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: INTRODUCTION: Data 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). 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 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 CONCLUSIONS: Despite improved outcomes over time, our findings highlight the need for rapid ART initiation and adherence support among PWID within Asian settings., INTRODUCTION Globally, injecting drug use is a major public health concern leading to substantial health burden and transmission risk of blood‐borne infections from injecting equipment sharing behaviours. In a multi‐stage [...]

: Introduction: Cotrimoxazole (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. 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., Introduction Cotrimoxazole (CTX) has been recommended as prophylaxis against Pneumocystis jiroveci pneumonia (PJP), toxoplasmosis, malaria and other serious bacterial infections in adults with severe or advanced HIV clinical disease, with [...]

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

HCV RNA test determines current active infection and is a requirement prior to initiating HCV treatment. We investigated trends and factors associated with post-diagnosis HCV RNA testing rates prior to HCV treatment, and risk factors for first positive HCV RNA among people living with HIV (PLHIV) with HCV in the Asia-Pacific region. PLHIV with positive HCV antibody and in follow-up after 2010 were included. Patients were considered HCV-antibody positive if they ever tested positive for HCV antibody (HCVAb). Repeated measures Poisson regression model was used to analyse factors associated with post-diagnosis HCV RNA testing rates from positive HCVAb test. Factors associated with time to first positive HCV RNA from positive HCVAb test were analysed using Cox regression model. There were 767 HCVAb positive participants included (87% from LMICs) of whom 11% had HCV RNA tests. With 163 HCV RNA tests post positive HCVAb test, the overall testing rate was 5.05 per 100 person-years. Factors associated with increased testing rates included later calendar years of follow-up, HIV viral load ≥1000 copies/mL and higher income countries. Later calendar years of follow-up, ALT >5 times its upper limit of normal, and higher income countries were associated with shorter time to first positive HCV RNA test. Testing patterns indicated that uptake was predominantly in high income countries possibly due to different strategies used to determine testing in LMICs. Expanding access to HCV RNA, such as through lower-cost point of care assays, will be required to achieve elimination of HCV as a public health issue., (© 2024 John Wiley & Sons Ltd.)

Objective: We described mortality and loss to follow-up (LTFU) in children and adolescents who were under care for more than 5 years following initiation of antiretroviral therapy (ART)., Methods: Patients were followed from 5 years after ART until the earlier of their 25th birthday, last visit, death, or LTFU. We used Cox regression to assess predictors of mortality and competing risk regression to assess factors associated with LTFU., Results: In total, 4488 children and adolescents initiating ART between 1997 and 2016 were included in the analysis, with a median follow-up time of 5.2 years. Of these, 107 (2.2%) died and 271 (6.0%) were LTFU. Mortality rate was 4.35 and LTFU rate 11.01 per 1000 person-years. Increased mortality was associated with AIDS diagnosis (adjusted hazard ratio [aHR] 1.71; 95% confidence interval [CI] 1.24-2.37), current CD4 count <350 cells/mm 3 compared with ≥500 (highest aHR 13.85; 95% CI 6.91-27.76 for CD4 <200), viral load ≥10 000 copies/mL compared with <400 (aHR 3.28; 95% CI 1.90-5.63), and exposure to more than one ART regimen (aHR 1.51; 95% CI 1.14-2.00). Factors associated with LTFU were male sex (adjusted subdistribution hazard ratio [asHR] 1.29; 95% CI 1.04-1.59), current viral load >1000 copies/mL compared with <400 (highest asHR 2.36; 95% CI 1.19-4.70 for viral load 1000-9999), and ART start after year 2005 compared with ≤2005 (highest asHR 5.96; 95% CI 1.98-17.91 for 2010-2016)., Conclusion: For children and adolescents surviving 5 years on ART, both current CD4 and viral load remained strong indicators that help to keep track of their treatment outcomes. More effort should be made to monitor patients who switch treatments., (© 2024 British HIV Association.)

