Dr David Boettiger

Introduction Despite recommendations from the WHO, antenatal care (ANC) coverage remains low in many low-income and middle-income countries (LMICs). Community health workers (CHWs) can play an important role in expanding ANC coverage through pregnancy identification, provision of health education, screening for complications, delivery of therapeutic care and referral to higher levels of care. However, despite the success of CHW programmes in various countries, WHO has called for additional research to develop evidence-based models that optimise CHW service delivery and that can be replicated across geographies. Methods The ProCCM Trial was a cluster-randomised controlled trial to compare proactive home visits by CHWs (intervention, 69 village clusters) to the provision of CHW care at community fixed sites only (control, 68 village clusters) in the Bankass health district in Central Mali. In this study, we conducted a cost-effectiveness analysis of proactive CHW home visits in improving ANC utilisation, a secondary outcome of the ProCCM trial. We analysed five ANC outcomes: (1) number of ANC contacts, (2) at least one ANC contact, (3) at least four ANC contacts, (4) at least eight ANC contacts and (5) ANC initiated in the first trimester. We assumed two perspectives, a CHW programme's and the Full ANC programme's perspective, which included facility-based as well as community-based ANC. We estimated programme costs, incremental cost-effectiveness ratios (ICERs) and probabilities of the intervention being more cost-effective than the control at different willingness-to-pay (WTP) thresholds. Results Proactive home visits were cost-saving from the CHW programme's perspective (ICERs: -$21.39 to -$79.20 per ANC utilisation outcome) and from the Full ANC programme perspective (ICERs: -$1.70 to -$6.30 per ANC utilisation outcome) compared with the fixed-site CHW care. The likelihood of the intervention being more cost-effective than the control was 100% at WTP thresholds $0 per ANC utilisation outcome and between $12.5 and $50.00 per ANC utilisation outcome in the CHW- and Full ANC programme perspectives, respectively. Conclusion Our results provide evidence that proactive home visits produce more value per dollar spent as a means of improving the uptake of ANC services compared with fixed-site CHW services.

Background: The influenza mortality burden has remained substantial in the United States (US) despite relatively high levels of influenza vaccine uptake. This has led to questions regarding the effectiveness of the program against this outcome, particularly in the elderly. The aim of this evaluation was to develop and explore a new approach to estimating the population-level effect of influenza vaccination uptake on pneumonia and influenza (P&I) associated deaths. Methods: Using publicly available data we examined the association between state-level influenza vaccination and all-age P&I associated deaths in the US from the 2013¿2014 influenza season to the 2018¿2019 season. In the main model, we evaluated influenza vaccine uptake in all those age 6 months and older. We used a mixed-effects regression analysis with generalised least squares estimation to account for within state correlation in P&I mortality. Results: From 2013¿2014 through 2018¿2019, the total number of all-age P&I related deaths during the influenza seasons was 480,111. The mean overall cumulative influenza vaccine uptake (age 6 months and older) across the states and years considered was 46.7%, with higher uptake (64.8%) observed in those aged = 65 years. We found that overall influenza vaccine uptake (6 months and older) had a statistically significant protective association with the P&I death rate. This translated to a 0.33 (95% CI: 0.20, 0.47) per 100,000 population reduction in P&I deaths in the influenza season per 1% increase in overall influenza vaccine uptake. Discussion: These results using a population-level statistical approach provide additional support for the overall effectiveness of the US influenza vaccination program. This reassurance is critical given the importance of ensuring confidence in this life saving program. Future research is needed to expand on our approach using more refined data.

Objectives To quantify the amount of unnecessary antibiotics, in particular ceftriaxone, given to men who have sex with men (MSM) with anogenital symptoms as part of presumptive management in an urban sexual health clinic and examine factors associated with unnecessary ceftriaxone. Methods This is a retrospective cross-sectional analysis of electronic records from all visits involving MSM reporting symptoms of bacterial sexually transmitted infection (STI) and who received presumptive antibiotics at Sydney Sexual Health Centre. The following variables were extracted: demographic and sexual behaviour data, presenting symptoms, prior STI diagnoses, use of anoscopy, use of point-of-care microscopy, prescriptions of antibiotics and subsequent nucleic acid amplification testing (NAAT) results for chlamydia and gonorrhoea in all anatomical sites (urethra, pharynx and rectum). We defined unnecessary antibiotic as an agent prescribed to treat an STI organism that was subsequently not detected. Results Among 1061 visits in this analysis, 41.8% yielded negative NAAT results for both chlamydia and gonorrhoea in all anatomical sites. There were 44.3% of visits which had positive gonorrhoea NAAT result in at least one anatomical site. There were 187 courses of ceftriaxone prescribed in patients who tested negative for gonorrhoea in all anatomical sites and therefore were unnecessary. Unnecessary ceftriaxone prescribing occurred in 50.2% of visits with anorectal symptoms, 19.6% of scrotal symptoms and 7.3% of urethral symptoms. Microscopy was associated with significantly less unnecessary ceftriaxone in urethral but not anorectal or scrotal presentations. In multivariable analysis, the following factors were associated with a higher likelihood of unnecessary ceftriaxone use: anorectal symptoms, scrotal symptoms, gonorrhoea in the preceding year, contact of a bacterial STI and living with HIV. Conclusions This study highlights the significant amount of unnecessary ceftriaxone used for STI symptoms in MSM. A new pathway incorporating rapid point-of-care molecular testing in symptomatic patients may improve the precision of antibiotic prescribing and reduce unnecessary use.

Background:The World Health Organization is committed to strengthening access to pre-exposure prophylaxis (PrEP) for HIV prevention and its integration into primary care services. Unfortunately, the COVID-19 pandemic has disrupted the delivery of primary care, including HIV-related services. To determine the extent of this disruption, we conducted a systematic review and meta-analysis of the changes in access to PrEP services during the pandemic and the reasons for these changes.Methods:A search was conducted using PubMed, Scopus, Embase, PsycINFO, and Cinahl for studies published between January 2020 and January 2023. Selected articles described self-reported disruptions to PrEP service access associated with the COVID-19 pandemic or its responses. Pooled effect sizes were computed using a random-effects model.Results:Thirteen studies involving 12,652 PrEP users were included in our analysis. The proportion of participants reporting a disruption in access to PrEP services during the COVID-19 pandemic ranged from 3% to 56%, with a pooled proportion of 21% (95% confidence intervals: 8% to 38%). Social restrictions, financial constraints, and limited health insurance coverage were key factors affecting access to PrEP services during the pandemic.Conclusions:To our knowledge, this is the first meta-analysis to quantify the extent of disruptions to accessing PrEP services because of the COVID-19 pandemic. To increase the ability of primary care services to maintain PrEP services during public health crises, a mixture of strategies is worth considering. These include multi-month PrEP prescriptions, telehealth services, deployment of peer support groups to provide a community-based service or home delivery, and provision of financial support interventions.

Background Indonesia has the second-highest burden of tuberculosis (TB) globally and is experiencing one of the fastest-growing HIV epidemics worldwide. The COVID-19 pandemic disrupted access to essential health services, including those for TB and HIV, due to health system overload, social distancing measures, and negative economic repercussions on the health sector and the population. An in-depth understanding of these challenges and the health system responses to mitigate the negative impact of the pandemic on TB and HIV services is crucial to building health system resilience and preparing for future emergencies. Methods This qualitative study, conducted in two cities in Indonesia, explored the impact of the COVID-19 pandemic on TB and HIV services including mitigation strategies to sustain the provision of testing and treatment in the midst of the pandemic. Between February and June 2022, semi-structured interviews were conducted with 16 healthcare workers and 16 clients at nine health centers (puskesmas), three hospitals, and one Community Center for Lung Health in Bandung and Yogyakarta. Themes were identified from transcripts using open and selective coding and then refined. Results Extraordinary measures were implemented in health facilities to sustain TB and HIV service delivery, and prevent the spread of COVID-19, including testing of clients for COVID-19 before receiving medical care, physical distancing when visiting healthcare facilities, revised schedules for medicine dispensing, involvement of community health workers and peers in community outreach activities such as the home delivery of medicines, and the use of telemedicine. Challenges encountered during the implementation of these strategies included medicine stock-outs, health worker overload, lack of sufficient client-provider interaction and technical difficulties when implementing telemedicine, and the risk or fear of exposure to COVID-19 among the community health workers and peers. Conclusions Significant efforts were made to mitigate disruptions to TB and HIV services during the COVID-19 pandemic. However, some challenges were encountered. Key policy recommendations to strengthen pandemic preparedness include investing in local manufacturing and robust drug supply networks to prevent medicine shortages, and supporting community health workers to alleviate workload issues, reduce the risk of disease exposure, and explore the potential for a financial incentive system. Equally vital is the need to invest in staff training and education, as well as implementing user-friendly telemedicine technologies.

