Declining levels of rescued lymphoproliferative response to human cytomegalovirus (HCMV) in AIDS patients with or without HCMV disease following long-term HAART

Objective: To investigate the lymphoproliferative response (LPR) to human c ytomegalovirus (HCMV) in two groups of AIDS patients undergoing long-term h ighly active antiretroviral therapy (HAART): group I (n = 22) with nadir CD 4(+) T cell count < 50/mul and no HCMV diseased group 2 (n = 16) with < 50/ mul CD4(+) T-cell count and HCMV disease. All patients had previously under gone antiretroviral monotherapy or dual therapy before initiating HAART. Study Design and Methods: The two groups of patients were tested prospectiv ely for CD4(+) T cell count, HIV RNA load, HCMV viremia, and LPR to HCMV at baseline, and then after 3 and 4 years of HAART. A control group of 13 rec ently diagnosed treatment-naive AIDS patients with CD4(+) T-cell counts < 1 00/mul was also investigated. Results: No LPR to HCMV was found in any of the treatment-naive patients no r in any patient of the two groups examined at baseline, when HCMV viremia was 13.6% in the patient group without disease and 87.5% in the group with disease (p < .0001). After 3 years of HAART, the frequency of patients who recovered an LPR to HCMV was not significantly different (81.8% in the grou p without HCMV disease, and 68.7% in the group with HCMV disease), whereas, compared With baseline, the HIV load decreased and the CD4(+) T-cell count increased significantly and to a comparable extent in the two groups of pa tients. In addition, the frequency of patients with HCMV viremia, although reduced, became comparable in both groups. After 4 years of HAART, the freq uency of responder, to HCMV without and with HCMV disease dropped to compar able levels (50.0 vs. 56.3%. respectively) in association with high median CD4(+) T-cell counts and low median HIV RNA plasma levels. In parallel, the frequency of patients with HCMV viremia did not change significantly. In a ddition, after between 3 and 4 years of HAART, although the frequency of st able responders and nonresponders remained unchanged (50%) in both groups, most of the remaining patients showed declining levels of responsiveness to HCMV. Although some patients from both groups were found to have CD4(+) T- cell counts > 150/mul in the absence of LPR to HCMV, thus suggesting dissoc iation of specific and nonspecific immune reconstitution, a significant cor relation was found between CD4(+) T-cell count and LPR to HCMV (r = 0.44; p < .001). From a clinical standpoint, anti-HCMV therapy could be safely dis continued in 8 patients with HCMV retinitis showing CD4(+) T-cell counts > 150/mul, recovery of HCMV LPR, and no HCMV viremia. Conclusions: Declining levels of the previously recovered LPR to HCMV are o ften observed after long-term HAART. However, because the role of LPR in th e evolution of HCMV infection and disease during HAART remains to be define d, the clinical impact of the declining LPR to HCMV must still be clarified in long-term prospective studies.