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: INTRODUCTION: Data on HIV treatment outcomes in people who inject drugs (PWID) in the Asia‐Pacific are sparse despite the high burden of drug use. We assessed immunological and virological responses, AIDS‐defining events and mortality among PWID receiving antiretroviral therapy (ART). METHODS: We investigated HIV treatment outcomes among people who acquired HIV via injecting drug use in the TREAT Asia HIV Observational Database (TAHOD) between January 2003 and March 2019. Trends in CD4 count and viral suppression (VS, HIV viral load RESULTS: Of 622 PWID from 12 countries in the Asia‐Pacific, 93% were male and the median age at ART initiation was 31 years (IQR, 28 to 34). The median pre‐ART CD4 count was 71 cells/µL. CD4 counts increased over time, with a mean difference of 401 (95% CI, 372 to 457) cells/µL at year‐10 (n = 78). Higher follow‐up HIV viral load and pre‐ART CD4 counts were associated with smaller increases in CD4 counts. Among 361 PWID with ≥1 viral load after six months on ART, proportions with VS were 82%, 88% and 93% at 2‐, 5‐ and 10‐years following ART initiation. There were 52 new AIDS‐defining events and 50 deaths during 3347 person‐years of follow‐up (PYS) (incidence 3.05/100 PYS, 95% CI, 2.51 to 3.70). Previous AIDS or TB diagnosis, lower current CD4 count and adherence CONCLUSIONS: Despite improved outcomes over time, our findings highlight the need for rapid ART initiation and adherence support among PWID within Asian settings., INTRODUCTION Globally, injecting drug use is a major public health concern leading to substantial health burden and transmission risk of blood‐borne infections from injecting equipment sharing behaviours. In a multi‐stage [...]

: Introduction: The clinical relevance of low‐level viraemia (LLV) and virological outcomes among children living with HIV (CLHIV) remains controversial. This study aimed to determine the impact of LLV on virological failure (VF) among Asian CLHIV on first‐line combination antiretroviral therapy (cART). Methods: CLHIV aged 14 days, or received treatment and care at sites with a pVL lower limit of detection >50 copies/mL were excluded. LLV was defined as a pVL 50 to 1000 copies/mL, and VF as a single pVL >1000 copies/mL. Baseline was the time of the second pVL < 50 copies/mL. Cox proportional hazards models were performed to assess the association between LLV and VF. Results: From January 2008 to September 2016, 508 CLHIV (55% female) were eligible for the study. At baseline, the median age was 9.6 (IQR: 7.0 to 12.3) years, cART duration was 1.4 (IQR: 1.3 to 1.8) years, 97% of CLHIV were on non‐nucleoside reverse transcriptase inhibitor‐based regimens, and the median CD4 was 25% (IQR: 20% to 30%). Over a median follow‐up time of 6.0 (IQR: 3.1 to 8.9) years from baseline, 86 CLHIV (17%) had ever experienced LLV, of whom 32 (37%) had multiple LLV episodes. Female sex, living in Malaysia (compared to Cambodia), having family members other than biological parents/grandparents as a primary caregiver, and baseline CD4 < 25% increased risk of LLV. Overall, 115 children (23%) developed VF, corresponding to a rate of 4.0 (95%CI: 3.4 to 4.9) per 100 person‐years of follow‐up (PYFU). VF was greater among children who had ever experienced LLV compared with those who maintained virological suppression throughout the study period (8.9 vs. 3.3 per 100 PYFU; p < 0.001). In multivariable analyses, ever experiencing LLV was associated with increased risk of subsequent VF (adjusted hazard ratio: 3.01; 95%CI: 1.97 to 4.60). Conclusions: LLV increased the risk of subsequent VF among Asian CLHIV who had previously been suppressed on first‐line cART. Adherence interventions and additional targeted pVL monitoring may be warranted among children with LLV to facilitate early detection of VF., INTRODUCTION HIV plasma viral load (pVL) is an important tool to monitor treatment response and assess medication adherence in people living with HIV. One of the primary aims of combination [...]

