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BACKGROUND This population pharmacokinetic-pharmacogenetic study aimed to investigate the optimal dose of RTV-boosted ATV (ATV/RTV) for Thai adult HIV-infected patients. METHODS A total of 1460 concentrations of ATV and RTV from 544 patients receiving an ATV/RTV-based regimen were analyzed. The CYP3A5 6986 A > G, ABCB1 3435 C > T, ABCB1 2677 G > T, SLCO1B1 521 T > C, and NR1I2 63396 C > T were genotyped. A population pharmacokinetic model was performed using a nonlinear mixed-effect model (NONMEM®). Monte Carlo simulations were conducted to compare the percentages of patients achieving the therapeutic range of ATV through concentrations (Ctrough). RESULTS The apparent oral clearance of ATV (CL/FATV) without RTV was 7.69 L/h with interindividual variability (IIV) of 28.7%. Patients with CYP3A5 6986 GG had a 7.1% lower CL/FATV than those with AA or AG genotype. The CL/FATV decreased by 10.8% for females compared with males. Simulation results showed higher percentages (~70%) of patient receiving doses of 200/100 or 200/50 mg achieved the target ATV Ctrough, while more patients (~40%) receiving a standard dose (300/100 mg) had ATV Ctrough above this target. CONCLUSIONS Both CYP3A5 6986 A > G and female decreased CL/FATV in Thai HIV-infected patients. Simulations supported that the reduced dose of ATV/RTV was sufficient to achieve the target concentration for Thai population.

Viral load (VL) testing is still challenging to monitor treatment responses of antiretroviral therapy (ART) for HIV treatment programme in Asia. We assessed the association between routine VL testing and virological failure (VF) and determine factors associated with switching to second-line regimen.Among 21 sites from the TREAT Asia HIV Observational Database (TAHOD), people living with HIV (PLHIV) aged ≥18 years initiating ART from 2003 to 2021 were included. We calculated the average number of VL tests per patient per year between the date of ART initiation and the most recent visit. If the median average number of VL tests was ≥ 0.80 per patient per year, the site was classified as a routine VL site. A site with a median0.80 was classified into the non-routine VL sites. VF was defined as VL ≥1000 copies/ml during first-line therapy. Factors associated with VF were analysed using generalized estimating equations with Poisson distribution.Of 6277 PLHIV starting ART after 2003, 3030 (48%) were from 11 routine VL testing sites and 3247 (52%) were from 10 non-routine VL testing sites. The median follow-up was 9 years (IQR 5-13). The median age was 35 (30-42) years; 68% were male and 5729 (91%) started non-nucleoside reverse-transcriptase inhibitor-based regimen. The median pre-ART CD4 count in PLHIV from routine VL sites was lower compared to non-routine VL sites (144 vs. 156 cells/mmPLHIV from non-routine VL sites had a higher incidence of persistent VF and a low switching regimen rate, reflecting possible under-utilized VL testing.

Immunogenicity following an additional dose of Coronavirus disease 2019 (COVID-19) vaccine was investigated in an extended primary series among kidney transplant (KT) recipients. Eighty-five KT participants were randomized to receive either an mRNA (M group; n = 43) or viral vector (V group; n = 42) vaccine. Among them, 62% were male, with a median (IQR) age of 50 (43-59) years and post-transplantation duration of 46 (26-82) months. At 2 weeks post-additional dose, there was no difference in the seroconversion rate between the M and V groups (70% vs. 65%, p = .63). A median (IQR) of anti-RBD antibody level was not statistically different between the M group compared with the V group (51.8 [5.1-591] vs. 28.5 [2.9-119.3] BAU/ml, p = .18). Furthermore, the percentage of participants with positive SARS-CoV-2 surrogate virus neutralization test results was not statistically different between groups (20% vs. 15%, p = .40). S1-specific T cell and RBD-specific B cell responses were also comparable between the M and V groups (230 [41-420] vs. 268 [118-510], p = .65 and 2 [0-10] vs. 2 [0-13] spot-forming units/10

BACKGROUND We validated the Data collection on Adverse events of anti-HIV Drugs (D:A:D) full-risk and short-risk score models for chronic kidney disease (CKD) in the Asian HIV cohorts. SETTINGS A validation study among people living with HIV (PLHIV) aged ≥18 years among the cohorts in the Asia-Pacific region. METHODS PLHIV with a baseline estimated glomerular filtration rate > 60 mL/min/1.73 m were included for validation of the D:A:D CKD full version and short version without cardiovascular risk factors. Those with

Background:Antiretroviral therapy (ART), especially with tenofovir disoproxil fumarate (TDF), has been associated with accelerated bone turnover and leads to significant bone loss.Objective:We aimed to determine the effect of vitamin D2 and calcium on bone mineral density (BMD) in HIV-infected patients receiving TDF/emtricitabine (FTC)/efavirenz (EFV).Methods:A prospective, open-label, randomized controlled study was conducted. Eligible patients were ART naïve HIV individuals who initiated TDF/FTC/EFV. The study group received supplementation with vitamin D2 and calcium carbonate, whereas the control group was administered only ART. The primary outcome was the percentage change in total hip BMD at week 24 compared with baseline.Results:A total of 18 patients were randomized (9 in each group). The mean (standard deviation; SD) total hip BMD significantly decreased from baseline in both groups, from 0.96 (0.14) g/cm2 to 0.93 (0.13) g/cm2 in the study group (p = 0.006) and from 0.87 (0.11) g/cm2 to 0.84 (0.11) g/cm2 in the control group (p = 0.004). The mean (SD) lumbar spine BMD significantly decreased from baseline in both groups, from 1.00 (0.13) g/cm2 to 0.97 (0.13) g/cm2 (p = 0.004) in the study group and from 0.90 (0.09) g/cm3 to 0.86 (0.08) g/cm2 in the control group (p = 0.006). At week 24, the mean (SD) lumbar spine BMD was significantly greater in the study group than in the control group (p = 0.042). However, there were no significant differences in the percentage change of total hip, lumbar spine, and femoral neck BMD between both groups. No adverse events were reported. In conclusion, as early as 24 weeks after TDF initiation, a significant decline in BMD was detected.Conclusion:Vitamin D2 and calcium supplements should be considered for HIV-infected patients receiving TDF/FTC/EFV in a resource-limited setting where there are limited ART options (Clinicaltrials. gov NCT0287643).

