Publications Archive

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.