Evolution of the HIV-1 protease region in heavily pretreated HIV-1 infected patients receiving Atazanavir.
BACKGROUND
Previous in vitro studies indicated that Atazanavir (ATV) has a distinct resistance profile than other protease inhibitors (PIs). In treatment-experienced patients ATV resistance is characterised by the accumulation of at least four mutations among those that confer cross-resistance to the PIs.


OBJECTIVE
We studied the evolution of PIs resistance mutations in 10 HAART-failed patients undergoing ATV enrolled in an early access program.


METHODS
Virus genotypic resistance was determined from plasma collected at baseline and during treatment. HIV-RNA was extracted and the pol region amplified and sequenced. Genotypic data were used to determine drug susceptibility. Phylogenetic analysis was performed.


RESULTS
At baseline, genotypic data showed cross-resistance patterns to approved PIs in 6 patients. In two of these subjects new mutations (I54V and A71V) conferring cross-resistance emerged after 3 months of therapy. The I50L mutation was evidenced in one subject after 12 months of treatment. The "virtual" phenotype analysis mirrored the resistance profiles to ATV and other PIs and evidenced differences with tipranavir and darunavir.


CONCLUSIONS
Genotype evolution within the protease region did not emerge at significant levels during salvage therapy of multidrug-experienced patients. ATV exhibited certain/same virologic effect on the majority of our patients.
Vergani
Barbara
B
Sezione di Malattie Infettive e Immunopatologia, Dipartimento di Scienze Cliniche Luigi Sacco, Universita' degli Studi, Milano, Italy.
Cicero
Mirko Lo
ML
Vigano'
Ottavia
O
Sirianni
Francesca
F
Ferramosca
Stefania
S
Vitiello
Paola
P
Di Vincenzo
Paola
P
Pia De Pasquale
Maria
M
Galli
Massimo
M
Rusconi
Stefano
S
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D000069446:Atazanavir Sulfate; D024882:Drug Resistance, Viral / Q000235:genetics*; D019143:Evolution, Molecular; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009842:Oligopeptides / Q000627:therapeutic use*; D010641:Phenotype; D010802:Phylogeny; D011725:Pyridines / Q000627:therapeutic use*; D017422:Sequence Analysis, DNA
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1