BACKGROUND: Neonates admitted to the neonatal intensive care unit (NICU) are at risk for healthcare-associated infections, including central line-associated bloodstream infections. We aimed to characterize the epidemiology of bloodstream infections among neonates with central venous catheters admitted to three Indian NICUs. METHODS: We conducted a prospective cohort study in three tertiary NICUs, from May 1, 2017 until July 31, 2019. All neonates admitted to the NICU were enrolled and followed until discharge, transfer, or death. Cases were defined as positive blood cultures in neonates with a central venous catheter in place for greater than 2 days or within 2 days of catheter removal. RESULTS: During the study period, 140 bloodstream infections were identified in 131 neonates with a central venous catheter. The bloodstream infection rate was 11.9 per 1000 central line-days. Gram-negative organisms predominated, with 38.6% of cases caused by Klebsiella spp. and 14.9% by Acinetobacter spp. Antimicrobial resistance was prevalent among Gram-negative isolates, with 86.9% resistant to third- or fourth-generation cephalosporins, 63.1% to aminoglycosides, 61.9% to fluoroquinolones, and 42.0% to carbapenems. Mortality and length of stay were greater in neonates with bloodstream infection than in neonates without bloodstream infection (unadjusted analysis, p < 0.001). CONCLUSIONS: We report a high bloodstream infection rate among neonates with central venous catheters admitted to three tertiary care NICUs in India. Action to improve infection prevention and control practices in the NICU is needed to reduce the morbidity and mortality associated with BSI in this high-risk population. [ABSTRACT FROM AUTHOR]

: Introduction: Cotrimoxazole (CTX) is recommended as prophylaxis against Pneumocystis jiroveci pneumonia, malaria and other serious bacterial infections in HIV‐infected patients. Despite its in vitro activity against Mycobacterium tuberculosis, the effects of CTX preventive therapy on tuberculosis (TB) remain unclear. Methods: Adults living with HIV enrolled in a regional observational cohort in Asia who had initiated combination antiretroviral therapy (cART) were included in the analysis. Factors associated with new TB diagnoses after cohort entry and survival after cART initiation were analysed using Cox regression, stratified by site. Results: A total of 7355 patients from 12 countries enrolled into the cohort between 2003 and 2016 were included in the study. There were 368 reported cases of TB after cohort entry with an incidence rate of 0.99 per 100 person‐years (/100 pys). Multivariate analyses adjusted for viral load (VL), CD4 count, body mass index (BMI) and cART duration showed that CTX reduced the hazard for new TB infection by 28% (HR 0.72, 95% CI l 0.56, 0.93). Mortality after cART initiation was 0.85/100 pys, with a median follow‐up time of 4.63 years. Predictors of survival included age, female sex, hepatitis C co‐infection, TB diagnosis, HIV VL, CD4 count and BMI. Conclusions: CTX was associated with a reduction in the hazard for new TB infection but did not impact survival in our Asian cohort. The potential preventive effect of CTX against TB during periods of severe immunosuppression should be further explored., Introduction Cotrimoxazole (CTX) has been recommended as prophylaxis against Pneumocystis jiroveci pneumonia (PJP), toxoplasmosis, malaria and other serious bacterial infections in adults with severe or advanced HIV clinical disease, with [...]

Objectives: India has the highest number of HIV‐infected adolescents in Asia, but little is known about their treatment outcomes. We assessed rates and factors associated with loss to follow‐up (LTFU) and mortality among Indian adolescents. Methods: The analysis included adolescents (10–19 years old) starting antiretroviral therapy (ART) between 2005 and 2014 at BJ Government Medical College, Pune, India. LTFU was defined as missing more than three consecutive monthly visits. The competing‐risks method was used to calculate subdistribution hazard ratios (SHRs) of predictors for LTFU, with death as the competing risk. Cox proportional hazard models were used to identify predictors of mortality. Results: Of 717 adolescents starting ART, 402 with complete data were included in the analysis. Of these, 61% were male and 80% were perinatally infected, and the median baseline CD4 count was 174 cells/μL. LTFU and mortality rates were 4.4 and 4.9/100‐person years, respectively. Cumulative LTFU incidence increased from 6% to 15% over 6 years. Age ≥ 15 years [adjusted SHR (aSHR) 2.44; 95% confidence interval (CI) 1.18–5.02] was a risk factor for LTFU. Cumulative mortality increased from 9.5% to 17.9% over 6 years. World Health Organization (WHO) stages III and IV [adjusted hazard ratio (aHR) 2.26; 95% CI: 1.14–4.48] and an increase in CD4 count by 100 cells/μL (aHR: 0.59; 95% CI: 0.43–0.83) were associated with mortality. Conclusions: A third of adolescents had been lost to follow‐up or died by follow‐up year 6. Older age was a risk factor for LTFU and advanced clinical disease for death. Strategies to improve retention counselling for older adolescents and closer clinical monitoring of all adolescents must be considered. [ABSTRACT FROM AUTHOR]

