18th International HIV Drug Resistance Workshop Basic Principles & Clinical Implications June 9–13 2009, Fort Myers, Florida, USA

MARKERS OF CELLULAR IMMUNE ACTIVATION DO NOT CORRELATE WITH LEVELS OF RESIDUAL VIREMIA IN PATIENTS ON LONG-TERM SUPPRESSIVE ANTIRETROVIRAL THERAPY

Antivir Ther 2009; 14 Suppl 1:A10 (abstract no. 8)

F Cossarini^1,2, A Wiegand¹, J Mican³, M Polis⁴, C Rehm⁴, A O’Shea³, C Poethke¹, J Spindler¹, R Dewar⁵, J Higgins⁵, M Kearney¹, J Coffin^1,6, J Mellors⁷ and F Maldarelli^1
1HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA; ²Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy; ³National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; ⁴Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA ⁵Collaborative Clinical Research Branch, SAIC, Laboratory of Immunoregulation NIAID, NIH, Frederick, MD, USA; ⁶Department of Microbiology and Immunology, Tufts University, Boston, MA, USA; ⁷Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, PA, USA

BACKGROUND: Markers of CD8+ T-cell activation correlate with HIV type-1 (HIV-1) RNA levels before treatment initiation. However, the relation between the level of residual viremia after long-term suppressive antiretroviral therapy (ART) and CD8+ T-cell activation markers is unknown. We therefore measured CD8+ T-cell activation markers and residual viremia in a cohort of patients on long-term suppressive ART.

METHODS: HIV-1-infected subjects (n=33) initiating ART and maintaining HIV-RNA<75 copies/ml for ≥3 years without viral blips (≥2 consecutive HIV-1 RNA≥500 copies/ml) were studied. CD8+ T-cell activation was determined as the expression of HLA-DR and CD38 on CD8+ cells and reported as percentages of CD8+ T-cells. HIV-1 RNA was measured by bDNA and by single-copy assay (sensitivity 0.3 copies/ml). CD8+ T-cell activation markers were also measured in healthy, HIV-1-uninfected controls (n=43) matched for gender, age and race.

RESULTS: As previously reported, pre-ART HIV-1 RNA was positively correlated with CD8+CD38+ T-cells (r=0.403; P=0.03). CD8+ T-cell subsets decreased steadily during the first 4 years of ART with half-lives of 30.9 and 39.6 months for CD8+HLA-DR+ and CD8+CD38+ T-cells, respectively, and remained stable thereafter. After 7 years on ART, CD8+ T-cells subsets were lower than pretherapy levels (P<0.0001 for CD8+HLA-DR+ and CD8+CD38+ T-cells). Compared with healthy uninfected controls, HIV-1-infected subjects had higher proportions of CD8+ T-cells, but there were no significant differences in the proportions of activated CD8+CD38+ and CD8+CD38+HLA-DR+ subsets (P=0.254 and P=0.325, respectively). A marginal difference in CD8+HLA-DR+ T-cells (P=0.020) was not significant after correction for multiple comparisons. Residual viremia was determined in 18 patients after a median of 7.7 years (range 3.4–9.2) on ART. Median HIV-1 RNA was 0.95 copies/ml (range 0.3–30.0). No significant correlation was found between the level of residual viremia and immune activation markers (r=0.106, P=0.339 for CD8+HLA-DR+ and r=0.119, P=0.319 for CD8+CD38+Tcells). For CD8+CD38+ HLA-DR+ T-cells, however, a higher r value was detected although it was not significant (r=0.294; P=0.118).

CONCLUSIONS: CD8+ T-cell activation decreases significantly after prolonged antiretroviral therapy reaching levels undistinguishable from those in uninfected persons. Despite a potential trend in CD8+CD38+ HLA-DR+ T-cells, the level of residual viremia on therapy did not correlate with CD8+HLA-DR+ or CD8+CD38+ T-cells, suggesting that low-level viremia may not be sufficient to stimulate CD8+ T-cell activation.

2009-06-09
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