CHANGES IN CD4(-CELL SUBSETS IN RESPONSE TO HIGHLY-ACTIVE ANTIRETROVIRAL THERAPY IN HIV TYPE 1-INFECTED PATIENTS WITH PRIOR PROTEASE INHIBITOR EXPERIENCE() AND CD8(+) T)

This study explores whether previous failures on antiretroviral drug r egimens preclude the possibility of immune restoration. This was asses sed by evaluating T cell subset changes in individuals who received a salvage regimen of highly active antiretroviral therapy (HAART) after initially failing protease inhibitor monotherapy, Ten HIV-l-infected a symptomatic patients received a regimen of indinavir, zidovudine, and 3TC after failing saquinavir monotherapy, Changes in absolute numbers of naive, memory, and activated CD4(+) and CD8(+) T cells expressing a selection of CD45RA, CD62L, CD45RO, HLA-DR, and CD38 markers mere mon itored prospectively over 6 months. These measurements were correlated with plasma viral load along with alterations in a selected CD8(+) V alpha/V beta T cell receptor (TCR) repertoire. Over 6 months there was a progressive increase in numbers of CD4(+) memory (CD45RA(-)CD62L(+) ) and naive (CD45RA(+)CD62L(+)) T cells, which displayed a modest inve rse correlation with viral load. Two phases of CD8(+) memory cell chan ges were identified, consisting of a transient increase in CD45RA(+)CD 62L(-) numbers after 2 months and thereafter a progressive rise in CD4 5RA(-)CD62L(+) cells until 6 months. A strong correlation existed betw een reduced viral load and loss of activated CD8(+)CD38(+)HLA-DR+ cell numbers. There was also a temporary broadening of the CD8(+) V alpha/ V beta TCR repertoire at 8 weeks, which became skewed after 6 months i n parallel with reduced viral suppression. Closer analysis of naive an d memory cell subset proportions in individual patients revealed that enlarged pools of naive subsets mere evident in those patients with re bounds in viral load. Overall, drug-experienced patients responding to HAART displayed increased numbers of naive and memory CD4(+) subsets, and reduced CD8(+) cell activation with a loss of TCR skewing.