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Triple-Class Resistance Halved in Catalonia From 2002 to 2005
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XVII International HIV Drug Resistance Workshop
June 10-14, 2008, Sitges, Spain
Mark Mascolini
While prevalence of resistance to the first three antiretroviral classes fell by half in Spain's Catalonia region, resistance to nonnucleosides (NNRTIs) remained stable [1]. Resistance to nucleosides (NRTIs) and protease inhibitors (PIs) dropped significantly during the study period.
Using the IAS-USA list of resistance mutations, Catalonia HIV Resistance Network investigators tracked resistance rates from 2002 through 2005 in 2098 adults with virologic failure, defined as a viral load above 1000 copies. The group's age averaged 41.1 years (range 18.2 to 81.8), 74.5% of them were men, and 37.1% had an AIDS diagnosis. Median viral load at failure measured 13,500 copies (interquartile range [IQR] of 3900 to 58,925 copies), and median CD4 count measured 307.5 (IQR 169 to 483).
Prevalence of mutations conferring resistance to NRTIs dropped significantly from 83.0% in 2002 to 72.8% in 2005 (P < 0.05), while PI resistance mutation rates eased nonsignificantly from 57.0% to 46.0% (P = 0.08). Prevalence of NNRTI-related resistance mutations stayed flat over that period at around 69%, but triple-class resistance plunged from 30.2% to 15.8%, a highly significant falloff (P < 0.001). Rates of several thymidine analog (zidovudine or stavudine) mutations fell steeply:
· T215Y/F: 49.6% to 37.8% (P < 0.001)
· M41L: 48.1% to 30.3% (P < 0.001)
· L210W: 30.5% to 18.6% (P < 0.01)
Prevalence of the tenofovir-induced K65R mutation vaulted from 3.6% in 2002 to 7.4% in 2003, then drifted back to 6.8% in 2004 and 4.3% in 2005, a nonsignificant shift (P = 0.2). That trend reflects a significant rise and fall in tenofovir use from 2002 (12.2%) through 2003 (35.5%), 2004 (45.6%), and 2005 (36.7%) (P < 0.0001).
Rates of two NNRTI mutations, G190A/S and Y181C (primarily related to nevirapine therapy) fell over the years (13.0% to 6.4%, and 13.0% to 4.7%), trends reflecting a fall in the nevirapine prescription rate (40.3% to 24.4%). Prevalence of the K103N mutation, primarily linked to efavirenz, remained stable over the years, as did efavirenz prescriptions.
Among PI mutations, only L90M became significantly less common over the study period (29.0% to 18.8%, P < 0.05). L90M ranks as a signature mutation of nelfinavir and saquinavir, according to the IAS-USA [2]. Use of those PIs has dwindled throughout Europe and North America, but the authors did not report nelfinavir and saquinavir prescription trends in Catalonia.
The investigators speculated that new antiretrovirals, new combinations, and changing prescribing patterns may account for the declining resistance rates observed.
References
1. Jaen A, Buira E, Gimenez A, et al. Epidemiological trends in genotypic resistance mutations in relation with antiretroviral exposure. XVII International HIV Drug Resistance Workshop. June 10-14, 2008, Sitges, Spain. Abstract 137.
2. Johnson VA, Brun-Vezinet F, Clotet B, et al. Update of the drug resistance mutations in HIV-1 : 2007. Topics HIV Med. 2007;15:119-125.
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