Low CD4 T-cell counts despite low levels of circulating HIV: insights from the comparison of HIV-1 infected patients with a discordant response to antiretroviral therapy to patients with untreated advanced HIV-2 disease.
A significant proportion of HIV-1+ patients with suppression of viremia under antiretroviral therapy fail to recover CD4(+) T-cell counts (ART-Discordants). Similarly, untreated HIV-2+ patients can also exhibit major CD4 depletion in spite of undetectable viremia. We characterize here the immunological disturbances associated with major CD4-lymphopenia in these two scenarios as compared to untreated viremic HIV-1+ patients with similar CD4-lymphopenia and HIV-1+ patients with successful immunological and virological responses under ART. Low CD4 counts were associated with major naive CD4 and CD8 depletion, irrespective of type of infection or ART-exposure. However, ART-Discordants exhibited lower levels of T-cell activation as compared to both untreated HIV-2 and HIV-1 cohorts, and a less marked increase in circulating IL-7 despite similar CD4 depletion. Nevertheless, ART-Discordants showed a preserved Bcl-2 expression, suggesting increased IL-7 consumption, which in conjunction with the relatively lower T-cell activation may contribute to their CD4 count stability and low rate of opportunistic infections.
Albuquerque
Adriana S
AS
Unidade de Imunologia Clínica, Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av Prof Egas Moniz, 1649-028, Lisboa, Portugal.
Foxall
Russell B
RB
Cortesão
Catarina S
CS
Soares
Rui S
RS
Doroana
Manuela
M
Ribeiro
Alice
A
Lucas
Margarida
M
Antunes
Francisco
F
Victorino
Rui M M
RM
Sousa
Ana E
AE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D015851:Interleukin-7 / Q000097:blood; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis / Q000187:drug effects; D014766:Viremia
D044966:Anti-Retroviral Agents; D015851:Interleukin-7; D019253:Proto-Oncogene Proteins c-bcl-2; D020395:Receptors, Interleukin-7