Introduction: Toxoplasma gondii can cause symptomatic toxoplasmosis in immunodeficient hosts, including in people living with human immunodeficiency virus (PLWH), mainly because of the reactivation of latent infection. We assessed the prevalence of toxoplasmosis and its associated risk factors in PLWH in the Asia-Pacific region using data from the TREAT Asia Human Immunodeficiency Virus (HIV) Observational Database (TAHOD) of the International Epidemiology Databases to Evaluate AIDS (IeDEA) Asia-Pacific., Methods: This study included both retrospective and prospective cases of toxoplasmosis reported between 1997 and 2020. A matched case-control method was employed, where PLWH diagnosed with toxoplasmosis (cases) were each matched to two PLWH without a toxoplasmosis diagnosis (controls) from the same site. Sites without toxoplasmosis were excluded. Risk factors for toxoplasmosis were analyzed using conditional logistic regression., Results: A total of 269/9576 (2.8%) PLWH were diagnosed with toxoplasmosis in 19 TAHOD sites. Of these, 227 (84%) were reported retrospectively and 42 (16%) were prospective diagnoses after cohort enrollment. At the time of toxoplasmosis diagnosis, the median age was 33 years (interquartile range 28-38), and 80% participants were male, 75% were not on antiretroviral therapy (ART). Excluding 63 out of 269 people without CD4 values, 192 (93.2%) had CD4 ≤200 cells/μL and 162 (78.6%) had CD4 ≤100 cells/μL. By employing 538 matched controls, we found that factors associated with toxoplasmosis included abstaining from ART (odds ratio [OR] 3.62, 95% CI 1.81-7.24), in comparison to receiving nucleoside reverse transcriptase inhibitors plus non-nucleoside reverse transcriptase inhibitors, HIV exposure through injection drug use (OR 2.27, 95% CI 1.15-4.47) as opposed to engaging in heterosexual intercourse and testing positive for hepatitis B virus surface antigen (OR 3.19, 95% CI 1.41-7.21). Toxoplasmosis was less likely with increasing CD4 counts (51-100 cells/μL: OR 0.41, 95% CI 0.18-0.96; 101-200 cells/μL: OR 0.14, 95% CI 0.06-0.34; >200 cells/μL: OR 0.02, 95% CI 0.01-0.06), when compared to CD4 ≤50 cells/μL. Moreover, the use of prophylactic cotrimoxazole was not associated with toxoplasmosis., Conclusions: Symptomatic toxoplasmosis is rare but still occurs in PLWH in the Asia-Pacific region, especially in the context of delayed diagnosis, causing advanced HIV disease. Immune reconstitution through early diagnosis and ART administration remains a priority in Asian PLWH., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: While national adoption of universal HIV treatment guidelines has led to improved, timely uptake of antiretroviral therapy (ART), longer-term care outcomes are understudied. There is little data from real-world service delivery settings on patient attrition, viral load (VL) monitoring, and viral suppression (VS) at 24 and 36 months after HIV treatment initiation., Methods and Findings: For this retrospective cohort analysis, we used observational data from 25 countries in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium's Asia-Pacific, Central Africa, East Africa, Central/South America, and North America regions for patients who were ART naïve and aged ≥15 years at care enrollment between 24 months before and 12 months after national adoption of universal treatment guidelines, occurring 2012 to 2018. We estimated crude cumulative incidence of loss-to-clinic (CI-LTC) at 12, 24, and 36 months after enrollment among patients enrolling in care before and after guideline adoption using competing risks regression. Guideline change-associated hazard ratios of LTC at each time point after enrollment were estimated via cause-specific Cox proportional hazards regression models. Modified Poisson regression was used to estimate relative risks of retention, VL monitoring, and VS at 12, 24, and 36 months after ART initiation. There were 66,963 patients enrolling in HIV care at 109 clinics with ≥12 months of follow-up time after enrollment (46,484 [69.4%] enrolling before guideline adoption and 20,479 [30.6%] enrolling afterwards). More than half (54.9%) were females, and median age was 34 years (interquartile range [IQR]: 27 to 43). Mean follow-up time was 