BackgroundAmong children, early mortality following highly active antiretroviral therapy (HAART) remains high. It is important to define correlates of mortality in order to improve outcome.MethodsHIV-1-infected children aged 18 months-12 years were followed up at Kenyatta National Hospital, Nairobi after initiating NNRTI-based HAART. Cofactors for mortality were determined using multivariate Cox regression models.ResultsBetween August 2004 and November 2008, 149 children were initiated on HAART of whom 135 were followed for a total of 238 child-years (median 21 months) after HAART initiation. Baseline median CD4% was 6.8% and median HIV-1-RNA was 5.98-log10 copies/ml. Twenty children (13.4%) died at a median of 35 days post-HAART initiation. Mortality during the entire follow-up period was 8.4 deaths per 100 child-years (46 deaths/100 child-years in first 4 months and 1.0 deaths/100 child-years after 4 months post-HAART initiation). On univariate Cox regression, baseline hemoglobin (Hb) <9 g/dl, weight-for-height z-score (WHZ) < -2, and WHO clinical stage 4 were associated with increased risk of death (Hb <9 g/dl HR 3.00 [95% C.I. 1.21-7.39], p = 0.02, WHZ < -2 HR 3.41 [95% C.I. 1.28-9.08], p = 0.01, and WHO clinical stage 4, HR 3.08 [1.17-8.12], p = 0.02). On multivariate analysis Hb < 9 g/dl remained predictive of mortality after controlling for age, baseline CD4%, WHO clinical stage and weight-for-height z-score (HR 2.95 (95% C.I. 1.04-8.35) p = 0.04).ConclusionHigh early mortality was observed in this cohort of Kenyan children receiving HAART, and low baseline hemoglobin was an independent risk factor for death.

Good early clinical and virologic response to NNRTI-based HAART was observed in HIV-1-infected Kenyan children with advanced HIV-1 disease.

Background-Pediatric human immunodeficiency virus type 1 (HIV-1) infection follows a bimodal clinical course with rapid progression in 10 -45% of children before the age of 2 years and slower progression in the remainder. A prospective observational study was undertaken to determine predictors of mortality in HIV-1-infected African infants during the first 2 years of life.

Background We evaluated the prognostic utility of interferon-gamma release assays (IGRAs) for active tuberculosis (TB) and mortality in Kenyan HIV-1 infected women and their infants. Methods Prevalence and correlates of Mycobacterium tuberculosis-specific T-SPOT.TB IGRA positivity were determined during pregnancy in a historical cohort of HIV-1 infected women. Hazard ratios, adjusted for baseline maternal CD4 count (aHRCD4) were calculated for associations between IGRA positivity and risk of active TB and mortality over 2-year postpartum follow-up in women and their infants. Results Of 333 women tested, 52 (15.6%) had indeterminate IGRAs. Of the remaining 281 women, 120 (42.7%) had positive IGRAs, which were associated with a 4.5-fold increased risk of active TB [aHRCD4: 4.5; 95% confidence interval (CI): 1.1–18.0; p=0.03]. Among immunosuppresed women (CD4<250 cell/mm3), positive IGRAs were associated with increased risk of maternal mortality (aHRCD4: 3.5; 95% CI: 1.02–12.1; p=0.045), maternal active TB or mortality (aHRCD4: 5.2; 95% CI: 1.7–15.6; p=0.004) and infant active TB or mortality, overall (aHRCD4: 3.0; 95% CI: 1.0–8.9; p= 0.05) and in HIV-1 exposed uninfected infants (aHRCD4: 7.3; 95% CI: 1.6–33.5; p =0.01). Conclusions Positive IGRAs in HIV-1 infected pregnant women were associated with postpartum active TB and mortality in mothers and their infants.

Human immunodeficiency virus type 1 (HIV-1) infection results in different patterns

