Evolution of HIV-1 Surveillance Drug Resistance Mutations Over 10 Years in New South Wales, Australia.

Abstract

New South Wales has the greatest burden of HIV in Australia, with 2012 and 2013 recording the highest rates of new diagnoses in 20 years. Concurrently, there has been significant changes in antiretroviral treatments and testing paradigms. We compiled a statewide resistance database to characterize changes in HIV-1 resistance mutations over time. Genotypic antiretroviral resistance testing (GART) was performed on request at three reference laboratories using commercial and in-house methods. In total, 7629 HIV-1 polymerase sequences obtained from GART from 2004 to 2013 were retrospectively collated, reformatted, de-identified, and analyzed using Stanford HIVdb program 7.0 and the 2009 World Health Organization (WHO) surveillance drug resistance mutations (SDRMs). Analyses were performed on subgroups of known treatment naives, treatment experienced, and seroconverters. There has been a decrease in overall rates of prevalent drug resistance mutations from 57.8% in 2004 to 21% in 2013. Dual and triple class resistance mutations have decreased from 32.7% in 2004 to 5.8% in 2013 and 16.4% to 1.2%, respectively. In treatment-naive individuals (n = 450), the frequency of protease inhibitor (PI) mutations remains low at 2.7%. In seroconverters, rates of transmitted drug resistance (TDR) are 6.6%, 3%, 3%, and 1.5% for overall, PI, non-nucleoside reverse transcription inhibitor (NNRTI), and NRTI, respectively. In treatment experienced, rates remain stable with 36.0%, 18.9%, 29.1%, and 6.4% for overall, NNRTI, NRTI, and PI mutations. The most common mutations in treatment experienced occurred at position M184, T215 (NRTI); K103 (NNRTI); I54 (PI). Apparent decreases in prevalent SDRMs can be attributed to changes in GART testing indications over time. In treatment-naive and -experienced subgroups, rates have been stable with low rates of TDR in seroconverters.