51 months (standard deviation: 17 months; range: 12, 110 months). Among patients enrolling before guideline adoption, crude CI-LTC was 23.8% (95% confidence interval [95% CI] 23.4, 24.2) at 12 months, 31.0% (95% CI [30.6, 31.5]) at 24 months, and 37.2% (95% [CI 36.8, 37.7]) at 36 months after enrollment. Adjusting for sex, age group, enrollment CD4, clinic location and type, and country income level, enrolling in care and initiating ART after guideline adoption was associated with increased hazard of LTC at 12 months (adjusted hazard ratio [aHR] 1.25 [95% CI 1.08, 1.44]; p = 0.003); 24 months (aHR 1.38 [95% CI 1.19, 1.59]; p < .001); and 36 months (aHR 1.34 [95% CI 1.18, 1.53], p < .001) compared with enrollment before guideline adoption, with no before-after differences among patients with no record of ART initiation by end of follow-up. Among patients retained after ART initiation, VL monitoring was low, with marginal improvements associated with guideline adoption only at 12 months after ART initiation. Among those with VL monitoring, VS was high at each time point among patients enrolling before guideline adoption (86.0% to 88.8%) and afterwards (86.2% to 90.3%), with no substantive difference associated with guideline adoption. Study limitations include lags in and potential underascertainment of care outcomes in real-world service delivery data and potential lack of generalizability beyond IeDEA sites and regions included in this analysis., Conclusions: In this study, adoption of universal HIV treatment guidelines was associated with lower retention after ART initiation out to 36 months of follow-up, with little change in VL monitoring or VS among retained patients. Monitoring long-term HIV care outcomes remains critical to identify and address causes of attrition and gaps in HIV care quality., Competing Interests: KNA receives royalties from Coursera. She was a consultant to the All of Us Research Program. She serves on the scientific advisory board for TrioHealth Inc. DN received consulting fees from Abbvie and Gilead and is the PI of a research grant from Pfizer to his institution’. All other authors have declared that no competing interests exist., (Copyright: © 2024 Brazier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Despite improvements in HIV testing and earlier antiretroviral therapy (ART) initiation in children living with HIV through the years, a considerable proportion start treatment with advanced disease. We studied characteristics of children and adolescents living with HIV and their level of immunodeficiency at ART initiation using data from a multi-country Asian cohort. We included children and adolescents who were ART-naïve and <18 years of age at ART initiation from 2011 to 2020 at 17 HIV clinics in six countries. Incidence rates of opportunistic infections (OIs) in the first two years of triple-drug ART (≥3 antiretrovirals) was also reported. Competing risk regression analysis was performed to identify factors associated with first occurrence of OI. In 2,027 children and adolescents (54% males), median age at ART initiation increased from 4.5 years in 2011-2013 to 6.7 in 2017-2020, median CD4 count doubled from 237 cells/μl to 466 cells/μl, and proportion of children who initiated ART as severely immunodeficient decreased from 70% to 45%. During follow-up, 275 (14%) children who received triple-drug ART as first treatment and had at least one clinic visit, developed at least one OI in the first two years of treatment (9.40 per 100 person-years). The incidence rate of any first OI declined from 12.52 to 7.58 per 100 person-years during 2011-2013 and 2017-2020. Lower hazard of OIs were found in those with age at first ART 2-14 years, current CD4 ≥200 cells/μl, and receiving ART between 2017 and 2020. The analysis demonstrated increasing number of children and adolescents starting ART with high CD4 count at ART start. The rate of first OI markedly decreased in children who started ART in more recent years. There remains a clear need for improvement in HIV control strategies in children, by promoting earlier diagnosis and timely treatment., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AHS receives grants to her institution from ViiV Healthcare. All other