Pattern and Predictors of Immunologic Recovery in Human Immunodeficiency Virus-Infected Children Receiving Non-Nucleoside Reverse Transcriptase Inhibitor-Based Highly Active Antiretroviral Therapy (original) (raw)
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HIV Medicine, 2019
The aim of the study was to explore factors associated with CD4 percentage (CD4%) reconstitution following treatment interruptions (TIs) of antiretroviral therapy (ART). Methods Data from paediatric HIV-infected cohorts across 17 countries in Europe and Thailand were pooled. Children on combination ART (cART; at least three drugs from at least two classes) for > 6 months before TI of ≥ 30 days while aged < 18 years were included. CD4% at restart of ART (r-ART) and in the long term (up to 24 months after r-ART) following the first TI was modelled using asymptotic regression. Results In 779 children with at least one TI, the median age at first TI was 10.1 [interquartile range (IQR) 6.4, 13.6] years and the mean CD4% was 27.3% [standard deviation (SD) 11.0%]; the median TI duration was 9.0 (IQR 3.5, 22.5) months. In regression analysis, the mean CD4% was 19.2% [95% confidence interval (CI) 18.3, 20.1%] at r-ART, and 27.1% (26.2, 27.9%) in the long term, with half this increase in the first 6 months. r-ART and long-term CD4% values were highest in female patients and in children aged < 3 years at the start of TI. Long-term CD4% was highest in those with a TI lasting 1 to <3 months, those with r-ART after year 2000 and those with a CD4% nadir ≥ 25% (all P < 0.001). The effect of CD4% nadir during the TI differed significantly (P = 0.038) by viral suppression at the start of the TI; in children with CD4% nadir < 15% during TI, recovery was better in those virally suppressed prior to the TI; viral suppression was not associated with recovery in children with CD4% nadir ≥ 25%. Conclusions After restart of ART following TI, most children reconstituted well immunologically. Nevertheless, several factors predicted better immunological reconstitution, including younger age and higher nadir CD4% during TI.
Journal of Blood & Lymph, 2017
Background: Highly active anti-retroviral therapy (HAART) has brought significant change in reducing morbidity and mortality among children living with HIV/AIDS. Decisions concerning initiation and/or shifting of antiretroviral therapy (ART) are guided by monitoring the laboratory parameters of plasma HIV RNA (viral load) and CD4+ T cell count in addition to the patient's over all clinical response. The demonstrations of the prognostic value of the CD4 cell count was of major importance in the development of therapeutic strategies. Therefore, the objective of this study was to assess factors predicting suboptimal CD4 cell recovery during first six months of ART. Methods: The study is retrospective cross sectional study to assess factors predicting suboptimal CD4 cell recovery. Medical records of patients' were retrieved and important variables are captured to standard questionnaire tool. T-test is used to assess changes in CD4 cell count after initiation of ART. Binary logistic and multiple regressions were used to assess factors predicting CD4 cell recovery. Results: Data of 360 children were analyzed. CD4 cell count at the start of HAART ranged from 3-2003 cell/mL with an interquartile range of 231-317 cell/mL. After 6 months of HAART, the CD4 cell count has increased ranging from 71-2300 cell/mL with inter quartile range of 458-612 cell/mL and mean CD4 cell count difference of 230, 95%CI (199.414-260.613); P<0.001. Advanced clinical stage of the disease, severe degree of immunosupression, presence of anemia, presence of chronic diarrhea at base line, poor weight gain during first six months of HAART adversely affect the trends of CD4 recovery. Conclusion: Our study demonstrated that advanced clinical stage of the disease, severe degree of immunosupression, presence of anemia at baseline and presence of chronic diarrhea, poor weight gain during first six months of HAART were factors adversely affect the trends of CD4 recovery.
AIDS, 2008
Background-The goal of HAART is to promote reconstitution of CD4 + T cells and other immune responses. We evaluated the extent and the kinetics of immune reconstitution in HIVinfected children over 144 weeks of successful HAART. Methods-Thirty-seven children receiving their first HAART regimen had plasma HIV RNA; T cells and subpopulations; T-cell rearrangement excision circles (TREC) DNA; candida, HIV CD4 and HIV CD8 enzyme-linked immunospot measured at regular intervals. Results-Plasma HIV RNA became undetectable in 81% of patients at 24 weeks and remained undetectable in 77% at 144 weeks. In contrast, CD4 + % continuously increased. Distribution of Tcell subpopulations changed rapidly during the first 48 weeks of HAART and more slowly thereafter. At 144 weeks, total, naive and activated CD4 + % and naive CD8 + % of HIV-infected children were not significantly different from those of healthy age-matched controls, whereas total and activated CD8 + % remained elevated. CD4 + and CD8 + TREC content increased only during the first 48 weeks of HAART. They positively correlated with each other and with total CD4 + %, naive CD4 + % and naive CD8 + %. Candida and HIV CD4 enzyme-linked immunospot increased over time reaching peak values at 48 weeks and 144 weeks, respectively. HIV CD8 enzyme-linked immunospot decreased in magnitude over 144 weeks of HAART but retained its breadth. Baseline CD4 + % positively correlated with CD4 + % and with functional immune reconstitution at week 144, whereas baseline TREC correlated with TREC at week 144. Conclusion-HIV-infected children acquired normal distribution of CD4 + T cells and other subpopulations and recovered CD4-mediated HIV immunity after 144 weeks of HAART.