Background: The Northern Territory (NT) has the highest prevalence of chronic hepatitis B (CHB) in Australia. The Hep B PAST program aims to improve health outcomes for people living with CHB. Methods: This mixed methods study involves First Nations peoples living in the NT. We used participatory action research principles across three steps: 1. Foundation step: establishing hepatitis B virus (HBV) status and linkage to care; 2. Capacity building: training the health workforce; 3. Supported transition to primary healthcare: implementation of the "Hub and Spoke" model and in-language resources. Analysis occurred at three time points: 1. Pre-Hep B PAST (2018); 2. Foundation step (2020); and 3. Completion of Hep B PAST (2023). Evaluation focuses on four key indicators, the number of people: 1) with documented HBV status; 2) diagnosed with CHB; 3) receiving care; and 4) receiving treatment. Findings: Hep B PAST (2018¿23) reached 40,555 people. HBV status was documented in 11% (1192/10,853), 79.2% (26,075/32,915) and 90.8% (28,675/31,588) of people at pre-Hep B PAST, foundation step, and completion respectively. An estimated 99.9% (821/822) of people were diagnosed, 86.3% (709/822) engaged in care, and 24.1% (198/822) on antiviral treatment at completion. CHB prevalence in the study population is 2.6%, decreasing from 6.1% to 0.4% in the pre- and post-vaccination cohorts. Interpretation: Hep B PAST is an effective model of care. Partner health services are exceeding elimination targets. This model could enable other countries to enhance the cascade of care and work towards eliminating HBV. Funding: National Health and Medical Research Council.

Hypertension has been rapidly growing in Bangladesh. However, there has been limited analysis of differences in the hypertension cascade across socio-demographic groups. This study was a secondary analysis of the 2017¿18 Bangladesh Demographic and Health Survey. Four dichotomous outcome variables ¿ hypertension prevalence, awareness among those with hypertension, treatment among those aware, and control among those treated ¿ were analyzed. The variation of each outcome was assessed across socio-demographic factors. The association between socio-demographic characteristics and outcomes was analyzed using logistic regression. Less than half of the hypertensive individuals were aware of their hypertension (42.5%), and awareness was higher among those who were older, female, of higher household wealth, and living in urban areas. Among those aware, most were receiving treatment (87.4%), and this proportion was higher in older individuals (89.2% among 65 + , 70.4% among 18¿24; p < 0.001). One-third of those treated (33.8%) had their blood pressure controlled, and this was higher among younger and more educated individuals. In multivariable models stratified by rural/urban community, most of the aforementioned trends remained with additional differences between communities. Notably, the association of higher education level with treatment odds differed in rural and urban communities (OR 0.34 [95%CI 0.16, 0.75] in rural; OR 2.83 [95%CI 1.04, 7.73] in urban). Efforts to improve hypertension awareness among individuals who are younger, male, of lower household wealth, and in rural areas are required to address disparities in care. Socio-demographic variations in hypertension awareness, treatment, and control must be considered to design targeted interventions for each step of the cascade.

Background: The number of people aged greater than 65 years per 100 people aged 20¿64 years is expected to almost double in The Kingdom of Saudi Arabia (KSA) between 2020 and 2030. We therefore aimed to quantify the growing non-communicable disease (NCD) burden in KSA between 2020 and 2030, and the impact this will have on the national health budget. Methods: Ten priority NCDs were selected: ischemic heart disease, stroke, type 2 diabetes, chronic obstructive pulmonary disease, chronic kidney disease, dementia, depression, osteoarthritis, colorectal cancer, and breast cancer. Age- and sex-specific prevalence was projected for each priority NCD between 2020 and 2030. Treatment coverage rates were applied to the projected prevalence estimates to calculate the number of patients incurring treatment costs for each condition. For each priority NCD, the average cost-of-illness was estimated based on published literature. The impact of changes to our base-case model in terms of assumed disease prevalence, treatment coverage, and costs of care, coming into effect from 2023 onwards, were explored. Results: The prevalence estimates for colorectal cancer and stroke were estimated to almost double between 2020 and 2030 (97% and 88% increase, respectively). The only priority NCD prevalence projected to increase by less than 60% between 2020 and 2030 was for depression (22% increase). It is estimated that the total cost of managing priority NCDs in KSA will increase from USD 19.8¿billion in 2020 to USD 32.4¿billion in 2030 (an increase of USD 12.6¿billion or 63%). The largest USD value increases were projected for osteoarthritis (USD 4.3¿billion), diabetes (USD 2.4¿billion), and dementia (USD 1.9¿billion). In scenario analyses, our 2030 projection for the total cost of managing priority NCDs varied between USD 29.2¿billion - USD 35.7¿billion. Conclusions: Managing the growing NCD burden in KSA's aging population will require substantial healthcare spending increases over the coming years.

Background: We compared weight changes in virally suppressed people living with HIV (PLWH) switching to integrase strand transfer inhibitors (INSTIs) with those remaining on an INSTI or non-INSTI regimen. Methods: PLWH aged =18years with weight measurements available at baseline between 2001 and 2020 were included. Viral suppression was defined as having had a viral load <400copies/mL for 6months. Baseline was defined as the time of switching from a non-INSTI to an INSTI regimen whilst virally suppressed (switch group) or the time that viral suppression was achieved (remain groups). Generalized estimating equations adjusted for age, sex and baseline weight were used to model weight changes 6, 12, 18 and 24months after baseline. Results: A total of 1673 PLWH contributed 1952 episodes of viral suppression - 143 (7.3%) episodes were among PLWH who had switched from a non-INSTI to an INSTI, 102 (5.2%) episodes were among PLWH who remained on an INSTI and 1707 (87.4%) episodes were among PLWH who remained on a non-INSTI. PLWH in the switch group had significantly greater weight gain than those in the remain groups at 6, 12 and 18months after achieving viral suppression. By 24months, weight change on all regimens started to converge. Tenofovir alafenamide use was not significantly associated with weight gain in adjusted models. Conclusions: Our findings suggest that the mechanisms of weight gain due to INSTI use go beyond their superior efficacy over other antiretrovirals in controlling HIV or the effect of the 'return-to-health' phenomenon. Further research is needed to understand the mechanisms of such weight gain.

Background: Bacterial pneumonia imparts a major morbidity and mortality burden on children living with HIV, yet effective prevention and treatment options are underutilized. We explored clinical factors associated with severe recurrent bacterial pneumonia among children living with HIV. Methods: Children enrolled in the TREAT Asia Pediatric HIV Observational Database were included if they started antiretroviral therapy (ART) on or after January 1st, 2008. Factors associated with severe recurrent bacterial pneumonia were assessed using competing-risk regression. Results: A total of 3,944 children were included in the analysis; 136 cases of severe recurrent bacterial pneumonia were reported at a rate of 6.5 [95% confidence interval (CI): 5.5¿7.7] events per 1,000 patient-years. Clinical factors associated with severe recurrent bacterial pneumonia were younger age [adjusted subdistribution hazard ratio (aHR): 4.4 for <5 years versus =10 years, 95% CI: 2.2¿8.4, P < 0.001], lower weight-for-age z-score (aHR: 1.5 for <-3.0 versus >-2.0, 95% CI: 1.1¿2.3, P = 0.024), pre-ART diagnosis of severe recurrent bacterial pneumonia (aHR: 4.0 versus no pre-ART diagnosis, 95% CI: 2.7-5.8, P < 0.001), past diagnosis of symptomatic lymphoid interstitial pneumonitis or chronic HIV-associated lung disease, including bronchiectasis (aHR: 4.8 versus no past diagnosis, 95% CI: 2.8-8.4, P < 0.001), low CD4% (aHR: 3.5 for <10% versus =25%, 95% CI: 1.9-6.4, P < 0.001) and detectable HIV viral load (aHR: 2.6 versus undetectable, 95% CI: 1.2-5.9, P = 0.018). Conclusions: Children <10-years-old and those with low weight-for-age, a history of respiratory illness, low CD4% or poorly controlled HIV are likely to gain the greatest benefit from targeted prevention and treatment programs to reduce the burden of bacterial pneumonia in children living with HIV.

Objective:To assess recent trends in the monitoring of antiretroviral therapy (ART) and detection of ART failure in adult and pediatric HIV clinics.Methods:We used data collected from 21 adult and 17 pediatric sites (across 13 and 6 countries/territories, respectively) in the International Epidemiology Databases to Evaluate AIDS-Asia-Pacific cohort. ART failure was defined as viral, immune, or clinical consistent with WHO guidelines.Results:A total of 8567 adults and 6149 children contributed data. Frequency of CD4 count monitoring declined between 2010 and 2019 among adult sites (from 1.93 to 1.06 tests/person per year, a 45.1% decline) and pediatric sites (from 2.16 to 0.86 testsperson per year, a 60.2% decline), whereas rates of viral load monitoring remained relatively stable. The proportion of adult and pediatric treatment failure detected as immune failure declined (from 73.4% to 50.0% and from 45.8% to 23.1%, respectively), whereas the proportion of failure detected as viral failure increased (from 7.8% to 25.0% and from 45.8% to 76.9%, respectively). The proportion of ART failure detected as clinical failure remained stable among adult and pediatric sites. The largest shifts in ART monitoring and failure type occurred in lower middle-income countries.Conclusions:Although viral failure in our Asian cohort now comprises a larger portion of ART failure than in prior years, the diagnostic characteristics of immune and clinical failure, and recommendations on their management, remain important inclusions for regional ART guidelines.