Background Immunization stress-related responses presenting as stroke-like symptoms could develop following COVID-19 vaccination. Therefore, this study aimed to describe the clinical characteristics of immunization stress-related responses causing stroke-like events following COVID-19 vaccination in Thailand. Methods We conducted a retrospective study of the secondary data of reported adverse events after COVID-19 immunization that presented with neurologic manifestations. Between March 1 and July 31, 2021, we collected and analyzed the medical records of 221 patients diagnosed with stroke-like symptoms following immunization. Two majority types of vaccines were used at the beginning of the vaccination campaign, including CoronaVac (Sinovac) or ChAdOx1 (AstraZeneca). Demographic and medical data included sex, age, vaccine type, sequence dose, time to event, laboratory data, and recovery status as defined by the modified Rankin score. The affected side was evaluated for associations with the injection site. Results Overall, 221 patients were diagnosed with immunization stress-related responses (stroke-like symptoms) following CoronaVac (Sinovac) or ChAdOx1 (AstraZeneca) vaccinations. Most patients (83.7%) were women. The median (interquartile range) age of onset was 34 (28–42) years in patients receiving CoronaVac and 46 (33.5–60) years in those receiving ChAdOx1. The median interval between vaccination and symptom onset for each vaccine type was 60 (16–960) min and 30 (8.8–750) min, respectively. Sensory symptoms were the most common symptomology. Most patients (68.9%) developed symptoms on the left side of the body; 99.5% of the patients receiving CoronaVac and 100% of those receiving ChAdOx1 had a good outcome (modified Rankin scores ≤2, indicating slight or no disability). Conclusions Immunization stress-related responses presenting as stroke-like symptoms can develop after COVID-19 vaccination. Symptoms more likely to occur on the injection side are transient (i.e., without permanent pathological deficits). Public education and preparedness are important for administering successful COVID-19 vaccination programs.

BackgroundPeople living with HIV (PLHIV) have an elevated risk of atherosclerotic cardiovascular disease (ASCVD) compared to their uninfected peers. Expanding statin use may help alleviate this burden. We evaluated the cost-effectiveness of reducing the recommend statin initiation threshold for primary ASCVD prevention among PLHIV in Thailand.MethodsOur decision analytic microsimulation model randomly selected (with replacement) individuals from the TREAT Asia HIV Observational Database (data collected between 1/January/2013 and 1/September/2019). Direct medical costs and quality-adjusted life-years were assigned in annual cycles over a lifetime horizon and discounted at 3% per year. We assumed the Thai healthcare sector perspective. The study population included PLHIV aged 35–75 years, without ASCVD, and receiving antiretroviral therapy. Statin initiation thresholds evaluated were 10-year ASCVD risk ≥10% (control), ≥7.5% and ≥5%.ResultsA statin initiation threshold of ASCVD risk ≥7.5% resulted in accumulation of 0.015 additional quality-adjusted life-years compared with an ASCVD risk threshold ≥10%, at an extra cost of 3,539 Baht ($US113), giving an incremental cost-effectiveness ratio of 239,000 Baht ($US7,670)/quality-adjusted life-year gained. The incremental cost-effectiveness ratio comparing ASCVD risk ≥5% to ≥7.5% was 349,000 Baht ($US11,200)/quality-adjusted life-year gained. At a willingness-to-pay threshold of 160,000 Baht ($US5,135)/quality-adjusted life-year gained, a 30.8% reduction in the average cost of low/moderate statin therapy led to the ASCVD risk threshold ≥7.5% becoming cost-effective compared with current practice.ConclusionsReducing the recommended 10-year ASCVD risk threshold for statin initiation among PLHIV in Thailand would not currently be cost-effective. However, a lower threshold could become cost-effective with greater preference for cheaper statins.

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.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).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.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.

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.Patients from TREAT Asia HIV Observational Database (September 2015 data transfer) aged 18 years and older with a CD4 count50 cells/mm at ART initiation were included. The effect of macrolide prophylaxis on HIV-associated mortality or AIDS-defining conditions (as a combined outcome) and HIV-associated mortality alone were evaluated using competing risk regression. Sensitivity analysis was conducted in patients with a CD4100 cells/mm at ART initiation.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 CD4100 cells/mm at ART initiation.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 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

Background Infectious Diseases Society of America (IDSA) guidelines suggest 7–14 days’ duration of antibiotic treatment for uncomplicated Gram-negative bacteria (GNB) catheter-related bloodstream infection (CRBSI). The objectives of this study were to review microbial epidemiology, to determine rate and risk factors for relapse, and to compare clinical outcomes in patients receiving long- versus short-duration antibiotic therapy. Methods A retrospective phase 1 study was conducted between January 2010 and October 2016 to review microbial epidemiology and to determine the incidence of and risk factors for relapse in patients with GNB CRBSI, according to the IDSA guidelines diagnostic criteria. In phase 2 of the study, patients without risk factors for relapse between November 2016 and October 2017 were prospectively recruited to receive antibiotic therapy for 7 days after catheter removal. Matched patients from the retrospective phase 1 study who had received antibiotic therapy for ≥14 days were selected as a phase 2 control group to compare outcomes. Results In phase 1, three most common pathogens identified among 174 cases were Pseudomonas aeruginosa (22.0%), Klebsiella pneumoniae (16.7%), and Stenotrophomonas maltophilia (13.4%). Eighty-nine episodes of infection occurred while patients were receiving antibiotic therapy. Of 140 cases, the relapse rate was 6.4%. Catheter retention was the only risk factor strongly associated with relapse (odds ratio = 145.32; 95% confidence interval 12.66–1667.37, P P = 1.000). Conclusions For the management of patients with uncomplicated GNB CRBSI, empiric broad-spectrum antibiotic therapy with adequate coverage of P. aeruginosa should be chosen. Catheter removal should be performed to prevent relapse and shortening the duration of treatment could be considered. Trial registration Thai Clinical Trial Registry: TCTR20190914001. Retrospectively registered on 13 September 2019.

Objectives We conducted a longitudinal cohort analysis to evaluate the association of pre-treatment body mass index (BMI) with CD4 recovery, virological failure (VF) and cardiovascular risk disease (CVD) markers among people living with HIV (PLHIV). Methods Participants who were enrolled between January 2003 and March 2019 in a regional Asia HIV cohort with weight and height measurements prior to antiretroviral therapy (ART) initiation were included. Factors associated with mean CD4 increase were analysed using repeated-measures linear regression. Time to first VF after 6 months on ART and time to first development of CVD risk markers were analysed using Cox regression models. Sensitivity analyses were done adjusting for Asian BMI thresholds. Results Of 4993 PLHIV (66% male), 62% had pre-treatment BMI in the normal range (18.5-25.0 kg/m2 ), while 26%, 10% and 2% were underweight ( 30 kg/m2 ), respectively. Both higher baseline and time-updated BMI were associated with larger CD4 gains compared with normal BMI. After adjusting for Asian BMI thresholds, higher baseline BMIs of 23-27.5 and > 27.5 kg/m2 were associated with larger CD4 increases of 15.6 cells/µL [95% confidence interval (CI): 2.9-28.3] and 28.8 cells/µL (95% CI: 6.6-50.9), respectively, compared with normal BMI (18.5-23 kg/m2 ). PLHIV with BMIs of 25-30 and > 30 kg/m2 were 1.27 times (95% CI: 1.10-1.47) and 1.61 times (95% CI: 1.13-2.24) more likely to develop CVD risk factors. No relationship between pre-treatment BMI and VF was observed. Conclusions High pre-treatment BMI was associated with better immune reconstitution and CVD risk factor development in an Asian PLHIV cohort.

