The median percentage reduction in proviral load was similar between CD4 T cells (64%; n = 12; 95% CI, 56–82) and CD8 DP T cells (82%; n = 9; 95% CI, 68–90). Moreover, there were no significant differences between the values for all eight paired samples (Z = −1.362; P = 0.173) and for just the four paired samples where CD8 DP T cell proviral load was positive during HAART (Z = −0.730; P = 0.465). Both T cell subsets showed a significant reduction in mean proviral load following therapy (CD4 T cells: n = 12; Z = −3.621; P < 0.001; CD8 DP T cells: n = 9; Z = −2.666; P = 0.008), irrespective of whether the detection limit or half its value was used as the proviral load for PCR-negative CD8 DP T cells (statistics identical).
Heterogeneity in both plasma viral load and the number of productively infected cells prior to the start of HAART influences the kinetics of HIV-1 DNA decay. Moreover, decay kinetics are biphasic, with a variable time period for first-phase clearance [33,34], and combined analyses of decay rates may show no significant trend in the temporal reduction of HIV-1 DNA during therapy [35,20]. All study subjects here, however, showed reductions in proviral load for both cell types, and mean proviral loads were significantly reduced after the 6–13 months on therapy. Values derived for individual study subjects likely represent an average rate covering both the initial rapid decay during the first few months of therapy and the slower second phase . Importantly, CD8 T cell subsets were highly pure, with negligible CD4 T cell contamination (Table 3). In addition, only 7 of 17 study subjects tested had HIV-1-positive CD14+CD3− monocytes (with very low proviral loads, average 5 copies/106 cells; results not shown) ensuring that CD8 T cell proviral loads are not obscured by contamination with other infected cell types. Our finding of a significant reduction in large CD4 and CD8 DP T cells during HAART most probably represents clearance of activated, acutely infected cells , as the increased size of T cells has been shown to be a sensitive corollary of activation .
The authors would like to thank the staff of the Regional Infectious Diseases Unit, Western General Hospital, Edinburgh for their invaluable help in collection of blood samples and provision of clinical data. We also thank Alison Hardie for assistance with the processing of samples, Shonna Johnston for FACS sorting of cells and Fraser Lewis for statistical advice.
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