1% to 90.2% in adults, and 60.6% to 80.4% in children. In adults, older age, higher CD4 count preART, and homosexual/bisexual HIV exposure were associated with VL suppression. In children, older age and higher CD4 percentage pre-ART showed significant associations with VL suppression. Conclusions: Large increases in the proportion of VL suppression in adults were observed when we excluded those who were LTFU or had died. The increases were less pronounced in children. Greater emphasis should be made to minimize LTFU and maximize patient retention in HIV-infected patients of all age groups. ; U.S. National Institutes of Health's National Institute of Allergy and Infectious Diseases ; Eunice Kennedy Shriver National Institute of Child Health and Human Development ; National Cancer Institute ; Centers for Disease Control and Prevention, USA ; Agency for Healthcare Research and Quality, USA ; Health Resources and Services Administration, USA ; Canadian Institutes of Health Research, Canada ; Ontario Ministry of Health and Long Term Care ; Government of Alberta, Canada ; Intramural Research Program of the National Cancer Institute ; Australian Government Department of Health and Ageing ; UNSW, Kirby Inst, Sydney, NSW 2052, Australia ; Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA ; Fdn Huesped, Buenos Aires, DF, Argentina ; Univ Chile, Sch Med, Santiago, Chile ; Fdn Arriaran, Santiago, Chile ; Univ Cape Town, Sch Publ Hlth & Family Med, Cape Town, South Africa ; Childrens Hosp 2, Ho Chi Minh City, Vietnam ; Univ Cape Town, Dept Paediat & Child Hlth, Cape Town, South Africa ; Univ Calgary, Calgary, AB, Canada ; YRGCARE Med Ctr, Madras, Tamil Nadu, India ; Univ Fed Sao Paulo, Pediat Infect Dis Div, Escola Paulista Med, Sao Paulo, Brazil ; Johns Hopkins Univ, Dept Med, Div Infect Dis, Baltimore, MD USA ; Univ Stellenbosch, Dept Med, Div Infect Dis, Cape Town, South Africa ; Tygerberg Hosp, Cape Town, South Africa ; Univ Bern, Inst Social & Prevent Med, Bern, Switzerland ; Univ Fed Sao Paulo, Pediat Infect Dis Div, Escola Paulista Med, Sao Paulo, Brazil ; NCI: U01AI035004 ; NCI: U01AI035039 ; NCI: U01AI035040 ; NCI: U01AI035041 ; NCI: U01AI035042 ; NCI: U01AI037613 ; NCI: U01AI037984 ; NCI: U01AI038855 ; NCI: U01AI038858 ; NCI: U01AI042590 ; NCI: U01AI068634 ; NCI: U01AI068636 ; NCI: U01AI069432 ; NCI: U01AI069434 ; Centers for Disease Control and Prevention, USA: CDC-200-2006-18797 ; Centers for Disease Control and Prevention, USA: CDC-200-2015-63931 ; Agency for Healthcare Research and Quality, USA: 90047713 ; Health Resources and Services Administration, USA: 90051652 ; Canadian Institutes of Health Research, Canada: CBR-86906 ; Canadian Institutes of Health Research, Canada: CBR-94036 ; Canadian Institutes of Health Research, Canada: HCP-97105 ; Canadian Institutes of Health Research, Canada: TGF-96118 ; NCI: P30AI027757 ; NCI: P30AI027763 ; NCI: P30AI027767 ; NCI: P30AI036219 ; NCI: P30AI050410 ; NCI: P30AI094189 ; NCI: P30AI110527 ; NCI: P30MH62246 ; NCI: R01AA016893 ; NCI: R01CA165937 ; NCI: R01DA004334 ; NCI: R01DA011602 ; NCI: R01DA012568 ; NCI: R24AI067039 ; NCI: U01AA013566 ; NCI: U01AA020790 ; NCI: U01AI1031834 ; NCI: U01AI034989 ; NCI: U01AI034993 ; NCI: U01AI034994 ; NCI: M01RR000052 ; NCI: U54MD007587 ; NCI: UL1RR024131 ; NCI: UL1TR000004 ; NCI: UL1TR000083 ; NCI: UL1TR000454 ; NCI: UM1AI035043 ; NCI: Z01CP010214 ; NCI: Z01CP010176 ; NCI: U01AI069907 ; NCI: U01AI069923 ; NCI: U01AI069924 ; NCI: U01AI069918 ; NCI: F31DA037788 ; NCI: G12MD007583 ; NCI: K01A1093197 ; NCI: K23EY013707 ; NCI: K24DA000432 ; NCI: K24AI065298 ; NCI: KL2TR000421 ; NCI: N02CP055504 ; NCI: U01AI103390 ; NCI: U01AI103397 ; NCI: U01AI103401 ; NCI: U01AI103408 ; NCI: U01DA036935 ; NCI: U01HD032632 ; NCI: U10EY008057 ; NCI: U10EY008052 ; NCI: U10EY008067 ; NCI: U24AA020794 ; Web of Science

