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
Low-dose lopinavir displayed adequate pharmacokinetic parameters and good efficacy as compared with standard-dose lopinavir in Thai children. A larger study to investigate the efficacy of low-dose lopinavir is warranted.
Administration of the 2 doses of varicella vaccine resulted in high seroconversion rates without serious adverse reactions. Varicella vaccination for HIV-infected children should be encouraged.
This study aimed to assess long COVID, and describe immunogenicity against Omicron variants following BNT162b2 vaccination. A prospective cohort study was conducted among children (aged 5–11) and adolescents (aged 12–17) who had SARS-CoV-2 infection from July to December 2021 (Delta predominant period). Long COVID symptoms were assessed by questionnaires at 3 months after infection. Immunogenicity was evaluated by using a surrogate virus-neutralizing antibody test (sVNT) against the Omicron variant. We enrolled 97 children and 57 adolescents. At 3 months, 30 children (31%) and 34 adolescents (60%) reported at least one long COVID symptom, with respiratory symptoms prevailing (25% children and 32% adolescents). The median time from infection to vaccination was 3 months in adolescents and 7 months in children. At 1 month following vaccination, in children who received one-dose and two-dose BNT162b2 vaccines, the median (IQR) sVNT against Omicron was 86.2% inhibition (71.1–91.8) and 79.2% inhibition (61.5–88.9), respectively (p = 0.26). Among adolescents who received one-dose and two-dose BNT162b2 vaccines, the median (IQR) sVNT against Omicron was 64.4% inhibition (46.8–88.8) and 68.8% inhibition (65.0–91.2) (p = 0.64). Adolescents had a higher prevalence of long COVID than children. Immunogenicity against the Omicron variant after vaccination was high and did not vary between one or two doses of the vaccine in either children or adolescents.
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