Background: Maternal human immunodeficiency virus (HIV) RNA load, CD4 cell count, breast-feeding, antiretroviral use, and malaria are well-established factors associated with mother-to-child transmission (MTCT) of HIV; the role of maternal tuberculosis (TB), however, has not been well established.Methods: The study population was 783 HIV-infected Indian mother-infant pair participants in randomized and ancillary HIV-infected cohorts of the Six Week Extended-Dose Nevirapine (SWEN) Study, a study comparing extended nevirapine versus single-dose nevirapine, to reduce MTCT of HIV among breast-fed infants. Using multivariable logistic regression, we assessed the impact of maternal TB occurring during pregnancy and through 12 months after delivery on risk of MTCT.Results: Of 783 mothers, 3 had prevalent TB and 30 had incident TB at 12 months after delivery. Of 33 mothers with TB, 10 (30%) transmitted HIV to their infants in comparison with 87 of 750 mothers without TB (12%; odds ratio [OR], 3.31; 95% confidence interval [CI], 1.53-7.29; P = .02). In multivariable analysis, maternal TB was associated with 2.51-fold (95% CI, 1.05-6.02; P = .04) increased odds of HIV transmission adjusting for maternal factors (viral load, CD4 cell count, and antiretroviral therapy) and infant factors (breast-feeding duration, infant nevirapine administration, gestational age, and birth weight) associated with MTCT of HIV.Conclusions: Maternal TB is associated with increased MTCT of HIV. Prevention of TB among HIV-infected mothers should be a high priority for communities with significant HIV/TB burden. [ABSTRACT FROM AUTHOR]

Background: Two thirds of children with tuberculosis have nonsevere disease, which may be treatable with a shorter regimen than the current 6-month regimen.Methods: We conducted an open-label, treatment-shortening, noninferiority trial involving children with nonsevere, symptomatic, presumably drug-susceptible, smear-negative tuberculosis in Uganda, Zambia, South Africa, and India. Children younger than 16 years of age were randomly assigned to 4 months (16 weeks) or 6 months (24 weeks) of standard first-line antituberculosis treatment with pediatric fixed-dose combinations as recommended by the World Health Organization. The primary efficacy outcome was unfavorable status (composite of treatment failure [extension, change, or restart of treatment or tuberculosis recurrence], loss to follow-up during treatment, or death) by 72 weeks, with the exclusion of participants who did not complete 4 months of treatment (modified intention-to-treat population). A noninferiority margin of 6 percentage points was used. The primary safety outcome was an adverse event of grade 3 or higher during treatment and up to 30 days after treatment.Results: From July 2016 through July 2018, a total of 1204 children underwent randomization (602 in each group). The median age of the participants was 3.5 years (range, 2 months to 15 years), 52% were male, 11% had human immunodeficiency virus infection, and 14% had bacteriologically confirmed tuberculosis. Retention by 72 weeks was 95%, and adherence to the assigned treatment was 94%. A total of 16 participants (3%) in the 4-month group had a primary-outcome event, as compared with 18 (3%) in the 6-month group (adjusted difference, -0.4 percentage points; 95% confidence interval, -2.2 to 1.5). The noninferiority of 4 months of treatment was consistent across the intention-to-treat, per-protocol, and key secondary analyses, including when the analysis was restricted to the 958 participants (80%) independently adjudicated to have tuberculosis at baseline. A total of 95 participants (8%) had an adverse event of grade 3 or higher, including 15 adverse drug reactions (11 hepatic events, all but 2 of which occurred within the first 8 weeks, when the treatments were the same in the two groups).Conclusions: Four months of antituberculosis treatment was noninferior to 6 months of treatment in children with drug-susceptible, nonsevere, smear-negative tuberculosis. (Funded by the U.K. Medical Research Council and others; SHINE ISRCTN number, ISRCTN63579542.). [ABSTRACT FROM AUTHOR]

Background: The safety, efficacy, and appropriate timing of isoniazid therapy to prevent tuberculosis in pregnant women with human immunodeficiency virus (HIV) infection who are receiving antiretroviral therapy are unknown.Methods: In this multicenter, double-blind, placebo-controlled, noninferiority trial, we randomly assigned pregnant women with HIV infection to receive isoniazid preventive therapy for 28 weeks, initiated either during pregnancy (immediate group) or at week 12 after delivery (deferred group). Mothers and infants were followed through week 48 after delivery. The primary outcome was a composite of treatment-related maternal adverse events of grade 3 or higher or permanent discontinuation of the trial regimen because of toxic effects. The noninferiority margin was an upper boundary of the 95% confidence interval for the between-group difference in the rate of the primary outcome of less than 5 events per 100 person-years.Results: A total of 956 women were enrolled. A primary outcome event occurred in 72 of 477 women (15.1%) in the immediate group and in 73 of 479 (15.2%) in the deferred group (incidence rate, 15.03 and 14.93 events per 100 person-years, respectively; rate difference, 0.10; 95% confidence interval [CI], -4.77 to 4.98, which met the criterion for noninferiority). Two women in the immediate group and 4 women in the deferred group died (incidence rate, 0.40 and 0.78 per 100 person-years, respectively; rate difference, -0.39; 95% CI, -1.33 to 0.56); all deaths occurred during the postpartum period, and 4 were from liver failure (2 of the women who died from liver failure had received isoniazid [1 in each group]). Tuberculosis developed in 6 women (3 in each group); the incidence rate was 0.60 per 100 person-years in the immediate group and 0.59 per 100 person-years in the deferred group (rate difference, 0.01; 95% CI, -0.94 to 0.96). There was a higher incidence in the immediate group than in the deferred group of an event included in the composite adverse pregnancy outcome (stillbirth or spontaneous abortion, low birth weight in an infant, preterm delivery, or congenital anomalies in an infant) (23.6% vs. 17.0%; difference, 6.7 percentage points; 95% CI, 0.8 to 11.9).Conclusions: The risks associated with initiation of isoniazid preventive therapy during pregnancy appeared to be greater than those associated with initiation of therapy during the postpartum period. (Funded by the National Institutes of Health; IMPAACT P1078 TB APPRISE ClinicalTrials.gov number, NCT01494038.). [ABSTRACT FROM AUTHOR]

