Objectives: Successful highly active antiretroviral therapy (HAART) is usua
lly 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 oc
cur in temporal association with plasma HIV RNA changes.
Design and methods: Eleven HIV-1-infected patients were enrolled into a pro
spective 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, eigh
t for 2 weeks, and six for greater than or equal to 3 weeks. When compared
to week 0, these patients had a greater than or equal to 2-log(10) decline
in HIV plasma RNA levels and/or a decline to less than or equal to 400 copi
es/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 spontaneousl
y 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 (me
dian, 0.6 versus 0.2% P = 0.037); and the percentage of CD3 T cells spontan
eously 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 spon
taneously producing TNF-alpha or interleukin-4 preceded changes in CD4 T ce
lls. If confirmed by others, these observations may be useful as early pred
ictors of response to and early failure of HAART. (C) 2001 Lippincott Willi
ams & Wilkins.