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Can highly active antiretroviral therapy be interrupted in patients with sustained moderate HIV RNA and > 400 CD4 + cells/µl? Impact on immunovirological parameters
Author(s) -
Pellegrin Isabelle,
Thiébaut Rodolphe,
Blanco Patrick,
Viallard JeanFrançois,
Schrive MarieHélène,
Merel Patrick,
Chêne Geneviève,
Fleury Hervé,
Moreau JeanFrançois,
Pellegrin JeanLuc
Publication year - 2005
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.20452
Subject(s) - reverse transcriptase , rna , viral load , genotyping , virology , genotype , antiretroviral therapy , peripheral blood mononuclear cell , human immunodeficiency virus (hiv) , biology , lentivirus , medicine , immunology , viral disease , gene , genetics , in vitro
Because the effects of treatment interruption on patients with >400 CD4 + cells/µl and prolonged moderate HIV loads is unknown, their HIV1 RNA and DNA loads, plasma, and PBMC resistance mutations and CD4 + kinetics were studied during 12 months of treatment interruption. Fifty‐seven patients were included: 28 with undetectable (median 40 months) and 29 with moderate (>1 year) HIV1 RNA levels (3.3 log 10 copies/ml) at the baseline M0. HIV1 RNA and CD4 + counts were determined monthly. PBMC HIV1 DNA was quantified (real‐time PCR) and its reverse transcriptase ( RT ) and protease ( PR ) genotypes analyzed (M0, M6, M12). Regardless of HIV1 RNA detectability at the baseline M0, all patients had comparable HIV1 RNA (median 4.6), DNA (median 2.9), CD4 + (median 455) at month 12 (M12). The decisive moment was month 1 (M1), when the HIV1 RNA increase and CD4 decline stabilized, rendering M0 differences non‐significant and predicting outcome. The lower the CD4 + nadir was before HAART, the steeper the CD4 + decline at M1. HIV1 DNA shifted to wild‐type genotype in 47% (M6) and 79% (M12) of RT ; 64% of PR major resistance mutations disappeared (M12). Treatment interruption is possible, regardless of the baseline M0 HIV RNA status, but it must take into consideration the CD4 + nadir, an outcome predictor, to initiate HAART before too severe depletion to preserve the possibility of treatment interruption. HIV1 DNA genotyping helps monitor patients with undetectable HIV RNA at M0. J. Med. Virol. 77:164–172, 2005. © 2005 Wiley‐Liss, Inc.