Efficacy and safety of switching to bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed Asian adults living with HIV: A pooled analysis from three international phase III randomized trials.

OBJECTIVES: Data on switching to bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) in virologically suppressed Asian people living with HIV are limited. We performed a pooled analysis of virologically suppressed Asian participants from three international phase III trials to evaluate the efficacy and safety of switching to B/F/TAF. METHODS: Virologically suppressed people living with HIV were randomized to switch to B/F/TAF or to stay on baseline regimens. The primary endpoint was the proportion of participants with plasma HIV-1 RNA ≥50 copies/ml at week 48. We analysed the incidence of adverse events (AEs), laboratory abnormalities, and changes in relevant tolerability parameters through 48 weeks. RESULTS: Overall, 136 Asian participants were included. The proportions of participants with plasma HIV-1 RNA ≥50 copies/ml at week 48 were low in both arms (0% for B/F/TAF vs 1.4% for those who stayed on baseline regimens). Those who switched to B/F/TAF had virological suppression rates similar to those who stayed on baseline regimens (100% vs 95.9%, p = 0.2485), with no treatment-emergent resistance. Drug-related AEs occurred in three participants in each arm; none were serious. No participants discontinued the study drug because of AEs, and no deaths were observed. No significant differences were observed between the arms in the median changes in estimated glomerular filtration rate, body weight, and most lipid parameters. Switching from tenofovir disoproxil fumarate-containing regimens to B/F/TAF resulted in a significant decrease in tubular proteinuria compared with those who stayed on baseline regimens (p < 0.01). CONCLUSIONS: Virologically suppressed Asian people living with HIV who switched to B/F/TAF maintained 100% virological suppression at week 48, with no treatment-emergent drug resistance and safety profiles comparable to those seen in people who stayed on baseline regimens. CLINICAL TRIAL NUMBER: ClinicalTrials.gov (NCT02603120, NCT02652624, and NCT02603107).

BMI as a predictor of high fasting blood glucose among people living with HIV in the Asia-Pacific region.

BACKGROUND: Non-Asian body mass index (BMI) classifications are commonly used as a risk factor for high fasting blood glucose (FBG). We investigated the incidence and factors associated with high FBG among people living with HIV in the Asia-Pacific region, using a World Health Organization BMI classification specific to Asian populations. METHODS: This study included people living with HIV enrolled in a longitudinal cohort study from 2003 to 2019, receiving antiretroviral therapy (ART), and without prior tuberculosis. BMI at ART initiation was categorized using Asian BMI classifications: underweight (<18.5 kg/m2 ), normal (18.5-22.9 kg/m2 ), overweight (23-24.9 kg/m2 ), and obese (≥25 kg/m2 ). High FBG was defined as a single post-ART FBG measurement ≥126 mg/dL. Factors associated with high FBG were analyzed using Cox regression models stratified by site. RESULTS: A total of 3939 people living with HIV (63% male) were included. In total, 50% had a BMI in the normal weight range, 23% were underweight, 13% were overweight, and 14% were obese. Median age at ART initiation was 34 years (interquartile range 29-41). Overall, 8% had a high FBG, with an incidence rate of 1.14 per 100 person-years. Factors associated with an increased hazard of high FBG included being obese (≥25 kg/m2 ) compared with normal weight (hazard ratio [HR] = 1.79; 95% confidence interval [CI] 1.31-2.44; p < 0.001) and older age compared with those aged ≤30 years (31-40 years: HR = 1.47; 95% CI 1.08-2.01; 41-50 years: HR = 2.03; 95% CI 1.42-2.90; ≥51 years: HR = 3.19; 95% CI 2.17-4.69; p < 0.001). CONCLUSION: People living with HIV with BMI >25 kg/m2 were at increased risk of high FBG. This indicates that regular assessments should be performed in those with high BMI, irrespective of the classification used.

Effects of pitavastatin on atherosclerotic-associated inflammatory biomarkers in people living with HIV with dyslipidemia and receiving ritonavir-boosted atazanavir: a randomized, double-blind, crossover study.

BACKGROUND: Chronic inflammation has been described in people living with HIV (PLHIV) receiving antiretroviral therapy (ART) despite viral suppression. Inflammation associated non-communicable diseases, including atherosclerosis, are becoming recognized complication of HIV infection. We studied the effect of pitavastatin on atherosclerotic-associated inflammatory biomarkers in PLHIV receiving ART. METHODS: A randomized, double-blind, crossover study was conducted in HIV-infected persons with dyslipidemia and receiving atazanavir/ritonavir (ATV/r) to evaluate the effect of 2 mg/day pitavastatin treatment versus placebo. High-sensitivity CRP (hs-CRP), cytokines, and cellular markers in PLHIV receiving 12 weeks of pitavastatin or placebo were investigated. RESULTS: A total of 24 HIV-infected individuals with a median (interquartile range) age of 46 (41-54) years were recruited, and the median CD4 T cell count was 662 (559-827) cells/mm3. The median duration of ATV/r use was 36 (24-48) months. Significant change in levels of basic fibroblast growth factor (FGF) between pitavastatin treatment and placebo at week 12 from baseline was observed (27.1 vs. 20.5 pg/mL; p=0.023). However, there were no significant changes from baseline of hs-CRP and other plasma cytokine levels at week 12 of pitavastatin or placebo. Regarding cellular markers, percentages of HLA-DR+CD38-CD4+ T cells and PD1+CD4+ T cells significantly decreased from baseline in PLHIV receiving pitavastatin for 12 weeks, as compared to placebo (- 0.27 vs. 0.02%; p=0.049 and - 0.23 vs. 0.23%; p=0.022, respectively). CONCLUSIONS: Pitavastatin treatment increases basic FGF levels, and lowers HLA-DR+CD38-CD4+ T cells, and PD1+CD4+ T cells. Further study on the effects of pitavastatin on preventing cardiovascular diseases in PLHIV should be pursued.

SARS-CoV-2-specific humoral and cell-mediated immune responses after immunization with inactivated COVID-19 vaccine in kidney transplant recipients (CVIM 1 study).

Immunogenicity following inactivated SARS-CoV-2 vaccination among solid organ transplant recipients has not been assessed. Seventy-five patients (37 kidney transplant [KT] recipients and 38 healthy controls) received two doses, at 4-week intervals, of an inactivated whole-virus SARS-CoV-2 vaccine. SARS-CoV-2-specific humoral (HMI) and cell-mediated immunity (CMI) were measured before, 4 weeks post-first dose, and 2 weeks post-second dose. The median (IQR) age of KT recipients was 50 (42-54) years and 89% were receiving calcineurin inhibitors/mycophenolate/corticosteroid regimens. The median (IQR) time since transplant was 4.5 (2-9.5) years. Among 35 KT patients, the median (IQR) of anti-RBD IgG level measured by CLIA after vaccination was not different from baseline, but was significantly lower than in controls (2.4 [1.1-3.7] vs. 1742.0 [747.7-3783.0] AU/ml, p < .01) as well as percentages of neutralizing antibody inhibition measured by surrogate viral neutralization test (0 [0-0] vs. 71.2 [56.8-92.2]%, p < .01). However, the median (IQR) of SARS-CoV-2 mixed peptides-specific T cell responses measured by ELISpot was significantly increased compared with baseline (30 [4-120] vs. 12 [0-56] T cells/106  PBMCs, p = .02) and not different from the controls. Our findings revealed weak HMI but comparable CMI responses in fully vaccinated KT recipients receiving inactivated SARS-CoV-2 vaccination compared to immunocompetent individuals (Thai Clinical Trials Registry, TCTR20210226002).

An additional dose of viral vector COVID-19 vaccine and mRNA COVID-19 vaccine in kidney transplant recipients: A randomized controlled trial (CVIM 4 study).

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/106 peripheral blood mononuclear cells, p = .60). In conclusion, compared with an additional dose of viral vector COVID-19 vaccine, a dose of mRNA COVID-19 vaccine did not elicit significantly different responses in KT recipients, regarding either humoral or cell-mediated immunity. (TCTR20211102003).

