Baseline Natural Killer and T Cell Populations Correlation with Virologic Outcome after Regimen Simplification to Atazanavir/Ritonavir Alone (ACTG 5201)
Year: 2014
Type: article
Abstract: OBJECTIVES: Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/r) provides an alternative treatment option for HIV-1 infection that spares nucleoside analogs (NRTI) for future use and decreased toxicity. We hypothesized that the level of immune activation (IA) and recovery of lymphocyte populations could influence virologic outcomes after regimen simplification. METHODS: Thirty-four participants with virologic suppression ≥ 48 weeks on antiretroviral therapy (2 NRTI plus protease inhibitor) were switched to ATV/r alone in the context of the ACTG 5201 clinical trial. Flow cytometric analyses were performed on PBMC isolated from 25 patients with available samples, of which 24 had lymphocyte recovery sufficient for this study. Assessments included enumeration of T-cells (CD4/CD8), natural killer (NK) (CD3+CD56+CD16+) cells and cell-associated markers (HLA-DR, CD's 38/69/94/95/158/279). RESULTS: Eight of the 24 patients had at least one plasma HIV-1 RNA level (VL) >50 copies/mL during the study. NK cell levels below the group median of 7.1% at study entry were associated with development of VL >50 copies/mL following simplification by regression and survival analyses (p = 0.043 and 0.023), with an odds ratio of 10.3 (95% CI: 1.92-55.3). Simplification was associated with transient increases in naïve and CD25+ CD4+ T-cells, and had no impact on IA levels. CONCLUSIONS: Lower NK cell levels prior to regimen simplification were predictive of virologic rebound after discontinuation of nucleoside analogs. Regimen simplification did not have a sustained impact on markers of IA or T lymphocyte populations in 48 weeks of clinical monitoring. TRIAL REGISTRATION: ClinicalTrials.gov NCT00084019.
Source: PLoS ONE
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Funders: Pfizer, Gilead Sciences, University of Nebraska Medical Center, Ohio State University, University of Texas Southwestern Medical Center, University of Pittsburgh, University of Cincinnati, ACT Government, National Institutes of Health, Weill Cornell Medical College, University of North Carolina at Chapel Hill, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Center for Research Resources
Awards: G1003640026, G1158968046, G1274611523, G1535406927, G160820906, G2088232294, G2157454218, G2328791590, G2368841045, G3013054560, G3219051927, University of Pittsburgh Clinical and Translational Science Institute, G3810609436, G3922356, G4553935269, G4649361189, G517149770, Integrated University of Puerto Rico Clinical Trials Unit, Anti-HIV T Cell Responses During Antiviral Drug Therapy, G5969636581, G604406090, G6186512954, G650174051, G653690408, University of Pittsburgh Clinical and Translational Science Institution, G7641155071, G7807354757, G8232721138, G857487509, G8603072122, G9000021013, G9000039438, G9000052321, G9000061540, G9000072212, Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections, AIDS Clinical Trial Group Laboratory Center, Statistical and Data Management Center (SDMC), Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG), University of North Carolina Global HIV Prevention and Treatment Clinical Trials Unit
OpenAlex ID: W2170423149