The global fight against HIV has made significant strides. Increased antiretroviral therapy (ART) coverage for pregnant women living with HIV has led to a dramatic decrease in perinatal infections (1). Children living with HIV (CLHIV) now have access to more convenient, once-daily dispersible formulations of highly effective medications (2). Despite these advancements, challenges remain. While the number of CLHIV is decreasing, the proportion receiving ART lags significantly behind adults (1). Tragically, children bear a disproportionate burden of deaths attributed to advanced HIV disease (AHD). Under the THRIVE project, Penta is conducting critical assessments to ensure that programs have evidence-backed solutions to address this challenge.
AHD in children presents a distinct picture compared to adults. Early diagnosis and prompt treatment initiation are critical to prevent AHD. However, the WHO recognizes the vulnerability of younger children, defining all those under five as having AHD regardless of traditional markers. Similarly, children above five with severe immune suppression (CD4 count <200 cells/mm3) or advanced clinical stage (WHO stage 3 or 4) are classified as having AHD (3). These definitions primarily refer to children who are newly diagnosed or have yet to initiate ART. However, it's crucial to recognize that children and adolescents who have experienced interruptions in ART and are re-engaging with care should also be assessed for AHD and offered appropriate care. This group is particularly vulnerable to developing advanced disease and requires careful monitoring and intervention.
The clinical manifestations of AHD also differ between children and adults. While cryptococcal meningitis plagues adults with AHD, it is uncommon in children under 10 (4). In low- and middle-income countries, morbidity and mortality in CLHIV with AHD are driven by infections like pneumonia, tuberculosis, and diarrheal diseases (5). Additionally, a concerning number exhibit developmental delays and HIV encephalopathy. Notably, around 30% of adolescents and CLHIV still present with severe immune suppression at diagnosis (6). This compromised immunity translates into high hospitalization mortality, even for those promptly initiated on ART (7). The post-discharge mortality rate is particularly worrying (8).
The WHO's 2020 technical brief on AHD in children provides a critical framework - "STOP AIDS". This strategy emphasizes early identification (screening), effective treatment (treat), ART optimization, and preventative measures (prevent) (1). Key interventions include screening for malnutrition and tuberculosis, treatment of common infections, and preventive measures against recurrent infections and vaccine-preventable diseases. For adolescents, screening and pre-emptive therapy for cryptococcal meningitis are crucial. Furthermore, access to CD4 testing remains vital for diagnosis, treatment decisions, and discontinuing unnecessary preventative interventions (9).
We must acknowledge the unique challenges CLHIV face with AHD. Implementing the STOP AIDS strategy along with ensuring universal access to ART is crucial. Continued research and development of child-tailored diagnostic tools and therapeutic approaches are vital to improve their long-term health outcomes.
Through this project, Penta is conducting critical assessments to address these gaps by generating operational evidence across three countries and identifying and overcoming barriers to implementation of the STOP AIDS package of care. Penta is also strengthening healthcare workforce capacity through training and tool development, including PentaTr@ining modules and simplified implementation guidance. In collaboration with CHAI, Afrocab, and other partners, Penta aims to reduce mortality among children and adults living with HIV by strengthening implementation of the STOP AIDS package of care in THRIVE focal countries and beyond, thereby improving access to essential prevention, screening, and treatment.
UNAIDS 2024 Global Report
Turkova A, White E, Mujuru H, et al. Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children N Engl J Med 2021;385:2531-2543
World Health Organization. WHO package of care for children and adolescents with advanced HIV disease: stop AIDS: technical brief. 2020
Zuma P, Ramsamy Y, Mlisana K, et al. Serum cryptococcal antigen testing in immunosuppressed HIV-positive children and adolescents. Pediatr Infect Dis J.2020;39(3):217–20
Ford N, Shubber Z, Meintjes G, et al. Causes of hospital admission among people living with HIV worldwide: a systematic review and meta-analysis. Lancet HIV. 2015;2(10):e438–44.
UNAIDS . UNAIDS Global AIDS Update — confronting inequalities — lessons for pandemic responses from 40 years of AIDS. 2021.
Njuguna IN, Cranmer LM, Otieno VO, , et al. Urgent versus post-stabilisation antiretroviral treatment in hospitalised HIV-infected children in Kenya (PUSH): a randomised controlled trial. Lancet HIV.2018;5(1):e12–22.
Bwakura-Dangarembizi M, Dumbura C, Amadi B, et al. Risk factors for postdischarge mortality following hospitalization for severe acute malnutrition in Zimbabwe and Zambia.
Frigati L, Gibb D, Harwell J, et al. The hard part we often forget: providing care to children and adolescents with advanced HIV disease. Journal of the International AIDS Society 2023, 26:e26041