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Association of Risk of Viremia, Immunosuppression, Serious Clinical Events, and Mortality With Increasing Age in Perinatally Human Immunodeficiency Virus-Infected Youth.

ABSTRACT: Importance:As perinatally human immunodeficiency virus-infected youth (PHIVY) in the United States grow older and more treatment experienced, clinicians need updated information about the association of age, CD4 cell count, viral load (VL), and antiretroviral (ARV) drug use with risk of opportunistic infections, key clinical events, and mortality to understand patient risks and improve care. Objective:To examine the incidence or first occurrence during follow-up of key clinical events (including Centers for Disease Control and Prevention stage B [CDC-B] and stage C [CDC-C] events) and mortality among PHIVY stratified by age, CD4 cell count, and VL and ARV status. Design, Setting, and Participants:Combining data from the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol and International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1074 multicenter cohort studies (March 2007 through April 2015), we estimated event rates during person-time spent in key strata of age (7-12, 13-17, and 18-30 years), CD4 cell count (<200, 200-499, and ?500/?L), and a combined measure of VL and ARV status (VL <400 or ?400 copies/mL; ARV therapy or no ARV therapy). A total of 1562 participants in the PHACS Adolescent Master Protocol and IMPAACT P1074 were eligible, and 1446 PHIVY from 41 ambulatory sites in the 12 US states, including Puerto Rico were enrolled. The dates of analysis were March 2015 through January 2017. Main Outcomes and Measures:Clinical event rates stratified by person-time in age, CD4 cell count, and VL and ARV categories. Results:A total of 1446 PHIVY participated in the study (mean [SD] age, 14.6 [4.6] years; 759 female [52.5%]; 953 black [65.9%]). During a mean (SD) follow-up of 4.9 (1.3) years, higher incidences of CDC-B events, CDC-C events, and mortality were observed as participants aged. Older PHIVY (aged 13-17 and 18-30 years) spent more time with a VL of 400 copies/mL or more and with a CD4 cell count of less than 200/µL compared with 7- to 12-year-old participants (30% and 44% vs 22% of person-time with a VL?400 copies/mL; 5% and 18% vs 2% of person-time with CD4 cell count <200/µL; P?

SUBMITTER: Neilan AM

PROVIDER: S-EPMC5411314 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Association of Risk of Viremia, Immunosuppression, Serious Clinical Events, and Mortality With Increasing Age in Perinatally Human Immunodeficiency Virus-Infected Youth.

Neilan Anne M AM Karalius Brad B Patel Kunjal K Van Dyke Russell B RB Abzug Mark J MJ Agwu Allison L AL Williams Paige L PL Purswani Murli M Kacanek Deborah D Oleske James M JM Burchett Sandra K SK Wiznia Andrew A Chernoff Miriam M Seage George R GR Ciaranello Andrea L AL

JAMA pediatrics 20170501 5

<h4>Importance</h4>As perinatally human immunodeficiency virus-infected youth (PHIVY) in the United States grow older and more treatment experienced, clinicians need updated information about the association of age, CD4 cell count, viral load (VL), and antiretroviral (ARV) drug use with risk of opportunistic infections, key clinical events, and mortality to understand patient risks and improve care.<h4>Objective</h4>To examine the incidence or first occurrence during follow-up of key clinical ev ...[more]

PMID: 28346597

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Project description:ObjectiveTo evaluate associations between human immunodeficiency virus (HIV) disease severity and psychiatric and functional outcomes in youth with perinatal HIV infection.DesignCross-sectional analysis of entry data from an observational,prospective 2-year study.Logistic and linear regression models adjusted for potential confounders were used.SettingTwenty-nine sites of the International Maternal Pediatrics Adolescent AIDS Clinical Trials Group study in the United States and Puerto Rico.ParticipantsYouth aged 6 to 17 years who had HIV infection (N=319).Main exposuresAntiretroviral treatment and perinatal HIV infection.Main outcome measuresYouth and primary caregivers were administered an extensive battery of measures that assessed psychiatric symptoms; cognitive, social,and academic functioning; and quality of life.ResultsCharacteristics of HIV were a current CD4 percentage of 25% or greater (74% of participants), HIV RNA levels of less than 400 copies/mL (59%), and current highly active antiretroviral therapy (81%). Analyses indicated associations of past and current Centers for Disease Control and Prevention class C designation with less severe attention-deficit/hyperactivity disorder inattention symptoms,older age at nadir CD4 percentage and lower CD4 percentage at study entry with more severe conduct disorder symptoms,higher RNA viral load at study entry with more severe depression symptoms, and lower CD4 percentage atstudy entry with less severe symptoms of depression. There was little evidence of an association between specific antiretroviral therapy and severity of psychiatric symptoms.A lower nadir CD4 percentage was associated with lower quality of life, worse Wechsler Intelligence Scale for Children Coding Recall scores, and worse social functioning.ConclusionHuman immunodeficiency virus illness severity markers are associated with the severity of some psychiatric symptoms and, notably, with cognitive, academic,and social functioning, all of which warrant additional study.

Project description:BackgroundIncreased incidence and prevalence of asthma have been documented for perinatally HIV-infected youth 10 to 21 years of age compared with HIV-exposed uninfected (HEU) youth.ObjectiveWe sought to perform objective pulmonary function tests (PFTs) in HIV-infected and HEU youth with and without diagnosed asthma.MethodAsthma was determined in 370 participants (218 HIV-infected and 152 HEU participants) by means of chart review and self-report at 13 sites. Interpretable PFTs (188 HIV-infected and 132 HEU participants) were classified as obstructive, restrictive, or normal, and reversibility was determined after bronchodilator inhalation. Values for HIV-1 RNA, CD4 and CD8 T cells, eosinophils, total IgE, allergen-specific IgE, and urinary cotinine were measured. Adjusted prevalence ratios (PRs) of asthma and PFT outcomes were determined for HIV-infected participants relative to HEU participants, controlling for age, race/ethnicity, and sex.ResultsCurrent asthma was identified in 75 (34%) of 218 HIV-infected participants and 38 (25%) of 152 HEU participants (adjusted PR, 1.33; P = .11). The prevalence of obstructive disease did not differ by HIV status. Reversibility was less likely in HIV-infected youth than in HEU youth (17/183 [9%] vs 21/126 [17%]; adjusted PR, 0.47; P = .020) overall and among just those with obstructive PFT results (adjusted PR, 0.46; P = .016). Among HIV-infected youth with current asthma, serum IgE levels were inversely correlated with CD8 T-cell counts and positively correlated with eosinophil counts and not associated with CD4 T-cell counts. HIV-infected youth had lower association of specific IgE levels to several inhalant and food allergens compared with HEU participants and significantly lower CD4/CD8 T-cell ratios (suggesting immune imbalance).ConclusionCompared with HEU youth, HIV-infected youth demonstrated decreased reversibility of obstructive lung disease, which is atypical of asthma. This might indicate an early stage of chronic obstructive pulmonary disease. Follow-up into adulthood is warranted to further define their pulmonary outcomes.

Dataset Information

Association of Risk of Viremia, Immunosuppression, Serious Clinical Events, and Mortality With Increasing Age in Perinatally Human Immunodeficiency Virus-Infected Youth.

Publications

Association of Risk of Viremia, Immunosuppression, Serious Clinical Events, and Mortality With Increasing Age in Perinatally Human Immunodeficiency Virus-Infected Youth.

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