Immunologic and virologic failure after first-line NNRTI-based antiretroviral therapy in Thai HIV-infected children

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

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

“…27 However, immunologic failure has a low sensitivity in detecting VF. 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.…”

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.…”

Outcomes after viral load rebound on first-line antiretroviral treatment in children with HIV in the UK and Ireland: an observational cohort study

“…We identified 17 publications with data on children from a variety of settings which analysed either long-term virological patient outcomes 1,3,4,13,25 , durability of first-line ART 2,9,18,19,22 or response to second-line ART 8,23,24,[26][27][28][29] . Only two studies have reported outcomes following viral load rebound and the probability of switch or resuppression without switch in routine care 19,22 .…”

“…Several papers report that within two years of first-line ART initiation, 33-38% of children experience virological failure; this varies with age and type of first-line ART [1][2][3][4] . This has raised concerns regarding the sustainability and long-term treatment options for children, who are recommended immediate ART from infancy and will require lifelong treatment but are faced with a limited range of antiretrovirals available in paediatric formulations 5,6 .…”