Prognosis of Children With HIV-1 Infection Starting Antiretroviral Therapy in Southern Africa

Abstract

Background Prognostic models for children starting antiretroviral therapy (ART) in Africa are lacking. We developed models to estimate the probability of death during the first year receiving ART in Southern Africa. Methods We analyzed data from children ≤10 years old who started ART in Malawi, South Africa, Zambia or Zimbabwe from 2004–2010. Children lost to follow-up or transferred were excluded. The primary outcome was all-cause mortality in the first year of ART. We used Weibull survival models to construct two prognostic models: one with CD4%, age, WHO clinical stage, weight-for-age z-score (WAZ) and anemia and one without CD4%, because it is not routinely measured in many programs. We used multiple imputation to account for missing data. Results Among 12655 children, 877 (6.9%) died in the first year of ART. 1780 children were lost to follow-up/transferred and excluded from main analyses; 10875 children were included. With the CD4% model probability of death at 1 year ranged from 1.8% (95% CI: 1.5–2.3) in children 5–10 years with CD4% ≥10%, WHO stage I/II, WAZ ≥−2 and without severe anemia to 46.3% (95% CI: 38.2–55.2) in children <1 year with CD4% <5%, stage III/IV, WAZ< −3 and severe anemia. The corresponding range for the model without CD4% was 2.2% (95% CI: 1.8–2.7) to 33.4% (95% CI: 28.2–39.3). Agreement between predicted and observed mortality was good (C-statistics=0.753 and 0.745 for models with and without CD4% respectively). Conclusion These models may be useful to counsel children/caregivers, for program planning and to assess program outcomes after allowing for differences in patient disease severity characteristics.

Immunodeficiency in Children Starting Antiretroviral Therapy in Low-, Middle-, and High-Income Countries

“…7 A recent prognostic model from Southern Africa estimated that mortality in the first year of treatment in children starting cART with CD4% ≥10% was about half that of children with CD4% <5%. 8 Similarly, mortality in children with WHO clinical stage 3/4 was about 40% higher compared to children in stages 1/2, and about four times higher in infants compared to children 5-10 years. 8 …”

Impact of Birth HIV-PCR Testing on the Uptake of Follow-up Early Infant Diagnosis Services in Cape Town, South Africa

“…However, delays in result return and high levels of loss to follow up (LTFU) within the early infant diagnosis (EID) cascade may fail to link many infants to life saving ART before the peak age of mortality at 11 weeks (10,11). Although there are limited data on diagnosis and treatments of infants immediately after birth, there is consensus amongst clinicians that early initiation of ART has the potential to limit viral reservoirs and prevent disease progression early in infancy (12–14). It is also argued that as ART coverage during labour rises the proportion of vertical infections that occur IU increases relative to intra-partum (IP) infections (15).…”

Paediatric ART outcomes in a decentralised model of care in Cape Town, South Africa

“…[5] More recent pooled data from southern African paediatric HIV programmes reported persistently high mortality in infants (46.3%) despite large-scale ART roll-out. [6] Combination antiretroviral therapy (ART) is the only effective treatment available for the suppression of HIV, and early ART initiation significantly reduces AIDS-related morbidity and mortality. [7,8] Children in developed countries receive ART as the standard of care upon initial diagnosis; however, it is estimated that only 1 in 4 children living in subSaharan Africa receives this life-sustaining treatment.…”