Journal of the Pediatric Infectious Diseases Society, 2016
Regular CD4 count testing is often used to monitor antiretroviral therapy efficacy. However, this practice may be redundant in children with a suppressed human immunodeficiency virus (HIV) viral load. Study end points were as follows: (1) a CD4 count <200 cells/mm(3) followed by a CD4 count ≥200 cells/mm(3) (transient CD4 <200); (2) CD4 count <200 cells/mm(3) confirmed within 6 months (confirmed CD4 <200); and (3) a new or recurrent World Health Organization (WHO) stage 3 or 4 illness (clinical failure). Kaplan-Meier curves and Cox regression were used to evaluate rates and predictors of transient CD4 <200, confirmed CD4…
The Pediatric Infectious Disease Journal, 2001
Background. Highly active antiretroviral therapy (HAART) has brought about rapid declines in HIV-1 RNA concentrations and an increase in CD4 ؉ counts in HIV-1-infected children. These changes are often accompanied by clinical improvement; however, the extent to which immune reconstitution occurs is not known. Design. We compared two cohorts (n ؍ 35) of HIV-1-infected children to evaluate the effects of HAART on immune recovery. Cohort 1 (C1) included clinically well children receiving HAART with a CD4 >22% at study initiation. Before HAART all children had moderately to severely suppressed immune function by CDC criteria (CD4 <25%) or CDC Category B or C disease. Cohort 2 (C2) included children with no current or past evidence of immunosuppression based on CDC criteria (CD4 >25%) and no evidence of clinical disease. Children in C2 were receiving a non-HAART regimen. Methods. Immunophenotyping was performed to characterize CD4 ؉ and CD8 ؉ subsets with regard to maturation and activation. T cell rearrangement excision circles (TRECs) were measured to quantify recent thymic emigrants. Results. No difference was found in percent CD4 ؉ or percent CD8 ؉ T cells or maturation markers between C1 and C2. There was significantly less expression of activation markers in both CD4 ؉ and CD8 ؉ cells in C1. There was no difference in TREC production between C1 and C2. Conclusion. Moderately to severely suppressed HIV-1-infected children receiving HAART are able to reconstitute their immune systems to a degree that is indistinguishable from that of stable, CDC Class A1 HIV-1-infected children with regard to CD4 ؉ and CD8 ؉ T cell subsets, expression of cellular maturation markers and TREC production.
Aids Research and Human Retroviruses, 2002
In this study, we sought to characterize the T lymphocyte recovery in vertically HIV-1-infected children who respond to long-term highly active antiretroviral therapy (HAART). A 3-year longitudinal retrospective study was used to perform a cross-sectional study of 32 children rated according to the time course of CD4 1 T cell percentages in response to antiretroviral therapy and CDC clinical classification: (1) long-term asymptomatic (LTA group): 8 children in A1 during the whole follow-up period; (2) responsive to HAART (Rec group): 13 children in C3 before HAART who achieved CD4 1 T cell counts of .
AIDS Research and Treatment, 2011
Background. CD4+ T-lymphocyte monitoring is not routinely available in most resource-limited settings. We investigated predictors of time to CD4+ T-lymphocyte recovery in HIV-infected children on highly active antiretroviral (HAART) at Korle-Bu Teaching Hospital, Ghana.Methods. Time to CD4+ T-lymphocyte recovery was defined as achieving percent CD4+ T-lymphocytes of 25%. We used Cox proportional hazard models for identifying significant predictor variables.Results. Of the 233 children with complete CD4+ T-lymphocyte data, the mean age at HAART initiation was 5.5 (SD=3.1) years. The median recovery time was 60 weeks (95% CL: 55–65). Evidence at baseline of severe suppression in CD4+ T-lymphocyte count adjusted for age, age at HAART initiation, gender, and having parents alive were statistically significant in predicting time to CD4+ T-lymphocyte recovery.Conclusions. A targeted approach based on predictors of CD4+ T-lymphocyte recovery can be a viable and cost-effective way of monito...