Abstract
Background. Initiation of combination antiretroviral therapy (ART) results in higher total CD4 cell counts, a surrogate for immune reconstitution. Whether the baseline CD4 cell count affects reconstitution of immune cell subsets has not been well characterized. Methods. Using data from 978 patients (621 with comprehensive immunological assessments) from the AIDS [Acquired Immunodeficiency Syndrome] Clinical Trials Group protocol 384, a randomized trial of initial ART, we compared reconstitution of CD4+, CD4 + naive and memory, CD4+ activation, CD8+, CD8+ activation, B, and natural killer cells among patients in different baseline CD4+ strata. Reference ranges for T cell populations in control patients negative for human immunodeficiency virus (HIV) infection were calculated using data from AIDS Clinical Trials Group protocol A5113. Results. Patients in the lower baseline CD4+ strata did not achieve total CD4+ cell counts similar to those of patients in the higher strata during 144 weeks of ART, although CD4+ cell count increases were similar. Ratios of CD4+ naive-memory cell counts and CD4+:CD8+ cell counts remained significantly reduced in patients with lower baseline CD4+ cell counts (≤350 cells/mm 3). These immune imbalances were most notable for those initiating ART with a baseline CD4+ cell count ≤200 cells/mm3, even after adjustment for baseline plasma HIV RNA levels. Conclusions. After nearly 3 years of ART, T cell subsets in patients with baseline CD4+ cell counts >350 cells/mm3 achieved or approached the reference range those of control individuals without HIV infection. In contrast, patients who began ART with ≤350 CD4+ cells/mm3 generally did not regain normal CD4+ naive-memory cell ratios. These results support current guidelines to start ART at a threshold of 350 cells/mm 3 and suggest that there may be immunological benefits associated with initiating therapy at even higher CD4+ cell counts.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 350-361 |
| Number of pages | 12 |
| Journal | Clinical Infectious Diseases |
| Volume | 48 |
| Issue number | 3 |
| DOIs | |
| State | Published - Feb 1 2009 |
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ASJC Scopus subject areas
- Infectious Diseases
- Microbiology (medical)
Cite this
Incomplete reconstitution of T cell subsets on combination antiretroviral therapy in the AIDS Clinical Trials Group Protocol 384. / Robbins, Gregory K.; Spritzler, John G.; Chan, Ellen S.; Asmuth, David; Gandhi, Rajesh T.; Rodriguez, Benigno A.; Skowron, Gail; Skolnik, Paul R.; Shafer, Robert W.; Pollard, Richard B.
In: Clinical Infectious Diseases, Vol. 48, No. 3, 01.02.2009, p. 350-361.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Incomplete reconstitution of T cell subsets on combination antiretroviral therapy in the AIDS Clinical Trials Group Protocol 384
AU - Robbins, Gregory K.
AU - Spritzler, John G.
AU - Chan, Ellen S.
AU - Asmuth, David
AU - Gandhi, Rajesh T.
AU - Rodriguez, Benigno A.
AU - Skowron, Gail
AU - Skolnik, Paul R.
AU - Shafer, Robert W.
AU - Pollard, Richard B
PY - 2009/2/1
Y1 - 2009/2/1
N2 - Background. Initiation of combination antiretroviral therapy (ART) results in higher total CD4 cell counts, a surrogate for immune reconstitution. Whether the baseline CD4 cell count affects reconstitution of immune cell subsets has not been well characterized. Methods. Using data from 978 patients (621 with comprehensive immunological assessments) from the AIDS [Acquired Immunodeficiency Syndrome] Clinical Trials Group protocol 384, a randomized trial of initial ART, we compared reconstitution of CD4+, CD4 + naive and memory, CD4+ activation, CD8+, CD8+ activation, B, and natural killer cells among patients in different baseline CD4+ strata. Reference ranges for T cell populations in control patients negative for human immunodeficiency virus (HIV) infection were calculated using data from AIDS Clinical Trials Group protocol A5113. Results. Patients in the lower baseline CD4+ strata did not achieve total CD4+ cell counts similar to those of patients in the higher strata during 144 weeks of ART, although CD4+ cell count increases were similar. Ratios of CD4+ naive-memory cell counts and CD4+:CD8+ cell counts remained significantly reduced in patients with lower baseline CD4+ cell counts (≤350 cells/mm 3). These immune imbalances were most notable for those initiating ART with a baseline CD4+ cell count ≤200 cells/mm3, even after adjustment for baseline plasma HIV RNA levels. Conclusions. After nearly 3 years of ART, T cell subsets in patients with baseline CD4+ cell counts >350 cells/mm3 achieved or approached the reference range those of control individuals without HIV infection. In contrast, patients who began ART with ≤350 CD4+ cells/mm3 generally did not regain normal CD4+ naive-memory cell ratios. These results support current guidelines to start ART at a threshold of 350 cells/mm 3 and suggest that there may be immunological benefits associated with initiating therapy at even higher CD4+ cell counts.
AB - Background. Initiation of combination antiretroviral therapy (ART) results in higher total CD4 cell counts, a surrogate for immune reconstitution. Whether the baseline CD4 cell count affects reconstitution of immune cell subsets has not been well characterized. Methods. Using data from 978 patients (621 with comprehensive immunological assessments) from the AIDS [Acquired Immunodeficiency Syndrome] Clinical Trials Group protocol 384, a randomized trial of initial ART, we compared reconstitution of CD4+, CD4 + naive and memory, CD4+ activation, CD8+, CD8+ activation, B, and natural killer cells among patients in different baseline CD4+ strata. Reference ranges for T cell populations in control patients negative for human immunodeficiency virus (HIV) infection were calculated using data from AIDS Clinical Trials Group protocol A5113. Results. Patients in the lower baseline CD4+ strata did not achieve total CD4+ cell counts similar to those of patients in the higher strata during 144 weeks of ART, although CD4+ cell count increases were similar. Ratios of CD4+ naive-memory cell counts and CD4+:CD8+ cell counts remained significantly reduced in patients with lower baseline CD4+ cell counts (≤350 cells/mm 3). These immune imbalances were most notable for those initiating ART with a baseline CD4+ cell count ≤200 cells/mm3, even after adjustment for baseline plasma HIV RNA levels. Conclusions. After nearly 3 years of ART, T cell subsets in patients with baseline CD4+ cell counts >350 cells/mm3 achieved or approached the reference range those of control individuals without HIV infection. In contrast, patients who began ART with ≤350 CD4+ cells/mm3 generally did not regain normal CD4+ naive-memory cell ratios. These results support current guidelines to start ART at a threshold of 350 cells/mm 3 and suggest that there may be immunological benefits associated with initiating therapy at even higher CD4+ cell counts.
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UR - http://www.scopus.com/inward/citedby.url?scp=58749093399&partnerID=8YFLogxK
U2 - 10.1086/595888
DO - 10.1086/595888
M3 - Article
C2 - 19123865
AN - SCOPUS:58749093399
VL - 48
SP - 350
EP - 361
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
SN - 1058-4838
IS - 3
ER -