Background: Abnormal levels of CD8+ T-cell activation persist in HIV-1–infected patients on suppressive antiretroviral therapy (ART) and may be deleterious.
Methods: CD8+ T-cell activation (% coexpressing CD38/HLA-DR) was analyzed on blood specimens from 833 HIV-1–infected patients on ART for ≥96 weeks with concurrent plasma HIV RNA (vRNA) ≤200 copies per milliliter. Factors associated with CD8+ T-cell activation were assessed using generalized estimating equations to incorporate longitudinal measurements (median 4/participant).
Results: Participants were 84% men, 47% white, 28% black, and 22% Hispanic, with median pre-ART age 38 years and median ART exposure 144 weeks. CD8+ T-cell activation was higher at timepoints when vRNA was 51–200 versus ≤50 copies per milliliter [mean CD8+ T-cell activation 23.4% vs. 19.7%; adjusted difference: 1.7% (95% confidence interval: 0.1 to 3.4), P = 0.042]. Restricting to vRNA ≤50 copies per milliliter, multivariable models showed the following factors associated with higher CD8+ T-cell activation: older age [≥45 vs. ≤30 years: 3.6% (1.4 to 5.7), P = 0.004], hepatitis C virus antibody positivity [3.6% (0.9 to 6.2), P = 0.032], Hispanic vs. white [7.2% (5.3 to 9.0), P < 0.001], lower concurrent CD4 count [≤200 vs. >500 cells/mm3: 2.2% (0.7 to 3.7), P < 0.001], lower concurrent CD4/CD8 ratio [−2.6% (−3.7 to −1.5) per 0.5 unit increase, P < 0.001], and higher pre-ART CD8+ T-cell activation [2.0% (1.6 to 2.5) per 10% higher, P < 0.001].
Conclusions: In participants included in our analysis, residual low-level viremia between 51 and 200 copies per milliliter during ART was shown to be associated with greater CD8+ T-cell activation than full suppression to <50 copies per milliliter. Older age, hepatitis C virus antibody positivity, race/ethnicity, higher pre-ART CD8+ T-cell activation, and lower concurrent CD4/CD8 ratio and CD4+ T-cell count also contribute to greater CD8+ T-cell activation during suppressive ART.
*Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA;
†Division of Infectious Diseases, Northwestern University, Chicago, IL;
‡Division of Infectious Diseases, Massachusetts General Hospital (MGH), Boston, MA;
§The Ragon Institute of MGH, Massachusetts Institute of Technology, and Harvard, Cambridge, MA;
‖Division of HIV/AIDS, San Francisco General Hospital, University of California at San Francisco, San Francisco, CA;
¶Division of Infectious Diseases; Department of Medicine; University of Washington, Seattle, WA;
#Division of Clinical Pharmacology, School of Medicine, Johns Hopkins University, Baltimore, MD; and
**Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA.
Correspondence to: Lu Zheng, PhD, Center for Biostatistics in AIDS Research, Harvard School of Public Health, FXB Building, Room 613, 651 Huntington Avenue, Boston, MA 02115 (e-mail: firstname.lastname@example.org).
Supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (AI-68636, AI-68634, AI-38858, AI-38855, and AI-69434).
Presented at the XIX International AIDS Conference, July 22–27, 2012, Washington, DC.
B.T. has served as an advisor and/or received research support (to Northwestern University) from Janssen, Pfizer, GlaxoSmithKline, and ViiV. R.T.G. has received institutional research grant support from Abbott, ViiV, and Janssen. A.C.C. received research support (to University of Washington) from Merck, Roche Molecular Systems, and Schering-Plough, previously owned stock in Abbott, Bristol-Myers Squibb, Johnson and Johnson, and Pfizer, and was a DSMB member for a Merck-sponsored study. C.F. reports receiving research grant support from Boehringer-Ingelheim and GlaxoSmithKline for research unrelated to this study and serving as a consultant to Bristol-Myers Squibb, Boehringer-Ingelheim, GlaxoSmithKline, Merck, Roche, Schering-Plough, Tobira Therapeutics, Tibotec, Vertex, Virostatics, and ViiV Healthcare. The remaining authors have no conflicts of interest to disclose.
Received October 15, 2013
Accepted April 26, 2014