Viral hepatitis and the cascade of care among people living with HIV in the Asia-Pacific.

BACKGROUND: Although the prevalence and mortality of hepatitis is high in the Asia-Pacific region, few studies are available on the diagnosis, treatment, and cure rates for viral hepatitis among people living with HIV in this area. This study aims to report the cascade of care (CoC) for hepatitis B (HBV) and C (HCV) among people living with HIV receiving combined antiretroviral therapy (ART). METHODS: Patients enrolled in the TREAT Asia HIV Observational Database Low Intensity Transfer (TAHOD-LITE) cohort, on ART, and with follow-up data from 2010 to 2019 were included. Patients were determined as positive for HCV or HBV co-infection if they ever tested positive for HCV antibody (anti-HCV) or HBV surface antigen (HBsAg), respectively. RESULTS: In total, 39% (8612/22 340) of the adult HIV cohort had undergone HBsAg testing, with 8% (672/8612) testing positive. HBV CoC demonstrated that 71% (474/672) of those with HBsAg positive results initiated treatment, 67% (318/474) of those on treatment had HBV DNA testing to evaluate treatment progression, and 18% (58/318) of those tested reached viral suppression. Of the cohort, 37% (8231/22 340) had anti-HCV testing, of whom 10% (779/8231) tested positive. The HCV CoC showed that 68% (526/779) of those with positive anti-HCV tests had HCV RNA tests, of whom 51% (267/526) had detectable HCV RNA. Among those with detectable HCV RNA, 65% (174/267) initiated HCV treatment. Of the 40% (69/174) who initiated HCV treatment, 90% (62/69) reached sustained virological response. CONCLUSION: Our findings identified less frequent testing in the healthcare system and limited access to treatment as gaps in the CoC for viral hepatitis. More routine HCV RNA and HBV DNA testing is required for patients with positive screening tests to identify those in need of treatment.

Weight changes, metabolic syndrome and all-cause mortality among Asian adults living with HIV.

OBJECTIVES: We investigated weight changes following antiretroviral therapy (ART) initiation, the development of metabolic syndrome (MetS) and its association with all-cause mortality among Asian adults living with HIV. METHODS: Participants enrolled in a regional Asian HIV-infected cohort with weight and height measurements at ART initiation were eligible for inclusion in the analysis. Factors associated with weight changes and incident MetS (according to the International Diabetic Federation (IDF) definition) were analysed using linear mixed models and Cox regression, respectively. Competing-risk regression models were used to investigate the association of MetS with all-cause mortality. RESULTS: Among 4931 people living with HIV (PLWH), 66% were male. At ART initiation, the median age was 34 [interquartile range (IQR) 29-41] years, and the median (IQR) weight and body mass index (BMI) were 55 (48-63) kg and 20.5 (18.4-22.9) kg/m2 , respectively. At 1, 2 and 3 years of ART, overall mean (± standard deviation) weight gain was 2.2 (±5.3), 3.0 (±6.2) and 3.7 (±6.5) kg, respectively. Participants with baseline CD4 count ≤ 200 cells/µL [weight difference (diff) = 2.2 kg; 95% confidence interval (CI) 1.9-2.5 kg] and baseline HIV RNA ≥ 100 000 HIV-1 RNA copies/mL (diff = 0.6 kg; 95% CI 0.2-1.0 kg), and those starting with integrase strand transfer inhibitor (INSTI)-based ART (diff = 2.1 kg; 95% CI 0.7-3.5 kg vs. nonnucleoside reverse transcriptase inhibitors) had greater weight gain. After exclusion of those with abnormal baseline levels of MetS components, 295/3503 had incident MetS [1.18 (95% CI 1.05-1.32)/100 person-years (PY)]. The mortality rate was 0.7 (95% CI 0.6-0.8)/100 PY. MetS was not significantly associated with all-cause mortality in the adjusted model (P = 0.236). CONCLUSIONS: Weight gain after ART initiation was significantly higher among those initiating ART with lower CD4 count, higher HIV RNA and an INSTI-based regimen after controlling for baseline BMI. Greater efforts to identify and manage MetS among PLWH are needed.

