Dataset Information

Responsiveness of T cells to interleukin-7 is associated with higher CD4+ T cell counts in HIV-1-positive individuals with highly active antiretroviral therapy-induced viral load suppression.

ABSTRACT: Despite suppression of the human immunodeficiency virus type 1 (HIV-1) load by highly active antiretroviral therapy (HAART), recovery of CD4+ T cell counts can be impaired. We investigated whether this impairment may be associated with hyporesponsiveness of T cells to gamma-chain (gammac) cytokines known to influence T cell homeostasis.The responsiveness of T cells to interleukin (IL)-2, IL-7, and IL-15 was determined by assessing cytokine-induced phosphorylation of the signal transducer and activator of transcription 5 (STAT5) in peripheral T cells obtained from 118 HIV-positive subjects and 13 HIV-negative subjects.The responsiveness of T cells to interleukin (IL)-7 but not to IL-2 or IL-15 was lower among HIV-positive subjects than among HIV-negative subjects. Among subjects with viral load suppression, the degree of IL-7 responsiveness (1) correlated with naive CD4+ T cell counts and was a better immune correlate of the prevailing CD4+ T cell count than were levels of human leukocyte antigen-DR1 or programmed death-1, which are predictors of T cell homeostasis during HIV infection; and (2) was greater in subjects with complete (i.e., attainment of >or=500 CD4+ T cells/mm3>or=5 years after initiation of HAART) versus incomplete immunologic responses. The correlation between plasma levels of IL-7 and CD4+ T cell counts during HAART was maximal in subjects with increased IL-7 responsiveness.Responsiveness of T cells to IL-7 is associated with higher CD4+ T cell counts during HAART and thus may be a determinant of the extent of immune reconstitution.

SUBMITTER: Camargo JF

PROVIDER: S-EPMC3777824 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Responsiveness of T cells to interleukin-7 is associated with higher CD4+ T cell counts in HIV-1-positive individuals with highly active antiretroviral therapy-induced viral load suppression.

Camargo Jose F JF Kulkarni Hemant H Agan Brian K BK Gaitan Alvaro A AA Beachy Lisa A LA Srinivas Sowmya S He Weijing W Anderson Stephanie S Marconi Vincent C VC Dolan Matthew J MJ Ahuja Sunil K SK

The Journal of infectious diseases 20090601 12

<h4>Background</h4>Despite suppression of the human immunodeficiency virus type 1 (HIV-1) load by highly active antiretroviral therapy (HAART), recovery of CD4+ T cell counts can be impaired. We investigated whether this impairment may be associated with hyporesponsiveness of T cells to gamma-chain (gammac) cytokines known to influence T cell homeostasis.<h4>Methods</h4>The responsiveness of T cells to interleukin (IL)-2, IL-7, and IL-15 was determined by assessing cytokine-induced phosphorylati ...[more]

PMID: 19432535

Similar Datasets

Project description:BackgroundEvidence favoring earlier HIV ART initiation at high CD4+ T-cell counts (CD4>350/uL) has grown, and guidelines now recommend earlier HIV treatment. However, the cost of providing ART to individuals with CD4>350 in Sub-Saharan Africa has not been well estimated. This remains a major barrier to optimal global cost projections for accelerating the scale-up of ART. Our objective was to compute costs of ART delivery to high CD4+count individuals in a typical rural Ugandan health center-based HIV clinic, and use these data to construct scenarios of efficient ART scale-up.MethodsWithin a clinical study evaluating streamlined ART delivery to 197 individuals with CD4+ cell counts >350 cells/uL (EARLI Study: NCT01479634) in Mbarara, Uganda, we performed a micro-costing analysis of administrative records, ART prices, and time-and-motion analysis of staff work patterns. We computed observed per-person-per-year (ppy) costs, and constructed models estimating costs under several increasingly efficient ART scale-up scenarios using local salaries, lowest drug prices, optimized patient loads, and inclusion of viral load (VL) testing.FindingsAmong 197 individuals enrolled in the EARLI Study, median pre-ART CD4+ cell count was 569/uL (IQR 451-716). Observed ART delivery cost was $628 ppy at steady state. Models using local salaries and only core laboratory tests estimated costs of $529/$445 ppy (+/-VL testing, respectively). Models with lower salaries, lowest ART prices, and optimized healthcare worker schedules reduced costs by $100-200 ppy. Costs in a maximally efficient scale-up model were $320/$236 ppy (+/- VL testing). This included $39 for personnel, $106 for ART, $130/$46 for laboratory tests, and $46 for administrative/other costs. A key limitation of this study is its derivation and extrapolation of costs from one large rural treatment program of high CD4+ count individuals.ConclusionsIn a Ugandan HIV clinic, ART delivery costs--including VL testing--for individuals with CD4>350 were similar to estimates from high-efficiency programs. In higher efficiency scale-up models, costs were substantially lower. These favorable costs may be achieved because high CD4+ count patients are often asymptomatic, facilitating more efficient streamlined ART delivery. Our work provides a framework for calculating costs of efficient ART scale-up models using accessible data from specific programs and regions.

Dataset Information

Responsiveness of T cells to interleukin-7 is associated with higher CD4+ T cell counts in HIV-1-positive individuals with highly active antiretroviral therapy-induced viral load suppression.

Publications

Responsiveness of T cells to interleukin-7 is associated with higher CD4+ T cell counts in HIV-1-positive individuals with highly active antiretroviral therapy-induced viral load suppression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets