419. Detection of Drug-Resistant Minority Variants (DRMVs) of HIV-1 in Antiretroviral Treatment (ART)-Naïve Subjects through Population-Based Genotypic Resistance Testing (PBGRT)
Session: Poster Abstract Session: HIV - Antiretroviral Therapy
Friday, October 21, 2011
Room: Poster Hall B1
Background: Undetected DRMVs are known to adversely impact the outcome of ART in HIV-1-infected, ART-naïve individuals.  It is also known that PBGRT reliably detects DRMVs only when these represent ≥20% of the viral pool.  Thus, PBGRT underestimates the prevalence of DRMVs compared to more sensitive yet more expensive and less available assays, and novel ways of using PBGRT to detect otherwise undetected DRMVs would be highly desirable.

Methods: We hypothesized that among individuals initiating NNRTI-NRTI ART, ART selective pressure would suppress wild-type HIV-1 variants but would confer a replicative advantage to DRMVs with undetected reverse transcriptase (RT) resistance.  Thus, shortly after initiating ART and despite a rapidly decreasing viral load (VL), the viral pool would become proportionally “enriched” with the DRMVs. Our study was a prospective single arm study of 46 ART-naïve individuals (screening VL ≥25,000 c/ml; no detectable NNRTI and/or NRTI resistance by PBGRT) selected by their physicians to begin efavirenz/tenofovir/emtricitabine. Blood was collected for PBGRT and VL before (Day 0), 4, and 7 days after initiating ART.  The subjects’ VL response to ART was followed over the subsequent 6 months.

Results: Among 46 participants, 42 sets of samples were available for an analysis of the VL (log10) drop (Table) and PBGRT.  No RT mutations were detected in any subjects at Day 0; only 1 subject had a K103N mutation detected at day Days 4 and 7 but achieved a VL <50 c/ml by Month 6.  No other subjects had RT mutations detected at any time point; VL <50 c/ml was achieved in 0/38 subjects at Day 7, 13/35 at Month 3, and 20/28 at Month 6.

 

 

Day 0

Day 4

Day 7

Month 3

Month 6

Samples (n)

42

42

38

35

28

Median VL

5.20

4.16

3.58

2.03

1.30

VL drop

 

1.04

1.62

3.17

3.90

Conclusion: An “enrichment” strategy through ART selective pressure unmasked previously undetected DRMVs in only 1 of 42 (2.4%) individuals through PBGRT.  Because of the known association between undetected DRMVs and ART failure, it is critical to identify DRMVs but the most effective methodology remains to be defined.


Subject Category: H. HIV/AIDS and other retroviruses

Tirdad Zangeneh, D.O., M.A.1, Charles Hicks, MD2, Deborah McMullen, RN2, Mary Ann Fletcher, Ph.D.1, Nobel Bellosillo, MD3, Jorge Villacian, MD4, Michael Kolber, Ph.D., M.D.1 and Rafael Campo, MD1, (1)University of Miami, Miami, FL, (2)Duke University, Durham, NC, (3)Virco Lab, Inc., Raritan, NJ, (4)Virco BVBA, Beerse, Belgium

Disclosures:

T. Zangeneh, None

C. Hicks, None

D. McMullen, None

M. A. Fletcher, None

N. Bellosillo, Virco Labs: Employee, Salary

J. Villacian, Virco Labs: Employee, Salary

M. Kolber, None

R. Campo, Gilead Sciences: Grant Investigator and Scientific Advisor, Consulting fee and Grant recipient
Pfizer: Grant Investigator, Grant recipient
Tibotec: Scientific Advisor, Consulting fee
Merck: Grant Investigator, Scientific Advisor and Wife is an employee and stockholder , Consulting fee, Grant recipient and Wife received salary and stock

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.