AbstractIntroduction: Our understanding of how to achieve optimal long‐term adherence to antiretroviral therapy (ART) in settings where the burden of HIV disease is highest remains limited. We compared levels and determinants of adherence over time between HIV‐positive persons receiving ART who were enrolled in a bi‐regional cohort in sub‐Saharan Africa and Asia.Methods: This multicentre prospective study of adults starting first‐line ART assessed patient‐reported adherence at follow‐up clinic visits using a 30‐day visual analogue scale. Determinants of suboptimal adherence (<95%) were assessed for six‐month intervals, using generalized estimating equations multivariable logistic regression with multiple imputations. Region of residence (Africa vs. Asia) was assessed as a potential effect modifier.Results: Of 13,001 adherence assessments in 3934 participants during the first 24 months of ART, 6.4% (837) were suboptimal, with 7.3% (619/8484) in the African cohort versus 4.8% (218/4517) in the Asian cohort (p < 0.001). In the African cohort, determinants of suboptimal adherence were male sex (odds ratio (OR) 1.27, 95% confidence interval (CI) 1.06–1.53; p = 0.009), younger age (OR 0.8 per 10 year increase; 0.8–0.9; p = 0.003), use of concomitant medication (OR 1.8, 1.0–3.2; p = 0.044) and attending a public facility (OR 1.3, 95% CI 1.1–1.7; p = 0.004). In the Asian cohort, adherence was higher in men who have sex with men (OR for suboptimal adherence 0.6, 95% CI 0.4–0.9; p = 0.029) and lower in injecting drug users (OR for suboptimal adherence 1.6, 95% CI 0.9–2.6; p = 0.075), compared to heterosexuals. Risk of suboptimal adherence decreased with longer ART duration in both regions. Participants in low‐ and lower‐middle‐income countries had a higher risk of suboptimal adherence (OR 1.6, 1.3–2.0; p < 0.001), compared to those in upper‐middle or high‐income countries. Suboptimal adherence was strongly associated with virological failure, in Africa (OR 5.8, 95% CI 4.3–7.7; p < 0.001) and Asia (OR 9.0, 95% CI 5.0–16.2; p < 0.001). Patient‐reported adherence barriers among African participants included scheduling demands, drug stockouts, forgetfulness, sickness or adverse events, stigma or depression, regimen complexity and pill burden.Conclusions: Psychosocial factors and health system resources may explain regional differences. Adherence‐enhancing interventions should address patient‐reported barriers tailored to local settings, prioritizing the first years of ART.