Tobacco minimum floor price laws (MFPLs) are a non-tax price policy that set a price below which tobacco products cannot be sold, thereby raising prices. Despite their growing interest among policy makers, little is known about the effects of local MFPLs on smoking prevalence or smoking intensity. We aimed to project the impact of a local tobacco MFPL on cigarette smoking prevalence and cigarette smoking intensity in Oakland, California, including detailed analysis of several important subpopulations. We used data collected between April 2017 and December 2019 from the California Behavioral Risk Factor Surveillance System and the National Youth Tobacco Survey to construct a static microsimulation model representative of Oakland. We projected the impact of MFPLs ranging from $8.00 to $13.00 per pack. All analyses were conducted between 2019 and 2020. With the introduction of an MFPL and assuming 15% policy evasion, mean price paid per pack was projected to increase by $1.05 to $4.69, cigarette smoking prevalence was projected to drop by 0.3% to 0.8%, and smoking intensity was projected to drop by 0.7% to 2.0% among continuing smokers. Total number of cigarettes smoked per month was projected to drop by 246,000 to 734,000 cigarettes, a 3.0% to 9.0% reduction from the current level (8.2 million cigarettes). The greatest reductions in cigarette smoking prevalence were among those aged 12 to 24-years-old, of non-Hispanic black or other race/ethnicity, and living below the federal poverty level. An MFPL in Oakland may substantially reduce cigarette use and target several important subpopulations.

Around two-thirds of all new HIV infections and 90% of syphilis cases occur in low-and middle-income countries (LMICs). Testing is a key strategy for the prevention and treatment of HIV and syphilis. Decision-makers in LMICs face considerable uncertainties about the costs of scaling up HIV and syphilis testing. This paper synthesizes economic evidence on the costs of scaling up HIV and syphilis testing interventions in LMICs and evidence on how costs change with the scale of delivery. We systematically searched multiple databases (Medline, Econlit, Embase, EMCARE, CINAHL, Global Health and the NHS Economic Evaluation Database) for peer-reviewed studies examining the costs of scaling up HIV and syphilis testing in LMICs. Thirty-five eligible studies were identified from 4869 unique citations. Most studies were conducted in Sub-Saharan Africa (N = 17) and most explored the costs of rapid HIV in facilities targeted the general population (N = 19). Only two studies focused on syphilis testing. Seventeen studies were cost analyses, 17 were cost-effectiveness analyses and 1 was cost-benefit analysis of HIV or syphilis testing. Most studies took a modelling approach (N = 25) and assumed costs increased linearly with scale. Ten studies examined cost efficiencies associated with scale, most reporting short-run economies of scale. Important drivers of the costs of scaling up included testing uptake and the price of test kits. The 'true' cost of scaling up testing is likely to be masked by the use of short-term decision frameworks, linear unit-cost projections (i.e. multiplying an average cost by a factor reflecting activity at a larger scale) and availability of health system capacity and infrastructure to supervise and support scale up. Cost data need to be routinely collected alongside other monitoring indicators as HIV and syphilis testing continues to be scaled up in LMICs.

Objective:Statins play a critical role in reducing the elevated risk of atherosclerotic cardiovascular disease (ASCVD) among people living with HIV (PLHIV). However, maintaining statin therapy is difficult and may be impeded further in PLHIV due to the risk of antiretroviral therapy (ART)/statin interactions. We estimated rates of statin discontinuation and reinitiation, and the percentage of days covered by statin use among PLHIV on ART, and investigated factors associated with these outcomes.Design:Observational cohort study.Methods:Clinical data from individuals attending the HIV-NAT Centre in Bangkok, Thailand between 2001 and 2020 were analyzed using Kaplan-Meier curves, competing-risk regression, and generalized estimating equations. Discontinuation was defined as statin cessation lasting 90 days.Results:Data on 318 PLHIV were included. After 1, 3, and 5 years, 22.3, 50.8, and 61.1% had discontinued statin use, respectively. Among those who discontinued (n=178), 52.0% reinitiated statin use within 5 years. Factors associated with statin discontinuation were low education level, fewer concomitant medications, and lack of ASCVD. Factors associated with statin reinitiation were older age, diabetes, and high levels of LDL cholesterol. The adjusted mean percentage of days covered by a statin was 86.7, 61.1, and 58.1% in the 6 months prior to 1, 3, and 5 years of follow-up, respectively.Conclusion:Maintenance of statin therapy is poor among PLHIV on ART but is not associated with using contraindicated antiretroviral/statin combinations. A better understanding of statin use in PLHIV will aid clinicians treating individuals and policy makers designing interventions for population-level ASCVD risk reduction.

Objectives: To identify social and structural barriers to timely utilisation of qualified providers among children under five years in a high-mortality setting, rural Mali and to analyse how utilisation varies by symptom manifestation. Methods: Using baseline household survey data from a cluster-randomised trial, we assessed symptom patterns and healthcare trajectories of 5117 children whose mothers reported fever, diarrhoea, bloody stools, cough and/or fast breathing in the preceding two weeks. We examine associations between socio-demographic factors, symptoms and utilisation outcomes in mixed-effect logistic regressions. Results: Almost half of recently ill children reported multiple symptoms (46.2%). Over half (55.9%) received any treatment, while less than one-quarter (21.7%) received care from a doctor, nurse, midwife, trained community health worker or pharmacist within 24¿h of symptom onset. Distance to primary health facility, household wealth and maternal education were consistently associated with better utilisation outcomes. While children with potentially more severe symptoms such as fever and cough with fast breathing or diarrhoea with bloody stools were more likely to receive any care, they were no more likely than children with fever to receive timely care with a qualified provider. Conclusions: Even distances as short as 2¿5¿km significantly reduced children's likelihood of utilising healthcare relative to those within 2¿km of a facility. While children with symptoms indicative of pneumonia and malaria were more likely to receive any care, suggesting mothers and caregivers recognised potentially severe illness, multiple barriers to care contributed to delays and low utilisation of qualified providers, illustrating the need for improved consideration of barriers.

Background: Human immunodeficiency virus (HIV)-positive gay and bisexual men (GBM) in Australia are well engaged in care. The World Health Organization's (WHO) hepatitis C virus (HCV) elimination target of an 80% reduction in incidence by 2030 may be reachable ahead of time in this population. Methods: We predicted the effect of treatment and behavioral changes on HCV incidence among HIV-positive GBM up to 2025 using a HCV transmission model parameterized with Australian data. We assessed the impact of changes in behavior that facilitate HCV transmission in the context of different rates of direct-acting antiviral (DAA) use. Results: HCV incidence in our model increased from 0.7 per 100 person-years in 2000 to 2.5 per 100 person-years in 2016 and had the same trajectory as previously reported clinical data. If the proportion of eligible (HCV RNA positive) patients using DAAs stays at 65% per year between 2016 and 2025, with high-risk sexual behavior and injecting drug use remaining at current levels, HCV incidence would drop to 0.4 per 100 person-years (85% decline from 2016). In the same treatment scenario but with substantial increases in risk behavior, HCV incidence would drop to 0.6 per 100 person-years (76% decline). If the proportion of eligible patients using DAAs dropped from 65% per year in 2016 to 20% per year in 2025 and risk behavior did not change, HCV incidence would drop to 0.7 per 100 person-years (70% reduction). Conclusions: Reaching the WHO HCV elimination target by 2025 among HIV-positive GBM in Australia is achievable.

Objectives: There is a paucity of data on cardiovascular disease (CVD) among people living with HIV (PLHIV) in resource-limited countries. We assessed factors associated with CVD and the impact of prevalent CVD on all-cause mortality in PLHIV on antiretroviral therapy in Brazil. Methods: Competing risk regression to assess factors associated with CVD and all-cause mortality in the HIV-Brazil Cohort Study between 2003 and 2014. Results: Among 5614 patients, the rate of CVD was 3.5 (95% confidence interval [95% CI] 2.9¿4.3) per 1000 person-years. CVD was associated with older age (adjusted hazard ratio [aHR] 6.4 for =55¿years vs. <35¿years, 95% CI: 2.5¿16.3, P¿<¿0.01), black race (aHR 1.8 vs. white race, 95% CI: 1.0¿3.1, P¿=¿0.04), past CVD (aHR 3.0 vs. no past CVD, 95% CI: 1.4¿6.2, P¿<¿0.01), hypertension (aHR 1.8 vs. no hypertension, 95% CI: 1.0¿3.1, P¿=¿0.04), high-grade dyslipidemia (aHR 9.3 vs. no high-grade dyslipidemia, 95% CI: 6.0¿14.6, P¿<¿0.01), ever smoking (aHR 2.4 vs. never, 95% CI: 1.2¿5.0, P¿=¿0.02) and low nadir CD4 cell count (aHR 1.8 for 100¿250¿cells/mm3 vs. >250¿cells/mm3, 95% CI: 1.0¿3.2, P¿=¿0.05). The rate of death was 16.6 (95% CI: 15.1¿18.3) per 1000 person-years. Death was strongly associated with having had a past CVD event (aHR 1.7 vs. no past CVD event, 95% CI: 1.1¿2.7, P¿=¿0.01). Conclusions: Traditional and HIV-specific factors associated with CVD among PLHIV in Brazil are similar to those identified among PLHIV in high-income countries. PLHIV in Brazil with a history of CVD have a high risk of death. CVD care and treatment remain priorities for PLHIV in Brazil as this population ages and antiretroviral therapy use expands.

