Intracellular cytokines in the acute response to highly active antiretroviral therapy.
OBJECTIVE
Successful highly active antiretroviral therapy (HAART) is usually associated with a rapid decline in HIV plasma RNA levels and a gradual increase in CD4 T cells. We examined whether changes in cytokine production and profile precede other immunological changes and whether these might occur in temporal association with plasma HIV RNA changes.


METHODS
Eleven HIV-1-infected patients were enrolled into a prospective cohort study; eight patients were naive to antiretroviral therapy. Blood samples were collected pre-therapy (week 0) and at 1, 2, and 3 weeks post-initiation of therapy.


RESULTS
All 11 patients enrolled remained on triple HAART for 1 week, eight for 2 weeks, and six for > or = 3 weeks. When compared to week 0, these patients had a > or = 2-log10 decline in HIV plasma RNA levels and/or a decline to < or = 400 copies/ml by week 3 of therapy (p = 0.004). The numbers and percentages of CD4 and CD8 T cells, and the percentage of naive, memory, and activated T cells did not change significantly between weeks 0 and 1 or 0 and 3. Of all the immune parameters examined only: the percentage of CD4 T cells spontaneously producing tumor necrosis factor (TNF)-alpha (median, 2.4 versus 0.5% P = 0.025); the percentage of CD8 T cells spontaneously producing TNF-alpha (median, 0.6 versus 0.2% P = 0.037); and the percentage of CD3 T cells spontaneously producing interleukin-4 (median, 1.8 versus 0.8% P = 0.004) changed significantly between weeks 0 and 3.


CONCLUSIONS
In these patients, decreases in the percentage of T cells spontaneously producing TNF-alpha or interleukin-4 preceded changes in CD4 T cells. If confirmed by others, these observations may be useful as early predictors of response to and early failure of HAART.
Lew
E
E
HIV Immunology and Diagnostics Branch, Division of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
Gallagher
L
L
Kuehnert
M
M
Rimland
D
D
Hubbard
M
M
Parekh
B
B
Zell
E
E
Jarvis
W
W
Jason
J
J
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015331:Cohort Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000096:biosynthesis*; D008297:Male; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4