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 cytomegalovirus (HCMV) in two groups of AIDS patients undergoing long-term highly active antiretroviral therapy (HAART): group 1 ( n = 22) with nadir CD4(+) cell count <50/microl and no HCMV disease; group 2 ( n = 16) with <50/microl CD4(+) T-cell count and HCMV disease. All patients had previously undergone antiretroviral monotherapy or dual therapy before initiating HAART.


METHODS
The two groups of patients were tested prospectively 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 recently diagnosed treatment-naive AIDS patients with CD4(+) T-cell counts <100/microl was also investigated.


RESULTS
No LPR to HCMV was found in any of the treatment-naive patients nor 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 group 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 patients. In addition, the frequency of patients with HCMV viremia, although reduced, became comparable in both groups. After 4 years of HAART, the frequency of responders to HCMV without and with HCMV disease dropped to comparable 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 addition, after between 3 and 4 years of HAART, although the frequency of stable 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/microl in the absence of LPR to HCMV, thus suggesting dissociation of specific and nonspecific immune reconstitution, a significant correlation 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 discontinued in 8 patients with HCMV retinitis showing CD4(+) T-cell counts >150/microl, recovery of HCMV LPR, and no HCMV viremia.


CONCLUSIONS
Declining levels of the previously recovered LPR to HCMV are often observed after long-term HAART. However, because the role of LPR in the evolution of HCMV infection and disease during HAART remains to be defined, the clinical impact of the declining LPR to HCMV must still be clarified in long-term prospective studies.
Gerna
G
G
Servizio di Virologia, IRCCS Policlinico San Matteo, Pavia, Italy. g.gerna@smatteo.pv.it
Piccinini
G
G
Genini
E
E
Percivalle
E
E
Zavattoni
M
M
Lilleri
D
D
Testa
L
L
Comolli
G
G
Maserati
R
R
Baldanti
F
F
Maccario
R
R
Monforte
A D
AD
Revello
M G
MG
D017088:AIDS-Related Opportunistic Infections / Q000209:etiology / Q000276:immunology* / Q000821:virology; D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load
D019380:Anti-HIV Agents; D012367:RNA, Viral