Effectiveness of Highly Active Antiretroviral Therapy in HIV-Positive Children: Evaluation at 12 Months in a Routine Program in Cambodia

Abstract

OBJECTIVE. Increasing access to highly active antiretroviral therapy to reach all those in need in developing countries (scale up) is slowly expanding to HIV-positive children, but documented experience remains limited. We aimed to describe the clinical, immunologic, and virologic outcomes of pediatric patients with >12 months of highly active antiretroviral therapy in 2 routine programs in Cambodia. METHODS. Between June 2003 and March 2005, 212 children who were younger than 13 years started highly active antiretroviral therapy. Most patients started a standard first-line regimen of lamivudine, stavudine, and nevirapine, using split adult fixed-dosage combinations. CD4 percentage and body weight were monitored routinely. A cross-sectional virologic analysis was conducted in January 2006; genotype resistance testing was performed for patients with a detectable viral load. RESULTS. Mean age of the subjects was 6 years. Median CD4 percentage at baseline was 6. Survival was 92% at 12 months and 91% at 24 months; 13 patients died, and 4 were lost to follow-up. A total of 81% of all patients had an undetectable viral load. Among the patients with a detectable viral load, most mutations were associated with resistance to lamivudine and non–nucleoside reverse-transcriptase inhibitor drugs. Five patients had developed extensive antiretroviral resistance. Being an orphan was found to be a predictor of virologic failure. CONCLUSIONS. This study provides additional evidence of the effectiveness of integrating HIV/AIDS care with highly active antiretroviral therapy for children in a routine setting, with good virologic suppression and immunologic recovery achieved by using split adult fixed-dosage combinations. Viral load monitoring and HIV genotyping are valuable tools for the clinical follow-up of the patients. Orphans should receive careful follow-up and extra support.

Comparison of Adherence Monitoring Tools and Correlation to Virologic Failure in a Pediatric HIV Clinical Trial

“…The VF rate in this study was similar to previous reports from other resource-limited settings; 13% in Ugandan children, 24 16% in Cambodian children, 25 and 16% in Thai children. 26 If HIV-RNA is not routinely available, WHO guidelines recommend clinical and immunologic monitoring.…”

“…28 Predictors of VF in HIV-infected children reported in other studies include physician documentation of poor adherence, lower baseline CD4%, male gender, and treatment with nevirapine versus efavirenz-based HAART, and being an orphan. 25,26,29,30 In US children, reporting a barrier to adherence in the PACTG adherence questionnaire was significantly associated with elevated HIV-RNA. 10 VF was significantly associated with reporting any barrier in the PACTG questionnaire in our study, so this tool could be useful for helping physicians to identify children at risk for VF, and address specific barriers that prevent them from adhering to their treatment regimens.…”

Extensive Drug Resistance in HIV-Infected Cambodian Children Who Are Undetected as Failing First-Line Antiretroviral Therapy by WHO 2010 Guidelines

“…22,23 Similar information from Cambodia is limited. In prior reports from Cambodia before 2007, extensive resistance was reported at 14% (5/36) after 12 months of first-line ART 29 and at 27% (6/22) after 24 months. 30 Despite the observed effectiveness of ART in these studies, with such little data, the extent of resistance and its effect on subsequent regimens in Cambodian CRF01_AE-infected children are not known.…”

“…This is an important consequence to consider, particularly in children who will require ART for long periods of time. According to reviewed pediatric data from RLS 28 and specifically from Cambodia [29][30][31] and Thailand, 13,22,23 57-100% of children failing first-line NNRTI-based ART had extensive NRTI and NNRTI resistance, with most common NRTI mutations M184V/I and D67N, and NNRTI mutations Y181C and G190A. Our results confirm and extend these observations, contribute to the limited genotypic data available for children failing first-line therapy in Cambodia, and emphasize the risk of the development of extensive drug resistance when guidelines that are not based on routine VL monitoring are used.…”

Impact of Antiretroviral Therapy on Quality of Life in HIV-Infected Southeast Asian Children in the PREDICT Study

“…[1][2][3] Currently, HIV-infected children treated with highly active antiretroviral therapy (HAART) have increased life expectancy. [4][5][6] Deaths related to HIV/AIDS mortality have decreased significantly, but the non-AIDSrelated conditions maintain a stable trend in children living with HIV-1 after treatment with HAART. 7 Unlike many other chronic illnesses, children with HIV infection are more likely to experience more difficulties in their daily lives (e.g., parental death from AIDS and social stigmatization 8,9 ) which may worsen their QOL.…”