authors report no potential conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Sornillo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Chronic hepatitis C virus (HCV) infection contributes to substantial morbidity and mortality among adults living with HIV. Cascades of HCV care support monitoring of program performance, but data from Asia are limited. We assessed regional HCV coinfection and cascade outcomes among adults living with HIV in care from 2010-2020., Methods: Patients ≥18 years old with confirmed HIV infection on antiretroviral therapy (ART) at 11 clinical sites in Cambodia, China, India, Indonesia, South Korea, Thailand and Vietnam were included. HCV- and HIV-related treatment and laboratory data were collected from those with a positive HCV antibody (anti-HCV) test after January 2010. An HCV cascade was evaluated, including proportions positive for anti-HCV, tested for HCV RNA or HCV core antigen (HCVcAg), initiated on HCV treatment, and achieved sustained virologic response (SVR). Factors associated with screening uptake, treatment initiation, and treatment response were analyzed using Fine and Gray's competing risk regression model., Results: Of 24,421 patients, 9169 (38%) had an anti-HCV test, and 971 (11%) had a positive result. The proportion with positive anti-HCV was 12.1% in 2010-2014, 3.9% in 2015-2017, and 3.8% in 2018-2020. From 2010 to 2014, 34% with positive anti-HCV had subsequent HCV RNA or HCVcAg testing, 66% initiated HCV treatment, and 83% achieved SVR. From 2015 to 2017, 69% with positive anti-HCV had subsequent HCV RNA or HCVcAg testing, 59% initiated HCV treatment, and 88% achieved SVR. From 2018 to 2020, 80% had subsequent HCV RNA or HCVcAg testing, 61% initiated HCV treatment, and 96% achieved SVR. Having chronic HCV in later calendar years and in high-income countries were associated with increased screening, treatment initiation or achieving SVR. Older age, injecting drug use HIV exposure, lower CD4 and higher HIV RNA were associated with reduced HCV screening or treatment initiation., Conclusions: Our analysis identified persistent gaps in the HCV cascade of care, highlighting the need for focused efforts to strengthen chronic HCV screening, treatment initiation, and monitoring among adult PLHIV in the Asia region., Competing Interests: AHS has received grants to her institution from ViiV Healthcare and Gilead Sciences. Other authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Children living with HIV (CLHIV) on prolonged antiretroviral therapy (ART) are at risk for lipid and glucose abnormalities. Prevalence and associated factors were assessed in a multicentre, Asian longitudinal paediatric cohort., Methods: CLHIV were considered to have lipid or glucose abnormalities if they had total cholesterol ≥200 mg/dL, high-density lipoprotein (HDL) ≤35 mg/dL, low-density lipoprotein (LDL) ≥100 mg/dL, triglycerides (TG) ≥110 mg/dL, or fasting glucose >110 mg/dL. Factors associated with lipid and glucose abnormalities were assessed by logistic regression., Results: Of 951 CLHIV, 52% were male with a median age of 8.0 (interquartile range [IQR] 5.0-12.0) years at ART start and 15.0 (IQR 12.0-18.0) years at their last clinic visit. 89% acquired HIV perinatally, and 30% had ever used protease inhibitors (PIs). Overall, 225 (24%) had hypercholesterolemia, 105 (27%) low HDL, 213 (58%) high LDL, 369 (54%) hypertriglyceridemia, and 130 (17%) hyperglycemia. Hypercholesterolemia was more likely among females (versus males, aOR 1.93, 95% CI 1.40-2.67). Current PIs use was associated with hypercholesterolemia (current use: aOR 1.54, 95% CI 1.09-2.20); low HDL (current use: aOR 3.16, 95% CI 1.94-5.15; prior use: aOR 10.55, 95% CI 2.53-43.95); hypertriglyceridemia (current use: aOR 3.90, 95% CI 2.65-5.74; prior use: aOR 2.89, 95% CI 1.31-6.39); high LDL (current use: aOR 1.74, 95% CI 1.09-2.76); and hyperglycemia (prior use: aOR 2.43, 95% CI 1.42-4.18)., Conclusion: More than half and one-fifth of CLHIV have dyslipidemia and hyperglycemia, respectively. Routine paediatric HIV care should include metabolic monitoring. The association between PIs use and dyslipidemia emphasizes the importance of rapidly transitioning to integrase inhibitor-containing regimens.