Factors associated with high alanine aminotransferase (ALT) and cirrhosis in people living with HIV on combination antiretroviral treatment (cART) in the Asia-Pacific.

Liver disease is a growing burden among people living with HIV (PLHIV) in resource-limited settings. As an indicator of liver disease, risk factors of high alanine aminotransferase (ALT) and cirrhosis were assessed among PLHIV in the TREAT Asia HIV Observational Database (TAHOD). Patients on combination antiretroviral therapy (cART) with a pre-cART ALT measurement and at least one follow-up ALT measurement were included. Factors associated with high ALT (ALT levels > 5 times its upper limit of normal) were analyzed using repeated measure logistic regression over a 10-year follow-up period. Liver cirrhosis was defined as having an AST to Platelet Ratio Index score > 1.5, fibrosis-4 score > 3.25, or a clinical diagnosis of cirrhosis. Cox regression analysis stratified by site was used to analyze factors associated with cirrhosis among those in follow-up after 2015. Of 5182 patients, 101 patients (1.9%) had high ALT levels with hepatitis C virus (HCV) antibody positive (odds ratio [OR]: 4.98, 95% confidence interval [CI]: 2.82-8.77, p < 0.001) and ever high alcohol consumption (OR: 2.33, 95% CI: 1.00-5.46, p = 0.050) as likely factors. Among 6318 PLHIV in the liver cirrhosis analysis, 151 (2%) developed cirrhosis (incidence rate = 0.82 per 100 person-years). Those HCV-antibody positive (hazard ratio [HR]: 5.54, 95% CI: 3.75-8.18, p < 0.001) and had high alcohol consumption (HR: 2.06, 95% CI: 1.23-3.45, p = 0.006) were associated with liver cirrhosis. HCV-antibody positive and high alcohol consumption are factors associated with high ALT. With raised ALT levels as a known factor associated with liver cirrhosis, greater efforts are required in managing ALT levels and reducing the risk of developing liver cirrhosis among those positive for HCV-antibody and those who consume alcohol.

Use of Favipiravir for the Treatment of Coronavirus Disease 2019 in the Setting of Hospitel.

Objective: In a setting with a limited capacity for hospitalization, "hospitels" have been developed by using hotels as extension healthcare facilities for patients with mild illness. This study examined the clinical evidence of patients with coronavirus disease 2019 (COVID-19) who were treated with favipiravir, the main medication for treating COVID-19, in the hospitel setting in Thailand. Methods: We retrospectively collected demographic and clinical information, medication treatment, and outcome data for all patients who received favipiravir for COVID-19 during admission to a hospitel from April 27, 2021, to July 2, 2021. Risk factors for adults who could not complete treatment in a hospitel and who required hospitel transfer were analyzed. Results: In total, 421 patients were included in the study. Most patients (94.5%) received favipiravir to treat COVID-19 pneumonia. Adjunctive corticosteroids were prescribed to 42.3% of patients. Concerning the treatment outcome, 83.6% of patients completed treatment at a hospitel, and only two deaths occurred. No serious adverse drug reactions were observed. On multivariate analysis, age (odds ratio (OR) = 1.06; 95% confidence interval (CI) = 1.02-1.10, P=0.002), dyspnea (OR = 2.84; 95% CI = 1.25-6.44, P=0.013), loss of taste (OR = 107.63; 95% CI = 1.24-9337.39, P=0.040), corticosteroid use (OR = 12.56; 95% CI = 3.65-43.18, P < 0.001), and an extended duration of favipiravir use (OR = 16.91; 95% CI = 7.29-39.24, P < 0.001) were associated with a higher risk of hospitel transfer. Conclusions: Low rates of hospitel transfer and mortality were observed in mild-to-moderate COVID-19 patients treated with favipiravir at hospitel. Caution might be required in elderly patients, patients with dyspnea or a loss of taste, and patients receiving a 10-day course of favipiravir or adjunctive corticosteroids because these patients might require further management in the hospitel.

