GENOTYPIC HIV-1 DRUG RESISTANCE AMONG RECENT SEROCONVERTERS: RESULTS FROM THE POLARIS HIV SEROCONVERSION STUDY

R Pilon¹, P Sandstrom¹, A Burchell², L Calzavara², C Major³, S Read⁴, K Logue⁵, M Ostrowski⁵, K Gough⁵, A Rachlis⁶, Polaris HIV Study Team
¹Centre for Infectious Disease Prevention and Control, Health Canada; ²HIV Studies Unit, University of Toronto; ³Ontario Ministry of Health, Toronto; ⁴Hospital for Sick Children, Toronto; ⁵Faculty of Medicine, University of Toronto; ⁶Sunnybrook and Women’s College Health Sciences Centre, University of Toronto, Ontario

Objectives: To determine the frequency of genotypic drug resistance among HIV-1 recent seroconverters in Ontario.
Methods: Analysis of genotypic drug resistance was performed by population based sequencing of PCR products from plasma of recent HIV-1 seroconverters enrolled in a prospective longitudinal study between 1998 and 2001.
Results: Sequence information was available from 63 patients at baseline (median of 7.1 months from presumed infection) of which 43 were identified as antiretroviral (ART) naïve. In these patients, mutations conferring resistance were detected in viruses from 5 (11.6%) patients at baseline: 3 (7%) to NNRTI and 2 (5%) to NRTI. We detected no genotypic protease inhibitor (PI) resistance mutations among ART-naïve individuals. With the exception of Y181C which causes high level resistance to nevirapine and delavirdine, all other mutations detected confer low to intermediate resistance. Two cases of K103R, which causes multi-drug resistance when present with other resistance-conferring mutations were also detected. Virus from two ART-naïve patients who initiated ART developed resistance to NRTI at 9 (M184V) and 28 (T69A) months after baseline. We detected 2 (3.2%) cases of PI resistance in individuals who were ART-experienced at baseline. These were detected at 3 and 15 months after diagnosis HIV infection. All cases of emerging resistance were detected in patients with low but detectable viral levels (<5,000 copies/ml). Patients who were ART-experienced at baseline and in whom we detected early resistance also had very low viral loads (145 and 148 copies/ml).
Conclusions: Our finding of 11.6% RTI resistance is at the lower end of recently published rates, possibly due to ever improving patient management. However, with long-term adherence problems and limited treatment options, treatment failures will increase, and the transmission of resistant viruses to new cases will also rise.