Background: We evaluated trends in CD4/CD8 ratio among people living with HIV (PLWH) starting antiretroviral therapy (ART) with first-line integrase strand transfer inhibitors (INSTI) compared with non-INSTI-based ART, and the incidence of CD4/CD8 ratio normalization., Methods: All PLWH enrolled in adult HIV cohorts of IeDEA Asia-Pacific who started with triple-ART with at least 1 CD4, CD8 (3-month window), and HIV-1 RNA measurement post-ART were included. CD4/CD8 ratio normalization was defined as a ratio ≥1. Longitudinal changes in CD4/CD8 ratio were analyzed by linear mixed model, the incidence of the normalization by Cox regression, and the differences in ratio recovery by group-based trajectory modeling., Results: A total of 5529 PLWH were included; 80% male, median age 35 years (interquartile range [IQR], 29-43). First-line regimens were comprised of 65% NNRTI, 19% PI, and 16% INSTI. The baseline CD4/CD8 ratio was 0.19 (IQR, 0.09-0.33). PLWH starting with NNRTI- (P = 0.005) or PI-based ART (P = 0.030) had lower CD4/CD8 recovery over 5 years compared with INSTI. During 24,304 person-years of follow-up, 32% had CD4/CD8 ratio normalization. After adjusting for age, sex, baseline CD4, HIV-1 RNA, HCV, and year of ART initiation, PLWH started with INSTI had higher odds of achieving CD4/CD8 ratio normalization than NNRTI- (P < 0.001) or PI-based ART (P = 0.015). In group-based trajectory modeling analysis, INSTI was associated with greater odds of being in the higher ratio trajectory., Conclusions: INSTI use was associated with higher rates of CD4/CD8 ratio recovery and normalization in our cohort. These results emphasize the relative benefits of INSTI-based ART for immune restoration., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: HIV self-testing (HIVST) is recommended by the World Health Organization, but implementation remains limited. This cross-sectional study evaluated HIVST uptake among female entertainment workers (EWs), men who have sex with men (MSM), and transgender women in Phnom Penh, Cambodia, to inform national implementation., Methods: Between December 2018 and September 2019, individuals reached through community outreach or via online advertising were offered HIVST or referrals to facility-based testing. Participants opting for HIVST could choose between test kits employing oral-fluid or finger-prick-based sample collection; and between an "assisted" option in which outreach staff offered instructions and assistance and an "unassisted" option in which participants received a kit with instructions for use. A structured questionnaire was administered to facilitate descriptive statistics and tests for associations between participant characteristics and HIV testing preferences and outcomes., Results: Among 1,241 eligible individuals; 1,210 (97.5%) provided responses for analysis. Of these, 1,203 (99.4%) were recruited through outreach; 7 (0.6%) through online advertising. Among those recruited by outreach, 1,186 (98.6%) opted for assisted HIVST, and 1,065 (88.5%) opted for oral-fluid versus finger-prick testing. All individuals recruited through online advertisements opted for unassisted oral-fluid testing. Among all participants, 455 (37.6%) were MSM, 325 (26.9%) were transgender women, 430 (35.5%) were female EWs, and overall, 71.7% reported never previously testing for HIV. A total of 84 participants (6.9%) received reactive screening results and 81 (97.5%) were linked to treatment., Conclusion: Uptake of HIVST was high, and most participants preferred oral-fluid over finger-prick-based testing. Many individuals (72%) who had never previously accessed HIV testing services participated in HIVST, with high rates of reactivity., (© Cassell et al.)

Introduction: Multiple 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., 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 < 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., Conclusions: In 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., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Adolescents living with HIV on antiretroviral therapy (ART) have worse treatment adherence, viral suppression, and mortality rates compared to adults. This study investigated factors associated with viral non-suppression among adolescents living with HIV in Cambodia., Methods: A cross-sectional study was conducted in August 2016 among 328 adolescents living with HIV aged 15-17 years who were randomly selected from 11 ART clinics in the capital city of Phnom Penh and 10 other provinces. Clinical and immunological data, including CD4 count and viral load, were obtained from medical records at ART clinics. Adolescents were categorized as having achieved viral suppression if their latest viral load count was < 1000 ribonucleic acid (RNA) copies/mL. Multivariate logistic regression analysis was performed to identify factors independently associated with viral non-suppression., Results: The mean age of the participants was 15.9 years (SD = 0.8), and 48.5% were female. Median duration on ART was 8.6 (interquartile range = 6.0-10.6) years. Of total, 76.8% of the participants had achieved viral suppression. After adjustment for other covariates, the likelihood of having viral non-suppression remained significantly lower among adolescents who were: older/aged 17 (AOR = 0.46, 95% CI 0.21-0.98), had been on ART for more than 9 years (AOR = 0.35, 95% CI 0.19-0.64), had most recent CD4 count of > 672 (AOR = 0.47, 95% CI 0.26-0.86), had a relative as the main daily caregiver (AOR = 0.37, 95% CI 0.17-0.80), and did not believe that there is a cure for AIDS (AOR = 0.40, 95% CI 0.21-0.75) compared to their reference group. The likelihood of having viral non-suppression also remained significantly higher among adolescents who had first viral load > 628 RNA copies/mL (AOR = 1.81, 95% CI 1.05-4.08) and among those who were receiving HIV care and treatment from an adult clinic (AOR = 2.95, 95% CI 1.56-5.59)., Conclusions: The proportion of adolescents living with HIV with viral suppression in this study was relatively high at 76.8%, but falls short of the global target of 90%. Programs targeting younger adolescents and adolescents in transition from pediatric to adult care with a range of interventions including psychosocial support and treatment literacy could further improve viral suppression outcomes.

