2383. Prevalence and Clinical Implications of Minority Variant (MV) HIV Drug-Resistance Mutations (DRMs) in ARV-Naïve Patients with and without Transmitted Drug Resistance (TDR)
Session: Oral Abstract Session: HIV Prevention and Diagnosis
Saturday, October 29, 2016: 3:00 PM
Room: 288-290
Background: MV-DRMs, defined as DRMs below the level of detection by Sanger sequencing, have been associated with treatment failures. We aimed to describe the prevalence of transmitted MV-DRMs in Northern California where TDR prevalence is high. Because NRTI DRMs are less fit than NNRTI DRMs, we hypothesized that patients with isolated NNRTI TDR may have also had NRTI TDR at infection that faded over time resulting in an increased prevalence of NRTI MV-DRMs.

Methods: We performed Primer ID Illumina next-generation sequencing (NGS) of HIV RT in 33 consecutive individuals in Kaiser Permanente Northern California with isolated NNRTI TDR by Sanger sequencing and HIV RNA levels >10,000 copies/ml and in 49 controls without TDR matched for HIV RNA level, CD4 count, and sampling year. The primer ID approach validates template sampling depth and greatly reduces the error rate of NGS. MV-DRMs were considered present if they occurred >10 times more often than the frequency predicted by the residual method error. Overall 50%, 35%, and 15% of patients received a raltegravir, boosted atazanavir, or other first-line regimen, respectively. We determined the overall prevalence of MV-DRMs and compared the prevalence in the NNRTI TDR and control patients. Rates of virological failure (VF), defined as an HIV RNA level >50 copies/ml at week 48, were assessed.

Results: Overall 32 (39%) patients had NRTI MV-DRMs, 30 (37%) had NNRTI MV-DRMs, and 33 (40%) had no MV-DRMs. There was no difference in the proportion of NRTI (10/33, 30% vs. 22/49, 45%; p=0.25) or NNRTI (11/33, 33% vs. 19/49, 39%; p=0.7) MV-DRMs between the NNRTI TDR and control patients. The overall VF rate was 10% with no difference in VF between the NNRTI TDR and control patients. Of 11 patients with MV-DRMs conferring significant resistance to the regimen they received (M184V/I in 9 and G190E in 2 at a median prevalence of 0.4%), one developed VF.

Conclusion: In patients from Northern California MV-DRMs were common, reflecting either transmitted variants that had faded to low levels or background HIV RT enzymatic errors. There was no evidence that MV-DRMs were more common in patients with isolated NNRTI TDR compared to patients without TDR detectible by Sanger sequencing.

Dana Clutter, MD1, Shuntai Zhou, MD2, Vici Varghese, PhD1, Soo-Yon Rhee, PhD1, Benjamin Pinsky, MD, PhD1, W. Jeffrey Fessel, MD3, Daniel Klein, MD3, Leo Hurley, MPH3, Michael Silverberg, PhD, MPH3, Ronald Swanstrom, PhD2 and Robert Shafer, MD1, (1)Infectious Diseases, Stanford University, Stanford, CA, (2)Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, (3)Kaiser Permanente Northern California, Oakland, CA

Disclosures:

D. Clutter, Bristol-Myers Squibb: Virology Fellow , Research support

S. Zhou, None

V. Varghese, None

S. Y. Rhee, None

B. Pinsky, None

W. J. Fessel, None

D. Klein, None

L. Hurley, None

M. Silverberg, None

R. Swanstrom, University of North Carolina: Co-inventor of Primer ID Method , Licensing agreement or royalty

R. Shafer, Celera: Consultant , Consulting fee
Roche Molecular: Collaborator , Research support
Bristol-Myers Squibb: Collaborator , Research support
Gilead Sciences: Collaborator , Research support
Merck: Collaborator , Research support

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