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.

Impact of Shifts to Birth Testing on Early Infant Diagnosis Program Outcomes in KwaZulu-Natal, South Africa.

BACKGROUND: South African early infant diagnosis guidelines shifted to recommending an initial HIV nucleic acid-based test (NAT) test at birth in 2015. Prior to this, initial NAT was recommended at 6 weeks of age. Here we examine parameters of early infant diagnosis performance in KwaZulu-Natal before and after this change. METHODS: Data on all HIV diagnostic NAT conducted for the province between January 2013 and April 2016 were assembled and analyzed. Laboratory barcodes allowed identification of repeat tests on the same child. We evaluated coverage, positivity rates, age at testing and frequency of repeat tests across birth cohorts. RESULTS: In birth cohorts 2013 and 2014, 62.1% and 61.8%, respectively, of tests <16 weeks were done in children who were 6-8 weeks of age. In birth cohort 2015, 41.3% of tests <16 weeks were done earlier at <2 weeks of age. The percentage of children with a positive result who had at least 1 follow-up test increased from 11.5% and 13.1% in birth cohorts 2013 and 2014, respectively, to 24.8% in 2015. The percentage of infants with an initial nonpositive result who received at least 1 follow-up test did not appreciably change from 15.0% and 14.4% in 2013 and 2014, respectively, to 14.7% in 2015. CONCLUSIONS: Birth testing allows for earlier identification of HIV-infected infants who need urgent antiretroviral treatment initiation. Although follow-up testing rates may be underestimated in this data source, repeat testing rates remained low. More effort is needed to ensure infants tested at birth continue to be engaged in care and undergo follow-up testing.

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.

Vaccine Oka varicella-zoster virus genotypes are monomorphic in single vesicles and polymorphic in respiratory tract secretions.

We previously found that, after immunization with vaccine Oka varicella-zoster virus, virus obtained from a single vesicle were monomorphic, and virus obtained from different individuals were heterogeneous. Here we show that virus obtained from the lungs of a patient were a mixture of vaccine Oka variants. We hypothesize that complications after immunization are unlikely to be caused by expansion of a single, biologically more virulent clone of virus that either pre-exists in the vaccine or develops after random mutation of different clones. We hypothesize that some clones are more trophic than others for skin.