Background: Acute febrile illness is one of the most common reasons for hospital admission in India. We sought to assess factors associated with distinct and similar presentation of malaria and dengue that create a diagnostic challenge for clinicians when rapid diagnostics are not available. Methods & Materials: Patients >12 years of age admitted to adult medicine wards at BJ Medical College - Sassoon General Hospital, in Pune, India with >1 day of fever were enrolled into a prospective cohort between July 2013 and September 2015. Enrollees underwent malaria rapid test (SD bioline) or smear and dengue early ELISA (PanBio), blood cultures and rapid tests for chikungunya and influenza. We assessed demographic, clinical, social, and meteorological data for univariate association with diagnoses of dengue and malaria separately. Factors that demonstrated univariate association were used to construct multivariate models to assess for independent association. Results: Of 786 adults and adolescents enrolled, 681 underwent dengue and malaria testing. Dengue was positive in 83 (12.2%), malaria in 61 (9.0%), both malaria and dengue in 2 (0.3%) patients. In a multivariate model shown in the figure, elevated humidity 14 days prior to hospital presentation was associated with both dengue (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.7- 3.3) and malaria (OR 1.4 (95% CI 1.03-1.94)). Farmers or laborers were more likely to have malaria (OR 2.9 (95% CI 1.5-5.6)) and patients with a child under age 5 at home were less likely to have malaria (OR 0.42 (95% CI 0.2-0.9)). Patients with low income had lower odds of dengue diagnosis OR 0.25 (0.1-0.6) and patients admitted after a higher environmental temperature 2 weeks prior to admission were more likely to be diagnosed with dengue (OR 1.7 (1.2-2.5)). Leukopenia, thrombocytopenia, and elevated hemoglobin were associated with dengue(Fig 1). Thrombocytopenia and low phosphorous were associated with malaria(Fig 2). Conclusion: Preceding hot and wet weather is associated with dengue and malaria diagnosis among patients admitted with acute febrile illness in Pune,India. Although the finding of thrombocytopenia is present in both patients with dengue and malaria, elevated hemoglobin and leukopenia were associated with dengue and low phosphorous was associated with malaria. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance is increasing worldwide, including in India. There is a concern that unfettered antibiotic use may be associated with increasing antimicrobial resistance. Surveillance for antimicrobial resistance may be accomplished by evaluating for stool colonization of drug resistant organisms. Methods & Materials: Patients >12 years of age admitted to adult medicine wards at BJ Medical College - Sassoon General Hospital, in Pune, India with >1 day of fever were enrolled into a prospective cohort between July 2013 and September 2015. A perianal swab sample was collected on the day of enrollment and on day 3-5 of hospitalization and stored at -80 °C pending processing. Samples were aspirated onto peptone broth impregnated with ceftriaxone and vancomycin, incubated, and then plated onto MacConkey and blood agar. Identification and drug susceptibility testing was performed on isolates using a Phoenix system (Becton Dickinson). Results: Perianal swabs were collected on 314 patients at the time of enrollment. Follow up swabs were collected on 181 patients - 158 on day 3, 22 on day 4, and 1 on day 5. There was growth of resistant gram negative rods (GNR) in 60 (19%) patients. In 9 (2.9%) of patients, there was growth of GNR resistant to imipenem. Seventeen patients who were not colonized with resistant GNR upon enrollment were colonized at the time of follow up. Inpatient use of cephalosporins was associated with acquisition of colonization with resistant GNR, odds ratio 3.68, 95% confidence interval 1.02-13.31. Conclusion: Perianal colonization with resistant gram negative rods is common among patients admitted to medicine wards in Pune, India. The association of acquisition of drug resistance during a brief hospitalization with prescription of cephalosporins highlights the need for improved antimicrobial stewardship. [ABSTRACT FROM AUTHOR]