Deletions in env gene of HIV-1 in AIDS patients treated with highly active antiretroviral therapy (HAART).
Many AIDS patients retain high CD4+ T-cell counts despite a significant increase in PCR viral load after varied periods of treatment on drug combination with Highly Active Antiretroviral Therapy (HAART). In order to investigate this contradictory phenomenon, we assayed for infectious HIV-1 from the plasma of such patients. Since the biological assays failed to reveal any infectious virus, we undertook molecular characterization of the plasma HIV-1 genes. These studies revealed large deletions in the env gene of the free virus, while there were no deletions in the proviral DNA obtained from the infected cells of the patients' blood. This suggests that the viral particles produced and released by the infected cells during the HAART treatment have deletions in the env gene. The deletions were large enough to produce an envelop-deficient virus, which can readily explain why it is not infectious. Such a defective virus is the most likely explanation for its failure to infect the T-cells, which in turn lead to the discordance between the high PCR viral load and stable CD4+ T cell counts.
Saurya
Shreesh
S
Department of Haematology, University of Cambridge Clinical School, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
Lichtenstein
Zelman
Z
Karpas
Abraham
A
D023241:Antiretroviral Therapy, Highly Active; D001483:Base Sequence; D015752:Genes, env / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000097:blood; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
D012367:RNA, Viral