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Resistance Mutation Rate Rising in Treatment-Naive US Trial Enrollees
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XVII International HIV Drug Resistance Workshop
June 10-14, 2008, Sitges, Spain
Mark Mascolini
Resistance mutation rates among 3542 untreated US clinical trial enrollees doubled from 2000 to 2007 [1] when GlaxoSmithKline researchers used either the IAS-USA mutation list [2] or a January 2008 catalog of transmitted mutations proposed for surveillance purposes. Mutation prevalence was highest in the South and West, but prevalence rose in every region. The findings run counter to trends in a recent European study of transmitted resistant virus [3].
Most Glaxo trial participants (83%) were men; 65% were gay, 49% white, 37% black, and 9% Hispanic. Median pretreatment viral load stood at 4.88 log (about 70,000 copies) and median CD4 count at 226. Only 11% had AIDS. These people lived in 36 of the 50 states and Washington, DC.
Overall 2000-2007 incidence of any mutation measured 17% by the IAS-USA list and 12% by the surveillance list. Prevalence of resistance mutations in untreated trial enrollees climbed significantly from 9% to 20% according to the IAS-USA list from 2000 to 2007 (P = 0.003) and from 5% to 13% by the surveillance index (P = 0.004). The risk of infection with a primary IAS-USA mutation from any class also rose significantly over the study period (P < 0.001).
Nonnucleoside-induced mutations accounted for most of the overall jump, as prevalence of these mutations shot from 6% to 15% by the IAS-USA list and from 2% to 8% by the surveillance list. Rates of nucleoside-related mutations climbed modestly, from 3% to 4% according to IAS-USA and from 4% to 5% by the surveillance list. Rates of protease inhibitor (PI) mutations in untreated people edged up from 2% to 3% by both IAS-USA and the surveillance lists. Prevalence of mutations conferring resistance to two or more antiretroviral classes stood at 2% according to either mutation scheme, and the overall triple-class mutation rate was below 1%.
According to the IAS-USA tables, resistance mutation prevalence in untreated trial enrollees jumped from 10% to 32% over the study period in the West, from 8% to 24% in the Northeast, from 9% to 18% in the South, and from 14% to 18% in the Midwest. Overall mutation prevalence for the 7-year study span measured 20% in the West, 17% in the South, and 15% in both the Northeast and Midwest. Subtype B HIV-1 continued its dominance in the United States at 97% prevalence, followed by subtype C at 1.5%, G at 0.55%, A at 0.45%, and D at 0.1%.
Multivariate analysis figured that blacks ran a 7% lower chance of infection with resistant virus than whites or others (P = 0.001). But older blacks were more likely to acquire PI-resistant virus than younger blacks. Overall, older people proved less likely to pick up
PI-resistant HIV everywhere except in the Midwest, where older people ran a higher risk of infection with PI-resistant virus. Lisa Ross and colleagues did not speculate on reasons for these curious differences. In general, results of this analysis may not reflect HIV resistance transmission trends in the entire US population because clinical trial volunteers may differ from the HIV population at large.
Results of a recent European study contrast with the US findings [3]. The shorter and smaller SPREAD analysis of 723 people genotyped within 6 months of HIV diagnosis in 20 European countries and Israel found a small decline in incidence of transmitted infections from 11% in the first half of 2003 to just under 10% in the second half of 2005, a nonsignificant dip. Incidence of PI mutations did fall significantly, from about 7% to 2% (P = 0.01), while rates of nucleoside and nonnucleoside mutations stayed flat.
References
1. Ross LL, Dix L, Wine B, et al. Change in regional prevalence, clade and epidemiology of HIV-1 drug resistance mutations and clade among antiviral therapy-naive patients in the United States from 2000 to 20007. XVII International HIV Drug Resistance Workshop. June 10-14, 2008, Sitges, Spain. Abstract 146.
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.
3. Vercauteren J, Wensing AMJ, van de Vijver D, et al. Trends in transmitted drug-resistant HIV-1 in Europe (Sept 2002-Dec 2005). 6th European HIV Drug Resistance Workshop. 26-28 March 2008. Budapest. Abstract 5.
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