IntroductionAdherence to antiretroviral therapy (ART) plays an important role in treatment outcomes. It is crucial to identify factors influencing adherence in order to optimize treatment responses. The aim of this study was to assess the rates of, and factors associated with, suboptimal adherence (SubAdh) in the first 24 months of ART in an Asian HIV cohort.MethodsAs part of a prospective resistance monitoring study, the TREAT Asia Studies to Evaluate Resistance Monitoring Study (TASER‐M) collected patients' adherence based on the World Health Organization‐validated Adherence Visual Analogue Scale. SubAdh was defined in two ways: (i) <100% and (ii) <95%. Follow‐up time started from ART initiation and was censored at 24 months, loss to follow‐up, death, treatment switch, or treatment cessation for >14 days. Time was divided into four intervals: 0–6, 6–12, 12–18 and 18–24 months. Factors associated with SubAdh were analysed using generalized estimating equations.ResultsOut of 1316 patients, 32% ever reported <100% adherence and 17% ever reported <95%. Defining the outcome as SubAdh <100%, the rates of SubAdh for the four time intervals were 26%, 17%, 12% and 10%. Sites with an average of >2 assessments per patient per year had an odds ratio (OR)=0.7 (95% confidence interval (CI) (0.55 to 0.90), p=0.006), compared to sites with ≤2 assessments per patient per year. Compared to heterosexual exposure, SubAdh was higher in injecting drug users (IDUs) (OR=1.92, 95% CI (1.23 to 3.00), p=0.004) and lower in homosexual exposure (OR=0.52, 95% CI (0.38 to 0.71), p<0.001). Patients taking a nucleoside transcriptase inhibitor and protease inhibitor (NRTI+PI) combination were less likely to report adherence <100% (OR=0.36, 95% CI (0.20 to 0.67), p=0.001) compared to patients taking an NRTI and non‐nucleoside transcriptase inhibitor (NRTI+NNRTI) combination. SubAdh decreased with increasing time on ART (all p<0.001). Similar associations were found with adherence <95% as the outcome.ConclusionsWe found that SubAdh, defined as either <100% and <95%, was associated with mode of HIV exposure, ART regimen, time on ART and frequency of adherence measurement. The more frequently sites assessed patients, the lower the SubAdh, possibly reflecting site resourcing for patient counselling. Although social desirability bias could not be excluded, a greater emphasis on more frequent adherence counselling immediately following ART initiation and through the first six months may be valuable in promoting treatment and programme retention.

IntroductionFirst‐line antiretroviral therapy (ART) failure often results from the development of resistance‐associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple‐nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second‐line ART.MethodsWe investigated patterns and factors associated with multi‐NRTI RAMs at first‐line failure in patients from The TREAT Asia Studies to Evaluate Resistance – Monitoring study (TASER‐M), and evaluated their impact on virological responses at 12 months after switching to second‐line ART. RAMs were compared with the IAS‐USA 2013 mutations list. We defined multi‐NRTI RAMs as the presence of either Q151M; 69Ins; ≥2 TAMs; or M184V+≥1 TAM. Virological suppression was defined as viral load (VL) <400 copies/ml at 12 months from switch to second‐line. Logistic regression was used to analyze (1) factors associated with multi‐NRTI RAMs at first‐line failure and (2) factors associated with virological suppression after 12 months on second‐line.ResultsA total of 105 patients from 10 sites in Thailand, Hong Kong, Indonesia, Malaysia and Philippines were included. There were 97/105 (92%) patients harbouring ≥1 RAMs at first‐line failure, 39/105 with multi‐NRTI RAMs: six with Q151M; 24 with ≥2 TAMs; and 32 with M184V+≥1 TAM. Factors associated with multi‐NRTI RAMs were CD4 ≤200 cells/µL at genotyping (OR=4.43, 95% CI [1.59–12.37], p=0.004) and ART duration >2 years (OR=6.25, 95% CI [2.39–16.36], p<0.001). Among 87/105 patients with available VL at 12 months after switch to second‐line ART, virological suppression was achieved in 85%. The median genotypic susceptibility score (GSS) for the second‐line regimen was 2.00. Patients with ART adherence ≥95% were more likely to be virologically suppressed (OR=9.33, 95% CI (2.43–35.81), p=0.001). Measures of patient resistance to second‐line ART, including the GSS, were not significantly associated with virological outcome.ConclusionsMulti‐NRTI RAMs at first‐line failure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving virological response. This emphasizes the importance of continued adherence counselling well into second‐line therapy.

AbstractIntroductionComorbidities including diabetes mellitus (DM) among people living with HIV (PLHIV) are of increasing clinical concerns in combination antiretroviral therapy (cART) era. We aimed to determine the incidence and risk factors of new‐onset DM among PLHIV in Asian settings.MethodsPLHIV 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 discussionOf 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 < 0.001) compared to <2010, older age (41 to 50 years: HR = 2.46, 95% CI 1.39 to 4.36, p = 0.002; and >50 years: HR = 4.19, 95% CI 2.12 to 8.28, p < 0.001) compared to <30 years, body mass index (BMI) >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).ConclusionsType 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.