Objectives: Integration of HIV and non-communicable disease services improves the quality and efficiency of care in low- A nd middle-income countries (LMICs). We aimed to describe current practices for the screening and management of atherosclerotic cardiovascular disease (ASCVD) among adult HIV clinics in Asia. Methods: Sixteen LMICsites included in the International Epidemiology Databases to Evaluate AIDS-Asia-Pacific network were surveyed. Results: Sites were mostly (81%) based in urban public referral hospitals. Half had protocols to assess tobacco and alcohol use. Protocols for assessing physical inactivity and obesity were in place at 31% and 38% of sites, respectively. Most sites provided educational material on ASCVD risk factors (between 56% and 75% depending on risk factors). Atotal of 94% reported performing routine screening for hypertension, 100% for hyperlipidaemia and 88% for diabetes. Routine ASCVD risk assessment was reported by 94% of sites. Protocols for the management of hypertension, hyperlipidaemia, diabetes, high ASCVD risk and chronic ischaemic stroke were in place at 50%, 69%, 56%, 19% and 38% of sites, respectively. Blood pressure monitoring was free for patients at 69% of sites; however, most required patients to pay some or all the costs for other ASCVD-related procedures. Medications available in the clinic or within the same facility included angiotensin-converting enzyme inhibitors (81%), statins (94%) and sulphonylureas (94%). Conclusion: The consistent availability of clinical screening, diagnostic testing and procedures and the availability of ASCVD medications in the Asian LMICclinics surveyed are strengths that should be leveraged to improve the implementation of cardiovascular care protocols.

Objectives. To estimate the combined effect of California's Tobacco 21 law (enacted June 2016) and $2-per-pack cigarette excise tax increase (enacted April 2017) on cigarette prices and sales, compared with matched comparator states.Methods. We used synthetic control methods to compare cigarette prices and sales after the policies were enacted, relative to what we would have expected without the policy reforms. To estimate the counterfactual, we matched pre-reform covariate and outcome trends between California and control states to construct a "synthetic" California.Results. Compared with the synthetic control in 2018, cigarette prices in California were $1.89 higher ($7.86 vs $5.97; P¿<¿.001), and cigarette sales were 16.6% lower (19.9 vs 16.6 packs per capita; P¿<¿.001). This reduction in sales equates to 153.9 million fewer packs being sold between 2017 and 2018.Conclusions. California's new cigarette tax was largely passed on to consumers. The new cigarette tax, combined with the Tobacco 21 law, have contributed to a rapid and substantial reduction in cigarette consumption in California.

Background: Co-trimoxazole is recommended for all children with human immunodeficiency virus. In this analysis, we evaluate trends in pediatric co-trimoxazole use and survival on co-trimoxazole in children using antiretroviral therapy (ART). Methods: We used data collected between January 1, 2006, and March 31, 2016, from the International Epidemiology Databases to Evaluate AIDS. Logistic regression was used to evaluate factors associated with using co-trimoxazole at ART initiation. Competing risk regression was used to assess factors associated with death. Results: A total of 54113 children were included in this study. The prevalence of co-trimoxazole use at ART initiation increased from 66.5% in 2006 to a peak of 85.6% in 2010 and then declined to 48.5% in 2015-2016. A similar trend was observed among children who started ART with severe immunodeficiency. After adjusting for year of ART initiation, younger age (odds ratio [OR], 1.18 for <1 vs 1 to <5 years of age [95% confidence interval (CI), 1.09-1.28]), lower height-for-age z score (OR, 1.15 for less than -3 vs greater than -2 [95% CI, 1.08-1.22]), anemia (OR, 1.08 [95% CI, 1.02-1.15]), severe immunodeficiency (OR, 1.25 [95% CI, 1.18-1.32]), and receiving care in East Africa (OR, 8.97 vs Southern Africa [95% CI, 8.17-9.85]) were associated with a high prevalence of co-trimoxazole use. Survival did not differ according to co-trimoxazole use in children without severe immunodeficiency (hazard ratio, 1.01 for nonusers versus users [95% CI, 0.77-1.34]). Conclusions: Recent declines in co-trimoxazole use may not be linked to the current shift toward early ART initiation. Randomized trial data might be needed to establish the survival benefit of co-trimoxazole in children without severe immunodeficiency.

Introduction: Extrapulmonary tuberculosis (EPTB) is difficult to confirm bacteriologically and requires specific diagnostic capacities. Diagnosis can be especially challenging in under-resourced settings. We studied diagnostic modalities and clinical outcomes of EPTB compared to pulmonary tuberculosis (PTB) among HIV-positive adults in antiretroviral therapy (ART) programmes in low- and middle-income countries (LMIC). Methods: We collected data from HIV-positive TB patients (=16¿years) in 22 ART programmes participating in the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium in sub-Saharan Africa, Asia-Pacific, and Caribbean, Central and South America regions between 2012 and 2014. We categorized TB as PTB or EPTB (EPTB included mixed PTB/EPTB). We used multivariable logistic regression to assess associations with clinical outcomes. Results and Discussion: We analysed 2695 HIV-positive TB patients. Median age was 36¿years (interquartile range (IQR) 30 to 43), 1102 were female (41%), and the median CD4 count at TB treatment start was 114 cells/µL (IQR 40 to 248). Overall, 1930 had PTB (72%), and 765 EPTB (28%). Among EPTB patients, the most frequently involved sites were the lymph nodes (24%), pleura (15%), abdomen (11%) and meninges (6%). The majority of PTB (1123 of 1930, 58%) and EPTB (582 of 765, 76%) patients were diagnosed based on clinical criteria. Bacteriological confirmation (using positive smear microscopy, culture, Xpert MTB/RIF, or other nucleic acid amplification tests result) was obtained in 897 of 1557 PTB (52%) and 183 of 438 EPTB (42%) patients. EPTB was not associated with higher mortality compared to PTB (adjusted odd ratio (aOR) 1.0, 95% CI 0.8 to 1.3), but TB meningitis was (aOR 1.9, 95% CI 1.0 to 3.1). Bacteriological confirmation was associated with reduced mortality among PTB patients (aOR 0.7, 95% CI 0.6 to 0.8) and EPTB patients (aOR 0.3 95% CI 0.1 to 0.8) compared to TB patients with a negative test result. Conclusions: Diagnosis of EPTB and PTB at ART programmes in LMIC was mainly based on clinical criteria. Greater availability and usage of TB diagnostic tests would improve the diagnosis and clinical outcomes of both EPTB and PTB.

Background:Mycobacterium avium complex prophylaxis is recommended for patients with advanced HIV infection. With the decrease in incidence of disseminated Mycobacterium avium complex infection and the availability of antiretroviral therapy (ART), the benefits of macrolide prophylaxis were investigated. This study examined the impact of macrolide prophylaxis on AIDS-defining conditions and HIV-associated mortality in a cohort of HIV-infected patients on ART.Methods:Patients from TREAT Asia HIV Observational Database (September 2015 data transfer) aged 18 years and older with a CD4 count <50 cells/mm3 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/mm3 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/mm3 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.

Introduction: Recommendations on the optimal frequency of plasma viral load (pVL) monitoring in children living with HIV (CLWH) who are stable on combination antiretroviral therapy (cART) are inconsistent. This study aimed to determine the impact of annual versus semi-annual pVL monitoring on treatment outcomes in Asian CLWH. Methods: Data on children with perinatally acquired HIV aged <18¿years on first-line, non-nucleoside reverse transcriptase inhibitor-based cART with viral suppression (two consecutive pVL <400¿copies/mL over a six-month period) were included from a regional cohort study; those exposed to prior mono- or dual antiretroviral treatment were excluded. Frequency of pVL monitoring was determined at the site-level based on the median rate of pVL measurement: annual 0.75 to 1.5, and semi-annual >1.5 tests/patient/year. Treatment failure was defined as virologic failure (two consecutive pVL >1000¿copies/mL), change of antiretroviral drug class, or death. Baseline was the date of the second consecutive pVL <400¿copies/mL. Competing risk regression models were used to identify predictors of treatment failure. Results: During January 2008 to March 2015, there were 1220 eligible children from 10 sites that performed at least annual pVL monitoring, 1042 (85%) and 178 (15%) were from sites performing annual (n¿=¿6) and semi-annual pVL monitoring (n¿=¿4) respectively. Pre-cART, 675 children (55%) had World Health Organization clinical stage 3 or 4, the median nadir CD4 percentage was 9%, and the median pVL was 5.2 log10 copies/mL. At baseline, the median age was 9.2¿years, 64% were on nevirapine-based regimens, the median cART duration was 1.6¿years, and the median CD4 percentage was 26%. Over the follow-up period, 258 (25%) CLWH with annual and 40 (23%) with semi-annual pVL monitoring developed treatment failure, corresponding to incidence rates of 5.4 (95% CI: 4.8 to 6.1) and 4.3 (95% CI: 3.1 to 5.8) per 100 patient-years of follow-up respectively (p¿=¿0.27). In multivariable analyses, the frequency of pVL monitoring was not associated with treatment failure (adjusted hazard ratio: 1.12; 95% CI: 0.80 to 1.59). Conclusions: Annual compared to semi-annual pVL monitoring was not associated with an increased risk of treatment failure in our cohort of virally suppressed children with perinatally acquired HIV on first-line NNRTI-based cART.