Background Breast-feeding by infants exposed to human immunodeficiency virus type 1 (HIV-1) provides an opportunity to assess the role played by repeated HIV-1 exposure in eliciting HIV-1–specific immunity and in defining whether immune responses correlate with protection from infection. Methods Breast-feeding infants born to HIV-1–seropositive women were assessed for HLA-selected HIV-1 peptide–specific cytotoxic T lymphocyte interferon (IFN)–γ responses by means of enzyme-linked immunospot (ELISpot) assays at 1, 3, 6, 9, and 12 months of age. Responses were deemed to be positive when they reached ⩾50 HIV-1–specific sfu/1 × 106 peripheral blood mononuclear cells (PBMCs) and were at least twice those of negative controls. Results A total of 807 ELISpot assays were performed for 217 infants who remained uninfected with HIV-1 at ∼12 months of age; 101 infants (47%) had at least 1 positive ELISpot result (median, 78–170 sfu/1 × 106 PBMCs). The prevalence and magnitude of responses increased with age (P = .01 and P = .007, respectively); the median log10 value for HIV-1–specific IFN-γ responses increased by 1.0 sfu/1 × 106 PBMCs/month (P < .001) between 1 and 12 months of age. Of 141 HIV-1–uninfected infants with 1-month ELISpot results, 10 (7%) acquired HIV-1 infection (0/16 with positive vs. 10/125 [8%] with negative ELISpot results; P = .6). Higher values for log10 HIV-1–specific spot-forming units at 1 month of age were associated with a decreased risk of HIV-1 infection, adjusted for maternal HIV-1 RNA level (adjusted hazard ratio, 0.09 [95% confidence interval, 0.01–0.72]). Conclusions Breast-feeding HIV-1–exposed uninfected infants frequently had HIV-1–specific IFN-γ responses. Greater early HIV-1–specific IFN-γ responses were associated with decreased HIV-1 acquisition.

Background: There is laboratory evidence of altered immune function in children with malaria. Bacterial infections have been documented to complicate severe forms of malaria. However, it remains unclear whether such infections are attributable to the malaria, other risk factors, or are coincidental. Objective: To determine the prevalence of bacteraemia and urinary tract infections (UTI) in febrile hospitalised children with and without malaria. Design: A cross-sectional survey. Setting: General paediatric wards, Kenyatta National Hospital, Nairobi. Subjects: Children aged between three months and 12 years admitted with an acute febrile illness, with no obvious focus of bacterial infection. Materials and Methods: Using a standardised questionnaire, information on sociodemography, symptomatology, and nutritional status was obtained. Malaria slides, blood and urine cultures were performed on each child. Results: Malaria parasitaemia was present in 158 (60%) of 264 children presenting with acute febrile illness with no obvious focus of bacterial infection. Bacteria were isolated from blood and/or urine of 62 (23%) of all enrolled children. Bacteraemia was prevalent among 11.4% of 158 children with malaria and among 13.2% of 106 without malaria. Gram-positive organisms comprised 28.1% of blood isolates, gram-negative 62.5%, and atypical bacteria 9.4%. UTI was prevalent among 13.3% of 158 children with malaria and 16.0% of 106 children without malaria. Gram-positive organisms comprised 18.4%, gram-negative 78.9%, and atypical bacteria 2.6% of the urine isolates. Presence of malaria parasitaemia was not associated with an increased risk of bacteraemia (OR 0.9, 95% CI [0.4-0.7], or UTI (OR 0.8 95% CI [0.4-1.6] in this study population. Conclusion: Among children hospitalised in Nairobi with fever and no obvious bacterial infective focus, there should be a high index of suspicion for malaria, followed by bacteraemia and UTI. Malaria parasitaemia does not appear to be associated with increased risk of bacterial co-infection.

Background. There is conflicting evidence regarding the effects of breast-feeding on maternal mortality from human immunodeficiency virus type 1 (HIV-1) infection, and little is known about the effects of breast-feeding on markers of HIV-1 disease progression.Methods. HIV-1-seropositive women were enrolled during pregnancy and received short-course zidovudine. HIV-1 RNA levels and CD4 cell counts were determined at baseline and at months 1, 3, 6, 12, 18, and 24 postpartum and were compared between breast-feeding and formula-feeding mothers.Results. Of 296 women, 98 formula fed and 198 breast-fed. At baseline, formula-feeding women had a higher education level and prevalence of HIV-1-related illness than did breast-feeding women; however, the groups did not differ with respect to CD4 cell counts and HIV-1 RNA levels. Between months 1 and 24 postpartum, CD4 cell counts decreased 3.9 cells/mL/month ( ), HIV-1 RNA levels increased 0.005 log 10 copies/mL/month P ! .001 ( ), and body mass index (BMI) decreased 0.03 kg/m 2 /month ( ). The rate of CD4 cell count decline P p .03 P ! .001 was higher in breast-feeding mothers (7.2 cells/mL/month) than in mothers who never breast-fed (4.0 cells/mL/ month) ( ). BMI decreased more rapidly in breast-feeding women ( ), whereas HIV-1 RNA levels P p .01 P p .04 and mortality did not differ significantly between breast-feeding and formula-feeding women.Conclusions. Breast-feeding was associated with significant decreases in CD4 cell counts and BMI. HIV-1 RNA levels and mortality were not increased, suggesting a limited adverse impact of breast-feeding in mothers receiving extended care for HIV-1 infection.