Me. Quinones-mateu et al., A dual infection/competition assay shows a correlation between ex vivo human immunodeficiency virus type 1 fitness and disease progression, J VIROLOGY, 74(19), 2000, pp. 9222-9233
This study was designed to examine the impact of human immunodeficiency vir
us type 1 (HIV-1) fitness on disease progression through the use of a dual
competition/heteroduplex tracking assay (HTA). Despite numerous studies on
the impact of HIV-1 diversity and HIV-specific immune response on disease p
rogression, we still do not have a firm understanding of the long-term path
ogenesis of this virus. Strong and early CD8-positive cytotoxic T-cell and
CD4-positive T-helper cell responses directed toward HIV-infected cells app
ear to curb HIV pathogenesis. However, the rate at which the virus infects
the CD4(+) T-cell population and possibly destroys the HIV-specific immune
response may also alter the rate of disease progression. For HIV-1 fitness
studies, we established conditions for dual HIV-1 infections of peripheral
blood mononuclear cells (PBMC) and a sensitive HTA to measure relative viru
s production, A pairwise comparison was then performed to estimate the rela
tive fitness of various non-syncytium-inducing/CCR5-tropic (NSI/R5) and syn
cytium-inducing/CXCR4-tropic (SI/X4) HIV-1 isolates. Four HIV-1 strains (tw
o NSI/R5 and two SI/X4) with moderate ex vivo fitness sere then selected as
controls and competed against primary HIV-1 isolates from an HIV-infected
Belgian cohort. HIV-1 isolates from long-term survivors (LTS) were outcompe
ted by control strains and were significantly less fit than HIV-1 isolates
from patients with accelerated progression to AIDS (PRO), In addition, NSI/
R5 HIV-1 isolates from PRO overgrew control SI/X4 strains, suggesting that
not an SI/X4 HIV-1 isolates replicate more efficiency than all NSI/R5 isola
tes. Finally, there Here strong, independent correlations between viral loa
d and the total relative fitness values of HIV-1 isolates from PRO (r = 0.8
4, P = 0.033) and LTS (r = 0.86, P = 0.028). Separation of the PRO and LTS
plots suggest that HIV-1 fitness together with viral load may be a strong p
redictor for the rate of disease progression.