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Antiretroviral treatment of US children with perinatally acquired HIV infection: temporal changes in therapy between 1991 and 2009 and predictors of immunologic and virologic outcomes.

ABSTRACT: Advances in therapy have allowed children with perinatal HIV infection in the United States to survive into adolescence. We sought to describe the disease status of a large cohort of such children and identify predictors of their current CD4 count and HIV viral load (VL).The Pediatric HIV/AIDS Cohort Study AMP Protocol is an ongoing prospective study conducted at 15 sites in the United States. Between 2007 and 2009, we enrolled a population-based sample of 451 children with perinatal HIV who were 7-16 years of age at entry.The median age of subjects at entry was 12.2 years, 53% were female, 70% were African-American, and 24% Hispanic. Their median entry CD4% was 33%, and 78% had a CD4% ?25%; 68% had a suppressed VL. The more recent birth cohorts (1994-2002) had a significantly higher CD4% over time than the earliest birth cohort (1991-1993). The significant independent predictors of a higher CD4% at entry were a suppressed entry VL, a higher nadir CD4%, and starting antiretroviral therapy at a younger age. The mean CD4% at entry for children with a nadir CD4% ?25% was 9.5% higher than for those with a nadir CD4% <15% (P < 0.001). Independent predictors of a suppressed entry VL were membership in a recent birth cohort, male gender, highly active combination antiretroviral therapy use at entry, and fewer prior antiretroviral therapy regimens.Most children with perinatal HIV maintain virologic suppression and good CD4 values. Earlier treatment results in better immune outcome.

SUBMITTER: Van Dyke RB

PROVIDER: S-EPMC3125481 | biostudies-other | 2011 Jun

REPOSITORIES: biostudies-other

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Antiretroviral treatment of US children with perinatally acquired HIV infection: temporal changes in therapy between 1991 and 2009 and predictors of immunologic and virologic outcomes.

Van Dyke Russell B RB Patel Kunjal K Siberry George K GK Burchett Sandra K SK Spector Stephen A SA Chernoff Miriam C MC Read Jennifer S JS Mofenson Lynne M LM Seage George R GR

Journal of acquired immune deficiency syndromes (1999) 20110601 2

<h4>Background</h4>Advances in therapy have allowed children with perinatal HIV infection in the United States to survive into adolescence. We sought to describe the disease status of a large cohort of such children and identify predictors of their current CD4 count and HIV viral load (VL).<h4>Methods</h4>The Pediatric HIV/AIDS Cohort Study AMP Protocol is an ongoing prospective study conducted at 15 sites in the United States. Between 2007 and 2009, we enrolled a population-based sample of 451 ...[more]

PMID: 21407086

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Project description:INTRODUCTION:Directly observed therapy of highly active antiretroviral therapy (DOT-HAART) is a feasible adherence intervention. Prospective DOT-HAART studies have shown mixed results, and optimal target groups have yet to be defined. We performed a meta-analysis and systematic review to assess the effect of DOT-HAART on adherence and virologic and immunologic response. METHODS:We performed a comprehensive search through August 2009 to identify peer-reviewed controlled studies that involved outpatient DOT-HAART among adults and reported at least 1 outcome assessed in this meta-analysis. Random-effects meta-analyses were performed; differences in effect on virologic suppression were examined using stratified meta-analyses and meta-regression on several study characteristics. RESULTS:Seventeen studies met inclusion criteria. Compared with control groups, DOT-HAART recipients were more likely to achieve an undetectable viral load (random effects risk ratio 1.24, 95% confidence interval (CI): 1.08 to 1.41), a greater increase in CD4 cell count (random effects weighted mean difference 43 cells/microL, 95% CI: 12 to 74 cells/microL), and HAART adherence of > or =95% (random effects risk ratio 1.17, 95% CI: 1.03 to 1.32). Results varied with respect to virologic response. DOT-HAART did not have a significant effect on virologic suppression when restricted to randomized controlled studies. Post-treatment effect was not observed in a limited number of studies. CONCLUSIONS:DOT-HAART had a significant effect on virologic, immunologic, and adherence outcomes, although its efficacy was not supported when restricting analysis to randomized controlled trials. DOT-HAART shows greatest treatment effect when targeting individuals with greater risk of nonadherence and when delivering the intervention that maximizes participant convenience and provides enhanced adherence support. Further investigation is needed to assess the postintervention effect and cost-effectiveness of DOT-HAART.

Project description:BackgroundSwitch from first to second-line ART is recommended by WHO for patients with virologic failure. Delays in switching may contribute to accumulated drug resistance, advanced immunosuppression, increased morbidity and mortality. The 3rd 90' of UNAIDS 90:90:90 targets 90% viral suppression for persons on ART. We evaluated the rate of switching to second-line antiretroviral therapy (ART), and the impact of delayed switching on immunologic, virologic, and mortality outcomes in the Rakai Health Sciences Program (RHSP) Clinical Cohort Study which started providing ART in 2004 and implemented 6 monthly routine virologic monitoring beginning in 2005.MethodsRetrospective cohort study of HIV-infected adults on first-line ART who had two consecutive viral loads (VLs) >1000 copies/ml after 6 months on ART between June 2004 and June 2011 was studied for switching to second-line ART. Immunologic decline after virologic failure was defined as decrease in CD4 count of ≥50 cells/ul and virologic increase was defined as increase of 0.5 log 10 copies/ml. Competing risk models were used to summarize rates of switching to second-line ART while cox proportional hazard marginal structural models were used to assess the risk of virologic increase or immunologic decline associated with delay to switch first line ART failing patients.ResultsThe cumulative incidence of switching at 6, 12, and 24 months following virologic failure were 30.2%, 44.6%, and 65.0%, respectively. The switching rate was increased with higher VL at the time of virologic failure; compared to those with VLs ≤ 5000 copies/ml, patients with VLs = 5001-10,000 copies/ml had an aHR = 1.81 (95% CI = 0.9-3.6), and patients with VLs > 10,000 copies/ml had an aHR = 3.38 (95%CI = 1.9-6.2). The switching rate was also increased with CD4 < 100 cells/ul at ART initiation, compared to those with CD4 ≥ 100 cells/ul (aHR = 2.30, 95% CI = 1.5-3.6). Mortality in patients not switched to second-line ART was 11.9%, compared to 1.2% for those who switched (p = 0.009). Patients switched after 12 months of of virologic failure were more likely to experience CD4 decline and/or further VL increases.ConclusionsIntervention strategies that aid clinicians to promptly switch patients to second-line ART as soon as virologic failure on 1st line ART is confirmed should be prioritized.

Dataset Information

Antiretroviral treatment of US children with perinatally acquired HIV infection: temporal changes in therapy between 1991 and 2009 and predictors of immunologic and virologic outcomes.

Publications

Antiretroviral treatment of US children with perinatally acquired HIV infection: temporal changes in therapy between 1991 and 2009 and predictors of immunologic and virologic outcomes.

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