Genotypic susceptibility scores and HIV type 1 RNA responses in treatment-experienced subjects with HIV type 1 infection.
This study compared the role of genotypic susceptibility scores (GSS) as a predictor of virologic response in a group (n = 234) of HIV-infected, protease inhibitor (PI)-experienced subjects. Two scoring methods [discrete genotypic susceptibility score (dGSS) and continuous genotypic susceptibility score (cGSS)] were developed. Each drug in the subject's regimen was given a binary susceptibility score using Stanford inferred drug resistance scores to calculate the dGSS. In contrast to the dGSS, the cGSS model was designed to reflect partial susceptibility to a drug. Both GSS were independent predictors of week 16 virologic response. We also compared the GSS to a phenotypic susceptibility score (PSS) model on a subset of subjects that had both GSS and PSS performed, and found that both models were predictive of virologic response. Genotypic analyses at enrollment showed that subjects who were virologic nonresponders at week 16 revealed enrichment of several mutated codons associated with nucleoside reverse transcriptase inhibitors (NRTI) (codons 67, 69, 70, 118, 215, and 219) or PI resistance (codons 10, 24, 71, 73, and 88) compared to subjects who were virologic responders. Regression analyses revealed that protease mutations at codons 24 and 90 were most predictive of poor virologic response, whereas mutations at 82 were associated with enhanced virologic response. Certain NNRTI-associated mutations, such as K103N, were rapidly selected in the absence of NRTIs. These data indicate that GSS may be a useful tool in selecting drug regimens in HIV-1-infected subjects to maximize virologic response and improve treatment outcomes.
Anderson
Jeffrey A
JA
UNC Center for AIDS Research, University of North Carolina, Chapel Hill, North Carolina 27759, USA.
Jiang
Hongyu
H
Ding
Xiao
X
Petch
Leslie
L
Journigan
Terri
T
Fiscus
Susan A
SA
Haubrich
Richard
R
Katzenstein
David
D
Swanstrom
Ronald
R
Gulick
Roy M
RM
D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D003062:Codon / Q000235:genetics; D018450:Disease Progression; D024882:Drug Resistance, Viral / Q000235:genetics; D015751:Genes, pol / Q000235:genetics; D005819:Genetic Markers; 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* / Q000235:genetics; D006801:Humans; D009154:Mutation; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D014481:United States; D019562:Viral Load
D019380:Anti-HIV Agents; D003062:Codon; D005819:Genetic Markers; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D016333:HIV Protease