Survival of HIV-1 vertically infected children

Abstract

Purpose of review: It is 20 years since the start of the combination antiretroviral therapy (cART) era and more than 10 years since cART scale-up began in resource-limited settings. We examined survival of vertically HIV-infected infants and children in the cART era.

Recent findings: Good survival has been achieved on cART in all settings with up to 10-fold mortality reductions compared with before cART availability. Although mortality risk remains high in the first few months after cART initiation in young children with severe disease, it drops rapidly thereafter even for those who started with advanced disease, and longer term mortality risk is low. However, suboptimal retention on cART in routine programs threatens good survival outcomes and even on treatment children continue to experience high comorbidity risk; infections remain the major cause of death. Interventions to address infection risk include a cotrimoxazole prophylaxis, isoniazid preventive therapy, routine childhood and influenza immunization, and improving maternal survival.

Summary: Pediatric survival has improved substantially with cART and HIV-infected children are aging into adulthood. It is important to ensure access to diagnosis and early cART, good program retention as well as optimal comorbidity prophylaxis and treatment to achieve the best possible long-term survival and health outcomes for vertically infected children.

Figure 1

Estimated risk of death within 12-months in Cross Continents Collaboration for Kids (3Cs4kids) (low and middle-income countries) compared with HIV Paediatric Prognostic Collaborative Study (HPPMCS)(USA and Europe) according to age and: (a) CD4% (b) CD4 cell count. Estimates in 3Cs4kids apply to a child receiving co-trimoxazole prophylaxis. Curves are truncated at the 5th and 95th centiles for each age. Source: Cross Continents Collaboration for Kids (3Cs4kids) Analysis and Writing Committee. Markers for predicting mortality in untreated HIV-infected children in resource-limited settings: a meta-analysis. AIDS. 2008; 22:97–105.

Figure 2

Estimated mortality from enrolment into HIV care in children aged 5–10 years at enrolment with initial CD4 >500 cells/μl from Southern Africa, West Africa and Europe comparing different cART initiation strategies as follows: immediate cART; cART at CD4 < 500 or weight-for-age z-score (WAZ)<−2; CD4 <350/WAZ <−2; CD4 <200/WAZ <−2; no cART. The mortality difference between immediate cART (solid green line) and deferring cART to CD4 >500 cells/μl or WAZ<−2 is 0.4% (95%CI: 0.02–0.6%). Mortality is estimated from g-computation to adjust for time-dependent confounding affected by prior treatment of CD4 count, CD4 percent and weight-for-age z-score.

Figure 3

Daily risk of death through 1 year on cART in children aged 4 months to 15 years in the ARROW RCT according to age and pre-cART CD4 count or percent using flexible parametric models on log-normal scale with 1 interior knot. Points show times when deaths occurred. Source: Walker AS, et al. Mortality in the year following antiretroviral therapy initiation in HIV-infected adults and children in Uganda and Zimbabwe. Clinical Infectious Diseases. 2012; 55:1707–18.