High survival and treatment success sustained after two and three years of first‐line ART for children in Cambodia

Abstract

BackgroundLong-term outcomes of antiretroviral therapy (ART) in children remain poorly documented in resource-limited settings. The objective of this study was to assess two-and three-year survival, CD4 evolution and virological response among children on ART in a programmatic setting in Cambodia.MethodsChildren treated with first-line ART for at least 24 months were assessed with viral load testing and genotyping. We used Kaplan-Meier analysis for survival and Cox regression to identify risk factors associated with treatment failure.ResultsOf 1168 registered HIV-positive children, 670 (57%) started ART between January 2003 and December 2007. Survival probability was 0.93 (95% CI: 0.91-0.95) and 0.91 (95% CI: 0.88-0.93) at 24 and 36 months after ART initiation, respectively. Median CD4 gain for children aged over five years was 704 cells/mm3 at 24 months and 737 at 36 months. Median CD4 percentage gain for children under five years old was 15.2% at 24 months and 15% at 36 months. One hundred and thirty children completed at least 24 months of ART, and 138 completed 36 months: 128 out of 268 (48%) were female. Median age at ART initiation was six years.Overall, 22 children had viral loads of >1000 copies/ml (success ratio = 86% on intention-to-treat-analysis) and 21 of 21 presented mutations conferring resistance mostly to lamivudine and non-nucleoside reverse transcriptase inhibitors. Risk factors for failure after 24 and 36 months were CD4 counts below the threshold for severe immunosupression at those months respectively. Only two out of 22 children with viral loads of >1000 copies/ml met the World Health Organization immunological criteria for failure (sensitivity = 0.1).ConclusionsGood survival, immunological restoration and viral suppression can be sustained after two to three years of ART among children in resource-constrained settings. Increased access to routine virological measurements is needed for timely diagnosis of treatment failure.

Increased Risk of Q151M and K65R Mutations in Patients Failing Stavudine-Containing First-Line Antiretroviral Therapy in Cambodia

“…This rate represented a good virological outcome and was consistent with studies previously conducted in Cambodia amongst HIV-1 infected patients after one to three years of first-line ARV regimen [19], [20], [21], [22]. Seven hundred and fourteen patients had detectable HIV-1 RNA VL.…”

Growth reconstitution following antiretroviral therapy and nutritional supplementation

“…Types of supplementation included: rice/corn and vegetable oil (Haiti [29]), high-energy protein (Zambia [24]), Plumpy’nut (Malawi [23]), other ready-to-use therapeutic food (Malawi [30]), nutritional porridge (Kenya [18, 31]), corn-soy blend ready-to-eat meal supplement (South Africa [32]), fortified amylase-enriched maize product (South Africa [28]), food supplementation or support (Malawi/Mozambique/Guinea [10], Ethiopia [8], Cambodia [33]), and multivitamins (Kenya [18], South Africa [32], Uganda [34], Uganda/Zimbabwe [35], and India [36]). One (Kenya [18]) study evaluated receipt and duration of nutritional supplementation in growth analyses, while a second (Malawi [30]) evaluated 6-month nutritional recovery in malnourished children initiating ART with ready-to-use therapeutic food.…”

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

“…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.…”

“…In a recent systematic review of first-line ART failure among children, 28 within 30 reviewed studies on 3,241 children, only 265 (8%) were from Cambodia and only 74 (2%) of those had genotypes available, some available only in poster form and after second-line ART failure. In the three available pediatric studies from Cambodia, reporting data from children on first-line ART with detectable VL and available genotypic resistance testing, 94% (34/36), 29 100% (21/21), 30 and 100% (2/2) 31 had drug-resistant mutations to NRTI and NNRTI without specific reports on resistance patterns or extent.…”