Genotypic susceptibility scores and HIV type 1 RNA responses in treatment-experienced subjects with HIV type 1 infection.

TitleGenotypic susceptibility scores and HIV type 1 RNA responses in treatment-experienced subjects with HIV type 1 infection.
Publication TypeJournal Article
Year of Publication2008
AuthorsAnderson JA, Jiang H, Ding X, Petch L, Journigan T, Fiscus SA, Haubrich R, Katzenstein D, Swanstrom R, Gulick RM
Corporate AuthorsAIDS Clinical Trials Group Study 359 Protocol Team
JournalAIDS Res Hum Retroviruses
Volume24
Issue5
Pagination685-94
Date Published2008 May
ISSN1931-8405
KeywordsAnti-HIV Agents, Antiretroviral Therapy, Highly Active, Codon, Disease Progression, Drug Resistance, Viral, Genes, pol, Genetic Markers, Genotype, HIV Infections, HIV Protease, HIV Protease Inhibitors, HIV-1, Humans, Mutation, Predictive Value of Tests, RNA, Viral, Treatment Outcome, United States, Viral Load
Abstract

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.

DOI10.1089/aid.2007.0127
Alternate JournalAIDS Res. Hum. Retroviruses
PubMed ID18462083
PubMed Central IDPMC2928289
Grant ListAI-38855 / AI / NIAID NIH HHS / United States
AI064086 / AI / NIAID NIH HHS / United States
AI25868 / AI / NIAID NIH HHS / United States
AI27666 / AI / NIAID NIH HHS / United States
AI27670 / AI / NIAID NIH HHS / United States
AI36214 / AI / NIAID NIH HHS / United States
I-6836 / / PHS HHS / United States
I69419 / / PHS HHS / United States
K24 AI051966 / AI / NIAID NIH HHS / United States
K24 AI064086 / AI / NIAID NIH HHS / United States
K24 AI064086-01A1 / AI / NIAID NIH HHS / United States
K24 AI064086-04 / AI / NIAID NIH HHS / United States
M01 RR000070 / RR / NCRR NIH HHS / United States
M01 RR000070-360399 / RR / NCRR NIH HHS / United States
M01RR00070 / RR / NCRR NIH HHS / United States
P30 AI036214 / AI / NIAID NIH HHS / United States
P30 AI036214-149009 / AI / NIAID NIH HHS / United States
P30 HD037260-019003 / HD / NICHD NIH HHS / United States
RR00047 / RR / NCRR NIH HHS / United States
U01 AI069432 / AI / NIAID NIH HHS / United States
UL1-RR24996 / RR / NCRR NIH HHS / United States