Composition and function of T cell subpopulations are slow to change despite effective antiretroviral treatment of HIV disease.
The ability to reconstitute a normal immune system with antiretroviral therapy in the setting of HIV infection remains uncertain. This study aimed to characterize quantitative and qualitative aspects of various T cell subpopulations that do not improve despite effective ART. CD4∶CD8 ratio was evaluated in HIV-infected subjects with viral loads >10,000 copies/µl ("non-controllers", n = 42), those with undetectable viral loads on ART ("ART-suppressed", n = 53), and HIV-uninfected subjects (n = 22). In addition, T cell phenotype and function were examined in 25 non-controllers, 18 ART-suppressed, and 7 HIV-uninfected subjects. CD4∶CD8 ratio in non-controllers, ART-suppressed, and HIV-uninfected subjects was 0.25, 0.48, and 1.95 respectively (P<0.0001 for all comparisons). The increased ratio in ART-suppressed compared to non-controllers was driven by an increase of CD4+ T cells, with no change in the expanded CD8+ T cell population. Expansion of differentiated (CD28-CD27-CD45RA+/-CCR7-) T cell subpopulations persisted despite ART and minimal changes were noted in naïve T cell frequencies over time. Increased number of CD8+CD28- T cells and increased CD8+ CMV-specific T cell responses were associated with a decreased CD4∶CD8 ratio. Measures of T cell function demonstrated persistence of high frequencies of CD8+ T cells producing IFN-γ. Lastly, though all CD8+ subpopulations demonstrated significantly lower Ki67 expression in ART-suppressed subjects, CD4+ T cell subpopulations did not consistently show this decrease, thus demonstrating different proliferative responses in the setting of T cell depletion. In summary, this study demonstrated that CD4∶CD8 ratios remained significantly decreased and naïve T cell numbers were slow to increase despite long-term viral suppression on ART. In addition, there is a evidence of differential regulation of the CD4+ and CD8+ T cell subpopulations, suggesting independent homeostatic regulation of the two compartments.
Department of Medicine, Yale University, New Haven, Connecticut, United States of America.
Brinda
B
Emu
Gladstone Institute of Virology and Immunology, San Francisco, California, United States of America.
Walter J
WJ
Moretto
Positive Health Program, University of California San Francisco, San Francisco, California, United States of America.
Rebecca
R
Hoh
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
Melissa
M
Krone
Positive Health Program, University of California San Francisco, San Francisco, California, United States of America ; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
Jeffrey N
JN
Martin
Division of Experimental Medicine, University of California San Francisco, San Francisco, California, United States of America.
Douglas F
DF
Nixon
Positive Health Program, University of California San Francisco, San Francisco, California, United States of America.
Steven G
SG
Deeks
Positive Health Program, University of California San Francisco, San Francisco, California, United States of America ; Division of Experimental Medicine, University of California San Francisco, San Francisco, California, United States of America.
Joseph M
JM
McCune
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology* / Q000821:virology; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000473:pathology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016176:T-Lymphocyte Subsets / Q000473:pathology* / Q000821:virology; D019562:Viral Load / Q000187:drug effects
D019380:Anti-HIV Agents; D015703:Antigens, CD