Reappearance of an 11-year-old sequence in an HIV-1 infected patient during treatment interruption

• DOI: 10.1080/00365540701558706
• Publication Date: 2008-01-11T19:42:52Z
• Authors: Tina Vasehus Madsen; Jan Gerstoft; Claus Nielsen; Louise Bruun Jørg...
• Keywords: Male; 0301 basic medicine; Receptors, CXCR4; 0303 health sciences; Genotype; Receptors, CCR5; Anti-HIV Agents; HIV Infections; Middle Aged; Genes, env; Genes, pol; Drug Administration Schedule; HIV Long-Term Survivors; 3. Good health; 03 medical and health sciences; Drug Resistance, Multiple, Viral; Antiretroviral Therapy, Highly Active; Mutation; HIV-1; Humans; Patient Compliance; Phylogeny

HIV-1 from a patient with multi-drug resistant virus was identified as wild type during treatment interruption. The aim of the study was to describe how the viral population is affected by treatment interruptions and use phylogeny to reconstruct the evolutionary pattern. 15 samples covering 13 y and 2 treatment interruptions were analysed in both pol and env. The wild type virus found in the sample from the second treatment interruption in 2002 had not been present as a dominant population since 1994. Phylogeny showed that the 2002 sample was more closely related to wild type sequences than to other sequences sampled in 2002. This indicated that the wild type virus was caused by recruitment from the viral archives rather than reversion of previously circulating resistant strains. A few weeks after re-initiated treatment, virus showed full resistance, indicating that resistant virus was present as a subpopulation and reselected due to higher fitness in the presence of drugs. Phylogeny of env showed that CCR5 and CXCR4 viruses coexist in the patient. In conclusion, the study showed that at all times during infection, virus is archived in the cells and can be recruited when the surrounding environment changes and the archived virus is more fit.