Abstract
BackgroundThere are limited data of immunologic and virologic failure in Asian HIV-infected children using non-nucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART). We examined the incidence rate of immunologic failure (IF) and virologic failure (VF) and the accuracy of using IF to predict VF in Thai HIV-infected children using first-line NNRTI-based HAART.MethodsAntiretroviral (ART)-naïve HIV-infected children from 2 prospective cohorts treated with NNRTI-based HAART during 2001-2008 were included. CD4 counts were performed every 12 weeks and plasma HIV-RNA measured every 24 weeks. Immune recovery was defined as CD4%≥25%. IF was defined as persistent decline of ≥5% in CD4% in children with CD4%<15% at baseline or decrease in CD4 count ≥30% from baseline. VF was defined as HIV-RNA>1,000 copies/ml after at least 24 weeks of HAART. Clinical and laboratory parameter changes were assessed using a paired t-test, and a time to event approach was used to assess predictors of VF. Sensitivity and specificity of IF were calculated against VF.Results107 ART-naive HIV-infected children were included, 52% female, % CDC clinical classification N:A:B:C 4:44:30:22%. Baseline data were median (IQR) age 6.2 (4.2-8.9) years, CD4% 7 (3-15), HIV-RNA 5.0 (4.9-5.5) log10copies/ml. Nevirapine (NVP) and efavirenz (EFV)-based HAART were started in 70% and 30%, respectively.At 96 weeks, none had progressed to a CDC clinical classification of AIDS and one had died from pneumonia. Overall, significant improvement of weight for age z-score (p = 0.014), height for age z-score, hemoglobin, and CD4 were seen (all p < 0.001). The median (IQR) CD4% at 96 weeks was 25 (18-30)%. Eighty-nine percent of children had immune recovery (CD4%≥25%) and 75% of children had HIV-RNA <1.7log10copies/ml.Thirty five (32.7%) children experienced VF within 96 weeks. Of these, 24 (68.6%) and 31 (88.6%) children had VF in the first 24 and 48 weeks respectively.Only 1 (0.9%) child experienced IF within 96 weeks and the sensitivity (95%CI) of IF to VF was 4 (0.1-20.4)% and specificity was 100 (93.9-100)%.ConclusionImmunologic failure, as defined here, had low sensitivity compared to VF and should not be recommended to detect treatment failure. Plasma HIV-RNA should be performed twice, at weeks 24 and 48, to detect early treatment failure.Trial RegistrationClinicaltrials.gov identification number NCT00476606
Highlights
There are limited data of immunologic and virologic failure in Asian HIV-infected children using nonnucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART)
Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART is commonly prescribed as the first-line regimen in resource-limited settings [2,3,4,5,6,7,8]
Materials and methods Data from HIV-infected children who were enrolled in 2 prospective cohorts at the HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), the Thai Red Cross AIDS Research Centre, Bangkok and Khon Kaen University, Khon Kaen, Thailand from December 2001 to March 2008 were used
Summary
There are limited data of immunologic and virologic failure in Asian HIV-infected children using nonnucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART). Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART is commonly prescribed as the first-line regimen in resource-limited settings [2,3,4,5,6,7,8]. Mee et al reported low sensitivity of CD4 criteria of 21.2% in detecting virologic failure in African HIV-infected adults [11]. Reports in African HIV-infected children have shown low sensitivity of 3.5% of clinical and immunologic criteria based on the WHO criteria for IF available at that time [2007] in identifying virologic failure [13]
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