Prognosis of children with HIV-1 infection starting antiretroviral therapy in Southern Africa: a collaborative analysis of treatment programs

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 of age who started ART in Malawi, South Africa, Zambia or Zimbabwe from 2004 to 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 2 prognostic models: 1 with CD4%, age, World Health Organization clinical stage, weight-for-age z-score (WAZ) and anemia and the other without CD4%, because it is not routinely measured in many programs. We used multiple imputation to account for missing data.

Results: Among 12,655 children, 877 (6.9%) died in the first year of ART. We excluded 1780 children who were lost to follow up/transferred from main analyses; 10,875 children were therefore included. With the CD4% model probability of death at 1 year ranged from 1.8% [95% confidence interval (CI): 1.5-2.3] in children 5-10 years with CD4% ≥10%, World Health Organization 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).

Conclusions: 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.

Figure 1

Figure 1 (a): Cumulative mortality predicted from prognostic models (dashed lines) compared with Kaplan-Meier observed mortality (solid lines) for five prognostic groups of children commencing antiretroviral therapy, ranging from worst to best prognosis. Prognostic groups were defined by ranking the children in order of mortality risk according to their risk factors. Mortality risk was estimated by the linear predictor of the prognostic model. The cut-points for each prognostic group were determined so that each group contained approximately 20% of deaths and were ordered from low to high risk. Number of patients in each group (%) is shown. Figure 1 (b): Cumulative mortality predicted from prognostic models (dashed lines) compared with Kaplan-Meier observed mortality (solid lines) for each region for three prognostic groups of children commencing antiretroviral therapy, ranging from worst to best prognosis. Prognostic groups were defined as for figure 1 (a) but only three prognostic groups were used due to the smaller number of children for individual regions. Each group contains approximately one third of deaths. Figure 1 (c): Cumulative mortality predicted from prognostic models (solid lines) compared with Kaplan-Meier observed mortality for each region (dashed lines) for patients with the most commonly occurring values of prognostic variables. Patients were age 5–10 years with WHO Stage III/IV disease, CD4≥10% and weight-for-age z-score −3 to −2.

Figure 1

Figure 1 (a): Cumulative mortality predicted from prognostic models (dashed lines) compared with Kaplan-Meier observed mortality (solid lines) for five prognostic groups of children commencing antiretroviral therapy, ranging from worst to best prognosis. Prognostic groups were defined by ranking the children in order of mortality risk according to their risk factors. Mortality risk was estimated by the linear predictor of the prognostic model. The cut-points for each prognostic group were determined so that each group contained approximately 20% of deaths and were ordered from low to high risk. Number of patients in each group (%) is shown. Figure 1 (b): Cumulative mortality predicted from prognostic models (dashed lines) compared with Kaplan-Meier observed mortality (solid lines) for each region for three prognostic groups of children commencing antiretroviral therapy, ranging from worst to best prognosis. Prognostic groups were defined as for figure 1 (a) but only three prognostic groups were used due to the smaller number of children for individual regions. Each group contains approximately one third of deaths. Figure 1 (c): Cumulative mortality predicted from prognostic models (solid lines) compared with Kaplan-Meier observed mortality for each region (dashed lines) for patients with the most commonly occurring values of prognostic variables. Patients were age 5–10 years with WHO Stage III/IV disease, CD4≥10% and weight-for-age z-score −3 to −2.

Figure 1

Figure 1 (a): Cumulative mortality predicted from prognostic models (dashed lines) compared with Kaplan-Meier observed mortality (solid lines) for five prognostic groups of children commencing antiretroviral therapy, ranging from worst to best prognosis. Prognostic groups were defined by ranking the children in order of mortality risk according to their risk factors. Mortality risk was estimated by the linear predictor of the prognostic model. The cut-points for each prognostic group were determined so that each group contained approximately 20% of deaths and were ordered from low to high risk. Number of patients in each group (%) is shown. Figure 1 (b): Cumulative mortality predicted from prognostic models (dashed lines) compared with Kaplan-Meier observed mortality (solid lines) for each region for three prognostic groups of children commencing antiretroviral therapy, ranging from worst to best prognosis. Prognostic groups were defined as for figure 1 (a) but only three prognostic groups were used due to the smaller number of children for individual regions. Each group contains approximately one third of deaths. Figure 1 (c): Cumulative mortality predicted from prognostic models (solid lines) compared with Kaplan-Meier observed mortality for each region (dashed lines) for patients with the most commonly occurring values of prognostic variables. Patients were age 5–10 years with WHO Stage III/IV disease, CD4≥10% and weight-for-age z-score −3 to −2.