413. Transmitted Drug Resistance Mutations and PI-Based Antiretroviral Treatment Failure
Session: Poster Abstract Session: HIV - Antiretroviral Therapy
Friday, October 21, 2011
Room: Poster Hall B1
Background: The most common transmitted drug resistance mutation (TDRM) among newly diagnosed HIV-1 infected persons is non-nucleoside reverse transcriptase inhibitor (NNRTI) –resistance, specifically K103N.  These mutations are known to be a risk factor for virologic failure among those started on NNRTI-based antiretroviral treatment (ART). Most persons with NNRTI resistance start treatment with protease inhibitor (PI)-based ART. We studied the association between TDRM and the virologic response to PI-based ART compared with a NNRTI-based ART.

Methods: This was a retrospective cohort study of 594 treatment naïve HIV-1 infected persons from 2001 to 2009 who were started on either NNRTI- (n=357) or PI-based (n= 237) ART after genotypic testing results were available. Virologic failure (HIV RNA levels > 400 copies/ml) by 48 weeks were assessed with multivariate Cox proportional hazards regression models. A sub-analysis was performed to compare those receiving either atazanavir/ritonavir (n= 103) or efavirenz (n=221) with tenofovir/emtricitabine.

Results: Persons receiving PI-based ART had a higher prevalence of nucleoside reverse transcriptase inhibitor (NRTI) resistance (11% vs. 4%, p=0.001) and NNRTI-resistance (27% vs. 2%, p<0.001). There was no difference in the prevalence of PI-resistance (2% vs. 4%, p=0.107). After adjusting for CD4 cell count, HIV RNA level, NRTI-resistance and time from initial clinic visit to initiation of ART, use of PI-based ART conferred a 1.3-fold increased risk of virologic failure compared to NNRTI-based ART. When confined to comparison of atazanavir/ritonavir and efavirenz with tenofovir/emtricitabine as backbone, use of atazanavir/ritonavir conferred a 1.4-fold increased risk of virologic failure compared to efavirenz.

Conclusion: HIV-1 infected patients with TDRM, particularly NNRTI-resistance, are more likely to initiate a PI-based ART, which conferred increased risk for virologic failure despite the guidance by genotypic testing.  These findings illustrate the significant consequences of TDRM. Further research is needed to address whether TDRM serves as a proxy for minority HIV-1 drug resistant mutations.


Subject Category: H. HIV/AIDS and other retroviruses

Toshibumi Taniguchi, MD, Jessica Grubb, MD, Nur Onen, BSc, MBChB and E. Turner Overton, MD, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO

Disclosures:

T. Taniguchi, None

J. Grubb, None

N. Onen, None

E. T. Overton, Gilead: Consultant, Consulting fee
Bristols-Myers Squibb: Consultant, Consulting fee
Glaxo-Smith-Kline: Consultant, Consulting fee
Tibotec: Speaker's Bureau, Research support
Merck: Consultant, Consulting fee
Monogram Science: Consultant, Consulting fee
Boehringer Ingelheim: Consultant, Consulting fee
Abbott: Research Contractor, Research support

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.