Introduction People living with HIV (PLHIV) have an elevated risk of atherosclerotic cardiovascular disease (CVD) compared to their HIV‐negative peers. Expanding statin use may help alleviate this burden. However, the choice of statin in the context of antiretroviral therapy is challenging. Pravastatin and pitavastatin improve cholesterol levels in PLHIV without interacting substantially with antiretroviral therapy. They are also more expensive than most statins. We evaluated the cost‐effectiveness of pravastatin and pitavastatin for the primary prevention of CVD among PLHIV in Thailand who are not currently using lipid‐lowering therapy. Methods We developed a discrete‐state microsimulation model that randomly selected (with replacement) individuals from the TREAT Asia HIV Observational Database cohort who were aged 40 to 75 years, receiving antiretroviral therapy in Thailand, and not using lipid‐lowering therapy. The model simulated each individual’s probability of experiencing CVD. We evaluated: (1) treating no one with statins; (2) treating everyone with pravastatin 20mg/day (drug cost 7568 Thai Baht ($US243)/year) and (3) treating everyone with pitavastatin 2 mg/day (drug cost 8182 Baht ($US263)/year). Direct medical costs and quality‐adjusted life‐years (QALYs) were assigned in annual cycles over a 20‐year time horizon and discounted at 3% per year. We assumed the Thai healthcare sector perspective. Results Pravastatin was estimated to be less effective and less cost‐effective than pitavastatin and was therefore dominated (extended) by pitavastatin. Patients receiving pitavastatin accumulated 0.042 additional QALYs compared with those not using a statin, at an extra cost of 96,442 Baht ($US3095), giving an incremental cost‐effectiveness ratio of 2,300,000 Baht ($US73,812)/QALY gained. These findings were sensitive to statin costs and statin efficacy, pill burden, and targeting of PLHIV based on CVD risk. At a willingness‐to‐pay threshold of 160,000 Baht ($US5135)/QALY gained, we estimated that pravastatin would become cost‐effective at an annual cost of 415 Baht ($US13.30)/year and pitavastatin would become cost‐effective at an annual cost of 600 Baht ($US19.30)/year. Conclusions Neither pravastatin nor pitavastatin were projected to be cost‐effective for the primary prevention of CVD among PLHIV in Thailand who are not currently using lipid‐lowering therapy. We do not recommend expanding current use of these drugs among PLHIV in Thailand without substantial price reduction.

To manage coronavirus disease 2019 (COVID-19), a national health authority has implemented a case definition of patients under investigation (PUIs) to guide clinicians’ diagnoses. We aimed to determine characteristics among all PUIs and those with and without COVID-19. We retrospectively reviewed clinical characteristics and risk factors for laboratory-confirmed COVID-19 cases among PUIs at a tertiary care center in Bangkok, Thailand, between March 23 and April 7, 2020. Reverse transcription-polymerase chain reaction for SARS-CoV-2 RNA was performed. There were 405 evaluable PUIs; 157 (38.8%) were men, with a mean age ± SD of 36.2 ± 12.6 years. The majority (68.9%) reported no comorbidities. There were 53 (13.1%) confirmed COVID-19 cases. The most common symptoms among those were cough (73.6%), fever (58.5%), sore throat (39.6%), and muscle pain (37.4%). Among these patients, diagnoses were upper respiratory tract infection (69.8%), viral syndrome (15.1%), pneumonia (11.3%), and asymptomatic infection (3.8%). Multivariate analysis identified close contact with an index case (OR, 3.49; 95%CI, 1.49–8.15; P = 0.004), visiting high-risk places (OR, 1.92; 95%CI, 1.03–3.56; P = 0.039), productive cough (OR, 2.03; 95%CI, 1.05–3.92; P = 0.034), and no medical coverage (OR, 3.91; 95%CI, 1.35–11.32; P = 0.012) as independent risk factors for COVID-19 among the PUIs. The majority had favorable outcomes, though one (1.9%) died from severe pneumonia. COVID-19 was identified in 13% of PUIs defined per a national health authority’s case definition. History of contact with a COVID-19 patient, visiting a high-risk place, having no medical coverage, and productive cough may identify individuals at risk of COVID-19 in Thailand.

More than half of newly diagnosed HIV-infected patients enter to care with a low CD4 count. A retrospective cohort study was conducted among newly diagnosed HIV-infected adults who were hospitalized. Of 148 patients, median (interquartile range [IQR]) age was 39.3 (30.5-47.1) years and 114 (77%) patients were male. Baseline median (IQR) CD4 count was 79 (24-218) cells/mm3. The median (IQR) length of hospital stay was 8 (4-16) days. Half of the patients were hospitalized with AIDS-defining illness (ADI). Common opportunistic infections were Pneumocystis jirovecii pneumonia (20.3%) and tuberculosis (18.9%). CD4 count was statistically significantly associated with hospitalization with ADI (odds ratio: 0.85, per 10 cells/mm3 increased; 95% confidence interval: 0.80-0.90). The mortality was 5.4%. In conclusion, half of newly diagnosed Thai HIV-infected patients were hospitalized with ADI. Early detection of HIV infection leading to early antiretroviral therapy initiation and prevention of serious complications is essential.

Background Comprehensive treatment and clinical management are central to improving outcomes for people living with HIV (PLHIV). We explored trends in HIV clinical care, treatment outcomes, and chronic kidney disease (CKD) and diabetes monitoring. Methods We included patients ≥18 years in care at ten clinical sites in eight Asian countries. Proportions of patients on antiretroviral therapy (ART), with annual viral load, and with viral load suppression (VLS; Results Among 31,346 patients (67% male), the proportions of patients on ART (median ART initiation year 2011, IQR 2007–2013), with annual viral load and VLS had substantially increased by 2016 (to 94%, 42% and 92%, respectively, in LMIC and 95%, 97% and 93%, respectively, in HIC) with the larger increases over time seen in LMIC. Among those on ART in 2016, monitoring proportions in LMIC were 53% for CKD and 26% for diabetes compared with 83% and 59%, respectively, in HIC. Overall, a decreased odds of monitoring was observed for male gender, heterosexual HIV exposure, no viral load and LMIC. Diabetes monitoring was also decreased in those with viral failure. Conclusions Our findings highlight suboptimal monitoring of viral load, CKD and diabetes in PLHIV in Asia. There is a need for affordable and scalable monitoring options to improve the joint care for HIV and non-communicable diseases.

