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Randomized Controlled Trial
. 2014 Oct 1;67(2):153-60.
doi: 10.1097/QAI.0000000000000286.

Factors associated with CD8+ T-cell activation in HIV-1-infected patients on long-term antiretroviral therapy

Lu Zheng  1 , Babafemi Taiwo, Rajesh T Gandhi, Peter W Hunt, Ann C Collier, Charles Flexner, Ronald J Bosch
Affiliations
Randomized Controlled Trial

Factors associated with CD8+ T-cell activation in HIV-1-infected patients on long-term antiretroviral therapy

Lu Zheng et al. J Acquir Immune Defic Syndr. .

Abstract

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/mm: 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.

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Conflict of interest statement

Potential Conflicts of Interest

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. receives research support from Merck and past research support from 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. All other authors report no potential conflict.

Figures

Figure 1
Figure 1
CD8+ T-cell activation (% co-expressing CD38/HLA-DR) levels pre-ART and at 96 and 144 weeks on ART. Top and bottom of the box represent the lower and upper quartiles. The bar and the symbol inside the box represent the median and the mean, respectively. The whiskers extend to the furthest measurement within 1.5 times the interquartile range from the upper or lower quartile.
Figure 2
Figure 2
Associations of demographics and clinical factors with CD8+ T-cell activation in subjects on ART ≥ 96 weeks with concurrent and previous HIV-1 RNA ≤ 50 copies/mL. Results are from a multivariable repeated measure model; the effects of each factor are adjusted for all the other listed factors, as well as concurrent ART class and assay laboratory.
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