Realizing the Promise of Dolutegravir in Effectively Treating Children and Adolescents Living With HIV in Real-world Settings in 6 Countries in Eastern and Southern Africa.

BACKGROUND: Despite encouraging results from clinical trials and in high-income countries, large-scale data on the effectiveness and safety of dolutegravir (DTG) in children and adolescents living with HIV (CALHIV) are lacking in low- and middle-income countries (LMICs). METHODS: Retrospective analysis was performed among CALHIV 0-19 years old and weighing greater than or equal to 20 kg who received DTG from 2017 to 2020 at sites in Botswana, Eswatini, Lesotho, Malawi, Tanzania and Uganda to determine effectiveness, safety and predictors of viral load suppression (VLS) among CALHIV using DTG, including through single drug substitutions (SDS). RESULTS: Among 9419 CALHIV using DTG, 7898 had a documented post-DTG VL, and VLS post-DTG was 93.4% (7378/7898). VLS for antiretroviral therapy (ART) initiations was 92.4% (246/263), and VLS was maintained for the ART-experienced [92.9% (7026/7560) pre- vs. 93.5% (7071/7560) post-DTG; P = 0.14). Among previously unsuppressed, 79.8% (426/534) achieved VLS with DTG. Only 5 patients reported a Grade 3 or 4 adverse event (0.057 per 100 patient-years) requiring DTG discontinuation. History of protease inhibitor-based ART [odds ratio (OR) = 1.53; 95% confidence interval (CI): 1.16-2.03], care in Tanzania (OR = 5.45; 95% CI: 3.41-8.70), and being 15-19 years old (OR = 1.31; 95% CI: 1.03-1.65) were associated with gain of VLS post-DTG. Predictors of VLS on DTG included VLS before DTG (OR = 3.87; 95% CI: 3.03-4.95) and using the once-daily, single tab tenofovir-lamivudine-DTG regimen (OR = 1.78; 95% CI: 1.43-2.22). SDS maintained VLS [95.9% (2032/2120) pre- vs. 95.0% (2014/2120) post-SDS with DTG; P = 0.19], and 83.0% (73/88) of unsuppressed gained VLS using SDS with DTG. CONCLUSIONS: We found DTG to be highly effective and safe within our cohort of CALHIV in LMICs. These findings can empower clinicians to prescribe DTG confidently to eligible CALHIV.

Achieving Antiretroviral Therapy Uptake and Viral Suppression Among Children and Adolescents Living With HIV in the UNAIDS 90-90-90 Era Across Six Countries in Eastern and Southern Africa-Lessons From the BIPAI Network.

BACKGROUND: Although achievements have been made globally since the UNAIDS 90-90-90 targets were announced, paediatric data remain sparse. We describe achievements toward antiretroviral therapy (ART) uptake and viral load (VL) suppression, existing gaps, and potential best practices among children and adolescents living with HIV (CALHIV) across 6 Eastern and Southern African countries. SETTING: Baylor College of Medicine International Paediatric AIDS Initiative Network sites in Botswana, Eswatini, Lesotho, Malawi, Tanzania, and Uganda. METHODS: We performed retrospective data analysis among CALHIV ages 0-19 years between 2014 and 2019. RESULTS: A total of 25,370 CALHIV received care, 85.8% (21,773/25,370) received ART, 84.4% (18,376/21,773) had documented VL results, and 74.6% (13,715/18,376) had VL < 1000 cps/mL. By 2019, the pooled proportion of CALHIV receiving ART and having viral suppression increased to 99.8% [95% confidence interval (CI): 98.1 to 100.0] and 89.8% (95 CI: 88.2 to 91.5) respectively. Lower rates of viral suppression and higher lost to follow-up (LTFU) were seen in the 0-4-year and 15-19-year cohorts. CALHIV on ART not achieving viral suppression were younger, received care in Malawi or Mbeya, had a history of tuberculosis, lower rates of integrase-strand inhibitor-based ART, and were on ART for shorter durations. Best practices reported included adopting universal ART, ART optimization with protease inhibitor-based and/or dolutegravir-based regimens, peer-supported activities, child/adolescent friendly services, community-supported activities, and technology-driven quality improvement activities and digital solutions. CONCLUSIONS: High rates of CALHIV receiving ART and having viral suppression can be achieved in settings in Eastern and Southern Africa through using pediatric best practices. Increased efforts must be made to address LTFU and to support under-fives and adolescents.

BUTIMBA: Intensifying the Hunt for Child TB in Swaziland through Household Contact Tracing.

BACKGROUND: Limited data exists to inform contact tracing guidelines in children and HIV-affected populations. We evaluated the yield and additionality of household contact and source case investigations in Swaziland, a TB/HIV high-burden setting, while prioritizing identification of childhood TB. METHODS: In partnership with 7 local TB clinics, we implemented standardized contact tracing of index cases (IC) receiving TB treatment. Prioritizing child contacts and HIV-affected households, screening officers screened contacts for TB symptoms and to identify risk factors associated with TB. We ascertained factors moderating the yield of contact tracing and measured the impact of our program by additional notifications. RESULTS: From March 2013 to November 2015, 3,258 ICs (54% bacteriologically confirmed; 70% HIV-infected; 85% adults) were enrolled leading to evaluation of 12,175 contacts (median age 18 years, IQR 24-42; 45% children; 9% HIV-infected). Among contacts, 196 TB cases (56% bacteriologically confirmed) were diagnosed resulting in a program yield of 1.6% for all forms of TB. The number needed to screen (NNS) to identify a bacteriologically confirmed TB case or all forms TB case traced from a child IC <5 years was respectively 62% and 40% greater than the NNS for tracing from an adult IC. In year one, we demonstrated a 32% increase in detection of bacteriologically confirmed child TB. Contacts were more likely to have TB if <5 years (OR = 2.0), HIV-infected (OR = 4.9), reporting ≥1 TB symptoms (OR = 7.7), and sharing a bed (OR = 1.7) or home (OR = 1.4) with the IC. There was a 1.4 fold increased chance of detecting a TB case in households known to be HIV-affected. CONCLUSION: Contact tracing prioritizing children is not only feasible in a TB/HIV high-burden setting but contributes to overall case detection. Our findings support WHO guidelines prioritizing contact tracing among children and HIV-infected populations while highlighting potential to integrate TB and HIV case finding.