A prediction model for pretreatment HIV RNA level =100,000 copies/ml would provide a useful tool for selection of abacavir (ABC) or rilpivirine (RPV) in the first-line regimen in a resource-limited setting. Factors associated with pretreatment HIV RNA =100,000 copies/ml were determined from a cohort of 1,223 patients divided into a derivation (n = 873) and the remaining in a validation group. Their median [interquartile range (IQR)] age was 36.3 (30.5-42.9) years, CD4 count 122 (39-216) cells/mm3 and pre-treatment HIV RNA level 100,000 (32,449-229,777) copies/ml. Factors associated with pretreatment HIV RNA =100,000 copies/ml were non-anemia [odds ratio (OR)= 2.05; 95% confidence interval (CI): 1.28-3.27, p= 0.003], CD4 count =200 cells/mm3 (OR= 3.00; 95% CI: 2.08-4.33, p<0.001) and non-heterosexual HIV exposure (OR= 1.61; 95% CI: 1.07-2.43, p= 0.021). The area under a receiver operating characteristic curve was 0.66 (95% CI: 0.62-0.69), but specificity was 97.3%. The prediction model identified a set of readily available clinical data but lacked the requisite predictive performance to fulfill its purpose.

Purpose: Renal disease is common among people living with human immunodeficiency virus (HIV). However, there is limited information on the incidence and risk factors associated with renal dysfunction among this population in Asia. Methods: We used data from the TREAT Asia HIV Observational Database. Patients were included if they started antiretroviral therapy during or after 2003, had a serum creatinine measurement at antiretroviral therapy initiation (baseline), and had at least 2 follow-up creatinine measurements taken =3¿months apart. Patients with a baseline estimated glomerular filtration rate (eGFR) =60¿mL/min/1.73¿m2 were excluded. Chronic kidney disease was defined as 2 consecutive eGFR values =60¿mL/min/1.73¿m2 taken =3¿months apart. Generalized estimating equations were used to identify factors associated with eGFR change. Competing risk regression adjusted for study site, age and sex, and cumulative incidence plots were used to evaluate factors associated with chronic kidney disease (CKD). Results: Of 2547 patients eligible for this analysis, tenofovir was being used by 703 (27.6%) at baseline. Tenofovir use, high baseline eGFR, advanced HIV disease stage, and low nadir CD4 were associated with a decrease in eGFR during follow-up. Chronic kidney disease occurred at a rate of 3.4 per 1000 patient/years. Factors associated with CKD were tenofovir use, old age, low baseline eGFR, low nadir CD4, and protease inhibitor use. Conclusions: There is an urgent need to enhance renal monitoring and management capacity among at-risk groups in Asia and improve access to less nephrotoxic antiretrovirals.

Background: We compared Kaposi sarcoma (KS) risk in adults who started antiretroviral therapy (ART) across the Asia-Pacific, South Africa, Europe, Latin, and North America. Methods: We included cohort data of human immunodeficiency virus (HIV)-positive adults who started ART after 1995 within the framework of 2 large collaborations of observational HIV cohorts. We present incidence rates and adjusted hazard ratios (aHRs). Results: We included 208 140 patients from 57 countries. Over a period of 1 066 572 person-years, 2046 KS cases were diagnosed. KS incidence rates per 100 000 person-years were 52 in the Asia-Pacific and ranged between 180 and 280 in the other regions. KS risk was 5 times higher in South African women (aHR, 4.56; 95% confidence intervals [CI], 2.73-7.62) than in their European counterparts, and 2 times higher in South African men (2.21; 1.34-3.63). In Europe, Latin, and North America KS risk was 6 times higher in men who have sex with men (aHR, 5.95; 95% CI, 5.09-6.96) than in women. Comparing patients with current CD4 cell counts =700 cells/µL with those whose counts were <50 cells/µL, the KS risk was halved in South Africa (aHR, 0.53; 95% CI, .17-1.63) but reduced by =95% in other regions. Conclusions. Despite important ART-related declines in KS incidence, men and women in South Africa and men who have sex with men remain at increased KS risk, likely due to high human herpesvirus 8 coinfection rates. Early ART initiation and maintenance of high CD4 cell counts are essential to further reducing KS incidence worldwide, but additional measures might be needed, especially in Southern Africa.

A significant obstacle in guiding evidence-based management of bullous pemphigoid (BP) is the lack of a standardised, validated scoring system for the condition. The aim of this study was to evaluate the suitability of the Bullous Pemphigoid Disease Area Index (BPDAI) and the Autoimmune Bullous Skin disorder Intensity Score (ABSIS) as outcome measures for BP in clinical trials. Thirty-two BP patients were repeatedly assessed over 4 years using Physician Global Assessment (PGA), anti-BP180 ELISA titres, BPDAI, ABSIS, BPDAI-Pruritus, Autoimmune Bullous Disease Quality of Life (ABQOL) and Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaires. The reliability, validity, responsiveness, and minimal clinically important differences (MCIDs) were calculated. For inter-rater reliability, the intraclass correlation coefficients (95% CI) were: BPDAI 0.957 (0.901-0.982) and ABSIS 0.881 (0.736-0.949). Compared to ABSIS, BPDAI was better correlated with PGA (r = 0.875, p < 0.001), BPDAI-Pruritus (r=0.632, p = 0.004), ABQOL (r = 0.521, p = 0.011) and TABQOL (r=0.538, p = 0.008). MCIDs for BPDAI were 4-points for assessing clinical improvement and 3-points for deterioration. ABSIS demonstrated less responsiveness with MCIDs at 8.6-points for improvement and 4-points for deterioration. These results indicate that BPDAI demonstrated excellent reliability, validity and responsiveness, while ABSIS had moderate to good reliability, validity and responsiveness.

Purpose To assess the incidence and predictors of postsuppression virologic rebound (VR) among adolescents on stable combination antiretroviral therapy in Asia. Methods Perinatally HIV-infected Asian adolescents (10¿19 years) with documented virologic suppression (two consecutive viral loads [VLs] <400 copies/mL =6 months apart) were included. Baseline was the date of the first VL <400 copies/mL at age =10 years or the 10th birthday for those with prior suppression. Cox proportional hazards models were used to identify predictors of postsuppression VR (VL >1,000 copies/mL). Results Of 1,379 eligible adolescents, 47% were males. At baseline, 22% were receiving protease inhibitor¿containing regimens; median CD4 cell count (interquartile range [IQR]) was 685 (448¿937) cells/mm3; 2% had preadolescent virologic failure (VF) before subsequent suppression. During adolescence, 180 individuals (13%) experienced postsuppression VR at a rate of 3.4 (95% confidence interval: 2.9¿3.9) per 100 person-years, which was consistent over time. Median time to VR during adolescence (IQR) was 3.3 (2.1¿4.8) years. Wasting (weight-for-age z-score <-2.5), being raised by grandparents, receiving second-line protease inhibitor¿based regimens, starting combination antiretroviral therapy after 2005, and having preadolescent VF were independent predictors of adolescent VR. At VR, median age, CD4 cell count, and VL (IQR) were 14.8 (13.2¿16.4) years, 507 (325¿723) cells/mm3, and 4.1 (3.5¿4.7) log10 copies/mL, respectively. Conclusions A modest and consistent incidence of postsuppression VR was documented during adolescence in our cohort. Having poor weight, receiving second-line regimens, and prior VF were associated with an increased VR rate. Adolescents at higher risk of VR may benefit from more intensive VL monitoring to enhance adherence management.

