Evolution of total and integrated HIV-1 DNA and change in DNA sequences in patients with sustained plasma virus suppression.
Blood samples from patients with plasma HIV-1 RNA <20 copies/ml for more than 2 years were studied. Significant decreases in total and integrated HIV-1 DNA were observed during the first 15 months of suppressive therapy before the concentrations became stable. Clonal analysis of HIV-1 pol demonstrated that the proportions of resistance mutations in DNA sequences after 2 years were lower than those in baseline DNA and RNA sequences. The changes in the clonal composition of HIV-1 env populations in three patients with evidence of changes in HIV-1 pol populations indicated a shift from predominantly R5-like viruses to predominantly X4-like viruses in two patients and the persistence of predominantly X4-like viruses in the third. Our analyses indicate the reemergence of ancestral sequences from long-lived cells or the residual production of wild-type virus from anatomic sites with limited access to antiretroviral drugs and the preferential infection of cells expressing CXCR4.
Izopet
Jacques
J
Laboratoire de Virologie, Hôpital Purpan, CHU Toulouse, 31059 Toulouse Cédex, France. izopet@cict.fr
Cazabat
Michèle
M
Pasquier
Christophe
C
Sandres-Sauné
Karine
K
Bonnet
Eric
E
Marchou
Bruno
B
Massip
Patrice
P
Puel
Jacqueline
J
D000595:Amino Acid Sequence; D023241:Antiretroviral Therapy, Highly Active; D004279:DNA, Viral / Q000097:blood / Q000235:genetics*; D024882:Drug Resistance, Viral / Q000235:genetics*; D019143:Evolution, Molecular; D015752:Genes, env / Q000235:genetics; D015751:Genes, pol / Q000235:genetics; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000145:classification* / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics; D011533:Proviruses; D017422:Sequence Analysis, DNA
D004279:DNA, Viral; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D054303:HIV Reverse Transcriptase; D016333:HIV Protease