The use of holding regimens for people living with HIV (PLWH) without effective antiretroviral options can have effects on outcomes and future treatment options. We aimed to investigate the use of holding regimens for PLWH in Asian countries. Data from adults enrolled in routine HIV care in IeDEA Asia-Pacific cohorts were included. Individuals were considered to be on holding regimen if they had been on combination antiretroviral therapy for at least 6 months, had two confirmed viral loads (VL) ≥1000 copies/mL, and had remained on the same medications for at least 6 months. Survival time was analyzed using Fine and Gray’s competing risk regression. Factors associated with CD4 changes and VL 50 years compared to age 31–40 years (sub-hazard ratio [SHR] 3.29, 95% CI 1.45–7.43, p = 0.004), and VL ≥1000 copies/ml compared to VL

Missed clinic visits can lead to poorer treatment outcomes in HIV-infected patients. Suboptimal antiretroviral therapy (ART) adherence has been linked to subsequent missed visits. Knowing the determinants of missed visits in Asian patients will allow for appropriate counselling and intervention strategies to ensure continuous engagement in care. A missed visit was defined as having no assessments within six months. Repeated measures logistic regression was used to analyse factors associated with missed visits. A total of 7100 patients were included from 12 countries in Asia with 2676 (37.7%) having at least one missed visit. Patients with early suboptimal self-reported adherence95% were more likely to have a missed visit compared to those with adherence ≥95% (OR = 2.55, 95% CI(1.81-3.61)). Other factors associated with having a missed visit were homosexual (OR = 1.45, 95%CI(1.27-1.66)) and other modes of HIV exposure (OR = 1.48, 95%CI(1.27-1.74)) compared to heterosexual exposure; using PI-based (OR = 1.33, 95%CI(1.15-1.53) and other ART combinations (OR = 1.79, 95%CI(1.39-2.32)) compared to NRTI+NNRTI combinations; and being hepatitis C co-infected (OR = 1.27, 95%CI(1.06-1.52)). Patients aged30 years (31-40 years OR = 0.81, 95%CI(0.73-0.89); 41-50 years OR = 0.73, 95%CI(0.64-0.83); and50 years OR = 0.77, 95%CI(0.64-0.93)); female sex (OR = 0.81, 95%CI(0.72-0.90)); and being from upper middle (OR = 0.78, 95%CI(0.70-0.80)) or high-income countries (OR = 0.42, 95%CI(0.35-0.51)), were less likely to have missed visits. Almost 40% of our patients had a missed clinic visit. Early ART adherence was an indicator of subsequent clinic visits. Intensive counselling and adherence support should be provided at ART initiation in order to optimise long-term clinic attendance and maximise treatment outcomes.

Severe dengue is more prevalent in adults than in children. Our objectives were to determine the clinical presentations of dengue in adults and to identify predictive factors for severe dengue. A retrospective cohort study was performed in adults with dengue, as confirmed by a positive NS1 antigen test result. Patients were classified as with non-severe or severe dengue. A total of 357 patients were enrolled; 45.4% were men, with a median (interquartile range [IQR]) age of 27.9 (21.8-43.5) years. Of all patients, 28.3% had warning signs and 10.6% had severe dengue. Patients with severe dengue were significantly older (35.1 [26.2-50.6] vs. 26.7 [21.7-43.3] years, P = 0.010), immunocompromised (7.9% vs. 0.9%, P = 0.018), and had cough (29% vs. 16%, P = 0.046), hepatomegaly (10.5% vs. 3.1%, P = 0.050), impaired consciousness (5.3% vs. 0%, P = 0.011) or higher (IQR) alanine aminotransferase (ALT) level (151 [57-295] vs. 66 [37-114] U/L, P = 0.008). By multivariate analysis, having cough (odds ratio [OR], 8.07; 95% confidence interval [CI], 2.51-30.16, P = 0.001) and ALT>120 U/L (OR, 3.51; 95% CI, 1.11-11.14, P = 0.033) were predictors of severe dengue. Early recognition of risk variables may be important for healthcare providers to appropriately manage dengue patients.

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

Background We aimed to project the 10-year future incidence of cardiovascular disease (CVD) and model several intervention scenarios based on a multi-site Asian HIV-positive cohort. Methods Analyses were based on patients recruited to the TREAT Asia HIV Observational Database (TAHOD), consisting of 21 sites in 12 countries. Patients on triple antiretroviral therapy (ART) were included if they were alive, without previous CVD, and had data on CVD risk factors. Annual new CVD events for 2019–2028 were estimated with the D:A:D equation, accounting for age- and sex-adjusted mortality. Modelled intervention scenarios were treatment of high total cholesterol, low high-density lipoprotein cholesterol (HDL) or high blood pressure, abacavir or lopinavir substitution, and smoking cessation. Results Of 3,703 included patients, 69% were male, median age was 46 (IQR 40–53) years and median time since ART initiation was 9.8 years (IQR 7.5–14.1). Cohort incidence rates of CVD were projected to increase from 730 per 100,000 person-years (pys) in 2019 to 1,432 per 100,000 pys in 2028. In the modelled intervention scenarios, most events can be avoided by smoking cessation, abacavir substitution, lopinavir substitution, decreasing total cholesterol, treating high blood pressure and increasing HDL. Conclusions Our projections suggest a doubling of CVD incidence rates in Asian HIV-positive adults in our cohort. An increase in CVD can be expected in any ageing population, however, according to our models, this can be close to averted by interventions. Thus, there is an urgent need for risk screening and integration of HIV and CVD programmes to reduce the future CVD burden.

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.

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.

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.Patients initiating cART between 2006 and 2013 were included. TI was defined as stopping cART for1 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 P0.10 in univariable analyses were included in multivariable analyses, where P0.05 was considered statistically significant.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, interruptions30 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); and365 days HR = 9.10, 95% CI (4.27-19.38), all P0.001, compared to 0-14 days). Reasons for previous TI were not statistically significant (P = 0.158).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.

