Dataset Information

Pre-cART Elevation of CRP and CD4+ T-Cell Immune Activation Associated With HIV Clinical Progression in a Multinational Case-Cohort Study.

ABSTRACT: BACKGROUND:Despite the success of combination antiretroviral therapy (cART), a subset of HIV-infected patients who initiate cART develop early clinical progression to AIDS; therefore, some cART initiators are not fully benefitted by cART. Immune activation pre-cART may predict clinical progression in cART initiators. METHODS:A case-cohort study (n = 470) within the multinational Prospective Evaluation of Antiretrovirals in Resource-Limited Settings clinical trial (1571 HIV treatment-naive adults who initiated cART; CD4 T-cell count <300 cells/mm; 9 countries) was conducted. A subcohort of 30 participants per country was randomly selected; additional cases were added from the main cohort. Cases [n = 236 (random subcohort 36; main cohort 200)] had clinical progression (incident WHO stage 3/4 event or death) within 96 weeks after cART initiation. Immune activation biomarkers were quantified pre-cART. Associations between biomarkers and clinical progression were examined using weighted multivariable Cox-proportional hazards models. RESULTS:Median age was 35 years, 45% were women, 49% black, 31% Asian, and 9% white. Median CD4 T-cell count was 167 cells per cubic millimeter. In multivariate analysis, highest quartile C-reactive protein concentration [adjusted hazard ratio (aHR), 2.53; 95% confidence interval (CI): 1.02 to 6.28] and CD4 T-cell activation (aHR, 5.18; 95% CI: 1.09 to 24.47) were associated with primary outcomes, compared with lowest quartiles. sCD14 had a trend toward association with clinical failure (aHR, 2.24; 95% CI: 0.96 to 5.21). CONCLUSIONS:Measuring C-reactive protein and CD4 T-cell activation may identify patients with CD4 T-cell counts <300 cells per cubic millimeter at risk for early clinical progression when initiating cART. Additional vigilance and symptom-based screening may be required in this subset of patients even after beginning cART.

SUBMITTER: Balagopal A

PROVIDER: S-EPMC4573329 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Pre-cART Elevation of CRP and CD4+ T-Cell Immune Activation Associated With HIV Clinical Progression in a Multinational Case-Cohort Study.

Balagopal Ashwin A Asmuth David M DM Yang Wei-Teng WT Campbell Thomas B TB Gupte Nikhil N Smeaton Laura L Kanyama Cecilia C Grinsztejn Beatriz B Santos Breno B Supparatpinyo Khuanchai K Badal-Faesen Sharlaa S Lama Javier R JR Lalloo Umesh G UG Zulu Fatima F Pawar Jyoti S JS Riviere Cynthia C Kumarasamy Nagalingeswaran N Hakim James J Li Xiao-Dong XD Pollard Richard B RB Semba Richard D RD Thomas David L DL Bollinger Robert C RC Gupta Amita A

Journal of acquired immune deficiency syndromes (1999) 20151001 2

<h4>Background</h4>Despite the success of combination antiretroviral therapy (cART), a subset of HIV-infected patients who initiate cART develop early clinical progression to AIDS; therefore, some cART initiators are not fully benefitted by cART. Immune activation pre-cART may predict clinical progression in cART initiators.<h4>Methods</h4>A case-cohort study (n = 470) within the multinational Prospective Evaluation of Antiretrovirals in Resource-Limited Settings clinical trial (1571 HIV treatme ...[more]

