HIV-1 resistant strains acquired at the time of primary infection massively fuel the cellular reservoir and persist for lengthy periods of time

AIDS
Jade GhosnFrench PRIMO Cohort Study Group (ANRS CO 06)

Abstract

Characterization of the early establishment of the viral reservoir in patients acquiring resistant strains at primary HIV-1 infection (PHI), and longitudinal analysis of resistance mutations in circulating virions and intracellular HIV strains. Drug-resistance was compared between HIV RNA and peripheral blood mononuclear cell (PBMC)-HIV DNA at the time of PHI in 44 patients enrolled in the Primo Cohort and harbouring plasma HIV-1 resistant to at least one antiretroviral drug. Longitudinal monitoring of viral load and resistance genotype was performed in plasma-HIV RNA and PBMC HIV DNA for at least 24 months in a subset of 10 patients. Phylogenetic analysis of HIV DNA protease gene clones was used to explore the diversity of quasi-species at baseline. Baseline resistance profile was identical in paired HIV RNA and PBMC HIV DNA for all 44 patients. All resistance-associated mutations persisted in plasma and PBMC over 2 years in the five untreated patients. Of the five patients started on empirical HAART, two achieved undetectable HIV RNA at month 6, with long-term persistence of archived drug-resistance mutations in PBMC HIV DNA. Virological failure was observed in the other three patients, resulting in the accumulation of additi...Continue Reading

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