Saliva sample pooling for the detection of SARS-CoV-2.

As the battle against coronavirus disease 2019 pandemic continues, an increase in workload and medical expenses have been a concern to the health care system worldwide. Developing a measure that helps to conserve the health care resource is, therefore, highly desirable, and the pooling of the specimens for testing is one of the attractive strategies. Recently, we showed that saliva could be a potential alternative specimen for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time polymerase chain reaction (RT-PCR). In the present study, we performed the pooling of saliva specimens for testing by SARS-CoV-2 RT-PCR. We showed that the saliva pool of either 5 or 10 samples, by allowing the detection of either gene in the pool at an increased cycle threshold cutoff value, further performing individual sample testing in the positive pools did not compromise the detection of SARS-CoV-2.

Infectious causes of acute meningitis among Thai adults in a university hospital.

INTRODUCTION: Knowing the epidemiology of acute meningitis may guide physicians to promptly administer appropriate empirical therapy, thereby minimizing morbidity and mortality. We aimed to determine the etiology, clinical manifestations, cerebrospinal fluid (CSF) findings, and outcomes of patients with acute meningitis. METHODS: We conducted a retrospective cohort study among a total 89 adult (age ≥15 years) patients with acute meningitis. RESULTS: Among them, 48 (53.9%) patients were men; the median age (interquartile range; IQR) was 49 (32.1-63.8) years. The most common coexisting conditions were HIV infection (30%), prednisolone therapy (16.9%), and diabetes mellitus (15.7%). Common clinical presentations were fever (74%), headache (70.8%), and confusion (31.5%). Causes of acute meningitis were Cryptococcus neoformans (37%), bacteria (31.5%), Mycobacterium tuberculosis (27%), and viruses (4.5%). In multivariate logistic regression, predicting factors of acute bacterial meningitis were higher white blood cells (WBCs) in a complete blood count [odds ratio (OR) 1.01 per increase of 100 cells/mm3; 95% confidence interval (CI) 1.00-1.02, p = 0.031], no HIV infection (OR 0.08; 95% CI 0.01-0.72, p = 0.023), and higher serum sodium (OR 1.13; 95% CI 1.01-0.23, p = 0.029). Overall, the median (IQR) duration of hospitalization was 23 (11-29) days. A total 26 (29%) patients had complications, such as septic shock, hydrocephalus, seizure, and brain edema. The in-hospital mortality rate was 7.9%. CONCLUSIONS: In this setting, the most common cause of acute meningitis in adults was cryptococcosis followed by tuberculosis. Awareness of local epidemiology and patients' risk factors are important to initiate appropriate antimicrobial therapy.

Microbial epidemiology and risk factors for relapse in gram-negative bacteria catheter-related bloodstream infection with a pilot prospective study in patients with catheter removal receiving short-duration of antibiotic therapy.

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 < 0.001). In phase 2, 11 patients with catheter removal were prospectively recruited to receive short-duration therapy. The number of patients with relapse receiving long- or short-duration therapy was 1 (3%) and 0 (0%), respectively (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.

Epidemiology and outcomes of dengue in kidney transplant recipients: A 20-year retrospective analysis and comparative literature review.

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.

Early suboptimal ART adherence was associated with missed clinical visits in HIV-infected patients in Asia.

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 adherence <95% 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 aged >30 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); and >50 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.

Changes in renal function with long-term exposure to antiretroviral therapy in HIV-infected adults in Asia.

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.

Prediction Model of Pre-treatment HIV RNA Levels in Naïve Thai HIV-infected Patients: Application for Resource-limited Settings.

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 pre-treatment 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.

Factors associated with pre-treatment HIV RNA: application for the use of abacavir and rilpivirine as the first-line regimen for HIV-infected patients in resource-limited settings.

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.

A randomized controlled trial of sitafloxacin vs. ertapenem as a switch therapy after treatment for acute pyelonephritis caused by extended-spectrum ß-lactamase-producing Escherichia coli: A pilot study.

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.

Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals.

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 vircoType(TM) HIV-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.