Many HIV-infected individuals do not enter health care until late in the infection course. Despite encouraging earlier testing, this situation has continued for several years. We investigated the prevalence of late presenters and factors associated with late presentation among HIV-infected patients in an Asian regional cohort. This cohort study included HIV-infected patients with their first positive HIV test during 2003–2012 and CD4 count and clinical status data within 3 months of that test. Factors associated with late presentation into care (CD4 count

ObjectivesWe extend the method of Significant Zero Crossings of Derivatives (SiZer) to address within-subject correlations of repeatedly collected longitudinal biomarker data and the computational aspects of the methodology when analyzing massive biomarker databases. SiZer is a powerful visualization tool for exploring structures in curves by mapping areas where the first derivative is increasing, decreasing or does not change (plateau) thus exploring changes and normalization of biomarkers in the presence of therapy.MethodsWe propose a penalized spline SiZer (PS-SiZer) which can be expressed as a linear mixed model of the longitudinal biomarker process to account for irregularly collected data and within-subject correlations. Through simulations we show how sensitive PS-SiZer is in detecting existing features in longitudinal data versus existing versions of SiZer. In a real-world data analysis PS-SiZer maps are used to map areas where the first derivative of weight change after antiretroviral therapy (ART) start is significantly increasing, decreasing or does not change, thus exploring the durability of weight increase after the start of therapy. We use weight data repeatedly collected from persons living with HIV initiating ART in five regions in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) worldwide collaboration and compare the durability of weight gain between ART regimens containing and not containing the drug stavudine (d4T), which has been associated with shorter durability of weight gain.ResultsThrough simulations we show that the PS-SiZer is more accurate in detecting relevant features in longitudinal data than existing SiZer variants such as the local linear smoother (LL) SiZer and the SiZer with smoothing splines (SS-SiZer). In the illustration we include data from 185,010 persons living with HIV who started ART with a d4T (53.1%) versus non-d4T (46.9%) containing regimen. The largest difference in durability of weight gain identified by the SiZer maps was observed in Southern Africa where weight gain in patients treated with d4T-containing regimens lasted 59.9 weeks compared to 133.8 weeks for those with non-d4T-containing regimens. In the other regions, persons receiving d4T-containing regimens experienced weight gains lasting 38-62 weeks versus 55-93 weeks in those receiving non-d4T-based regimens.DiscussionPS-SiZer, a SiZer variant, can handle irregularly collected longitudinal data and within-subject correlations and is sensitive in detecting even subtle features in biomarker curves.

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.

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.

Background Health care providers usually focus on index HIV-infected patients and seldom obtain information from their partners. We aimed to determine HIV-preventative measures among couples, the prevalence of HIV infection, and treatment outcomes of partners. Methods This cross-sectional study was conducted in two hospital settings, a university hospital in Bangkok and a general hospital in northeastern Thailand, from January 2011-October 2015. Factors associated with serodiscordant relationships were determined by logistic regression. Results A total of 393 couples were enrolled for analysis; 156 (39.7%) were serodiscordant. The median relationship duration of serodiscordant couples was shorter than that of seroconcordant couples (6.4 years vs 11.6 years, p < 0.001). Of 237 HIV-infected partners, 17.7% had AIDS-defining illness, the median nadir CD4 count (interquartile range) was 240 (96–427) cells/mm3, 83.5% received antiretroviral therapy (ART), 98.3% had adherence > 95%, 90.3% had undetectable HIV RNA, and 22.9% had a prior history of treatment failure. There was no significant difference in condom usage in the prior 30 days between serodiscordant and seroconcordant couples. Factors of index HIV-infected patients associated with serodiscordant relationships were younger age (odds ratio [OR] 1.04 per 5 years; 95% confidence interval [CI] 1.01–1.06), receiving care at the general hospital (OR 1.73; 95% CI 1.08–2.78), a shorter duration of relationship (OR 1.04 per year; 95% CI 1.01–1.07), a higher nadir CD4 count (OR 1.06 per 50 cells/mm3; 95% CI 1.1–1.13), and not receiving a protease inhibitor-based regimen (OR 2.04; 95% CI 1.06–3.96). Conclusions A high number of serodiscordant couples was determined. Partners’ information should be retrieved as a holistic approach. Interventions for minimizing HIV transmission within serodiscordant couples should be evaluated and implemented.

Summary Background Once daily regimens are preferred for HIV-1 treatment, to facilitate adherence and improve quality of life. We compared a new once daily formulation of raltegravir to the currently marketed twice daily formulation. Methods In this randomised, double-blind, parallel-group, phase 3, non-inferiority study, we enrolled participants aged 18 years or older with HIV-1 RNA of 1000 or more copies per mL and no previous antiretroviral treatment at 139 sites worldwide. We randomly assigned participants (2:1) via an interactive voice and web response system to raltegravir 1200 mg (two 600 mg tablets) orally once daily or raltegravir 400 mg (one tablet) orally twice daily, each with tenofovir disoproxil fumarate and emtricitabine orally once daily, for up to 96 weeks. A computer-generated allocation schedule stratified randomisation by screening HIV-1 RNA value and co-infection with hepatitis B or C. Participants, sponsor personnel, investigators, and study site personnel involved in the treatment or evaluation of the participants were unaware of the treatment group assignments. The primary endpoint was the proportion of participants with HIV-1 RNA less than 40 copies per mL at week 48 assessed with the US Food and Drug Administration Snapshot algorithm. Non-inferiority was concluded if the lower bound of the two-sided 95% CI was greater than −10%. We assessed efficacy and safety in all participants who received one dose or more of study treatment. This study is registered with ClinicalTrials.gov, number NCT02131233. Findings Between May 26, 2014, and Dec 5, 2014, 802 participants were enrolled and randomly assigned, 533 to once daily treatment and 269 to twice daily; 797 received study therapy, 531 once daily and 266 twice daily. At week 48, 472 (89%) of 531 once daily recipients and 235 (88%) of 266 twice daily recipients achieved HIV-1 RNA less than 40 copies per mL (treatment difference 0·5%, 95% CI −4·2 to 5·2). Drug-related adverse events occurred in 130 (24%) of 531 participants in the once daily group (one of which was serious; none led to treatment discontinuation) and 68 (26%) of 266 participants in the twice daily group (two of which were serious; two led to treatment discontinuation). The most common drug-related adverse events were nausea (39 [7%] vs 18 [7%]), headache (16 [3%] vs 12 [5%]), and dizziness (12 [2%] vs eight [3%]). No treatment-related deaths were reported. Interpretation A once daily raltegravir 1200 mg regimen was non-inferior compared with raltegravir 400 mg twice daily for initial treatment of HIV-1 infection. These results support the use of raltegravir 1200 mg once daily for first-line therapy. Funding Merck & Co, Inc.

