Longitudinal changes in CD4(+) T cell antigen receptor diversity and naive/memory cell phenotype during 9 to 26 months of antiretroviral therapy of HIV-infected patients

Although skewing of the CD4(+) TCR repertoire in advanced HIV infection is well documented, increases in polyclonality during antiretroviral therapy h ave been less consistently observed. Ten patients, each with documented abn ormalities within the CD4(+) TCR repertoire, were studied by CDR3 spectraty ping, semiquantitative PCR, and SSCP during 9-26 months of therapy. Naive a nd memory cell phenotypes were analyzed by flow cytometry. Six of 10 patien ts showed increased polyclonality of their TCR repertoires, 1 showed no cha nge, and 3 showed increased TCR skewing, despite suppressed viral replicati on. Overall, there was no significant change in the percentage of abnormal BV subfamilies (from a mean of 25.5 to 17.1%) or the percentage of naive CD 4(+) T cells (from a mean of 18 to 25%). Further, progression of TCR repert oire disruptions was observed in some patients even with suppression of pla sma viral RNA below 500 copies/ml. Although a spectrum of changes may be se en within the CD4(+) TCR repertoire in the setting of antiretroviral therap y, increases in polyclonality are observed in some patients.