Reactivation of ancestral strains of HIV-1 in the gp120 V3 env region in patients failing antiretroviral therapy and subjected to structured treatment interruption.
We analyzed gp120V3 HIV-1 env region genetic diversity of 27 patients failing antiretrovirals and subjected to 12-week structured treatment interruption (STI). Based on heteroduplex mobility assays, eight patients presented low pre- and post-STI genetic diversity (G1); five presented high pre-STI but low post-STI diversity (G2); five presented low pre-STI and high post-STI diversity (G3); and nine, high pre- and post-STI diversity (G4). One patient from G1, two from G2 and two from G3 were subjected to proviral DNA end-point PCR and sequencing. In three patients, the dramatic disturbance caused by STI resulted in ancestral viral progeny activation, which repopulated the cell reservoir. In two patients presenting highly homogeneous sequences and low immune selective pressure (dN/dS ratio <1), this phenomenon was not observed. The mechanisms involved in viral evolution, in which antiretroviral therapy also applies selective pressure, sometimes affects coreceptor usage of circulating viruses, leading to the suppression of x4 strains.
Silva
Wilson Pereira
WP
Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Pedro de Toledo, 781-16 andar-CEP 04039-032, São Paulo, SP, Brazil.
Santos
Domingos E M
DE
Leal
Elcio
E
Brunstein
Adriana
A
Sucupira
Maria Cecilia A
MC
Sabino
Ester C
EC
Diaz
Ricardo Sobhie
RS
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D016000:Cluster Analysis; D004279:DNA, Viral / Q000235:genetics; D019143:Evolution, Molecular; D014644:Genetic Variation; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000235:genetics; D012641:Selection, Genetic; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D019380:Anti-HIV Agents; D004279:DNA, Viral; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments