Growth and CD4 patterns of adolescents living with perinatally acquired HIV worldwide, a CIPHER cohort collaboration analysis.

INTRODUCTION: Adolescents living with HIV are subject to multiple co-morbidities, including growth retardation and immunodeficiency. We describe growth and CD4 evolution during adolescence using data from the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) global project. METHODS: Data were collected between 1994 and 2015 from 11 CIPHER networks worldwide. Adolescents with perinatally acquired HIV infection (APH) who initiated antiretroviral therapy (ART) before age 10 years, with at least one height or CD4 count measurement while aged 10-17 years, were included. Growth was measured using height-for-age Z-scores (HAZ, stunting if <-2 SD, WHO growth charts). Linear mixed-effects models were used to study the evolution of each outcome between ages 10 and 17. For growth, sex-specific models with fractional polynomials were used to model non-linear relationships for age at ART initiation, HAZ at age 10 and time, defined as current age from 10 to 17 years of age. RESULTS: A total of 20,939 and 19,557 APH were included for the growth and CD4 analyses, respectively. Half were females, two-thirds lived in East and Southern Africa, and median age at ART initiation ranged from <3 years in North America and Europe to >7 years in sub-Saharan African regions. At age 10, stunting ranged from 6% in North America and Europe to 39% in the Asia-Pacific; 19% overall had CD4 counts <500 cells/mm3 . Across adolescence, higher HAZ was observed in females and among those in high-income countries. APH with stunting at age 10 and those with late ART initiation (after age 5) had the largest HAZ gains during adolescence, but these gains were insufficient to catch-up with non-stunted, early ART-treated adolescents. From age 10 to 16 years, mean CD4 counts declined from 768 to 607 cells/mm3 . This decline was observed across all regions, in males and females. CONCLUSIONS: Growth patterns during adolescence differed substantially by sex and region, while CD4 patterns were similar, with an observed CD4 decline that needs further investigation. Early diagnosis and timely initiation of treatment in early childhood to prevent growth retardation and immunodeficiency are critical to improving APH growth and CD4 outcomes by the time they reach adulthood.

Comparison of knowledge of HIV status and treatment coverage between non-citizens and citizens: Botswana Combination Prevention Project (BCPP).

INTRODUCTION: Non-citizens often face barriers to HIV care and treatment. Quantifying knowledge of positive HIV status and antiretroviral therapy (ART) coverage among non-citizens in a high HIV-prevalence country like Botswana that is close to achieving UNAIDS "90-90-90" targets may expose important gaps in achieving universal HIV testing and treatment. METHODS: The Botswana Combination Prevention Project (BCPP) is a pair-matched cluster-randomized trial evaluating the impact of prevention interventions on HIV incidence in 30 rural or peri-urban communities. Community case finding and HIV testing were conducted in home and mobile venues in 15 intervention communities from October 2013-September 2017. In this secondary analysis, we compared HIV positivity, knowledge of positive HIV-status, and ART status among all citizens and non-citizens assessed at intake in the intervention communities. RESULTS: HIV status was assessed in 57,556 residents in the intervention communities; 4% (n = 2,463) were non-citizens. Five communities accounted for 81% of the total non-citizens assessed. A lower proportion of non-citizens were HIV-positive (15%; n = 369) compared to citizens (21%; n = 11,416) [p = 0.026]; however, a larger proportion of non-citizens did not know their HIV-positive status prior to BCPP testing (75%) as compared to citizens (15%) [p = 0.003]. Among residents with knowledge of their HIV-positive status before BCPP, 79% of the non-citizens (72/91) were on ART compared to 86% (8,267/9,652) of citizens (p = 0.137). CONCLUSIONS: Although non-citizens were less likely to know their HIV-positive status compared to citizens, there were no differences in treatment uptake among non-citizens and citizens who knew their status. Designing interventions for non-citizens that provide HIV testing and treatment services commensurate to that of citizens as well as targeting communities with the largest number of non-citizens may help close a meaningful gap in the HIV care cascade and ensure ethical treatment for all HIV-positive persons. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01965470 (Botswana Combination Prevention Project).

Effect of co-trimoxazole on mortality in HIV-exposed but uninfected children in Botswana (the Mpepu Study): a double-blind, randomised, placebo-controlled trial.

BACKGROUND: Co-trimoxazole prophylaxis reduces mortality among HIV-infected children, but efficacy in HIV-exposed but uninfected (HEU) children in a non-malarial, low-breastfeeding setting with a low risk of mother-to-child transmission of HIV is unclear. METHODS: HEU children in Botswana were randomly assigned to receive co-trimoxazole (100 mg/20 mg once daily until age 6 months and 200 mg/40 mg once daily thereafter) or placebo from age 14-34 days to age 15 months. Mothers chose whether to breastfeed or formula feed their children. Breastfed children were randomly assigned to breastfeeding for 6 months (Botswana guidelines) or 12 months (WHO guidelines). The primary outcome, analysed by a modified intention-to-treat approach, was cumulative child mortality from treatment assignment to age 18 months. We also assessed HIV-free survival by duration of breastfeeding. This trial is registered with ClinicalTrials.gov, number NCT01229761. FINDINGS: From June 7, 2011, to April 2, 2015, 2848 HEU children were randomly assigned to receive co-trimoxazole (n=1423) or placebo (n=1425). The data and safety monitoring board stopped the study early because of a low likelihood of benefit with co-trimoxazole. Only 153 (5%) children were lost to follow-up (76 in the co-trimoxazole group and 77 in the placebo group), and 2053 (72%) received treatment continuously to age 15 months, death, or study closure. Mortality after the start of study treatment was similar in the two study groups: 30 children died in the co-trimoxazole group, compared with 34 in the placebo group (estimated mortality at 18 months 2·4% vs 2·6%; difference -0·2%, 95% CI -1·5 to 1·0, p=0·70). We saw no difference in hospital admissions between groups (12·5% in the co-trimoxazole group vs 17·4% in the placebo group, p=0·19) or grade 3-4 clinical adverse events (16·5% vs 18·4%, p=0·18). Grade 3-4 anaemia did not differ between groups (8·1% vs 8·3%, p=0·93), but grade 3-4 neutropenia was more frequent in the co-trimoxazole group than in the placebo group (8·1% vs 5·8%, p=0·03). More co-trimoxazole resistance in commensal Escherichia coli isolated from stool samples was seen in children aged 3 or 6 months in the co-trimoxazole group than in the placebo group (p=0·001 and p=0·01, respectively). 572 (20%) children were breastfed. HIV infection and mortality did not differ significantly by duration of breastfeeding (3·9% for 6 months vs 1·9% for 12 months, p=0·21). INTERPRETATION: Prophylactic co-trimoxazole seems to offer no survival benefit among HEU children in non-malarial, low-breastfeeding areas with a low risk of mother-to-child transmission of HIV. FUNDING: US National Institutes of Health.