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Resistance Testing Is Not Standard-of-Care After Antiretroviral Failure in Europe
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7th European HIV Drug Resistance Workshop, March 25-27, 2009, Stockholm
Mark Mascolini
Despite long-standing guidelines recommending resistance testing after virologic failure, more than two thirds of EuroSIDA cohort members had no recorded resistance test after taking a failing regimen 4 months or longer [1]. In people who did get a resistance test after failure, time from failure to testing averaged about 7 months.
Zoe Fox and EuroSIDA colleagues dissected records of 2479 cohort members who started at least a triple combination after 2000 and met the study criterion for needing a resistance test--a viral load above 1000 copies for at least 4 months while taking at least one drug.
Of these 2479 people, 1538 (62%) had a confirming viral load test above 1000 at the next study visit and 1523 (61.2%) had a viral load below 500 copies while taking the regimen that failed. At virologic failure, these people had taken the same regimen for a median of 10 months (interquartile range [IQR] 6 to 22.5). Follow-up after virologic failure lasted a median of 3.3 years (IQR 1.8 to 5.1). The final follow-up visit of the observation period came in April 2008.
Whereas 74 people (3%) had a resistance test before failure (as defined in this analysis), only 775 (31.3%) had a resistance test after failure. And 38 of those 775 already had a pre-failure test. Thus 881 of these 2479 people (32.7%) had a resistance test around the time of virologic failure. Among people who had a resistance test, median time from failure to testing measured 7 months (IQR 0.7 to 19.7).
Kaplan-Meier analysis calculated the following probabilities of having a resistance test after failure:
• 20.8% by 1 year
• 27.9% by 2 years
• 33.3% by 3 years
• 37.6% by 4 years
• 40.8% by 5 years
• 43.5% by 6 years
• 44.2% by 7 years
Multivariate statistical analysis adjusting for predictors of resistance testing (excluding adherence because of the small number of people with adherence data) picked out five independent predictors of resistance testing:
• Women had a 21% lower chance of resistance testing than men (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.65 to 0.98, P = 0.02).
• People in central Europe were 58% more likely to be tested than people in southern Europe (HR 1.58, 95% CI 1.31 to 1.91, P < 0.0001).
• People seen in 2002, 2003, and 2004 were more likely to be tested than those seen in 2000 (P < 0.0001).
• Every additional failed regimen raised chances of testing 12% (HR 1.12, 95% CI 1.08 to 1.16, P < 0.0001).
• Every additional 6 months with a viral load above 1000 copies lowered chances of testing 23% (HR 0.77, 95% CI 0.74 to 0.80, P < 0.0001)
Fox and coworkers speculated that the low probability of having a resistance test in 2007, the most recent year analyzed (HR 0.51 versus 2000), could reflect reporting delays.
Most resistance tests did detect one or more resistance mutations, a finding emphasizing "that resistance tests are not commonly used to screen for virologic failure early in the course of combination antiretroviral therapy, when the chance of resistance is intrinsically lower."
Reference
1. Fox ZV, Phillips AN, Cozzi-Lepri A, et al. Predictors of having a resistance test following at least one episode of viral load (VL) failure of cART: data from EuroSIDA. 7th European HIV Drug Resistance Workshop, March 25-27, 2009, Stockholm. Abstract 8.
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