Background: Adolescents living with HIV experience worse HIV care outcomes compared to adults, especially during transition from pediatric to adult care. However, data regarding adolescents are limited. This paper describes and compares characteristics of male and female adolescents living with HIV preparing for transition from pediatric to adult care in Cambodia., Methods: This cross-sectional study was conducted in August 2016 among 328 adolescents aged 15-17, randomly selected from 11 antiretroviral therapy (ART) clinics. Data were collected using a structured questionnaire, and descriptive analyses were conducted to compare characteristics of male and female adolescents., Results: Of total, 55.2% were male, and 40.8% were living with parents. Majority (82.6%) got HIV infection from their mothers. Overall, adolescents had received ART for an average of 8.4 years, and HIV care for 9.5 years. Additionally, 82.4% were on first line ART regimen. Mean CD4 count from the most recent test was 672 cells/mm 3 , and viral load was 7686 copies/mL. Overall, 95.6% were adherent to ART on Visual Analogue Scale. About half (50.7%) had never disclosed their HIV status to anyone, while the remaining had disclosed it to their siblings (24.2%), friends (13.0%), schoolteachers (2.4%), or other (5.8%). A fifth reported having had boy or girlfriends, but few (2.1%) had ever had sexual intercourse. Females were more likely to have been engaged in sexual intercourse, and none reported having used a condom in their last intercourse. Few participants reported having ever used tobacco (1.8%), or any kind of illicit drugs (0.9%), but almost a fifth (20.7%) had a history of alcohol use. The majority (82.1%) were aware that they were receiving ART. HIV-related knowledge was suboptimal among the sample., Conclusions: This study provides a snapshot of immunological, virological, adherence, and disclosure outcomes that should be tracked during and following healthcare transition to evaluate the effectiveness of the transition program. Findings showed high ART adherence, low likelihood of disclosure outside of family circles, sub-optimal condom use, and poor knowledge of HIV. To provide individualized support for healthcare transition, pediatric and adult clinics need to ensure that these characteristics are taken into account.

Background: Understanding the circumstances of adolescents living with HIV is critical in designing adolescent-friendly services that will facilitate successful transition from pediatric to adult care. This study describes access, utilization and ongoing social support needs among adolescents living with HIV aged 15-17 in transition from pediatric to adult HIV care in Cambodia., Methods: A cross-sectional study was conducted among 328 adolescents, randomly selected from 11 antiretroviral therapy (ART) clinics across the country. Descriptive analyses were conducted to summarize their characteristics, access to social support and ongoing support needs among male and female adolescents., Results: Mean age of the study participants was 15.8 (SD = 0.8) years. Just over half (55.2%) were male. Most had at least one deceased parent (mother 50.9%; father 60.5%), and majority were living with biological parents (40.8%) or relatives (49.3%). A third came from families with an ID poor card, and 21.0% were working for pay. Almost half (46.6%) reported that their family had received social support for their health care, including food support (76.5%), school allowance (62.1%), transport allowance to ART clinics (53.6%), psychosocial counseling (35.3%), vocational training (22.9%) or home visits (11.1%). Several ongoing social support needs were identified, including ongoing inability to cover health expenses unless they are supported by health insurance or health equity fund (55.0%). In addition, adolescents reported having been asked to come back earlier than their scheduled appointment (13.7%), having had to purchase their own drugs (2.7%), experiencing HIV stigma (32.0%), having been denied housing or food due to HIV (8.2%) or failing to attend school within the past month partly because of HIV (16.8%). Two-thirds did not have access to peer support groups., Conclusions: Social protection mechanisms are reaching some adolescents in need, while other remain without social support due to discontinuities in health and social care. Multi-sectoral interventions, supporting school attendance, adolescent-friendly clinic scheduling, reductions in child employment, mitigation of HIV-related stigma and strengthening of peer-to-peer support are required to improve coverage of social protection interventions for adolescents in transition.

