Emergence of protease inhibitor resistance-associated mutations in plasma HIV-1 precedes that in proviruses of peripheral blood mononuclear cells by more than a year

HIV-1 genotype assay Using plasma Viruses has been widely applied for detection of resistant Viruses ill infected individuals, whereas there are only a few reports about proviral genotype ill peripheral blood mononuclear cells (PBMCs). To determine which sample, plasma or PBMC, should be used for early detection of drug-resistant viruses during,, antiretroviral treatment, we analyzed 275 plasma-derived and 2 1 1 PBMC-derived HIV-1 protease sequences obtained from HIV-1-infected patients during protease inhibitor(PI) therapy. In 70 of 107 pairs (65.4%) of plasma and PBMC samples taken from the same blood draws, the numbers of PI resistance-associated Mutations in the plasma-derived genotype were different from those in the PBMC-derived genotype. Plasma viruses had more PI resistance-associated mutations than PBMC proviruses (P = 0.0004). Analysis of serial samples showed that plasma-derived genotype assay Could detect primary mutations about 425 days earlier than PBMC-derived genotype when the plasma viral load was less than 10(4) copies/mL. Our data suggest that genetic turnover of PBMC proviruses is slower than that of plasma viruses and that time lag between emergence Of mutations in plasma-derived and PBMC-derived genotypes correlates inversely with viral load. Plasma Viruses should be the material of choice for early detection of drug resistance during antiretroviral treatment.