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 30 kg/m2 (OR 2.4 vs. 350 cells/mm3 (OR 3.9 vs. 2000 cells/mm3 (OR 1.7 vs. 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

Background In the era of effective antiretroviral treatment (ART) CD4:CD8 ratio is proposed as a potential marker for HIV-positive (HIV+) patients at increased risk for non-AIDS comorbidities. The current study aims to compare CD4:CD8 ratio between Asian and Caucasian HIV+ patients. Methods HIV+ patients from the Australian HIV Observational Database (AHOD) and the TREAT Asia HIV Observational Database (TAHOD) meeting specific criteria were included. In these analyses Asian and Caucasian status were defined by cohort. Factors associated with a low CD4:CD8 ratio (cutoff 1) at 12 and 24 months post ART commencement were assessed using logistic regression. Results There were 591 patients from AHOD and 2,620 patients from TAHOD who met the inclusion criteria. TAHOD patients had a significantly ( P1 ( P=0.475). Conclusions We found a significantly lower CD4:CD8 ratio prior to commencing ART in TAHOD compared to AHOD even after adjusting for confounders. However, after adjustment, there was no significant difference between the cohorts in odds of achieving normal ratio. Baseline CD4+ and CD8+ counts seem to be the main driver for this difference between these two populations.

Background The overuse and misuse of carbapenems have contributed to the antibiotic resistance crisis. The role of oral fluoroquinolones as a switch therapy for the treatment of urinary tract infection from Escherichia coli (ESBL-EC) is limited. Objective To compare the clinical and bacteriological efficacy of sitafloxacin and ertapenem for non-bacteremic acute pyelonephritis caused by ESBL-EC. Methods A prospective randomized controlled trial of patients with acute pyelonephritis caused by ESBL-EC was performed as a pilot study. One of the carbapenems was initially given to the patients. After day 3, patients were randomized to receive either sitafloxacin or ertapenem. Results Thirty-six patients were enrolled: 19 (52.8%) in the sitafloxacin group and 17 (47.2%) in the ertapenem group. There was no statistically significant difference in baseline characteristics between the two groups except a lower proportion of previous urinary catheter insertion in the sitafloxacin group (15.8% vs. 52.9%, p = 0.018). Signs and symptoms at presentation were similar between the two groups except a higher proportion of patients with chills in the sitafloxacin group (68.4% vs. 29.4%, p = 0.019). At day 10, all but one patient in the ertapenem group had clinical cure. Microbiological eradication was comparable between the sitafloxacin and ertapenem groups (84.2% vs. 75%, p = 0.677). There were no significant adverse effects. Conclusions Treatment of non-bacteremic acute pyelonephritis caused by ESBL-EC with carbapenem followed by oral sitafloxacin is effective and well-tolerated. Sitafloxacin may be considered as an alternative choice of switch therapy in this clinical setting.

Clinical presentations of patients with 2009 H1N1 influenza are generally similar to those of patients with seasonal influenza. A cross-sectional study was conducted among adults at an outpatient clinic in a university hospital setting during the 2009 epidemic. Infections in all patients were confirmed by real-time reverse transcription-polymerase chain reaction. There were 269 patients with 2009 H1N1 influenza and 128 patients with seasonal influenza. Compared with patients with seasonal influenza, patients with 2009 H1N1 influenza were more likely to be aged

Objectives: To examine whether the lipid parameters are predicting factors for human immunodeficiency virus (HIV)–associated lipodystrophy. Methods: Whole-body fat compositions of HIV-positive patients receiving stavudine-containing antiretroviral regimens (n = 79) were determined. Lipodystrophy was defined as a ratio of trunk fat mass/lower limb fat mass greater than 2.28. Blood samples were analyzed for total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), small-dense LDL-C (sdLDL-C), apoAI, apoB, lipoprotein(a), and CD4 cell counts. Large-buoyant LDL-C (lbLDL-C) was calculated (LDL-C minus sdLDL-C). Results: Twenty-six patients were classified as having lipodystrophy. The mean values of triglycerides, HDL-C, sdLDL-C, apoB, TC/HDL-C, apolipoprotein (apo) B/apoAI, and sdLDL-C/lbLDL-C showed significant differences between patients with and without lipodystrophy (P < .02). Using logistic regression analysis, sdLDL-C/lbLDL-C was identified as a significant predictor of lipodystrophy (P < .001). At a ratio of 0.554, the odds ratio was 17.8 with a likelihood ratio of 5.5. Conclusions: The sdLDL-C/lbLDL-C ratio is an excellent marker for indicating lipodystrophy in HIV-infected patients.

Elevated CD8 counts with combination antiretroviral therapy (cART) initiation may be an early warning indicator for future treatment failure. Thus, we investigated whether elevated CD8 counts were associated with virological failure (VF) in the first 4 years of cART in Asian HIV-infected patients in a multicenter regional cohort. We included patients from the TREAT Asia HIV Observational Database (TAHOD). Patients were included in the analysis if they started cART between 1996 and 2013 with at least one CD8 measurement within 6 months prior to cART initiation and at least one CD8 and viral load (VL) measurement beyond 6 months after starting cART. We defined VF as VL ≥400 copies/mL after 6 months on cART. Elevated CD8 was defined as CD8 ≥1200 cells/μL. Time to VF was modeled using Cox regression analysis, stratified by site. In total, 2475 patients from 19 sites were included in this analysis, of whom 665 (27%) experienced VF in the first 4 years of cART. The overall rate of VF was 12.95 per 100 person-years. In the multivariate model, the most recent elevated CD8 was significantly associated with a greater hazard of VF (HR = 1.35, 95% CI 1.14–1.61; P = 0.001). However, the sensitivity analysis showed that time-lagged CD8 measured at least 6 months prior to our virological endpoint was not statistically significant (P = 0.420). This study indicates that the relationship between the most recent CD8 count and VF was possibly due to the CD8 cells reacting to the increase in VL rather than causing the VL increase itself. However, CD8 levels may be a useful indicator for VF in HIV-infected patients after starting cART.

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 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 50 vs. ≤30, hazard ratio [HR] 5.39, 95%CI 2.52-11.50, p

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. Keywords: syphilis; incidence; seroconversion; HIV; MSM. (Published: 21 October 2016) Citation: Ahn JY et al. Journal of the International AIDS Society 2016, 19 :20965 http://www.jiasociety.org/index.php/jias/article/view/20965 | http://dx.doi.org/10.7448/IAS.19.1.20965

Autoantibodies against interferon-γ are associated with severe disseminated opportunistic infection, but their importance and prevalence are unknown.We enrolled 203 persons from sites in Thailand and Taiwan in five groups: 52 patients with disseminated, rapidly or slowly growing, nontuberculous mycobacterial infection (group 1); 45 patients with another opportunistic infection, with or without nontuberculous mycobacterial infection (group 2); 9 patients with disseminated tuberculosis (group 3); 49 patients with pulmonary tuberculosis (group 4); and 48 healthy controls (group 5). Clinical histories were recorded, and blood specimens were obtained.Patients in groups 1 and 2 had CD4+ T-lymphocyte counts that were similar to those in patients in groups 4 and 5, and they were not infected with the human immunodeficiency virus (HIV). Washed cells obtained from patients in groups 1 and 2 had intact cytokine production and a response to cytokine stimulation. In contrast, plasma obtained from these patients inhibited the activity of interferon-γ in normal cells. High-titer anti-interferon-γ autoantibodies were detected in 81% of patients in group 1, 96% of patients in group 2, 11% of patients in group 3, 2% of patients in group 4, and 2% of controls (group 5). Forty other anticytokine autoantibodies were assayed. One patient with cryptococcal meningitis had autoantibodies only against granulocyte-macrophage colony-stimulating factor. No other anticytokine autoantibodies or genetic defects correlated with infections. There was no familial clustering.Neutralizing anti-interferon-γ autoantibodies were detected in 88% of Asian adults with multiple opportunistic infections and were associated with an adult-onset immunodeficiency akin to that of advanced HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research; ClinicalTrials.gov number, NCT00814827.).