Background: Assessment of virological outcomes among HIV-infected patients receiving protease (PR) inhibitor-based second-line regimen are uncommon in Cambodia. The objective of this study is to assess the virological effectiveness of this regimen as well as impact of adherence boosting for patients experiencing virological failure., Methods: The 2PICAM study (Clinicaltrial: NCT01801618) is a cross-sectional study of HIV-infected adults on PR inhibitor-based second-line regimen since at least 6 months, conducted in 13 representative sites, comprising more than 90% of the target population. Adults with HIV RNA above 250 copies/mL (threshold of the assay) at inclusion received boosted adherence counseling during 3 months followed by HIV RNA control. For confirmed virological failure, genotype resistance test was performed and expert committee used results for therapeutic decision., Results: Among the 1,317 adults enrolled, the median duration of second-line regimen was 5 years. At inclusion, 1,182 (89.7%) patients achieved virological success (<250 copies/mL) and 135 (10.3%) experienced a virological failure (>250 copies/mL). In multivariable analysis, factors associated with virological success were: CD4 cell count between 201 and 350/mm 3 (OR: 4.66, 95% CI: 2.57-8.47, p  < 0.0001) and >350/mm 3 (OR: 6.67, 95% CI: 4.02-11.06, p  < 0.0001), duration of PI-based regimen >2 years (OR: 1.64, 95% CI: 1.03-2.62, p  = 0.037), ATV-containing regimen (0R: 1.65, 95% CI: 1.04-2.63, p  = 0.034) and high level of adherence (OR: 2.41, 95% CI: 1.07-5.41, p  = 0.033). After adherence counseling, 63 (46.7%) patients were rescued while 72 (53.3%) were not. For the 54 patients with genotype resistance tests available, high or intermediate levels of resistance to lopinavir, atazanavir, and darunavir were reported for 13 (24%), 12 (22.2%), and 2 (3.7%) patients, respectively. Change to an alternative PR inhibitor-based regimen was recommended for 17 patients and to third-line regimen, including integrase inhibitors for 12., Conclusion: This study reports high rate of virological suppression of second-line regimen and importance of adherence boosting prior to deciding any change of ART regimen. Genotype resistance tests appear necessary to guide decisions. Such information was of great importance for National HIV Program to adapt guidelines and program needs for third-line regimen.

Objectives: To investigate whether adherence to antiretroviral treatment (ART) can be explained not only by individual factors but also by health care facilities' characteristics, among a sample of people living with HIV (PLWH) treated with PI-based regimens in Cambodia., Methods: The ANRS 12276 2PICAM cross-sectional survey was conducted between February 2013 and April 2014 among PLWH followed up in 13 health care facilities. The 1316 patients in this analysis corresponded to 90% of the total number of adult patients treated with 2nd-line PI-based regimens in Cambodia in the study period. A variable indicating whether patients were non-adherent (=1) or completely adherent (=0) was constructed. Health care facilities and individual characteristics were included in a two-level logistic model to investigate their influence on patients' adherence to ART., Results: A total of 17% of participants did not adhere to ART. Patients in health care facilities outside the capital Phnom Penh were six times more likely to be non-adherent than those treated in health care facilities in the capital (OR: 6.15, 95% CI [1.47, 25.79]). Providing psychosocial care (provided by psychologist counsellors and/or full-time coaches) was found to be a structural facilitator of adherence, as the probability of non-adherence fell by 38.5% per each additional psychological worker present in health care facilities (OR: 0.62, 95% CI [0.43, 0.89]). Financial constraints were the main individual factor preventing adherence., Conclusions: Our results suggest that inefficiencies in health care delivery are detrimental to PLWH health and to the exceptional progress currently being made by Cambodia in response to HIV. Policy makers should focus on increasing the number of psychosocial workers, especially in areas outside the capital., (© 2017 John Wiley & Sons Ltd.)

