Dataset Information

People with HIV have higher percentages of circulating CCR5+ CD8+ T cells and lower percentages of CCR5+ regulatory T cells.

ABSTRACT: CCR5 is the main HIV co-receptor. We aimed to (1) compare CCR5 expression on immune cells between people living with HIV (PLHIV) using combination antiretroviral therapy (cART) and HIV-uninfected controls, (2) relate CCR5 expression to viral reservoir size and (3) assess determinants of CCR5 expression. This cross-sectional study included 209 PLHIV and 323 controls. Percentages of CCR5+ cells (%) and CCR5 mean fluorescence intensity assessed by flow cytometry in monocytes and lymphocyte subsets were correlated to host factors, HIV-1 cell-associated (CA)-RNA and CA-DNA, plasma inflammation markers and metabolites. Metabolic pathways were identified. PLHIV displayed higher percentages of CCR5+ monocytes and several CD8+ T cell subsets, but lower percentages of CCR5+ naive CD4+ T cells and regulatory T cells (Tregs). HIV-1 CA-DNA and CA-RNA correlated positively with percentages of CCR5+ lymphocytes. Metabolome analysis revealed three pathways involved in energy metabolism associated with percentage of CCR5+ CD8+ T cells in PLHIV. Our results indicate that CCR5 is differently expressed on various circulating immune cells in PLHIV. Hence, cell-trafficking of CD8+ T cells and Tregs may be altered in PLHIV. Associations between energy pathways and percentage of CCR5+ CD8+ T cells in PLHIV suggest higher energy demand of these cells in PLHIV.

SUBMITTER: van Eekeren LE

PROVIDER: S-EPMC9259737 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BACKGROUND:PRO 140 (a humanized form of the PA14 antibody, a monoclonal CCR5 antibody) inhibits CCR5-tropic (R5) type 1 human immunodeficiency virus (HIV). This may be an effective new treatment with the potential to address the limitations of currently available therapies for HIV-infected patients. OBJECTIVES:We aimed to assess the efficacy, safety, clinical disease progression and immunologic (CD4 count/percentage) and virologic (plasma HIV RNA viral load) markers of PRO 140 for HIV-infected patients in randomized controlled trials (RCTs) and quasi-randomized controlled trials (quasi-RCTs). SEARCH METHODS:We searched databases including The Cochrane Central Register of Controlled Trials (The Cochrane Library 2014, Issue 4), MEDLINE (PubMed, January 1966 to April 2014), EMBASE (January 1978 to April 2014) and ISI Web of Knowledge (January 1966 to April 2014), online trials registries and other sources. We also screened the reference lists of related literature and eligible studies, and presentations from major HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) conferences. SELECTION CRITERIA:We included RCTs and quasi-RCTs comparing PRO 140 with placebo or other antiretroviral drugs, or different doses of PRO 140 for individuals infected with HIV. DATA COLLECTION AND ANALYSIS:Two reviewers (L Li and JH Tian) independently screened all retrieved citations and selected eligible studies. Two authors (P Zhang and WQ Jia) independently extracted data. Any disagreements when selecting studies and extracting data were adjudicated by the review mentor (KH Yang). We used Review Manager (RevMan) software for statistical analysis based on an intention-to-treat analysis. We examined heterogeneity using the Chi(2) statistic. We regarded I(2) estimates greater than 50% as moderate or high levels of heterogeneity. According to the level of heterogeneity, we used either a fixed or random-effects model.If significant heterogeneity existed and the reasons could not be found, we reported the results qualitatively. MAIN RESULTS:We included three trials comparing PRO 140 with placebo in adult patients with HIV infection. Our review indicates that PRO 140 may offer significant dose-dependent HIV-1 RNA suppression with tolerable side effects. PRO 140 2 mg/kg, 5 mg/kg, 10 mg/kg, 162 mg weekly, 324 mg biweekly, and 324 mg weekly showed statistically significant differences in the changes of HIV-1 RNA levels. HIV-1 RNA levels were reduced by intravenous (IV) infusion of PRO 140 2 mg/kg or 5 mg/kg on day 10, 5 mg/kg or 10 mg/kg on day 12, 162 mg weekly, 324 mg biweekly, or 324 mg weekly on day 22. PRO 140 2 mg/kg, 5 mg/kg, 10 mg/kg, 162 mg weekly, 324 mg biweekly, and 324 mg weekly demonstrated greater antiviral response. PRO 140 324 mg weekly, 5 mg/kg, and 10 mg/kg showed more patients with ? 400 copies/mL HIV-1 RNA. Only PRO 140 5 mg/kg showed greater change in CD4(+) cell count on day eight. Headache, lymphadenopathy, diarrhoea, fatigue, hypertension, nasal congestion and pruritus were reported to be the most frequent adverse events. AUTHORS' CONCLUSIONS:Limited evidence from three small trials suggests that PRO 140 might demonstrate potent, short-term, dose-dependent, highly significant antiviral activity. However, as the evidence is insufficient, recommendations cannot yet be made. Larger, longer-term, double-blind RCTs are required to provide conclusive evidence.

Dataset Information

People with HIV have higher percentages of circulating CCR5+ CD8+ T cells and lower percentages of CCR5+ regulatory T cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets