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.

"I Have Actually not Lost any Adolescent Since I Started Engaging Them one on one:" Training Satisfaction and Subsequent Practice among Health Providers Participating in a Standardized Patient Actor Training to Improve Adolescent Engagement in HIV Care.

BACKGROUND: Poor health care worker (HCW) interactions with adolescents negatively influence engagement in HIV care. We assessed the impact of standardized patient actor training on HCW competence in providing adolescent HIV care in Kenya. METHODS: We conducted pre-post cross-sectional surveys and qualitative exit interviews during a stepped wedge randomized trial. Cross-sectional surveys assessed self-rated competence in providing adolescent services before and after the intervention, and training satisfaction. In-depth interviews with a subset of HCW participants one year after training. RESULTS: Over 90% of HCWs reported satisfaction with the training and there was significant improvement in self-rated competence scores (mean = 4.63 [highest possible score of 5] post-training vs 3.86 pre-training, p < 0.001). One-year following training, HCWs reported using skills in patient-centered communication and structuring an adolescent clinical encounter. CONCLUSIONS: This SP training intervention improved self-rated competence and showed sustained perceived impact on HCW skills in adolescent HIV service provision one year later.

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.

Differences in virologic and immunologic response to antiretroviral therapy among HIV-1-infected infants and children.

BACKGROUND: Virologic and immunologic responses to antiretroviral treatment (ART) in infants may differ from older children due to immunologic, clinical, or epidemiologic characteristics. METHODS: Longitudinal ART responses were modeled and compared in HIV-infected infants and children enrolled in cohorts in Nairobi, Kenya. Participants were enrolled soon after HIV diagnosis, started on ART, and followed for 2 years. Viral load decline was compared between infant and child cohorts using a nonlinear mixed effects model and CD4% reconstitution using a linear mixed effects model. RESULTS: Among 121 infants, median age at ART was 3.9 months; among 124 children, median age was 4.8 years. At baseline, viral load was higher among infants than children (6.47 vs. 5.91 log10 copies/ml, P < 0.001). Infants were less likely than children to suppress viral load to less than 250 copies/ml following 6 months of ART (32% infants vs. 73% children, P < 0.0001). CD4% was higher at baseline in infants than children (19 vs. 7.3%, P < 0.001). Older children had more rapid CD4% reconstitution than infants, but failed to catch up to infant CD4%. CONCLUSION: Despite substantially higher CD4% at ART initiation, viral suppression was significantly slower among infants than older children. New strategies are needed to optimize infant outcomes on ART.