AbstractIntroductionMultiple comorbidities among HIV‐positive individuals may increase the potential for polypharmacy causing drug‐to‐drug interactions and older individuals with comorbidities, particularly those with cognitive impairment, may have difficulty in adhering to complex medications. However, the effects of age‐associated comorbidities on the treatment outcomes of combination antiretroviral therapy (cART) are not well known. In this study, we investigated the effects of age‐associated comorbidities on therapeutic outcomes of cART in HIV‐positive adults in Asian countries.MethodsPatients 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.ResultsThe 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 < 0.001). However, the multivariate model showed that age‐related comorbidities were not significant factors for virological failure (hazard ratio 1.31, 95% CI 0.98 to 1.74, p = 0.07). There were 391 immunological failures, with an incidence of 2.75/100 person‐years. On multivariate analysis, those aged <50 years without comorbidities (p = 0.025) and age <50 years with comorbidities (p = 0.001) were less likely to develop immunological failure compared to those aged ≥50 years with comorbidities.ConclusionsIn our Asia regional cohort, age‐associated comorbidities did not affect virologic outcomes of cART. Among those with comorbidities, patients <50 years old showed a better CD4 response.

AbstractINTRODUCTIONData on HIV treatment outcomes in people who inject drugs (PWID) in the Asia‐Pacific are sparse despite the high burden of drug use. We assessed immunological and virological responses, AIDS‐defining events and mortality among PWID receiving antiretroviral therapy (ART).METHODSWe 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.RESULTSOf 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.CONCLUSIONSDespite improved outcomes over time, our findings highlight the need for rapid ART initiation and adherence support among PWID within Asian settings.

AbstractIntroductionCotrimoxazole (CTX) is recommended as prophylaxis against Pneumocystis jiroveci pneumonia, malaria and other serious bacterial infections in HIV‐infected patients. Despite its in vitro activity against Mycobacterium tuberculosis, the effects of CTX preventive therapy on tuberculosis (TB) remain unclear.MethodsAdults 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.ResultsA 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.ConclusionsCTX 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.

AbstractIntroductionViral load (VL) testing is still challenging to monitor treatment responses of antiretroviral therapy (ART) for HIV treatment programme in Asia. We assessed the association between routine VL testing and virological failure (VF) and determine factors associated with switching to second‐line regimen.MethodsAmong 21 sites from the TREAT Asia HIV Observational Database (TAHOD), people living with HIV (PLHIV) aged ≥18 years initiating ART from 2003 to 2021 were included. We calculated the average number of VL tests per patient per year between the date of ART initiation and the most recent visit. If the median average number of VL tests was ≥ 0.80 per patient per year, the site was classified as a routine VL site. A site with a median < 0.80 was classified into the non‐routine VL sites. VF was defined as VL ≥1000 copies/ml during first‐line therapy. Factors associated with VF were analysed using generalized estimating equations with Poisson distribution.ResultsOf 6277 PLHIV starting ART after 2003, 3030 (48%) were from 11 routine VL testing sites and 3247 (52%) were from 10 non‐routine VL testing sites. The median follow‐up was 9 years (IQR 5–13). The median age was 35 (30–42) years; 68% were male and 5729 (91%) started non‐nucleoside reverse‐transcriptase inhibitor‐based regimen. The median pre‐ART CD4 count in PLHIV from routine VL sites was lower compared to non‐routine VL sites (144 vs. 156 cells/mm3, p <0.001). Overall, 1021 subsequent VF at a rate of 2.15 (95% CI 2.02–2.29) per 100 person‐years (PY). VF was more frequent at non‐routine VL sites (adjusted incidence rate ratio 2.85 [95% CI 2.27–3.59]) compared to routine VL sites. Other factors associated with an increased rate of VF were age <50 years and CD4 count <350 cells/mm3. A total of 817 (13%) patients switched to second‐line regimen at a rate of 1.44 (95% CI 1.35–1.54) per 100 PY. PLHIV at routine VL monitoring sites were at higher risk of switching than those at non‐routine VL sites (adjusted sub‐hazard ratio 1.78 95% CI [1.17–2.71]).ConclusionsPLHIV from non‐routine VL sites had a higher incidence of persistent VF and a low switching regimen rate, reflecting possible under‐utilized VL testing.