HIV This Week

Effectiveness of paediatric antiretroviral therapy in resource-limited settings: a systematic review and meta-analysis.

Ciaranello AL, Chang Y, Margulis AV, Bernstein A, Bassett IV, Losina E, Walensky RP. Clin Infect Dis. 2009;49:1915-27.

Responses to antiretroviral therapy (ART) among human immunodeficiency virus (HIV)-infected children in resource-limited settings have recently been reported, but outcomes vary. The authors sought to derive pooled estimates of the 12-month rate of virologic suppression (HIV RNA, <400 copies/mL) and gain in CD4 cell percentage (DeltaCD4%) for children initiating antiretroviral therapy in resource-limited settings. Ciaranello et al conducted a systematic review and meta-analysis of published reports of HIV RNA and CD4 outcomes for treatment-naive children aged 0-17 years old by means of the Medline, EMBASE (Excerpta Medica Database), and LILACS (Latin American and Caribbean Health Sciences Literature) electronic databases and the Cochrane Clinical Trials Register. Pooled estimates of the reported proportion with HIV RNA <400 copies/mL and DeltaCD4% after 12 months of antiretroviral therapy were derived using patient-level estimates and fixed- and random-effects models. To approximate intention-to-treat analyses, in sensitivity analyses children with missing 12-month data were assumed to have HIV RNA>400 copies/mL or DeltaCD4% of zero. In patient-level estimates after 12 months of antiretroviral therapy, the pooled proportion with virologic suppression was 70% (95% confidence interval [CI], 67%-73%); the pooled DeltaCD4% was 13.7% (95% CI, 11.8%-15.7%). Results from the fixed- and random-effects models were similar. In approximated intention-to-treat analyses, the pooled estimates decreased to 53% with virologic suppression (95% CI, 50%-55%) and to a DeltaCD4% of 8.5% (95% CI, 5.5%-11.4%). Pooled estimates of reported virologic and immunologic benefits after 12 months of antiretroviral therapy among HIV-infected children in resource-limited settings are comparable with those observed among children in developed settings. Consistency in reporting on reasons for missing data will aid in the evaluation of antiretroviral therapy outcomes in resource-limited settings.

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Editors’ note: Treatment outcomes for treatment-naïve children after 1 year are similar in resource-poor settings as they are in the United States of America and Europe, despite advanced stages of HIV disease at initiation of antiretroviral treatment, substantial barriers to service delivery, and predominantly non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. This is great news from this first study to provide pooled estimates of the virological suppression rate and change in CD4 percentage in children in countries with emerging or developing economies. These findings have particular importance for the estimated 90% of children living with HIV who reside in resource-limited settings and should spur on the movement to treat all children living with HIV.

Six-month gain in weight, height, and CD4 predict subsequent antiretroviral treatment responses in HIV-infected South African children.

Yotebieng M, Van Rie A, Moultrie H, Meyers T. AIDS. 2010 24:139-46.

The aim of the study was to construct percentile curves for 6-month gain in weight, height, CD4 cell count, and CD4 percentage (CD4%) in children initiating antiretroviral therapy, and to assess the association between lower percentiles and subsequent antiretroviral therapy responses. A cohort of 1394 HIV-infected children initiating antiretroviral therapy between April 2004 and March 2008, Johannesburg, South Africa were enrolled. The generalized additive model for location, scale, and shape was used to construct percentile curves for 6-month gain in weight, height, CD4 cell count, and CD4%. Cox proportional models were used to assess the association between lower percentiles of each distribution and death, virological suppression, and treatment failure between 6 to 36 months post-antiretroviral therapy initiation. Lower percentiles for gain in weight, CD4, and CD4% count after 6 months of antiretroviral therapy, but not height, were associated with poor subsequent treatment outcomes independent of baseline characteristics, with increasing strength of association as percentiles decreased. Age-specific 6-month post-antiretroviral therapy weight gain in this cohort was substantially higher compared with 6-month weight gain in non-HIV-infected American children of the Fels Institute cohort and the attained weight-for-age at 6 months post- antiretroviral therapy plotted on WHO weight-for-age growth charts were not associated with subsequent treatment outcomes. Gain in CD4% in the first 6 months of antiretroviral therapy was the best predictor of poor subsequent antiretroviral therapy outcomes. In areas with limited access to CD4%, weight gain post- antiretroviral therapy using these newly developed reference distributions for HIV-infected children on antiretroviral therapy is a good alternative to CD4%, and clearly superior to the commonly used 'Road-to-Health' weight-for-age charts.

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Editors’ note: A third of children vertically infected do not survive to their first birthday and more than half die before age 2. When children start antiretroviral treatment, it is important to monitor their clinical improvement to assess whether they are benefitting. This innovative study developed HIV-specific weight gain reference curves that can be used by health workers in settings without CD4 percentage laboratory tests to identify which children on treatment are likely to be virologically suppressed and which ones are at higher risk for treatment failure and subsequent death. These reference curves should be tested in other settings and adjusted as necessary to develop international weight gain reference curves for children starting antiretroviral treatment.