Persistent production of an integrase-deleted HIV-1 variant with no resistance mutation and wild-type proviral DNA in a treated patient
Abstract
An HIV-infected patient presenting an unexpected viral escape under combined antiretroviral treatment is described. The virus isolated from plasma contained a large deletion in the HIV-1 integrase gene but no known resistance mutation. Nested polymerase chain reactions (PCRs) with patient virus integrase-specific primers and probes were developed and used to detect the mutant from plasma, blood, rectal biopsies, and sperm. The variant progressively emerged during a period of therapy-induced virosuppression, and persisted at a low but detectable level for at least 5 years. Surprisingly, proviral DNA from lymphocytes, rectal cells, and sperm cells was, and remained, mainly wild type. Cellular HIV RNA with the deletion was detected only once from the rectum. The origin and mechanisms underlying this so far not described production at a detectable level are largely hypothetical. This observation raised concern about the ability of defective viruses to spread.
Keywords
Molecular Sequence Data
Mononuclear/virology
Proviruses/genetics
Sequence Analysis
Sequence Deletion
Viral Load/drug effects
Viral/genetics
Zidovudine/therapeutic use
Lopinavir/therapeutic use
Leukocytes
Lamivudine/therapeutic use
Integrases/*genetics
DNA
Anti-HIV Agents/*therapeutic use
Base Sequence
Combination
Defective Viruses/genetics/*pathogenicity
Drug Therapy
HIV Infections/*drug therapy/genetics
HIV-1/*genetics
Immune Evasion/genetics
Humans