Data on markers of hepatitis C virus (HCV) disease in HIV-HCV-coinfected patients in resource-limited settings are scarce. We assessed HCV RNA, HCV genotype (GT), IL28B GT and liver fibrosis (FibroScan®) in 480 HIV-infected patients with positive HCV antibody in four HIV treatment centres in South-East Asia. We enrolled 165 (34.4%) patients in Jakarta, 158 (32.9%) in Bangkok, 110 (22.9%) in Hanoi and 47 (9.8%) in Kuala Lumpur. Overall, 426 (88.8%) were male, the median (IQR) age was 38.1 (34.7-42.5) years, 365 (76.0%) reported HCV exposure through injecting drug use, and 453 (94.4%) were on combination antiretroviral therapy. The median (IQR) CD4 count was 446 (325-614) cells/mm3 and 208 (94.1%) of 221 patients tested had HIV-1 RNA <400 copies/mL. A total of 412 (85.8%) had detectable HCV RNA, at a median (IQR) of 6.2 (5.4-6.6) log10 IU/mL. Among 380 patients with HCV GT, 223 (58.7%) had GT1, 97 (25.5%) had GT3, 43 (11.3%) had GT6, eight (2.1%) had GT4, two (0.5%) had GT2, and seven (1.8%) had indeterminate GT. Of 222 patients with IL28B testing, 189 (85.1%) had rs12979860 CC genotype, and 199 (89.6%) had rs8099917 TT genotype. Of 380 patients with FibroScan®, 143 (37.6%) had no/mild liver fibrosis (F0-F1), 83 (21.8%) had moderate fibrosis (F2), 74 (19.5%) had severe fibrosis (F3), and 79 (20.8%) had cirrhosis (F4). One patient (0.3%) had FibroScan® failure. In conclusion, a high proportion of HIV-HCV-coinfected patients had chronic HCV infection. HCV GT1 was predominant, and 62% of patients had liver disease warranting prompt treatment (=F2).

Background. Regular CD4 count testing is often used to monitor antiretroviral therapy efficacy. However, this practice may be redundant in children with a suppressed human immunodeficiency virus (HIV) viral load. Methods Study end points were as follows: (1) a CD4 count <200 cells/mm3 followed by a CD4 count =200 cells/mm3 (transient CD4 <200); (2) CD4 count <200 cells/mm3 confirmed within 6 months (confirmed CD4 <200); and (3) a new or recurrent World Health Organization (WHO) stage 3 or 4 illness (clinical failure). Kaplan-Meier curves and Cox regression were used to evaluate rates and predictors of transient CD4 <200, confirmed CD4 <200, and clinical failure among virally suppressed children aged 5-15 years who were enrolled in the TREAT Asia Pediatric HIV Observational Database. Results Data from 967 children were included in the analysis. At the time of confirmed viral suppression, median age was 10.2 years, 50.4% of children were female, and 95.4% were perinatally infected with HIV. Median CD4 cell count was 837 cells/ mm3, and 54.8% of children were classified as having WHO stage 3 or 4 disease. In total, 18 transient CD4 <200 events, 2 confirmed CD4 <200 events, and 10 clinical failures occurred at rates of 0.73 (95% confidence interval [95% CI], 0.46-1.16), 0.08 (95% CI, 0.02-0.32), and 0.40 (95% CI, 0.22-0.75) events per 100 patient-years, respectively. CD4 <500 cells/mm3 at the time of viral suppression confirmation was associated with higher rates of both CD4 outcomes. Conclusions Regular CD4 testing may be unnecessary for virally suppressed children aged 5-15 years with CD4 =500 cells/ mm3.

Background: Abacavir and rilpivirine are alternative antiretroviral drugs for treatment-naïve HIV-infected patients. However, both drugs are only recommended for the patients who have pre-treatment HIV RNA <100,000 copies/mL. In resource-limited settings, pre-treatment HIV RNA is not routinely performed and not widely available. The aims of this study are to determine factors associated with pre-treatment HIV RNA <100,000 copies/mL and to construct a model to predict this outcome. 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 < 0.01), CD4 count >350 cells/mm3 (OR 3.9 vs. <100 cells/mm3; 95% CI 2.0-4.1, p < 0.01), total lymphocyte count >2000 cells/mm3 (OR 1.7 vs. <1000 cells/mm3; 95% CI 1.3-2.3, p < 0.01), and no prior AIDS-defining illness (OR 1.8; 95% CI 1.5-2.3, p < 0.01). Receiver-operator characteristic (ROC) analysis yielded area under the curve of 0.70 (95% CI 0.67-0.72) among derivation patients and 0.69 (95% CI 0.65-0.74) among validation patients. A cut off score >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.

Background: Direct acting antivirals are expected to drastically reduce the burden of hepatitis C virus (HCV) in people living with Human Immunodeficiency Virus (HIV). However, rates of HCV testing, re-testing and incident infection in this group remain uncertain in Australia. We assessed trends in HCV testing, re-testing and incident infection among HIV-positive individuals, and evaluated factors associated with HCV re-testing and incident infection. Methods: The study population consisted of HIV-positive individuals who visited a sexual health service involved in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance (ACCESS) between 2007 and 2015. Poisson regression was used to assess trends and to evaluate factors associated with HCV re-testing and incident HCV infection. Results: There were 9227 HIV-positive individuals included in our testing rate analysis. Of 3799 HIV-positive/HCV-negative people that attended an ACCESS sexual health service more than once, 2079 (54.7%) were re-tested for HCV and were therefore eligible for our incidence analysis. The rate of HCV testing increased from 17.1 to 51.4 tests per 100 patient years between 2007 and 2015 (p for trend <0.01). Over the same period, HCV re-testing rates increased from 23.9 to 79.7 tests per 100 person years (p for trend <0.01). A clear increase in testing and re-testing began after 2011. Patients who identified as men who have sex with men and those with a history of injecting drug use experienced high rates of HCV re-testing over the course of the study period. Among those who re-tested, 157 incident HCV infections occurred at a rate of 2.5 events per 100 person years. Between 2007 and 2009, 2010-2011, 2012-2013 and 2014-2015, rates of incident HCV were 0.8, 1.5, 3.9 and 2.7 events per 100 person years, respectively (p for trend <0.01). Incident HCV was strongly associated with a history of injecting drug use. Conclusions: High rates of HCV testing and re-testing among HIV-positive individuals in Australia will assist strategies to achieve HCV elimination through rapid treatment scale up. Continued monitoring of HCV incidence in this population is essential for guiding both HCV prevention and treatment strategies.

Introduction: Although substitutions of antiretroviral regimen are generally safe, most data on substitutions are based on results from clinical trials. The objective of this study was to evaluate the treatment outcomes of substituting antiretroviral regimen in virologically suppressed HIV-infected patients in non-clinical trial settings in Asian countries. 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.

Objectives: Treatment interruptions (TIs) of combination antiretroviral therapy (cART) are known to lead to unfavourable treatment outcomes but do still occur in resource-limited settings. We investigated the effects of TI associated with adverse events (AEs) and non-AE-related reasons, including their durations, on treatment failure after cART resumption in HIV-infected individuals in Asia. Methods: Patients initiating cART between 2006 and 2013 were included. TI was defined as stopping cART for >1 day. Treatment failure was defined as confirmed virological, immunological or clinical failure. Time to treatment failure during cART was analysed using Cox regression, not including periods off treatment. Covariables with P < 0.10 in univariable analyses were included in multivariable analyses, where P < 0.05 was considered statistically significant. Results: Of 4549 patients from 13 countries in Asia, 3176 (69.8%) were male and the median age was 34 years. A total of 111 (2.4%) had TIs due to AEs and 135 (3.0%) had TIs for other reasons. Median interruption times were 22 days for AE and 148 days for non-AE TIs. In multivariable analyses, interruptions >30 days were associated with failure (31-180 days HR = 2.66, 95%CI (1.70-4.16); 181-365 days HR = 6.22, 95%CI (3.26-11.86); and >365 days HR = 9.10, 95% CI (4.27-19.38), all P < 0.001, compared to 0-14 days). Reasons for previous TI were not statistically significant (P = 0.158). Conclusions: Duration of interruptions of more than 30 days was the key factor associated with large increases in subsequent risk of treatment failure. If TI is unavoidable, its duration should be minimised to reduce the risk of failure after treatment resumption.

HIV drug resistance assessments and interpretations can be obtained from genotyping (GT), virtual phenotyping (VP) and laboratory-based phenotyping (PT). We compared resistance calls obtained from GT and VP with those from PT (GT-PT and VP-PT) among CRF01_AE and subtype B HIV-1 infected patients. GT predictions were obtained from the Stanford HIV database. VP and PT were obtained from Janssen Diagnostics BVBA's vircoTypeTMHIV-1 and Antivirogram®, respectively. With PT assumed as the "gold standard," the area under the curve (AUC) and the Bland-Altman plot were used to assess the level of agreement in resistance interpretations. A total of 80 CRF01_AE samples from Asia and 100 subtype B from Janssen Diagnostics BVBA's database were analysed. CRF01_AE showed discordances ranging from 3 to 27 samples for GT-PT and 1 to 20 samples for VP-PT. The GT-PT and VP-PT AUCs were 0.76-0.97 and 0.81-0.99, respectively. Subtype B showed 3-61 discordances for GT-PT and 2-75 discordances for VP-PT. The AUCs ranged from 0.55 to 0.95 for GT-PT and 0.55 to 0.97 for VP-PT. Didanosine had the highest proportion of discordances and/or AUC in all comparisons. The patient with the largest didanosine FC difference in each subtype harboured Q151M mutation. Overall, GT and VP predictions for CRF01_AE performed significantly better than subtype B for three NRTIs. Although discrepancies exist, GT and VP resistance interpretations in HIV-1 CRF01_AE strains were highly robust in comparison with the gold-standard PT. © 2015 Wiley Periodicals, Inc.

Objective: Nelfinavir exhibits potent anticancer properties against a range of tumours. However, in 2006/2007, nelfinavir supplies were accidently contaminated with a carcinogen. This analysis investigated the association between nelfinavir use and cancer risk in HIV-positive persons. Design: Observational cohort study. Methods: D:A:D study data was analysed using Poisson regression models to examine associations between cancer incidence and cumulative nelfinavir exposure, current nelfinavir exposure, and exposure to nelfinavir between 1 July 2006-30 June 2007. Results: A total of 42 006 individuals (50% white, 73% male) contributed 303 005 person-years of follow-up between 1 January 2004 and 1 February 2014. At study enrolment, median age was 40 [interquartile range (IQR) 33-46] years and 8305 individuals had a history of nelfinavir use [median duration 1.7 (IQR 0.7-3.4) years]. During follow-up, nelfinavir was used by 2476 individuals for a median of 1.7 (IQR 0.7-3.8) years; 1063 were exposed to nelfinavir between 1 July 2006 and 30 June 2007. Overall, 2279 cancers were diagnosed at a rate of 0.75 [95% confidence interval (95% CI) 0.72-0.78] per 100 person-years. Neither greater cumulative exposure to nelfinavir [adjusted risk ratio (aRR) 0.93 for every additional 5 years, 95% CI 0.82-1.06, P = 0.26] nor current use of nelfinavir (aRR 0.98 vs other protease inhibitor use, 95% CI 0.68-1.41, P = 0.92) were associated with cancer risk. The adjusted risk of cancer for participants exposed to nelfinavir between 1 July 2006 and 30 June 2007 compared to those receiving other treatment over this period was 1.07 (95% CI 0.78-1.46, P = 0.68). Conclusion: Nelfinavir use was not associated with a lower cancer incidence than other protease inhibitor regimens. As of February 2014, exposure to the 2006/2007 contamination of nelfinavir does not appear to be associated with increased cancer incidence.

Background: Information on antiretroviral therapy (ART) use in HIV-infected children with severe malnutrition (SM) is lacking. We investigated long-term ART outcomes in this population. Methods: Children enrolled in the TREAT Asia Pediatric HIV Observational Database who had SM (weight-for-height or body mass index-for-age Z score less than -3) at ART initiation were analyzed. Generalized estimating equations were used to investigate poor weight recovery (weight-for-age Z score less than -3) and poor CD4% recovery (CD4% <25), and competing risk regression was used to analyze mortality and toxicity-associated treatment modification. Results: Three hundred fifty-five (11.9%) of 2993 children starting ART had SM. Their median weight-for-age Z score increased from -5.6 at ART initiation to -2.3 after 36 months. Not using trimethoprim-sulfamethoxazole prophylaxis at baseline was associated with poor weight recovery [odds ratio: 2.49 vs. using; 95% confidence interval (CI): 1.66-3.74; P < 0.001]. Median CD4% increased from 3.0 at ART initiation to 27.2 after 36 months, and 56 (15.3%) children died during follow-up. More profound SM was associated with poor CD4% recovery (odds ratio: 1.78 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.08-2.92; P = 0.023) and mortality (hazard ratio: 2.57 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.24-5.33; P = 0.011). Twenty-two toxicity-associated ART modifications occurred at a rate of 2.4 per 100 patient-years, and rates did not differ by malnutrition severity. Conclusion: Trimethoprim-sulfamethoxazole prophylaxis is important for the recovery of weight-for-age in severely malnourished children starting ART. The extent of SM does not impede weight-for-age recovery or antiretroviral tolerability, but CD4% response is compromised in children with a very low weight-for-height/body mass index-for-age Z score, which may contribute to their high rate of mortality.

Objectives In multisite human immunodeficiency virus (HIV) observational cohorts, clustering of observations often occurs within sites. Ignoring clustering may lead to "Simpson's paradox" (SP) where the trend observed in the aggregated data is reversed when the groups are separated. This study aimed to investigate the SP in an Asian HIV cohort and the effects of site-level adjustment through various Cox regression models. Study Design and Setting Survival time from combination antiretroviral therapy (cART) initiation was analyzed using four Cox models: (1) no site adjustment; (2) site as a fixed effect; (3) stratification through site; and (4) shared frailty on site. Results A total of 6,454 patients were included from 23 sites in Asia. SP was evident in the year of cART initiation variable. Model (1) shows the hazard ratio (HR) for years 2010¿2014 was higher than the HR for 2006¿2009, compared to 2003¿2005 (HR¿=¿0.68 vs. 0.61). Models (2)¿(4) consistently implied greater improvement in survival for those who initiated in 2010¿2014 than 2006¿2009 contrasting findings from model (1). The effects of other significant covariates on survival were similar across four models. Conclusions Ignoring site can lead to SP causing reversal of treatment effects. Greater emphasis should be made to include site in survival models when possible.

Purpose About a third of untreated, perinatally HIV-infected children reach adolescence. We evaluated the durability and effectiveness of non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) in this population. Methods Data from perinatally HIV-infected, antiretroviral-naïve patients initiated on NNRTI-based ART aged 10-19 years who had =6 months of follow-up were analyzed. Competing risk regression was used to assess predictors of NNRTI substitution and clinical failure (World Health Organization Stage 3/4 event or death). Viral suppression was defined as a viral load <400 copies/mL. Results Data from 534 adolescents met our inclusion criteria (56.2% female; median age at treatment initiation 11.8 years). After 5 years of treatment, median height-for-age z score increased from -2.3 to -1.6, and median CD4+ cell count increased from 131 to 580 cells/mm3. The proportion of patients with viral suppression after 6 months was 87.6% and remained >80% up to 5 years of follow-up. NNRTI substitution and clinical failure occurred at rates of 4.9 and 1.4 events per 100 patient-years, respectively. Not using cotrimoxazole prophylaxis at ART initiation was associated with NNRTI substitution (hazard ratio [HR], 1.5 vs. using; 95% confidence interval [CI] = 1.0-2.2; p =.05). Baseline CD4+ count =200 cells/mm3 (HR, 3.3 vs. >200; 95% CI = 1.2-8.9; p =.02) and not using cotrimoxazole prophylaxis at ART initiation (HR, 2.1 vs. using; 95% CI = 1.0-4.6; p =.05) were both associated with clinical failure. Conclusions Despite late ART initiation, adolescents achieved good rates of catch-up growth, CD4+ count recovery, and virological suppression. Earlier ART initiation and routine cotrimoxazole prophylaxis in this population may help to reduce current rates of NNRTI substitution and clinical failure.

Background. The growth benefits of cotrimoxazole during early antiretroviral therapy (ART) are not well characterized. Methods. Individuals enrolled in the Therapeutics Research, Education, and AIDS Training in Asia Pediatric HIV Observational Database were included if they started ART at ages 1 month-14 years and had both height and weight measurements available at ART initiation (baseline). Generalized estimating equations were used to identify factors associated with change in height-for-age z-score (HAZ), follow-up HAZ = -2, change in weight-for-age z-score (WAZ), and follow-up WAZ = -2. Results. A total of 3217 children were eligible for analysis. The adjusted mean change in HAZ among cotrimoxazole and non-cotrimoxazole users did not differ significantly over the first 24 months of ART. In children who were stunted (HAZ < -2) at baseline, cotrimoxazole use was not associated with a follow-up HAZ = -2. The adjusted mean change in WAZ among children with a baseline CD4 percentage (CD4%) >25% became significantly different between cotrimoxazole and non-cotrimoxazole users after 6 months of ART and remained significant after 24 months (overall P <. 01). Similar changes in WAZ were observed in those with a baseline CD4% between 10% and 24% (overall P <. 01). Cotrimoxazole use was not associated with a significant difference in follow-up WAZ in children with a baseline CD4% <10%. In those underweight (WAZ < -2) at baseline, cotrimoxazole use was associated with a follow-up WAZ = -2 (adjusted odds ratio, 1.70 vs not using cotrimoxazole [95% confidence interval, 1.28-2.25], P <. 01). This association was driven by children with a baseline CD4% =10%. Conclusions. Cotrimoxazole use is associated with benefits to WAZ but not HAZ during early ART in Asian children.

