Predictors of poor CD4 and weight recovery in HIV-infected children initiating ART in South Africa.

OBJECTIVE: To identify baseline demographic and clinical risk factors associated with poor CD4 and weight response after initiation of antiretroviral therapy (ART) in a cohort of human immunodeficiency virus (HIV)-infected children in KwaZulu-Natal, South Africa. METHODS: We performed a retrospective cohort study of 674 children initiating antiretroviral therapy at McCord and St. Mary's hospitals in KwaZulu-Natal, South Africa, from August 2003 to December 2008. We extracted data from paper charts and electronic medical records to assess risk factors associated with CD4 and weight response using logistic regression. RESULTS: From the initial cohort of 901 children <10 years old initiating ART between August 2003 and December 2008, we analyzed 674 children with complete baseline data. Viral suppression rates (<400 copies/ml) were 84% after six months of therapy and 88% after 12 months of therapy. Seventy-three percent of children achieved CD4 recovery after six months and 89% after 12 months. Weight-for-age Z-score (WAZ) improvements were seen in 58% of children after six months of ART and 64% after 12 months. After six months of ART, lower baseline hemoglobin (p = 0.037), presence of chronic diarrhea (p = 0.007), and virologic failure (p = 0.046) were all associated with poor CD4 recovery by multivariate logistic regression. After 12 months of ART, poor CD4 recovery was associated with higher baseline CD4% (p = 0.005), chronic diarrhea (p = 0.02), and virologic failure (p<0.001). Age less than 3 years at ART initiation (p = 0.0003), higher baseline CD4% (p<0.001), and higher baseline WAZ (p<0.001) were all associated with poor WAZ improvements after 6 months by multivariate logistic regression. CONCLUSION: The presence of chronic diarrhea at baseline, independent of nutritional status and viral response, predicts poor CD4 recovery. Age at initiation of ART is an important factor in early WAZ response to ART, while viral suppression strongly predicts CD4 recovery but not WAZ improvement.

Risk factors associated with increased mortality among HIV infected children initiating antiretroviral therapy (ART) in South Africa.

OBJECTIVE: To identify demographic and clinical risk factors associated with mortality after initiation of antiretroviral therapy (ART) in a cohort of human immunodeficiency (HIV) infected children in KwaZulu-Natal, South Africa. METHODS: We performed a retrospective cohort study of 537 children initiating antiretroviral therapy at McCord Hospital in KwaZulu-Natal, South Africa. Data were extracted from electronic medical records and risk factors associated with mortality were assessed using Cox regression analysis. RESULTS: Overall there were 47 deaths from the cohort of 537 children initiating ART with over 991 child-years of follow-up (median 22 months on ART), yielding a mortality rate of 4.7 deaths per 100 child years on ART. Univariate analysis indicated that mortality was significantly associated with lower weight-for-age Z-score (p<0.0001), chronic diarrhea (p = 0.0002), lower hemoglobin (p = 0.002), age <3 years (p = 0.003), and CD4% <10% (p = 0.005). The final multivariable Cox proportional hazards mortality model found age less than 3 years (p = 0.004), CD4 <10% (p = 0.01), chronic diarrhea (p = 0.03), weight-for-age Z-score (<0.0001) and female gender as a covariate varying with time (p = 0.03) all significantly associated with mortality. CONCLUSION: In addition to recognized risk factors such as young age and advanced immunosuppression, we found female gender to be significantly associated with mortality in this pediatric ART cohort. Future studies are needed to determine whether intrinsic biologic differences or socio-cultural factors place female children with HIV at increased risk of death following initiation of ART.

Impact of tuberculosis cotreatment on viral suppression rates among HIV-positive children initiating HAART.

OBJECTIVE: To evaluate the association between treatment of HIV-tuberculosis (TB) coinfection and primary virologic failure among children initiating antiretroviral therapy in South Africa. DESIGN: We performed a retrospective cohort study of 1029 children initiating antiretroviral therapy at two medical centers in KwaZulu Natal, South Africa, a region of very high TB incidence. METHODS: Data were extracted from electronic medical records and charts and the impact of TB cotreatment on viral suppression at 6 and 12 months was assessed using logistic regression. RESULTS: The overall rate of virologic suppression (<400 HIV RNA copies/ml) was 85% at 6 months and 87% at 12 months. Children who received concurrent treatment for TB had a significantly lower rate of virologic suppression at 6 months (79 vs. 88%; P = 0.003). Those who received nonnucleoside reverse transcriptase inhibitor-based HAART had similar rates of viral suppression regardless of whether they received concurrent TB therapy. In contrast, children who received protease inhibitor-based HAART had significantly lower viral suppression rates at both 6 and 12 months if treated concurrently for TB (P = 0.02 and 0.03). Multivariate logistic regression revealed that age at initiation, protease inhibitor therapy, and TB coinfection were each independently associated with primary virologic failure. CONCLUSION: Concurrent treatment for TB is associated with lower rates of viral suppression among children receiving protease inhibitor-based HAART, but not among those receiving nonnucleoside reverse transcriptase inhibitor-based HAART. Guidelines for the care of young HIV-TB coinfected infants should be continually evaluated, as protease inhibitor-based antiviral therapy may not provide optimal viral suppression in this population.