Dataset Information

Regulatory T Cells, Frailty, and Immune Activation in Men Who Have Sex With Men in the Multicenter AIDS Cohort Study.

ABSTRACT: Both HIV infection and frailty have been associated with chronic immune activation. One possible explanation for this chronic immune activation could be low levels of CD4(+) T regulatory cells (Tregs), which suppress immune responses.HIV-uninfected (HIV-) and HIV-infected (HIV+) men in the Multicenter AIDS Cohort Study (MACS) were classified as frail (or nonfrail) if they expressed (or did not express) the Fried frailty phenotype at two consecutive study visits. Percentages and absolute numbers of total Tregs, and percentages of different subsets of Tregs and of activated T cells were measured by flow cytometry. The function of Tregs was measured by suppression of T-cell proliferation.Percentages of Tregs were higher, rather than lower, in frail men than in nonfrail men, and this difference was significant for HIV- men. Percentages of subsets of Tregs did not differ significantly by frailty status. Among HIV+ men, the suppressive function of Tregs was similar between frail and nonfrail men. Percentages of Tregs and activated T cells were negatively correlated in nonfrail men (HIV- and HIV+) and in frail HIV- men, but this correlation was strongly positive in frail HIV+ men.These data suggest that: (a) Tregs were not deficient in frail men; and (b) the immunological pathophysiology of frailty may differ by HIV status.

SUBMITTER: Zhang W

PROVIDER: S-EPMC4751226 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Regulatory T Cells, Frailty, and Immune Activation in Men Who Have Sex With Men in the Multicenter AIDS Cohort Study.

Zhang Weiying W Nilles Tricia L TL Johnson Jacquett R JR Margolick Joseph B JB

The journals of gerontology. Series A, Biological sciences and medical sciences 20150822 12

<h4>Background</h4>Both HIV infection and frailty have been associated with chronic immune activation. One possible explanation for this chronic immune activation could be low levels of CD4(+) T regulatory cells (Tregs), which suppress immune responses.<h4>Methods</h4>HIV-uninfected (HIV-) and HIV-infected (HIV+) men in the Multicenter AIDS Cohort Study (MACS) were classified as frail (or nonfrail) if they expressed (or did not express) the Fried frailty phenotype at two consecutive study visits ...[more]

PMID: 26297938

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Project description:ObjectiveWe evaluated trends and population effectiveness (tolerability, HIV suppression) of current combination antiretroviral therapy (cART) regimens mindful of treatment guidelines.MethodTrend analyses included 18 017 person-visits (1457 men) on cART during 2008-2017 in the Multicenter AIDS Cohort Study. Effectiveness analyses of current regimens used 3598 person-visit-pairs (745 men) on cART in 2014-2017. Inverse-probability-of-treatment-and-censoring weighted Poisson regression with robust variances was used to evaluate the association between regimens and switching, adherence and HIV RNA <20 copies/mL.ResultsIntegrase strand transfer inhibitor (INSTI)-based regimen usage has increased since 2008. Almost 90% of cART initiators started with INSTI-cART in 2016-2017; cART adherence was stable around 90% and 83%-85% suppressed virus (<20 cp/mL). Commonly used regimens in 2014-2017 contained disoproxil fumarate/emtricitabine (TDF/FTC) backbone with efavirenz (EFV, n = 1161 person-visits), elvitegravir/cobicistat (EVG/c, n = 551), rilpivirine (RPV, n = 492), darunavir/ritonavir (DRV/r, n = 351), or atazanavir (ATV)/r (n = 333). Others were dolutegravir/abacavir/lamivudine (DTG/ABC/3TC, n = 401) and EVG/c/tenofovir alafenamide/FTC (EVG/c/TAF/FTC, n = 309). Compared to EFV/TDF/FTC users, ATV/r+TDF/FTC users switched more (rate ratio [RR] = 1.80, 95% confidence interval (CI), 1.17-2.76), while those on DTG/ABC/3TC (RR [95% CI] = 0.16 [0.08-0.31]) or EVG/c/TAF/FTC (RR [95% CI] = 0.12 [0.06-0.27]) switched less. The rate of suppressed HIV RNA was 15% (95% CI, 2%-26%) lower among younger EVG/c/TDF/FTC users and 18% (95% CI, 3%-34%) higher in older DRV/r+TDF/FTC users; adherence did not differ by regimen.ConclusionsConsistent with guidelines, recent cART initiators started with INSTI-cART, which was associated with less switching early after initiation. Factors beyond those studied here, such as need for salvage therapy, unique personal characteristics, drug interactions, and cost may influence treatment decisions.

Dataset Information

Regulatory T Cells, Frailty, and Immune Activation in Men Who Have Sex With Men in the Multicenter AIDS Cohort Study.

Publications

Regulatory T Cells, Frailty, and Immune Activation in Men Who Have Sex With Men in the Multicenter AIDS Cohort Study.

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