Can highly active antiretroviral therapy be interrupted in patients with sustained moderate HIV RNA and > 400 CD4+ cells/microl? Impact on immunovirological parameters.
Because the effects of treatment interruption on patients with >400 CD4(+) cells/microl 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 log10 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.
Pellegrin
Isabelle
I
Department of Virology and Immunology, Bordeaux University Hospital, Bordeaux, France. isabelle.pellegrin@chu-bordeaux.fr
Thiébaut
Rodolphe
R
Blanco
Patrick
P
Viallard
Jean-François
JF
Schrive
Marie-Hélène
MH
Merel
Patrick
P
Chêne
Geneviève
G
Fleury
Hervé
H
Moreau
Jean-François
JF
Pellegrin
Jean-Luc
JL
D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000097:blood; D004334:Drug Administration Schedule; D024921:Drug Resistance, Multiple, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012367:RNA, Viral / Q000097:blood*; D019562:Viral Load
D019380:Anti-HIV Agents; D004279:DNA, Viral; D012367:RNA, Viral