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.

Factors associated with antiretroviral therapy adherence among adolescents living with HIV in the era of isoniazid preventive therapy as part of HIV care.

High levels of adherence to antiretroviral therapy (ART) are essential to promoting viral suppression and consequential good treatment outcomes. Adolescents living with HIV (ALHIV) in sub-Saharan Africa are less adherent to ART compared to adults, leading to lower rates of viral suppression and immunological recovery. We conducted a mixed-method study utilizing a convergent parallel approach to explore factors associated with ART adherence among ALHIV in the era of isoniazid preventive therapy (IPT) as part of HIV care. The quantitative data were collected from patient records from the period between 1 February 2017 and 31 January 2018 (6 months before and after IPT introduction), while qualitative data was collected from purposively selected patients and healthcare workers by in-depth interviews through a pretested interview guide. A total of 385 patient records (age 10-19 years) were analyzed in the two time periods, while 16 ALHIV (age 10-19 years) and three healthcare workers directly involved in adolescent care were interviewed. Quantitative data utilized logistic regression to measure the strength of association between IPT addition and ART adherence, whereas, qualitative data were analyzed using a thematic analysis approach. The mean age of participants in the quantitative section was 14.3 years (SD 2.7) and 178 were females, while the median age for adolescents interviewed was 14 (IQR 12-17) and 8 were females. Overall, we found an interaction of factors that influenced ART adherence. Added pill burden, on its own, did not affect ART adherence. Commonly reported factors that led to poor adherence were lack of status disclosure within the family, school pressure, and inadequate support from guardians and parents. According to retrospective patient records, complex ART regimens also worsened adherence (p = 0.0462). ART regimen was independently associated with adherence (OR 2.11 95% CI 0.97-4.53). Being on ART for a longer duration, enrolment into teen clubs, clinical psychosocial support, and self-reinforcement techniques were suggested to improve ART adherence. The interplay of multiple factors leads to poor rates of adherence. The introduction of IPT to ART packages may not independently affect ART adherence. Readily available psychosocial services and the presence of peer and guardian support is critical to optimal ART adherence. There is a need for ART centers that provide HIV care to adolescents to consider integrating psychosocial and other youth-friendly services into day-to-day clinic operations.

Infection or drug toxicity? Acute ataxia and encephalopathy after uncomplicated falciparum malaria and efavirenz dose adjustment.

Acute ataxia in children is a rare clinical syndrome usually caused by an infectious, post-infectious, or toxin-related aetiology. Although infrequent, acute ataxia can be related to more common diseases and treatments in Southern African countries including side effects of efavirenz-based anti-retroviral therapy (ART) for HIV or the post-malaria neurologic syndrome (PMNS) after infection with falciparum malaria. We describe a case from Lilongwe, Malawi of a 16-year-old HIV-positive patient with viral load suppression who presented with acute ataxia, confusion, and diplopia. Although he was on efavirenz-based ART for many years, his dose was increased 6 weeks prior, and he was treated for uncomplicated falciparum malaria 5 weeks prior with resolution of symptoms. Studies including cerebrospinal fluid analyses were normal, and he had rapid improvement of symptoms following discontinuation of efavirenz-based ART. Several case series have described supratherapeutic levels of efavirenz leading to acute ataxia as well as the self-limiting PMNS after non-complicated falciparum malaria. Though rare, recognition of efavirenz and PMNS as causes of ataxia is important to inform prompt treatment for HIV patients with acute ataxia in Malawi and other similar settings.

An Analysis of the Last Clinical Encounter before Outpatient Mortality among Children with HIV Infection and Exposure in Lilongwe, Malawi.

BACKGROUND: Human immunodeficiency virus (HIV) contributes to nearly 20% of all deaths in children under five years of age in Malawi. Expanded coverage of antiretroviral therapy has allowed children to access treatment on an outpatient basis. Little is known about characteristics of the final outpatient encounter prior to mortality in the outpatient setting. METHODS: This retrospective cohort study assessed clinical factors associated with mortality among HIV-exposed infants and HIV-infected children less than 18 years of age at the Baylor College of Medicine Abbott Fund Children's Center of Excellence in Lilongwe, Malawi. We compared clinical indicators documented from the final outpatient encounter for patients who died in the outpatient setting versus those who were alive after their penultimate clinical encounter. RESULTS: Of the 8,546 patients who were attended to over a 10-year period at the Baylor Center of Excellence, 851 had died (10%). Of children who died, 392 (46%) were directly admitted to the hospital after their last clinical encounter and died as inpatients. Of the remaining 459 who died as outpatients after their last visit, 53.5% had a World Health Organization (WHO) stage IV condition at their last visit, and 25% had a WHO stage III condition. Multivariate regression analysis demonstrated that poor nutritional status, female gender, shorter time as a patient, more clinical encounters in the prior month, if last visit was an unscheduled sick visit, and if the patient had lost weight since their prior visit independently predicted increased mortality in the outpatient setting after the final clinical encounter. CONCLUSION: Clinical indicators may assist in identifying children with HIV who have increased risk of mortality in the outpatient setting. Recognizing these indicators may aid in identifying HIV-infected children who require a higher level of care or closer follow-up.