Clinical Outcomes in Children With Human Immunodeficiency Virus Treated for Nonsevere Tuberculosis in the SHINE Trial.

BACKGROUND: Children with human immunodeficiency virus (HIV, CWH) are at high risk of tuberculosis (TB) and face poor outcomes, despite antiretroviral therapy (ART). We evaluated outcomes in CWH and children not living with HIV treated for nonsevere TB in the SHINE trial. METHODS: SHINE was a randomized trial that enrolled children aged <16 years with smear-negative, nonsevere TB who were randomized to receive 4 versus 6 months of TB treatment and followed for 72 weeks. We assessed TB relapse/recurrence, mortality, hospitalizations, grade ≥3 adverse events by HIV status, and HIV virological suppression in CWH. RESULTS: Of 1204 children enrolled, 127 (11%) were CWH, of similar age (median, 3.6 years; interquartile range, 1.2, 10.3 versus 3.5 years; 1.5, 6.9; P = .07) but more underweight (weight-for-age z score, -2.3; (3.3, -0.8 versus -1.0; -1.8, -0.2; P < .01) and anemic (hemoglobin, 9.5 g/dL; 8.7, 10.9 versus 11.5 g/dL; 10.4, 12.3; P < .01) compared with children without HIV. A total of 68 (54%) CWH were ART-naive; baseline median CD4 count was 719 cells/mm3 (241-1134), and CD4% was 16% (10-26). CWH were more likely to be hospitalized (adjusted odds ratio, 2.4; 1.3-4.6) and to die (adjusted hazard ratio [aHR], 2.6; 95% confidence interval [CI], 1.2 to 5.8). HIV status, age <3 years (aHR, 6.3; 1.5, 27.3), malnutrition (aHR, 6.2; 2.4, 15.9), and hemoglobin <7 g/dL (aHR, 3.8; 1.3,11.5) independently predicted mortality. Among children with available viral load (VL), 45% and 61% CWH had VL <1000 copies/mL at weeks 24 and 48, respectively. There was no difference in the effect of randomized treatment duration (4 versus 6 months) on TB treatment outcomes by HIV status (P for interaction = 0.42). CONCLUSIONS: We found no evidence of a difference in TB outcomes between 4 and 6 months of treatment for CWH treated for nonsevere TB. Irrespective of TB treatment duration, CWH had higher rates of mortality and hospitalization than their counterparts without HIV. Clinical Trials Registration. ISRCTN63579542.

Factors associated with unfavourable treatment outcomes among persons with Pulmonary Tuberculosis: a multicentric prospective cohort study from India.

In this prospective cohort of 2,006 individuals with non-MDR tuberculosis in India, 18% had unfavorable treatment outcomes (4.7% treatment failure, 2.5% recurrent infection, 4.1% death, 6.8% loss to follow-up) over a median 12-month follow-up period. Age, male sex, low education, nutritional status, and alcohol use were predictors of unfavorable outcomes.

Resurgence of respiratory syncytial virus infection during COVID-19 pandemic in Pune, India.

INTRODUCTION: Respiratory Syncytial Virus (RSV) is a leading cause of acute lower respiratory infection in children worldwide. Understanding its prevalence, variations, and characteristics is vital, particularly in the context of the COVID-19 pandemic. OBJECTIVE: The study aimed to investigate the RSV positivity rate, subtype prevalence, age and gender distribution, symptomatology, and co-infection rates during pre-pandemic and pandemic periods. METHODS: We analyzed data from 15,381 patients tested for RSV between 2017 and 2023. RESULTS: Our analysis revealed a 7.2% average RSV positivity rate in the pre-pandemic period, with significant fluctuations during the pandemic (1.5% in 2020 to 32.0% in 2021). We observed variations in RSVA and RSVB detection rates. The 0-4 years' age group was consistently the most affected, with a slight male predominance. Fever and cough were common symptoms. Therapeutic interventions, particularly antiviral usage and ventilation requirements, decreased during the pandemic. We also identified variations in co-infection rates with other respiratory viruses. CONCLUSION: Our study offers critical insights into the impact of the COVID-19 pandemic on RSV prevalence, subtype distribution, patient characteristics, and clinical management. These findings underscore the need for ongoing surveillance and adaptive public health responses.

Over Investigation: An Ethical Debate.