Background: Preparing adolescents for transition into adult care and supporting their acquisition of self-health care management skills is a critical determinant of their post-transition HIV care outcomes. However, there is a scarcity of research on effective transition strategies. This study explores factors associated with adolescent preparedness for transition into adult care in Cambodia., Methods: In August 2016, a cross-sectional study was conducted among 223 adolescents living with HIV aged 15-17, randomly selected from 11 antiretroviral therapy clinics, utilizing a structured questionnaire. The level of preparedness was determined using a pre-existing scale, and adolescents were categorized as having a high- or low level of preparedness for transition. Bivariate and multivariate analyses were conducted., Results: Of 223 adolescents, 55.2% were male, and their mean age was 15.8 years. Overall, 53.3% had a high level of preparedness for transition. As part of the transition protocol, 2.7% had completed a transfer form, 24.7% had a transition case manager, 29.6% had been counselled about the transition, and 19.7% had visited an adult ART clinic. In multivariate analysis, a higher level of preparedness for transition was independently associated with older age (AOR 2.44, 95% CI 1.34-4.46; p = 0.004), family having received social support for their health (AOR 5.32, 95% CI 1.97-14.36; p = 0.001), knowing the kind of treatment they received (ART) (AOR 12.67, 95% CI 2.91-15.19; p = 0.001), trust in friends or family for HIV treatment (AOR 7.82, 95% CI 1.13-8.89; p = 0.008), receiving counseling on transition (AOR 3.17, 95% CI 1.15-8.76; p = 0.03), having a 'Case Manager' identified to support them during the preparation process for transition (AOR 3.89, 95% CI 1.08-13.96; p = 0.04), and satisfaction with preparation process for transition in general (AOR 0.35, 95% CI 0.03-0.87; p = 0.01)., Conclusions: A range of individual, social and health system and services factors may determine successful transition preparedness among adolescents in Cambodia. Strengthening implementation of age-appropriate and individualized case management transition at all sites, while creating supportive family, peer, and healthcare environments for adolescent transition is required.

Background: The Social Health Clinic at the National Center for HIV/AIDS, Dermatology & STDs (SHC-NCHADS) in Phnom Penh is a major provider of antiretroviral therapy (ART) in Cambodia. However, patient access to viral load monitoring is uncommon. We conducted a cross-sectional evaluation of HIV viral load in SHC-NCHADS patients on ART to determine the proportion experiencing virological failure and to identify factors associated with virological failure in this population., Methods: Patients who had been using their current first- or second-line ART regimen for ≥6 months were eligible. Virological failure was defined as a viral load >1,000 copies/ml, death, lost-to-follow-up or the absence of viral load testing despite presenting for care. Factors associated with virological failure were evaluated using logistic regression., Results: Overall, 463 patients (53.1% male, median age 42.1 years) were included in the investigation. At the time of current regimen initiation, median CD4 + T-cell count was 101 cells/mm 3 and 89.0% of patients had experienced a WHO stage III/IV event. At the time of testing/last clinic visit, 28 (6.0%) patients met our definition of virological failure. Median viral load among those failing was 9,633 copies/ml. Shorter time on current ART regimen, low CD4 + T-cell count at the time of viral load testing/last clinic visit and a record of suboptimal adherence were the strongest predictors of virological failure., Conclusions: This work demonstrates the high rate of viral suppression being achieved by the treatment programme at SHC-NCHADS and the need for future work to phase-in routine viral load monitoring in Cambodia., Competing Interests: The authors report no conflicts of interest.

Background: Antiretroviral treatment (ART) for HIV-positive patients has expanded rapidly in Asia over the last 10 years. Our study aimed to describe the time trends and risk factors for overall survival in patients receiving first-line ART in Asia., Methods: We included HIV-positive adult patients who initiated ART between 2003-2013 (n=16,546), from seven sites across six Asia-Pacific countries. Patient follow-up was to May 2014. We compared survival for each country and overall by time period of ART initiation using Kaplan-Meier curves. Factors associated with mortality were assessed using Cox regression, stratified by site. We also summarized first-line ART regimens, CD4 + T-cell count at ART initiation, and CD4 + T-cell and HIV viral load testing frequencies., Results: There were 880 deaths observed over 54,532 person-years of follow-up, a crude rate of 1.61 (95% CI 1.51, 1.72) per 100 person-years. Survival significantly improved in more recent years of ART initiation. The survival probability at 4 years follow-up for those initiating ART in 2003-2005 was 92.1%, 2006-2009 was 94.3% and 2010-2013 was 94.5% (P<0.001). Factors associated with higher mortality risk included initiating ART in earlier time periods, older age, male sex, injecting drug use as HIV exposure and lower pre-ART CD4 + T-cell count. Concurrent with improved survival was increased tenofovir use, ART initiation at higher CD4 + T-cell counts and greater monitoring of CD4 + T-cells and HIV viral load., Conclusions: Our results suggest that HIV-positive patients from Asia have improved survival in more recent years of ART initiation. This is likely a consequence of improvements in treatment, patient management and monitoring over time., Competing Interests: The authors do not have any competing interests to declare.