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HIV
drugs resistance profiles in tissues—
Study
results presented at Treatment Strategies Workshop
Dr. Peter Anton and colleagues at UCLA, along with researchers
from Virco, have compared the drug resistance profiles of
HIV from gut with that of HIV from plasma. This work is an
extension of the collaboration between Dr. Anton and AIDS
Research Alliance of America. The following abstract was presented
at the 3rd International Workshop on HIV Drug Resistance and
Treatment Strategies (held in San Diego, CA, June, 1999),
and is reprinted with permission from Antiviral Therapy, Volume
4, Supplement 1.
Comparative
patterns of HIV-1 genotypic and phenotypic resistance profiles
in gut and plasma.
PA Anton1, L Michiels2, J Vingerhoets2, A Scholliers2, M Poles1,
J Elliott1, D Mark1, DP Shi1, P Stoffels2, B Larder2, K Hertogs2
UCLA AIDS Institute1, Los Angeles, CA; VIRCO2, Mechelen, Belgium.
Purpose:
Antiretroviral medications are known to have varying degrees
of penetration into certain compartments. The gastrointestinal
tract is the body's largest immune organ and is a main site
of HIV replication and spread. Incomplete drug penetration
in this compartment would favor emergence of resistant viral
quasispecies.
Methods:
8 sets of blood and endoscopic rectal biopsies were obtained
from 7 subjects with plasma viral load >1000 copies/ml. Tissue
and plasma RNA was extracted sent for resistance testing.
Genotypic analysis was performed by full sequence analysis
and interpretational software (VircoGEN'). Phenotype testing
was assessed by recombinant virus assay methodology (Antivirogram').
Results: Genotypic and phenotypic resistance profiles
for 14 drugs were obtained in plasma and tissue from all subjects.
Profiles of genotypic resistance showed a high correlation
between plasma and gut (R=1.0 in 7/8). Phenotypic profiles
between the 2 compartments were also highly correlated (R>0.85
in 7/8; R=0.149 in 1 subject). Within compartments, there
was high concordance between genotypic and phenotypic profiles
and resistance correlated very highly with therapy. In both
analyses, most observed differences between gut and plasma
were at the level of mutant/WT mixtures. Interestingly, these
mixtures were always found in gut samples. Corresponding plasma
samples were always found to harbor a completely mutant quasispecies.
As expected, profiles from the ART-naive subject were pan-sensitive
in both compartments at 2 different time points; the subject
off therapy showed resistance only to AZT (not used in over
6 months).
Conclusions:
Suitable HIV-1 RNA for resistance testing can be obtained
from rectal biopsy samples. There is a high concordance of
resistance profiles from blood and gut compartments in this
population of subjects. Sequential sampling is now required
to determine if limited drug penetration into tissue contributes
to the evolution of viral resistance.
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