Vitamin D plays role in bone health and the regulation of the immune system. A cross-sectional study of serum 25-hydroxyvitamin D (25[OH]D) levels was conducted among HIV-1-infected Thai patients to determine the prevalence and associated factors of low vitamin D levels (25[OH]D

In this prospective cohort study, we investigated the prevalence of Clostridium difficile-associated diarrhea (CDAD) in adult patients with nosocomial diarrhea by performing enzyme immunoassay (EIA) for detecting toxins A and B and polymerase chain reaction (PCR) for detecting the presence of the tcdB gene in stool samples. We determined the factors associated with CDAD, and the treatment outcome of CDAD from May 2010 to January 2011. A total of 175 stool samples were tested by EIA and PCR. In total, 26.9% patients tested positive for C. difficile: 12.6% by EIA and 24.0% by PCR. The kappa coefficient and total agreement of both the tests were 0.46 and 83.2%, respectively. Onset of diarrhea after antibiotic administration for 10 days or more (OR, 2.71; 95% CI, 1.14-6.44; P = 0.024) and leukocyte count >15,000 cells/mm(3) (OR, 3.12; 95% CI, 1.24-7.88; P = 0.016) were significantly associated with occurrence of CDAD. The non-response rate to CDAD treatment was 24.1%, and the all-cause mortality rate was 31.9% in the CDAD group as against 35.9% in the non-CDAD group (P = 0.721). In our study, the performance of direct PCR of stool samples for detecting tcdB was better, with the number of positive results for stool toxins A and B being twofold higher than that in the case of EIA. Patients who have diarrhea after receiving antibiotics for 10 days or more or those who have a leukocyte count of >15,000 cells/mm(3) should be investigated for CDAD.

Although hepatitis B serology screening has been recommended for HIV care, it has not been routinely performed. We aimed to assess compliance and timing of hepatitis B serology screening among HIV-infected patients in a resource-limited setting. A cross-sectional study was conducted in Thailand. Compliance, timing of hepatitis B serology screening, and factors associated with no HBsAg screening were determined. A total of 416 HIV-infected patients with 61% males were enrolled. Median (range) age at HIV diagnosis was 34 (16-75) years and 92% had heterosexual risk. Proportion of HBsAg screening and prevalence of positive HBsAg were 69.2% and 9.0%, respectively. There was no difference in the proportion of no HBsAg screening during the period 1990-2008 (p = 0.865). Proportion of anti-HBs and anti-HBc screening were 40.9% and 21.2%, respectively. HBsAg was screened before or on the day of anti-HIV testing in 9.1% and before antiretroviral therapy (ART) initiation in 27.2%. By Kaplan-Meier analysis, median time from anti-HIV testing to HBsAg screening was 55.9 (95% confidence interval [CI] 43.9, 68.3) months. By multivariate logistic regression, duration of HIV infection (odds ratio [OR] 1.14; 95% CI 1.07, 1.21), no anti-HBs screening (OR 1.65; 95% CI 1.4-2.63), and no anti-HCV screening (OR 2.60; 95% CI 1.62, 4.17) were associated with no HBsAg screening before ART initiation. In conclusion, compliance with hepatitis B serology screening was relatively low and late. Educational program regarding hepatitis B serology screening, identification of barriers, and interventions to eliminate these barriers in resource-limited settings are crucial to improve HIV care.

We read with interest the recent letter by van Griensven and colleagues published in the 1st April, 2014 edition of JAIDS.1 Using routinely collected, cross-sectional data from HIV-infected patients attending the Sihanouk Hospital Center of HOPE, Phnom Penh, Cambodia the authors generated a clinical prediction tool (CPT) for targeted creatinine testing during pre-antiretroviral therapy (ART) evaluation. Such a tool may prevent superfluous renal function assessment prior to initiating the nephrotoxic antiretroviral, tenofovir. This will become increasingly important in coming years given the World Health Organisation’s (WHO’s) recommendation of tenofovir in first-line ART 2, 3 and expanding global use of tenofovir.4-7 Details on the generation of the CPT can be found in van Griensven et al 1 and elsewhere.8-11 The primary outcome was kidney dysfunction (KD) at pre-ART evaluation, defined as an estimated creatinine clearance 50% (sensitivity 90.8%, specificity 52.9% with cutoff score at ≥1). A cutoff score of ≥2 for the primary CPT also performed well in the TAHOD cohort (sensitivity 85.1%, specificity 59.3%) and was the pick of the CPTs in van Griensven’s validation cohort (sensitivity 91.5%, specificity 54.7%). Nevertheless, since the aim of the CPT is to avert unnecessary creatinine testing, the primary CPT, which requires a blood test result (haemoglobin), may not be entirely logical. The alternate CPT only needs basic patient data and a medical history. With a cutoff score of ≥2, it performed reasonably well in our independent validation. Sensitivity was 86.5% and specificity was 56.0%, which translates to 54.1% of patients avoiding creatinine testing during their pre-ART evaluation and 13.5% of patients with KD being considered fit to initiate tenofovir. We believe this may be a clinically acceptable tool, however future investigation will need to confirm its cost-effectiveness. Serum creatinine testing is not particularly expensive in Asia (approximately $US3 per test at one TAHOD centre in Thailand) whilst the cost of managing a patient with chronic renal failure may be substantial. Using data from a large, multicentre cohort of HIV-infected patients in Asia, we have provided supportive evidence for a CPT that could limit unnecessary renal function testing prior to tenofovir initiation. Further validation and cost-effectiveness analysis is required and will need to consider the savings achievable with this tool as tenofovir use expands. Optimising resources is of the utmost importance to the sustained global scale-up of ART.

