Long-term suppression of plasma viremia with highly active antiretroviral therapy despite virus evolution and very limited selection of drug-resistant genotypes.
HIV-1 evolution and the possible emergence of mutations associated with resistance to antiretroviral inhibitors have been evaluated in a cohort of sixty-three patients successfully treated with highly active antiretroviral therapy (HAART). The patients under effective HAART were recruited in three different hospitals in Spain, and none of them had been treated (naïve) before entering this study. HIV-1 RNA levels, CD4+, and CD8+ T-cell counts were determined, and nucleotide sequences of proviral regions encoding protease and reverse transcriptase (RT) were obtained for longitudinal blood samples spanning a mean follow-up period of 88 weeks. Phylogenetic reconstructions and calculations of genetic distances among the different sequences of each patient were performed. All except one of the patients under study showed an early and sustained decrease in plasma HIV-1 RNA to levels that were below 200 copies/ml. The plasma viral decline paralleled a significant increase in the CD4+ T-lymphocyte counts. Amino acid sequence analyses revealed the occurrence of mutations associated with antiretroviral resistance in nine patients (14.3%) during HAART treatment, that in some cases could be attributed to excess G to A transitions. In six of the nine patients, the mutations conferred resistance to inhibitors administered in the treatment regime, although the mutations did not result in treatment failure. Sequence comparisons revealed viral evolution during the period of treatment in 47.5% of the patients. The results indicate successful suppression of HIV-1 under HAART for extended time periods, indistinguishable for patients in which evidence of virus evolution could or could not be documented.
Pariente
Nonia
N
Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Cantoblanco, Madrid, Spain.
Pernas
María
M
de la Rosa
Rafael
R
Gómez-Mariano
Gema
G
Fernández
Guerau
G
Rubio
Amalia
A
López
Mariola
M
Benito
José Miguel
JM
López-Galíndez
Cecilio
C
Leal
Manuel
M
Domingo
Esteban
E
Martinez
Miguel Angel
MA
Mas
Antonio
A
D000328:Adult; D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D004279:DNA, Viral / Q000737:chemistry / Q000302:isolation & purification; D024882:Drug Resistance, Viral / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D011533:Proviruses / Q000235:genetics; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D013030:Spain; D017211:Treatment Failure; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000821:virology
D019380:Anti-HIV Agents; D004279:DNA, Viral; D012367:RNA, Viral; D054303:HIV Reverse Transcriptase; D016333:HIV Protease