490-M.
|
Immunological and Virological Characteristics of HIV-Infected Patients with Discordant Response to Highly Active Antiretroviral Therapy
S. Vella*1, G. D’Ettorre2, L. Palmisano1, E. Nicastri4, S. G. Parisi, M. Andreotti1, L. Sarmati3, C. M. Galluzzo1, C. Mastroianni2, V. Vullo2, E. Concia5, and M. Andreoni3
1Inst. Superiore di Sanità, Rome; 2Univ. La Sapienza, Rome; 3Univ. Tor Vergata, Rome; 4IRCCS L. Spallanzani, Rome; and 5Univ. of Verona, Italy
|
Background: Discordant response to HAART is reported in 20-40% of HIV+ subjects. So far, pathogenic mechanisms involved have not been fully clarified, and there is no agreement about therapeutic management of these subjects.
Methods: 2 groups of patients were studied: A) 20 with immunological response (>100 CD4+ cells/muL respect to baseline) but HIV viremia persistently >10.000 copies/mL after 12 months of HAART (mean CD4+ count=449+257 cells/muL; mean HIV-RNA= 4.7+4.6 log10); B) 23 with virological (mean VL=5.5+5.9 log10) and immunological (mean CD4+ count=136+114 cells/muL) failure. The 2 groups were homogenous for demographic characteristics and antiretroviral history. Sequence analysis of HIV-1 protease (PRO) and reverse transcriptase (RT) genes from plasma was performed. Virus isolation was obtained from PBMC and plasma. In a subset of 10 subjects in group A and 10 in group B lymphoproliferative response (LPA) to recall and HIV antigens and IL-15 production by PBMC stimulated with Candida and LPS, were assessed.
Results: Resistance mutations in both PRO and RT genes were found in all but 1 patient in group A. Median number of mutations was not different in the 2 groups (A:8.1, range 0-17; B:6.5, range 1-17) (p=0.5). Despite a comparable number of 3TC-experienced patients in both groups, the M184V mutation in RT gene was significantly more frequent in group A (17/20 vs 3/23, p=0.0001). Virus isolation was obtained from plasma and PBMC in 30 and 90% of group A, and in 80 and 100% of group B, respectively. LPA response to Candida and p24 was detectable in 100% and 70% of group A, while in group B there was no response to Candida and 10% response to p24. Higher levels of IL-15 production were observed in group A patients (p<0.001). All subjects changed the treatment according to genotypic results. After 4 month of follow-up, 10 of 17 individuals (A) and 4 of 12 individuals (B) showed viral load values <500 copies/mL. Three discordant subjects with HIV RNA <500 copies/mL lost LPA to Candida and p24.
Conclusions: The low HIV-1 isolation rate in discordant subjects, the high frequency of the M184V mutation and the good level of immune recovery suggest a substantial involvement of both viral and immunological factors. After the genotypic-driven change of therapy, the discordant group showed a high proportion of patients with undetectable viremia.
|