PMID: 26017661

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Project description:Background & aimsNutritional deficiency and inflammation may impact CD4+ T cell recovery during combination antiretroviral therapy (cART), particularly in resource-limited settings where malnutrition is prevalent. The aim of this study was to investigate the relationship of micronutrient and inflammation biomarkers to CD4 recovery after cART initiation.MethodsWe conducted a secondary analysis of a random sub-cohort sample (n = 270) from a multinational randomized trial of cART regimen efficacy among 1571 cART-naïve adults. We measured pre-cART serum levels of micronutrients (Vitamin A, B6, B12, D, total carotenoids, selenium, and iron) and inflammation (C-reactive protein, soluble CD14 (sCD14), IFNγ, TNFα, Interleukin-6, and C-X-C motif chemokine 10 (CXCL10/IP10), EndoCab (IgM)) biomarkers. Biomarker status (i.e. micronutrient deficiency vs. sufficiency and elevated vs. low inflammation) was defined using established cutoffs or quartiles. Mixed-effects linear regression models were used to determine the association of baseline (pre-cART) concentrations of individual biomarkers with CD4 recovery through 96 weeks post-cART initiation.ResultsIn models adjusting for time-dependent viral load and baseline CD4 count, age, sex, body mass index, country, treatment regimen, anemia and hypoalbuminemia status, pre-cART vitamin D deficiency was associated with lower CD4 recovery (-14.9 cells/mm3, 95% CI: -27.9, -1.8) compared to sufficiency. In contrast, baseline selenium deficiency (20.8 cells/mm3, 95% CI: 3.3, 38.3), vitamin A deficiency (35.9 cells/mm3, 95% CI: 17.6, 54.3) and high sCD14 (23.4 cells/mm3, 95% CI: 8.9, 37.8) were associated with higher CD4 recovery compared to sufficient/low inflammation status.ConclusionsIn summary, baseline vitamin D deficiency was associated with diminished CD4 recovery after cART initiation; impaired CD4 recovery may contribute to the poor clinical outcomes recently observed in individuals with vitamin D deficiency. Vitamin A, selenium and sCD14 were associated with CD4 recovery but future studies are needed to further explore these relationships.

Project description:BackgroundYouth have residual thymic tissue and potentially greater capacity for immune reconstitution than adults after initiation of combination antiretroviral therapy (cART). However, youth face behavioral and psychosocial challenges that may make them more likely than adults to delay ART initiation and less likely to attain similar CD4 outcomes after initiating cART. This study compared CD4 outcomes over time following cART initiation between ART-naïve non-perinatally HIV-infected (nPHIV) youth (13-24 years-old) and adults (?25-44 years-old).MethodsRetrospective analysis of ART-naïve nPHIV individuals 13-44 years-old, who initiated their first cART between 2008 and 2011 at clinical sites in the HIV Research Network. A linear mixed model was used to assess the association between CD4 levels after cART initiation and age (13-24, 25-34, 35-44 years), accounting for random variation within participants and between sites, and adjusting for key variables including gender, race/ethnicity, viral load, gaps in care (defined as > 365 days between CD4 tests), and CD4 levels prior to cART initiation (baseline CD4).ResultsAmong 2,595 individuals (435 youth; 2,160 adults), the median follow-up after cART initiation was 179 weeks (IQR 92-249). Baseline CD4 was higher for youth (320 cells/mm3) than for ages 25-34 (293) or 35-44 (258). At 239 weeks after cART initiation, median unadjusted CD4 was higher for youth than adults (576 vs. 539 and 476 cells/mm3, respectively), but this difference was not significant when baseline CD4 was controlled. Compared to those with baseline CD4 ?200 cells/mm3, individuals with baseline CD4 of 201-500 and >500 cells/mm3 had greater predicted CD4 levels: 390, 607, and 831, respectively. Additionally, having no gaps in care and higher viral load were associated with better CD4 outcomes.ConclusionsDespite having residual thymic tissue, youth attain similar, not superior, CD4 gains as adults. Early ART initiation with minimal delay is as essential to optimizing outcomes for youth as it is for their adult counterparts.

Dataset Information

Pre-cART Elevation of CRP and CD4+ T-Cell Immune Activation Associated With HIV Clinical Progression in a Multinational Case-Cohort Study.

Publications

Pre-cART Elevation of CRP and CD4+ T-Cell Immune Activation Associated With HIV Clinical Progression in a Multinational Case-Cohort Study.

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