icon-folder.gif   Conference Reports for NATAP  
  XVII International HIV Drug Resistance Workshop
June 10-14, 2008
Sitges, Spain
Back grey_arrow_rt.gif
Resistance Risk Higher in Injecting Drug Users, Regardless of Adherence
  XVII International HIV Drug Resistance Workshop
June 10-14, 2008, Sitges, Spain
Mark Mascolini
Injecting drug users (IDUs) in British Columbia run a higher risk of resistance to antiretrovirals than non-IDUs, regardless of pretreatment variables or adherence figured by two methods [1]. The findings confirm and extend earlier work by this group showing a higher risk of resistance during 30 months of follow-up in IDUs starting antiretrovirals than in others [2].
Vikram Gill and colleagues analyzed 6066 genotypes from 2350 people starting their first triple regimen between August 1, 1996 and November 30, 2004; follow-up continued through November 30, 2005. Everyone was at least 18 years old, and no one had antiretroviral experience when they started their first triple combination. The investigators measured adherence by prescription refill percentage in the first year of therapy and, in a 751-person subgroup that began therapy between August 1996 and September 1999, by unscheduled measures of drug concentrations in plasma.
Most cohort members (82%) were men, 51% had a pretreatment CD4 count under 200, and 58% started treatment with a viral load under 10,000 copies. While 42% began a nonboosted protease inhibitor (PI), 20% started a boosted PI and 38% a nonnucleoside. Just more than half of the cohort (54%) had at least 95% adherence, while 18% had less than 80% adherence and 13% less than 40% adherence.
IDUs had more than a 70% higher risk of resistance than non-IDUs (adjusted odds ratio [OR] 1.71, 95% confidence interval [CI] 1.39 to 2.11) in an analysis that factored in numerous pretreatment and on-treatment variables: viral load, CD4 count, age, gender, IDU history, adherence, year treatment began, and type of initial regimen. IDUs also had a higher resistance risk than non-IDUs when the investigators compared IDUs and non-IDUs with the same adherence level or taking the same type of first regimen. The higher resistance risk in IDUs held true for both men and women. Adherence measured by either prescription refill or unscheduled drug levels did not account for the resistance difference between IDUs and others.
Resistance risk was consistently 50% to 60% higher in IDUs for three antiretroviral categories--lamivudine/emtricitabine, nonnucleosides, and PIs. The one exception was resistance to nucleosides excluding lamivudine and emtricitabine, for which the resistance risk was only 11% higher in IDUs, a nonsignificant difference (95% CI 0.82 to 1.50). Risk of resistance to more than one drug group was almost 50% higher for IDUs than non-IDUs (OR 1.47, 95% CI 1.15 to 1.89), and risk of resistance to more than two drug groups was about one third higher among IDUs, though the latter difference fell just short of statistical significance (OR 1.36, 95% CI 0.94 to 1.97).
The British Columbia team did not speculate on why IDUs run a higher resistance risk regardless of adherence and other variables that affect resistance.
1. Gill VS, Lima VD, Fernandes KA, Harrigan PR. Injection drug users have a higher probability of developing resistance than non-injection drug users regardless of adherence or initial treatment regimen. XVII International HIV Drug Resistance Workshop. June 10-14, 2008, Sitges, Spain. Abstract 143.
2. Harrigan PR, Hogg RS, Dong WWY, et al. Predictors of HIV drug-resistance mutations in a large antiretroviral-naive cohort initiating triple antiretroviral therapy. J Infect Dis. 2005;191:339-347.