Over investigations contribute to escalating health costs driven by multiple factors including physician decisions, patient requests, information overload, technological advances, marketing, hospital management policies, insurance requirements and defensive practices. The reconciliation between knowledge and clinical wisdom while dealing with uncertainties in medicine is the primary way forward through this ethical maze. A case scenario illustrates what pediatricians need to reflect upon while facing decisions on rational investigations to maximize beneficence while being aware of economics of healthcare delivery.

Pharmaceutical cost dynamics for the treatment of rifampicin-resistant tuberculosis in children and adolescents in South Africa, India, and the Philippines.

Rifampicin-resistant (RR) tuberculosis (TB) in children is a major global health concern but is often neglected in economics research. Accurate cost estimations across the spectrum of paediatric RR-TB treatment regimens are critical inputs for prioritisation and budgeting decisions, and an existing knowledge gap at local and international levels. This normative cost analysis was nested in a Phase I/II pharmacokinetics, safety, tolerability, and acceptability trial of TB medications in children in South Africa, the Philippines and India. It assessed the pharmaceutical costs of 36 childhood RR-TB regimens using combinations from 16 different medicines in 34 oral formulations (adult and child-friendly) in 11 weight bands in children <15 years of age. The analysis used local and Global Drug Facility pricing, and local and international guideline recommendations, including adaptions of BPaL and BPaLM regimens in adults. Costs varied significantly between regimen length, age/weight banding, severity of disease, presence of fluroquinolone resistance, and different country guideline recommendations. WHO recommended regimen costs ranged 12-fold: from US$232 per course (short regimen in non-severe disease) to US$2,761 (long regimen in severe, fluroquinolone-resistant disease). Regimen treating fluoroquinolone-resistant infection cost US$1,090 more than comparable WHO-recommended regimen. Providing child-friendly medicine formulations in <5-year-olds across all WHO-recommended regimens is expected to cost an additional $380 (range $212-$563) per child but is expected to have wider benefits including palatability, acceptability, adherence, tolerability, and dose accuracy. There were substantial differences in regimen affordability between countries when adjusted for purchasing power and domestic spending on health. Appropriate, effective, and affordable treatment options are an important component of the fight against childhood RR-TB. A comprehensive understanding of the cost and affordability dynamics of treatment options will enable national TB programs and global collaborations to make the best use of limited healthcare resources for the care of children with RR-TB.

Effects of preterm birth, maternal ART and breastfeeding on 24-month infant HIV-free survival in a randomized trial.

BACKGROUND: IMPAACT 1077BF/FF (PROMISE) compared the safety/efficacy of two HIV antiretroviral therapy (ART) regimens to zidovudine (ZDV) alone during pregnancy for HIV prevention. PROMISE found an increased risk of preterm delivery (<37 weeks) with antepartum triple ART (TDF/FTC/LPV+r or ZDV/3TC/LPV+r) compared with ZDV alone. We assessed the impact of preterm birth, breastfeeding, and antepartum ART regimen on 24-month infant survival. METHODS: We compared HIV-free and overall survival at 24 months for liveborn infants by gestational age, time-varying breastfeeding status, and antepartum ART arm at 14 sites in Africa and India. Kaplan-Meier survival probabilities and Cox proportional hazards ratios were estimated. RESULTS: Three thousand four hundred and eighty-two live-born infants [568 (16.3%) preterm and 2914 (83.7%) term] were included. Preterm birth was significantly associated with lower HIV-free survival [0.85; 95% confidence interval (CI) 0.82-0.88] and lower overall survival (0.89; 95% CI 0.86-0.91) versus term birth (0.96; 95% CI 0.95-0.96). Very preterm birth (<34 weeks) was associated with low HIV-free survival (0.65; 95% CI 0.54-0.73) and low overall survival (0.66; 95% CI 0.56-0.74). Risk of HIV infection or death at 24 months was higher with TDF-ART than ZDV-ART (adjusted hazard ratio 2.37; 95% CI 1.21-4.64). Breastfeeding initiated near birth decreased risk of infection or death at 24 months (adjusted hazard ratio 0.05; 95% CI 0.03-0.08) compared with not breastfeeding. CONCLUSION: Preterm birth and antepartum TDF-ART were associated with lower 24-month HIV-free survival compared with term birth and ZDV-ART. Any breastfeeding strongly promoted HIV-free survival, especially if initiated close to birth. Reducing preterm birth and promoting infant feeding with breastmilk among HIV/antiretroviral drug-exposed infants remain global health priorities.