Large-scale paediatric treatment shows success in South-East Asia

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Long-term treatment success in children in both Thailand and Cambodia demonstrates the sustainability of paediatric antiretroviral therapy (ART) in resource-limited settings at clinic, district and provincial levels, as reported in studies by Michelle McConnell and Petros Isaakidis, respectively, at the Fifth IAS Conference on Pathogenesis, Treatment and Prevention, held in Cape Town.

An absence of documentation on the long-term outcomes of children on ART in resource-limited settings impedes effective management of HIV in children. A better understanding of outcomes will support earlier initiation of treatment as well as helping in the diagnosis of treatment failure, improving overall morbidity and mortality rates in children.

In Thailand, national antiretroviral treatment began in 2000. Michelle McConnell of the US Centers for Disease Control and colleagues from the Thai Ministry of Public Health reviewed outcomes for HIV-positive children, under 15 years of age, who began ART between 2000 and 2005 in district/community hospitals as well as at provincial (larger) hospitals. Eligibility criteria for ART included being under one year of age or having a CD4 percentage ≤ 20 or CDC clinical stage B or C. Follow-up data for patients were included through March 2007.

Glossary

treatment failure

Inability of a medical therapy to achieve the desired results. 

inter-quartile range

The spread of values, from the smallest to the largest. The inter-quartile range (IQR) only includes the middle 50% of values and measures the degree of spread of the most common values.

paediatric

Of or relating to children.

WHO stage

A simplified system to describe four clinical stages of HIV-related disease, based on clinical parameters (symptoms, weight loss and different opportunistic infections) rather than decreasing CD4 cell count. Stage I is asymptomatic, stage II mild symptoms, stage III advanced symptoms and stage IV severe symptoms (an AIDS diagnosis).

CD4 cell percentage

The CD4 cell percentage measures the proportion of all white blood cells that are CD4 cells.

In Cambodia, Petros Isaakidis of Médecins sans Frontières and his Cambodian colleagues undertook a cross-sectional survey within a cohort study in two paediatric HIV-clinics. Three-year survival rates, as well as changes in CD4 counts and viral load, were evaluated to determine the risk factors for treatment failure. Assessment of viral load and viral genotyping for drug resistance were undertaken on children who had been on first-line treatment for at least two years.

In the national Thai programme, analysis included 3409 children at 327 hospitals of whom 20% began ART at a district/community hospital and 80% in the larger hospitals. The median age at the start of antiretroviral treatment was 7.3 years, weight for age z-score was -2.0 (IQR = 2.6 to 1.4) and CD4 percentage 5.0% (IQR =1.9 to 13.0%). Close to 75% were on nevirapine-based regimens and just over 20% on efavirenz-based treatment.

Approximately 10% (346) were lost to follow-up (defined as more than three months late for a clinic visit, cross-checked against the national death registry) and another 9% died (90% (274) of deaths were related to HIV). Median time to death was 3.6 months (IQR= 1.4 to 10.7). Of note, unlike Thailand, most resource-poor countries do not have national death registries limiting an understanding of the causes of HIV mortality.

Survival probability for one year and for five years was 0.93(95% CI: 0.93 to 0.94) and 0.88 (95% CI :0.86 to 0.90) respectively. Factors associated with survival included being in a district/community hospital, having a higher weight-for-age ratio at baseline and being at a better clinical stage.

In Cambodia, 57% of 1168 HIV-positive children registered at the two paediatric clinics began antiretroviral treatment between January 2003 and December 2007. Survival probabilities for one year, two years and three years were 0.95 (95% CI: 0.93 to 0.97), 0.93 (95% CI: 0.91 to 0.95) and 0.91 (95% CI: 0.88 to 0.93) respectively. The median duration of antiretroviral treatment was just over three years. Median CD4 count gains for children over the age of five were +304, +704 and +737 cells/mm3 at six months, two years and three years respectively.

An intention-to-treat analysis demonstrated an 85% virological success rate. 93.5% of 138 children who had been on ART for at least three years had an undetectable viral load. A CD4 count below 100 (threshold) at two years (24 months) and three years (36 months) was predictive of failure after month 24 and month 36 respectively. Of the 22 children with viral loads >1000 copies/ml, two met the World Health Organization criteria for failure. Resistance, primarily to 3TC (lamivudine, Epivir) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), was detected in 21 children. Orphan status did not affect outcome.

Long-term survival with good treatment outcomes in these two large cohorts of children demonstrates the sustainability of antiretroviral treatment programmes for children in resource-limited settings at the clinic, district and provincial levels. Earlier initiation, as well as routine viral load testing, is needed, with scale-up to support better outcomes that include timely and accurate diagnosis of treatment failure.

Further information

Powerpoint presentations by Michelle McConnell and Petros Isaakidis and a webcast of the conference session in which they were presented are available on the IAS 2009 website.