Effect of the Timing of Antiretroviral Treatment Initiation on Outcomes in Children Living With Human Immunodeficiency Virus Admitted With Severe Acute Malnutrition.

BACKGROUND: Delays in early infant diagnosis and antiretroviral treatment (ART) initiation in developing countries frequently result in malnutrition at initial presentation with associated higher mortality and delayed immune recovery. The optimal timing of ART initiation is yet to be established. METHODS: Eighty-two children admitted with HIV and severe acute malnutrition (SAM) between July 2012 and December 2015 were enrolled. Patients were randomized to initiate ART within 14 days from admission (early arm) or delay ART initiation until nutritional recovery and >14 days after admission (delayed arm). All patients received a standardized treatment and feeding protocol and were followed to 48 weeks. RESULTS: The mean age of the patients at baseline was 23.3 months (standard deviation [SD], 27.9; range, 1.6-129 months). The mean time from admission to ART initiation was 5.6 days (SD, 4.4) in the early arm and 23 days (SD, 5.8) in the delayed arm (P < .001). There was no significant difference in mortality (P = .62), virologic response (P = .53), and anthropometric response (P = .57) between the 2 groups at 48 weeks. However, the rates of change in CD4, viral load, weight for age z score, and height for age z score occurred earlier and favored the delayed arm at early time points but were not significant at 24 and 48 months. CONCLUSIONS: Despite initial improved responses in the delayed arm, lack of difference in outcome at 48 weeks supports a pragmatic approach with earlier ART initiation in children living with HIV admitted with SAM.In this randomised controlled study of ART initiation in children admitted with HIV and severe acute malnutrition (SAM), despite initial improved responses in the delayed arm, lack of difference in outcome at 48 weeks supports a pragmatic approach with earlier ART initiation in children living with HIV admitted with SAM. CLINICAL TRIALS REGISTRATION: PACTR 21609001751384.

Bacterial infections in HIV-infected children admitted with severe acute malnutrition in Durban, South Africa.

BACKGROUND: Bacterial infections in HIV-infected children admitted with severe acute malnutrition (SAM) contribute to higher mortality and poorer outcomes. This study describes the spectrum of bacterial infections in antiretroviral treatment (ART)-naïve, HIV-infected children admitted with SAM. METHODS: Between July 2012 and February 2015, 82 children were prospectively enrolled in the King Edward VIII Hospital, Durban. Specimens obtained on and during admission for microbiological evaluation, if clinically indicated, included blood, urine (obtained by catheterisation or suprapubic aspiration), induced sputum and cerebrospinal fluid. All positive bacterial cultures between admission and 30 days after enrollment were documented and characterised into samples taken either within 2 days of admission (infections on admission) or within 2-30 days of admission (hospital-acquired infections, HAIs). RESULTS: On admission, 67% of patients had abnormal white blood cell counts (WBCC) (>12 or <4 × 109/L) and 70% had elevated CRP; 65% were classified as severely immunosuppressed according to the WHO immunological classification.1 A pathogen was isolated on the admission blood culture in four patients (6%) and in 27% of urine specimens. HAIs were predominately Gram-negative (39/43), and 39.5% were extended-spectrum ß-lactamase-positive. Mortality was not significantly associated with isolation of a bacterial pathogen. CONCLUSIONS: Routine pre-hospital administration of antibiotics as per the Integrated Management of Childhood Illness (IMCI) guidelines may be responsible for the low rates of positive admission blood cultures. HAIs with drug-resistant Gram-negative organisms are an area of concern and strategies to improve the prevention of HAIs in this vulnerable population are urgently needed.

A strategy for developing future academic leaders for South Africa in a resource-constrained environment.

A key challenge in addressing the shortage of health care workers in resource-constrained environments is ensuring that there is optimal academic capacity for their training. South Africa's University of KwaZulu-Natal has placed academic and research capacity building at the heart of its program with the Medical Education Partnership Initiative in a program called ENhancing Training and REsearch capacity and Expertise (ENTREE). The program aims to increase the quantity, quality, and retention of health care graduates. It is premised on the basis that research capacity development will lead to an increase in teachers who will be essential to improving the quality and quantity of health care workers needed to meet South Africa's health challenges. This is being achieved through four components of the program: (1) infusion of the undergraduate program with research modules; (2) attraction of academically talented students in the middle of their undergraduate program into a parallel track that has research capacity as its major thrust; (3) attraction of qualified health care personnel into a supported PhD program; and (4) providing strong research ethics training and mentorship. A significant proportion of the program is being executed in rural training sites, to increase the probability that trainees will return to the sites as mentors.