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Rising Rates of 3-Class Exposure But Falling Failure Rate in US Cities
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Mark Mascolini
XVIII International Drug Resistance Workshop, June 9-13, 2009, Fort Myers, Florida
A 6-center US study found that rates of triple-class exposure rose from 23% in 2000 to 35% in 2008, but over the same period virologic failure rates in these people dropped from 45% to 13% [1]. By 2008, people with triple-class exposure no longer ran a higher risk of failure than people without three-class exposure. African Americans had a higher failure risk.
Jeannette Aldous (University of California, San Diego) and colleagues at other sites in Alabama, California, Massachusetts, and Ohio evaluated antiretroviral exposure and response rates on the last day of 2000, 2002, 2004, and 2006, and on July 31, 2008. They considered patients as members of the study cohort if they visited the clinic within 180 days of those dates. The researchers defined triple-class exposure as treatment with at least 2 nucleosides, at least 1 nonnucleoside, and at least 2 protease inhibitors. Four-class exposure meant treatment with that many drugs plus at least one fusion inhibitor, integrase inhibitor, or CCR5 antagonist. Failure meant a viral load above 200 copies after 24 weeks of therapy.
Study cohorts included 2012 people in 2000, 2668 in 2002, 3582 in 2004, 4219 in 2006, and 3832 in 2008. Prevalence (and 95% confidence intervals) of triple-class exposure and quadruple-class exposure rose steadily over those years:
· 2000: 23% (21% to 25%), 0.3% (0.1% to 0.5%)
· 2002: 27% (25% to 28%), 0.6% (0.3% to 0.9%)
· 2004: 31% (29% to 32%), 1.7% (1.3% to 2.2%)
· 2006: 33% (31% to 34%), 2.3% (1.9% to 2.8%)
· 2008: 35% (34% to 37%), 5.3% (4.6% to 6.0%)
Movement of people in and out of the cohort did not explain these steady upticks. Prevalence of three-class exposure rose faster over the study period among women than men and among African Americans than other racial/ethnic groups. Incidence of triple-class exposure rose 9% to 13% yearly among women and 8% to 14% yearly among African Americans.
Virologic failure rates dwindled steadily over the years. By 2008, the failure-rate difference between people with and without triple-class exposure lost statistical significance:
· 2000: 45% versus 26%, P < 0.001
· 2002: 36% versus 21%, P < 0.001
· 2004: 25% versus 13%, P < 0.001
· 2006: 18% versus 11%, P < 0.001
· 2008: 13% versus 10%, P = 0.4
Prevalence of virologic failure did not differ by gender, but African Americans had higher failure rates than other groups. Rates of exposure to raltegravir (6%), enfuvirtide (3%), and maraviroc (1%) were low in this cohort in 2008, so one wonders regarding the impact of not using these drugs.
Aldous and colleagues looked for independent predictors of virologic failure in an analysis that considered study site, three-class exposure, four-class exposure, gender, race, ethnicity, and CD4 count. Three factors raised the risk of virologic failure: a lower starting CD4 count (P < 0.001 in every study year), age under 40 years (P < 0.05 in 2000, 2006, and 2008), and African-American race (P = 0.05 to 0.001 in every study year except 2002).
Because virologic failure rates fell as antiretroviral exposure rose, the investigators suggested factors other than failure must be driving drug switches in their cohort.
Reference
1. Aldous JL, Jain S, Sun S, et al. Increasing prevalence of triple-class antiretroviral experienced patients is not associated with virologic failure: data from the CFAR network of integrated clinical systems (CNICS) cohort. XVIII International Drug Resistance Workshop. June 9-13, 2009. Fort Myers, Florida. Abstract 73.
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