BACKGROUND Kidney transplant (KT) recipients in dengue-endemic areas are at risk of exposure. We investigated the epidemiology and outcomes from dengue in KT recipients at our transplant center and conducted a literature review. MATERIALS AND METHODS We conducted a 20-year retrospective study of KT recipients who were diagnosed with laboratory-confirmed dengue from January 1997 to September 2017 according to the 2009 World Health Organization (WHO) classification. We analyzed clinical characteristics and treatment outcomes. RESULTS There were 13 (0.7%) dengue cases among 1917 KT recipients with a median age of 39 years (interquartile ranges [IQR], 22-46); 54% were males. Cases occurred with a median onset of 24 months (IQR, 6-122) after KT. Dengue was diagnosed via dengue NS1 antigen (85%), IgM antibodies (38.5%), or RT-PCR (15.4%). Patients were classified as having dengue without warning sign (30.8%), with warning sign (53.8%), or severe dengue (15.4%). All patients resolved without complications, except one had hemophagocytic lymphohistiocytosis. Ten (76.9%) patients experienced eGFR reduction with a median of 13.7 mL/min/1.73 m2 (IQR, 8.3-20.5); eight (80%) had a full allograft function recovery. CONCLUSIONS Dengue in KT recipients in endemic areas is uncommon. Although a transient decline in allograft function can occur, the overall clinical and allograft outcomes seem to be favorable.

Objectives: We aimed at determining the incidence and factors for tenofovir disoproxil fumarate (TDF)- associated renal function decline among Thai HIV-infected patients. Methods: Retrospective and prospective cohort studies were conducted. We enrolled HIV-infected adults who had initiated TDF. Renal function decline was defined by a decrease of 25% in glomerular filtration rate (GFR) from the baseline. Factors associated with the renal function decline were determined. Results: A total of 405 patients with a median (interquartile range, IQR) body weight of 56.5 (50.5-65.0) kg were enrolled. All but four (99%) were antiretroviral treatment-experience patients. A median (IQR) duration of receiving TDF was 16 (8-21) months. Of these, 78 (19.3%) patients had a 25% decrease in GFR with the incidence rate of 16.2 per 100 person- years. By Kaplan-Meier survival analysis, median time to a 25% decrease in GFR was 28 [95% confidence interval (CI) 25.2-30.8] months. By multiple logistic regression, lower body weight [odds ratio (OR) 1.15 per 5 kg, 95% CI 1.00-1.33], lower body mass index (BMI) (OR 2.26 per 1 kg/m2, 95% CI 1.74-2.94), baseline GFR (OR 1.62 per 10 ml/min/1.73m2, 95% CI 1.39-1.88), protease inhibitor (OR 2.12, 95% CI 1.15-3.92), and nephrotoxic drug (OR 3.16, 95% CI 1.44-6.98) were statistically significant factors associated with a 25% decrease in GFR. Conclusions: The study revealed high incidence of TDF-associated renal function decline among patients with low-body weight and BMI. Additional risk factors were baseline GFR, receiving protease inhibitor, and nephrotoxic drugs. Close monitoring of renal function is warranted among patients with these risk factors.

Summary Skin rash associated with nevirapine (NVP) is common and efavirenz (EFV) is often used as a substitute. We aimed to determine the predicting factors for unsuccessful switching from NVP to EFV. A retrospective cohort study was conducted in HIV-infected patients who developed rash after taking NVP. There were 109 patients with a mean standard deviation (SD) age of 36.6 (7.4) years and 45% were males. Median (interquartile range) CD4 cell count and HIV RNA at the time of NVP initiation were 163 (50–273) cells/mm3 and 4.6 (1.7–5.4) log copies/mL, respectively. Twenty (18.3%) patients subsequently developed EFV-associated rash. By logistic regression, history of drug allergy apart from NVP (odds ratio [OR] 11.42) and CD4 cell count 3 (OR 6.14) were significant predicting factors for EFV-associated rash. Two predicting factors for unsuccessful switching from NVP to EFV were found. Patients who have these factors need to have a close follow-up if EFV is substituted.

Cryptococcosis is a life-threatening fungal infection among human immunodeficiency virus (HIV)-positive patients and also occurs frequently in HIV-negative patients. A retrospective cohort study was conducted among patients with cryptococcosis. Clinical manifestations, laboratory findings, treatment, and outcomes for 149 HIV-positive and 29 HIV-negative patients were compared. Neurological involvement occurred more frequently in HIV-positive patients (91.9 versus 20.7%, P0.001), whereas pulmonary involvement was more frequently observed in HIV-negative patients (34.5 versus 2.7%, P0.001). Ninety percent of HIV-positive patients and 74% of HIV-negative patients had positive serum cryptococcal antigen (P=0.119). HIV-positive patients were more likely to have a cerebrospinal fluid (CSF) preparation that is positive for India ink staining (81 versus 50%, P0.001) and a CSF cryptococcal antigen titer ofor =1:1,024 (61.1 versus 16.7%, P=0.038). Most of the patients in both groups received amphotericin B as the primary therapy. Cryptococcosis-related mortality was high and did not differ between the two groups (22.2 versus 34.5%, P=0.162). Kaplan-Meier analysis revealed that HIV-positive patients had a higher relapse rate (P=0.011), especially among those lacking antiretroviral therapy. In conclusion, clinical presentation of cryptococcosis among HIV-negative patients varies and differs from that of HIV-positive patients. Awareness and prompt management are crucial for establishing a diagnosis and initiating proper treatment.

Nevirapine (NVP) is commonly used as a component of first-line antiretroviral therapy in resource-limited countries. We aimed to determine the risk factors for NVP-associated rash among HIV-infected patients who were initiated NVP at low CD4 cell counts in a resource-limited setting. A case-control study was conducted in HIV-infected patients who developed rash after taking NVP (case) and those who did not have rash (control). A total of 357 patients with a mean (SD) age of 36.4 (7.5) years and 52.1% male were included in the study. Mean body weight (SD) was 55.5 (10.5) kg. Of all, 179 (49.0%) patients had a history of AIDS-defining illness and 57 (16.0%) patients had history of drug allergy. Median (IQR) CD4 cell counts at the time of NVP initiation was 95 (31-226) cells/mm(3). There were 115 patients in case group and 242 patients in control group. In case group, 43.0%, 54.4%, and 2.6% of patients developed grade 2, 3, and 4 of rash, respectively. Median time to develop rash was 12 (95%CI, 10.5-13.5) days. By logistic regression, history of drug allergy (OR, 3.41; 95%CI, 1.79-6.52), body weight (OR, 1.22 per each 5 kg decrement; 95%CI, 1.08-1.38), CD4 cells counts (OR, 1.20 per each 50 cells/mm(3) increment; 95%CI, 1.12-1.30), and AIDS-defining illness (OR, 0.42; 95%CI, 0.25-0.70) were significantly associated with rash. In resource-limited settings where patients were initiated NVP at low CD4 cell counts, history of drug allergy, lower body weight, and higher CD4 cell count are the risk factors for NVP-associated rash. Initiation of NVP in patients with these risks needs closed monitoring.