Background: The World Health Organization recommends HBV-HIV-coinfected individuals start antiretroviral therapy containing tenofovir. Here we describe irst-line tenofovir use and treatment outcomes in coinfected patients in Asia. Methods: HBV surface antigen positive patients enrolled in the TREAT Asia HIV Observational Database who started irst-line antiretroviral therapy were included. Logistic regression adjusted for period of treatment initiation was used to determine factors associated with tenofovir use. Generalized estimating equations were used to evaluate factors associated with alanine transaminase levels and CD4+ T-cell count on treatment. Results: There were 548 eligible patients, of whom 149 (27.2%) started tenofovir. Patients treated in high/highmiddle income countries (odds ratio 4.4 versus low/lowmiddle, 95% CI 2.6, 7.4; P<0.001) and those with elevated baseline alanine transaminase (odds ratio 4.2 versus normal, 95% CI 2.4, 7.2; P<0.001) were more likely to receive tenofovir. Hepatitis C antibody positive patients (odds ratio 0.4 versus negative, 95% CI 0.2, 0.8; P=0.008) were less likely. In those starting antiretroviral therapy with elevated alanine transaminase, mean reduction after tenofovir initiation was 11.2 IU/l (95% CI 0.9, 21.6; P=0.034) lower compared with those using a non-tenofovir-based regimen although this did not signiicantly increase the chance of alanine transaminase normalization. Tenofovir use was not associated with a superior CD4+ T-cell response. Conclusions: HBV-HIV-coinfected patients in Asia are most likely to receive tenofovir if they are treated in a high/highmiddle income country, have elevated alanine transaminase levels and are hepatitis C antibody negative. Compared to other antiretroviral therapies, tenofovir-based regimens more effectively reduce liver inlammation in HBV-HIV-coinfection but do not result in superior CD4+ T-cell recovery.

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/mm3 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.

Objectives: The aim of the study was to assess the prevalence and characteristics associated with current smoking in an Asian HIV-positive cohort, to calculate the predictive risks of cardiovascular disease (CVD), coronary heart disease (CHD) and myocardial infarction (MI), and to identify the impact that simulated interventions may have. Methods: Logistic regression analysis was used to distinguish associated current smoking characteristics. Five-year predictive risks of CVD, CHD and MI and the impact of simulated interventions were calculated utilizing the Data Collection on Adverse Effects of Anti-HIV Drugs Study (D:A:D) algorithm. Results: Smoking status data were collected from 4274 participants and 1496 of these had sufficient data for simulated intervention calculations. Current smoking prevalence in these two groups was similar (23.2% vs. 19.9%, respectively). Characteristics associated with current smoking included age >¿50¿years compared with 30¿39¿years [odds ratio (OR) 0.65; 95% confidence interval (CI) 0.51¿0.83], HIV exposure through injecting drug use compared with heterosexual exposure (OR 3.03; 95% CI 2.25¿4.07), and receiving antiretroviral therapy (ART) at study sites in Singapore, South Korea, Malaysia, Japan and Vietnam in comparison to Thailand (all OR¿>¿2). Women were less likely to smoke than men (OR 0.11; 95% CI 0.08¿0.14). In simulated interventions, smoking cessation demonstrated the greatest impact in reducing CVD and CHD risk and closely approximated the impact of switching from abacavir to an alternate antiretroviral in the reduction of 5-year MI risk. Conclusions: Multiple interventions could reduce CVD, CHD and MI risk in Asian HIV-positive patients, with smoking cessation potentially being the most influential.

Background: Severe anemia is common among children infected with human immunodeficiency virus (HIV). The choice of antiretroviral (ART) regimen needs careful consideration. No information is available regarding the initial ART regimens used in the Asia-Pacific region and the rate of switch of ART regimens in HIV-infected children with severe anemia. Objectives: To study the initial ART regimens and the rate of switch of ART regimens used during the first 36 months in HIV-infected children with severe anemia and to evaluate their clinical and laboratory outcomes. Methods: We analyzed regional cohort data of 130 Asian children aged <18 years with baseline severe anemia (hemoglobin <7.5 g/dl) who started antiretroviral therapy (ART) between January 2003 and September 2013. Results: At ART initiation, median age was 3.5 years old (interquartile range (IQR) 1.7 to 6.3) and median hemoglobin was 6.7 g/dL (IQR 5.9-7.1, range 3.0-7.4). Initial ART regimens included stavudine (85.4%), zidovudine (13.8%), and abacavir (0.8%). In 81 children with available hemoglobin data after 6 months of ART, 90% recovered from severe anemia with a median hemoglobin of 10.7 g/dL (IQR 9.6-11.7, range 4.4-13.5). Those starting AZT-based ART had a mortality rate of 10.8 (95% confidence interval (CI) 4.8-23.9) per 100 patient-years compared to 2.7 (95% CI 1.6-4.6) per 100 patient-years among those who started d4T-based ART. Conclusions: With the phase-out of stavudine, age-appropriate non-zidovudine options are needed for younger Asian children with severe anemia.

Introduction: Outbreaks of syphilis have been described among HIV-infected men who have sex with men (MSM) in Western communities, whereas reports in Asian countries are limited. We aimed to characterize the incidence and temporal trends of syphilis among HIV-infected MSM compared with HIV-infected non-MSM in Asian countries. Methods: Patients enrolled in the TREAT Asia HIV Observational Database cohort and with a negative non-treponemal test since enrolment were analyzed. Incidence of syphilis seroconversion, defined as a positive non-treponemal test after previously testing negative, was evaluated among patients at sites performing non-treponemal tests at least annually. Factors associated with syphilis seroconversion were investigated at sites doing non-treponemal testing in all new patients and subsequently testing routinely or when patients were suspected of having syphilis. Results: We included 1010 patients from five sites that performed non-treponemal tests in all new patients; those included had negative non-treponemal test results during enrolment and subsequent follow-ups. Among them, 657 patients were from three sites conducting regular non-treponemal testing. The incidence of syphilis seroconversion was 5.38/100 person-years (PY). Incidence was higher in MSM than non-MSM (7.64/100 PY vs. 2.44/100 PY, p<0.001). Among MSM, the incidence rate ratio (IRR) for every additional year from 2009 was 1.19 (p=0.051). MSM status (IRR 3.48, 95% confidence interval (CI) 1.88-6.47), past syphilis diagnosis (IRR 5.15, 95% CI 3.69-7.17) and younger age (IRR 0.84 for every additional 10 years, 95% CI 0.706-0.997) were significantly associated with syphilis seroconversion. Conclusions: We observed a higher incidence of syphilis seroconversion among HIV-infected MSM and a trend to increasing annual incidence. Regular screening for syphilis and targeted interventions to limit transmission are needed in this population.

Setting: World Health Organization advocates for integration of HIV-tuberculosis (TB) services and recommends intensive case finding (ICF), isoniazid preventive therapy (IPT), and infection control ("Three I's") for TB prevention and control among persons living with HIV. Objective: To assess the implementation of the "Three I's" of TB-control at HIV treatment sites in lower income countries. Design: Survey conducted between March-July, 2012 at 47 sites in 26 countries: 6 (13%) Asia Pacific, 7 (15%), Caribbean, Central and South America, 5 (10%) Central Africa, 8 (17%) East Africa, 14 (30%) Southern Africa, and 7 (15%) West Africa. Results: ICF using symptom-based screening was performed at 38% of sites; 45% of sites used symptom-screening plus additional diagnostics. IPT at enrollment or ART initiation was implemented in only 17% of sites, with 9% of sites providing IPT to tuberculin-skin-test positive patients. Infection control measures varied: 62% of sites separated smear-positive patients, and healthcare workers used masks at 57% of sites. Only 12 (26%) sites integrated HIV-TB services. Integration was not associated with implementation of TB prevention measures except for IPT provision at enrollment (42% integrated vs. 9% nonintegrated; p = 0.03). Conclusions: Implementation of TB screening, IPT provision, and infection control measures was low and variable across regional HIV treatment sites, regardless of integration status.

Background: In resource-limited settings, routine monitoring of renal function during antiretroviral therapy (ART) has not been recommended. However, concerns for tenofovir disoproxil fumarate (TDF)-related nephrotoxicity persist with increased use. 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.

Objectives: The proportion of people living with HIV/AIDS in the ageing population (>50 years old) is increasing. We aimed to explore the relationship between older age and treatment outcomes in HIV-positive persons from the Asia Pacific region. Methods: Patients from the Australian HIV Observational Database (AHOD) and the TREAT Asia HIV Observational Database (TAHOD) were included in the analysis. We used survival methods to assess the association between older age and all-cause mortality, as well as time to treatment modification. We used regression analyses to evaluate changes in CD4 counts after combination antiretroviral therapy (cART) initiation and determined the odds of detectable viral load, up to 24 months of treatment. Results: A total of 7142 patients were included in these analyses (60% in TAHOD and 40% in AHOD), of whom 25% were >50 years old. In multivariable analyses, those aged >50 years were at least twice as likely to die as those aged 30-39 years [hazard ratio (HR) for 50-59 years: 2.27; 95% confidence interval (CI) 1.34-3.83; HR for >60 years: 4.28; 95% CI 2.42-7.55]. The effect of older age on CD4 count changes was insignificant (p-trend=0.06). The odds of detectable viral load after cART initiation decreased with age (p-trend=<0.0001). The effect of older age on time to first treatment modification was insignificant (p-trend=0.21). We found no statistically significant differences in outcomes between AHOD and TAHOD participants for all endpoints examined. Conclusions: The associations between older age and typical patient outcomes in HIV-positive patients from the Asia Pacific region are similar in AHOD and TAHOD. Our data indicate that 'age effects' traverse the resource-rich and resource-limited divide and that future ageing-related findings might be applicable to each setting.