Dataset Information

Current and Past Immunodeficiency Are Associated With Higher Hospitalization Rates Among Persons on Virologically Suppressive Antiretroviral Therapy for up to 11 Years.

ABSTRACT:

Background

Persons with human immunodeficiency virus (PWH) with persistently low CD4 counts despite efficacious antiretroviral therapy could have higher hospitalization risk.

Methods

In 6 US and Canadian clinical cohorts, PWH with virologic suppression for ≥1 year in 2005-2015 were followed until virologic failure, loss to follow-up, death, or study end. Stratified by early (years 2-5) and long-term (years 6-11) suppression and lowest presuppression CD4 count <200 and ≥200 cells/µL, Poisson regression models estimated hospitalization incidence rate ratios (aIRRs) comparing patients by time-updated CD4 count category, adjusted for cohort, age, gender, calendar year, suppression duration, and lowest presuppression CD4 count.

Results

The 6997 included patients (19 980 person-years) were 81% cisgender men and 40% white. Among patients with lowest presuppression CD4 count <200 cells/μL (44%), patients with current CD4 count 200-350 vs >500 cells/μL had aIRRs of 1.44 during early suppression (95% confidence interval [CI], 1.01-2.06), and 1.67 (95% CI, 1.03-2.72) during long-term suppression. Among patients with lowest presuppression CD4 count ≥200 (56%), patients with current CD4 351-500 vs >500 cells/μL had an aIRR of 1.22 (95% CI, .93-1.60) during early suppression and 2.09 (95% CI, 1.18-3.70) during long-term suppression.

Conclusions

Virologically suppressed patients with lower CD4 counts experienced higher hospitalization rates and could potentially benefit from targeted clinical management strategies.

SUBMITTER: Davy-Mendez T

PROVIDER: S-EPMC8366443 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

Current and Past Immunodeficiency Are Associated With Higher Hospitalization Rates Among Persons on Virologically Suppressive Antiretroviral Therapy for up to 11 Years.

Davy-Mendez Thibaut T Napravnik Sonia S Eron Joseph J JJ Cole Stephen R SR van Duin David D Wohl David A DA Hogan Brenna C BC Althoff Keri N KN Gebo Kelly A KA Moore Richard D RD Silverberg Michael J MJ Horberg Michael A MA Gill M John MJ Mathews W Christopher WC Klein Marina B MB Colasanti Jonathan A JA Sterling Timothy R TR Mayor Angel M AM Rebeiro Peter F PF Buchacz Kate K Li Jun J Nanditha Ni Gusti Ayu NGA Thorne Jennifer E JE Nijhawan Ank A Berry Stephen A SA

The Journal of infectious diseases 20201226 4

<h4>Background</h4>Persons with human immunodeficiency virus (PWH) with persistently low CD4 counts despite efficacious antiretroviral therapy could have higher hospitalization risk.<h4>Methods</h4>In 6 US and Canadian clinical cohorts, PWH with virologic suppression for ≥1 year in 2005-2015 were followed until virologic failure, loss to follow-up, death, or study end. Stratified by early (years 2-5) and long-term (years 6-11) suppression and lowest presuppression CD4 count <200 and ≥200 cells/µ ...[more]

PMID: 34398239

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Project description:BackgroundPersistence of latent, replication-competent provirus in CD4+ T cells of human immunodeficiency virus (HIV)-infected individuals on antiretroviral treatment (ART) is the main obstacle for virus eradication. Methylation of the proviral 5' long terminal repeat (LTR) promoter region has been proposed as a possible mechanism contributing to HIV latency; however, conflicting observations exist regarding its relevance. We assessed 5'-LTR methylation profiles in total CD4+ T cells from blood of 12 participants on short-term ART (30 months) followed up for 2 years, and a cross-sectional group of participants with long-term ART (6-15 years), using next generation sequencing. We then looked for associations between specific 5'-LTR methylation patterns and baseline and follow-up clinical characteristics.Results5'-LTR methylation was observed in all participants and behaved dynamically. The number of 5'-LTR variants found per sample ranged from 1 to 13, with median sequencing depth of 16270× (IQR 4107×-46760×). An overall significant 5'-LTR methylation increase was observed at month 42 compared to month 30 (median CpG Methylation Index: 74.7% vs. 0%, p = 0.025). This methylation increase was evident in a subset of participants (methylation increase group), while the rest maintained fairly high and constant methylation (constant methylation group). Persons in the methylation increase group were younger, had higher CD4+ T cell gain, larger CD8% decrease, and larger CD4/CD8 ratio change after 48 months on ART (all p < 0.001). Using principal component analysis, the constant methylation and methylation increase groups showed low evidence of separation along time (factor 2: p = 0.04). Variance was largely explained (21%) by age, CD4+/CD8+ T cell change, and CD4+ T cell subpopulation proportions. Persons with long-term ART showed overall high methylation (median CpG Methylation Index: 78%; IQR 71-87%). No differences were observed in residual plasma viral load or proviral load comparing individuals on short-term (both at 30 or 42 months) and long-term ART.ConclusionsOur study shows evidence that HIV 5'-LTR methylation in total CD4+ T cells is dynamic along time and that it can follow different temporal patterns that are associated with a combination of baseline and follow-up clinical characteristics. These observations may account for differences observed between previous contrasting studies.

Dataset Information

Current and Past Immunodeficiency Are Associated With Higher Hospitalization Rates Among Persons on Virologically Suppressive Antiretroviral Therapy for up to 11 Years.

Background

Methods

Results

Conclusions

Publications

Current and Past Immunodeficiency Are Associated With Higher Hospitalization Rates Among Persons on Virologically Suppressive Antiretroviral Therapy for up to 11 Years.

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