No transmission of integrase-resistant HIV seen in California cohort

Genotypic analysis of transmitted drug resistance (TDR) in a large California cohort disclosed not a single case of TDR to integrase inhibitors. TDR rates involving NRTIs, NNRTIs and PIs were in line with previously reported findings.

Integrase inhibitors have been on the market since 2007, noted Monogram Biosciences researchers who conducted this study. But rates of TDR to this increasingly used antiretroviral class remain poorly characterised. The Monogram team found only three cases of integrase inhibitor TDR reported in the literature. In contrast, volumes of work have addressed TDR to the first three antiretroviral classes.

To learn more about recent TDR to integrase inhibitors and the first three classes, Monogram investigators analyzed genotype resistance test results in their commercial database from March 2013 through June 2015. They looked specifically at samples from 13 California sites of the AIDS Healthcare Foundation Network, and they characterised a sample as resistant according to the surveillance drug resistance mutations list in the Stanford University HIV Drug Resistance Database (http://cpr.stanford.edu/input/sdrm/SDRM_2009.txt).

The analysis involved 339 genotypic results of HIV-positive people who had not begun antiretroviral therapy. Overall 2013-2015 TDR prevalence stood at 24.9% but varied substantially from year to year – 24.2% in 2013, 30.2% in 2014, and 15.9% in 2015. For the whole 3-year period, TDR prevalence was highest for NNRTIs (16.9%), followed by NRTIs (6.5%), and PIs (4.2%). No samples harboured integrase inhibitor TDRs.

NNRTI TDR prevalence jumped from 13.2% in 2013 to 22.6% in 2014 then dropped to 10.2% in 2015. NRTI TDR prevalence fell through the three study years, from 9.9% to 5.7% to 4.5%. PI TDR rates stayed nearly flat: 4.4% to 4.4% to 3.4%. The most frequently transmitted mutations were K103N/S (13.0%), L90M (2.7%), and Y181C/I/V, M41L, and M184V/I (2.1% each).

Prevalence of TDR involving the first three antiretroviral classes proved lowest in 149 samples from people 19 to 29 years old (about 20%), rose to about 30% in 163 samples from people 30 to 49 years old, and came close to 60% in 26 samples from people 50 or older.

Monogram data indicate that prevalence of integrase inhibitor mutations acquired during therapy has stayed low across the 3 years of study – below 4% in 2013 and 2014, and below 3% in 2015.

“Despite predictions to the contrary,” the Monogram team concluded, “the study demonstrates that TDR involving integrase inhibitors has been and remains surprisingly rare.” But substantial prevalence of TDR to the other classes, they suggested, supports continued use of pretreatment HIV resistance testing.

Volpe JM, Yang O, Petropoulos CJ, Walworth CM. Absence of integrase inhibitor resistant HIV-1 transmission in the California AIDS Healthcare Foundation Network. ICAAC 2015, September 17-21, 2015, San Diego.