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Long-Term Resistance Rate Low When Starting ART
Within Year of HIV Diagnosis
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Tenth International Congress on Drug Therapy in HIV Infection, November 7-11, 2010, Glasgow
Mark Mascolini
Resistance rates remained low 4 to 8 years after people started antiretroviral therapy (ART) within a year of their HIV diagnosis [1]. CASCADE cohort researchers believe their findings counter the argument that starting ART at high CD4 counts puts people at undue risk of eventual resistance.
This analysis involved 1223 CASCADE cohort members, all of whom have well established dates of HIV seroconversion. Everyone in this study started antiretrovirals within 1 year of their HIV diagnosis. The study group included people with a drug resistance test if their viral load exceeded 1000 copies while on treatment and people whose viral load always stayed below 1000 copies. For purposes of this analysis, the investigators assumed that people who maintained a sub-1000 viral load did not have resistance mutations. Follow-up continued until a resistance mutation was detected or until the last viral load measurement on record.
The study group had a median age of 34 (interquartile range [IQR] 29 to 41) and a median pretreatment CD4 count of 432 (IQR 299 to 610). Most cohort members (85%) were men, and 71% started a protease inhibitor regimen. Median time on treatment stood at 12 months (IQR 6 to 24), and 733 people (60%) interrupted treatment at some point. The CASCADE investigators counted 119 virologic failures (10%).
Four years after antiretroviral therapy began, 11% had a virologic failure and 3% had detectable resistance mutations. Eight years into treatment, the virologic failure rate was 13% and the detectable mutation rate 6%. Most virologic failures occurred during the first 2 years of therapy.
Statistical analysis that factored in gender, HIV transmission risk group, antiretroviral class, age, and calendar year of antiretroviral initiation found an association between resistance and only two factors: Every 100-cell higher CD4 count when therapy began was associated with an 8% lower risk of virologic failure and a 26% lower risk of detectable mutations after treatment began. Every additional 10 years of age lowered the virologic failure risk 30% and the detectable mutation rate 30%.
Sara Lodi and CASCADE colleagues underlined two limitations to their analysis. First, half of the patients who had a viral load above 1000 copies had no genotypic results available, so the resistance detection rate may be an underestimate. Second, seroconverters who begin treatment early--like people in this CASCADE group--may be a select cluster of motivated individuals who would have a lower risk of poor resistance, virologic failure, and resistance than the general population of people with HIV.
With those caveats in mind, the investigators concluded that the probability of detectable resistance mutations 8 years after starting antiretroviral during early infection ranges from 6% to 13%. Even though almost two thirds of the study group interrupted antiretrovirals at some point during follow-up, the CASCADE team noted, the rate of detectable resistance mutations "was remarkably low compared to those of patients initiating combination ART in chronic infection."
Reference
1. Lodi S, Kucherer C, Bakken Kran AM, et al. Long-term probability of detecting drug-resistant IHV in patients starting antiretroviral therapy within the first year of HIV infection. Tenth International Congress on Drug Therapy in HIV Infection. November 7-11, 2010. Glasgow. Abstract O114.
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