Newly diagnosed HIV positive children: a unique index case to improve HIV diagnosis and linkage to care of parents.

Newly diagnosed HIV positive children may be unique index cases to identify undiagnosed parents. Data was used from the Pediatric Urgent Start of HAART (NCT02063880) trial, which enrolled hospitalized, ART-naïve, HIV positive children ages 0-12 years in Kenya. Exact McNemar's tests were used to compare proportions of mothers and fathers tested for HIV, linked to care, and on ART at baseline and 6 months. This analysis included 87 newly diagnosed children with HIV who completed 6 months of follow-up. Among 83 children with living mothers, there were improvements in maternal linkage to care and treatment comparing baseline to 6 months (36% vs. 78%; p < 0.0001 and 22% vs. 52%; p < 0.0001). Among 80 children with living fathers, there were increases from baseline to 6 months in the number of fathers who knew the child's HIV status (34% vs. 78%; p < 0.0001), fathers ever tested for HIV (43% vs. 65%; p < 0.0001), fathers ever tested HIV positive (21% vs. 43%; p < 0.0001), fathers ever linked to care (15% vs. 35%; p < 0.0001), and fathers ever initiated on ART (11% vs. 23%; p = 0.0039). Newly diagnosed HIV positive children can be important index cases to identify parents with undiagnosed HIV or poor engagement in care.

Urgent versus post-stabilisation antiretroviral treatment in hospitalised HIV-infected children in Kenya (PUSH): a randomised controlled trial.

BACKGROUND: Urgent antiretroviral therapy (ART) among hospitalised HIV-infected children might accelerate recovery or worsen outcomes associated with immune reconstitution. We aimed to compare urgent versus post-stabilisation ART among hospitalised HIV-infected children in Kenya. METHODS: In this unmasked randomised controlled trial, we randomly assigned (1:1) HIV-infected, ART-naive children aged 0-12 years who were eligible for treatment to receive ART within 48 h (urgent group) or in 7-14 days (post-stabilisation group) at four hospitals in Kenya (two in Nairobi and two in western Kenya). We excluded children with suspected or confirmed CNS infection. A statistician not involved in study procedures did block randomisation with variable block sizes generated using STATA version 12. We followed children for 6 months for primary outcomes: mortality, drug toxicity, and immune reconstitution inflammatory syndrome (IRIS). We did all analyses in a modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02063880. FINDINGS: We began enrolment on April 24, 2013, and completed follow-up on Nov 17, 2015. We enrolled 191 (76%) of 250 hospitalised HIV-infected children. Of these, 183 children were randomly assigned: 90 to urgent ART and 93 to post-stabilisation ART. 181 (99%) of 183 children were included in the modified intention-to-treat analysis. Median age was 1·9 years (IQR 0·8-4·8). Baseline sociodemographic, clinical, and virological characteristics did not differ between groups except median CD4 cell percentage, which was lower in the urgent group (13% [IQR 9-18] vs 17% [IQR 9-24]; p=0·052). Of 181 admission diagnoses, 118 (65%) were pneumonia, 58 (32%) malnutrition, and 27 (15%) suspected tuberculosis. Median time to ART was 1 day (IQR 1-1) in the urgent group and 8 days (IQR 7-11) in the post-stabilisation group. Overall, mortality risk at 6 months was 61 per 100 person-years. Mortality risk did not differ by group (70 per 100 person-years in the urgent group vs 54 per 100 person-years in the post-stabilisation group; hazard ratio [HR] 1·26, 95% CI 0·67-2·37) p=0.47, even after adjusting for baseline CD4 cell percentage (adjusted HR 1·30, 95% CI 0·69-2·45; p=0·41). The incidence of IRIS, and drug toxicity was not significantly different between trial arms. There were no differences between treatment groups in the proportion of grade 3 or 4 adverse events (34 [38%] of 90 children in the urgent group vs 40 [44%] of 91 children in the post-stabilisation group; p=0·40) or the proportion of any change in ART regimen (five [7%] vs six [8%]; p=0·79). We discontinued randomisation at interim review when the futility boundary was crossed. INTERPRETATION: Early mortality risk was extremely high among hospitalised HIV-infected children. Urgent ART did not improve survival. FUNDING: National Institute of Child Health and Human Development, National Institutes of Health, USA.

Hospitalized Children Reveal Health Systems Gaps in the Mother-Child HIV Care Cascade in Kenya.

To identify missed opportunities in HIV prevention, diagnosis, and linkage to care, we enrolled 183 hospitalized, HIV-infected, ART-naïve Kenyan children 0-12 years from four hospitals in Nairobi and Kisumu, and reviewed prevention of mother-to-child transmission of HIV (PMTCT), hospitalization, and HIV testing history. Median age was 1.8 years (IQR = 0.8, 4.5). Most mothers received HIV testing during pregnancy (77%). Among mothers tested, 60% and 40% reported HIV-negative and positive results, respectively; 33% of HIV-diagnosed mothers did not receive PMTCT antiretrovirals. First missed opportunities for pediatric diagnosis and linkage were due to failure to test mothers (23.1%), maternal HIV acquisition following initial negative test (45.7%), no early infant diagnosis (EID) or provider-initiated testing (PITC) (12.7%), late breastfeeding transmission (8.7%), failure to collect child HIV test results (1.2%), and no linkage to care following HIV diagnosis (8.7%). Among previously hospitalized children, 38% never received an HIV test. Strengthening initial and repeat maternal HIV testing and PITC are key interventions to prevent, detect, and treat pediatric HIV infections.

Emergence of Community-Acquired, Multidrug-Resistant Invasive Nontyphoidal Salmonella Disease in Rural Western Kenya, 2009-2013.

BACKGROUND: Nontyphoidal Salmonella (NTS), mainly serotypes Typhimurium and Enteritidis, cause invasive infections with high mortality in children in sub-Saharan Africa. Multidrug resistance is common, and resistance to third-generation cephalosporins has emerged. METHODS: We reviewed clinical features, outcomes, and antimicrobial resistance patterns in invasive NTS infections among children aged 6 weeks to 5 years participating in malaria vaccine studies in an area of high malaria and human immunodeficiency virus (HIV) transmission in Siaya, western Kenya. Blood culture was performed in hospitalized children and pediatric outpatients with prolonged fever. RESULTS: From July 2009 to December 2013, 1696 children aged 6 weeks to 17 months were enrolled into vaccine trials and followed for up to 53 months. We obtained 1692 blood cultures from 847 children. Of 134 bacterial pathogens isolated, 102 (76.1%) were Salmonella serogroup B or D. Invasive NTS disease occurred in 94 (5.5%) children, with an incidence of 1870, 4134, and 6510 episodes per 100 000 person-years overall, in infants, and in HIV-infected children, respectively. Malaria infection within the past 2 weeks occurred in 18.8% (3/16) of invasive NTS episodes in HIV-infected and 66.2% (53/80) in HIV-uninfected children. Case fatality rate was 3.1%. Salmonella group B resistant to ceftriaxone emerged in 2009 and 2010 (6.2% [2/32 isolates]), rising to 56.5% (13/23 isolates) in 2012 and 2013. CONCLUSIONS: Incidence of invasive NTS disease was high in this area of high malaria and HIV transmission, especially in HIV-infected children. Rapidly emerging resistance against ceftriaxone requires urgent reevaluation of antibiotic recommendations and primary prevention of exposure to Salmonella.