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Evolving Resistance Pattern Before Antiretroviral Therapy Starts
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5th European HIV Drug Resistance Workshop
Cascais, Portugal
March 29, 2007
Mark Mascolini
Detectable resistance mutations changed in 20% of people with two genotypic assays before they started antiretrovirals [1], a finding suggesting the importance of repeating resistance testing immediately before beginning therapy in treatment-naive people who already had one test. This single-center study from Italy's University of Brescia found a surprisingly high overall rate of pretreatment mutations, perhaps because of the broad list of potential mutations used.
The study involved 600 people who had a pretreatment resistance test from 2001 through 2006, 47 of them with a diagnosis of acute or recent HIV infection. A total of 280 people (47%) had one or more resistance mutations, 253 (42%) with one or more nucleoside mutations, 43 (7%) with at least one nonnucleoside mutation, and 28 (6%) with one or more mutations conferring resistance to protease inhibitors (PIs).
The high nucleoside mutation rate partly reflects inclusion of the minor Q151M complex mutations (A62V, V75I, F77L, and F116Y) and T215Y/F mutations evolving back toward the nonmutant T215T ("T215 revertants"). The most common nucleoside mutation, A62V, appearing in virus of 162 people (64% of the 253 people with nucleoside mutations), came from this group of minor mutations or revertants. K70R, the second most common nucleoside mutation, could be detected in virus from 60 people (24%). Seventeen people (7%) had T215 revertants, and 7 (3%) had T215Y/F.
The most frequent nonnucleoside mutations were K103N in 24 people (59% of the 43 people with nonnucleoside mutations) and K103R/S/Q/T in 10 (23%). V106A showed up in 2 people and Y188L in 3. I50V proved the most common PI mutation, appearing in
14 of 28 people (50%) with PI mutations, followed by M46I/L in 8 (29%), L33F in 7 (25%), and V82A/F/T/Sl/L in 7 (25%).
Being an immigrant to Italy lowered the risk of infection with resistant virus by two thirds (odds ratio 0.33, 95% confidence interval 0.11 to 0.98, P = 0.036). Factors that did not affect risk of infection with resistant virus were calendar year, age, gender, HIV risk factor, and acute versus recent infection.
Among 35 people who had a second genotype before starting therapy, 28 (80%) had no genotypic change a median of 4 months (range 1 to 18 months) after their first genotype. Seven people (20%) had a different mutation set on the second assay. Three of these 7 lost one or more mutations (K103R, K219Q, and M184V + G48V + L90M + M41I/L), while 2 had a T215Y reversion. New mutations--A62V (a minor Q151M complex mutation) and K70R (a thymidine analog mutation)--emerged in 2 people in their second genotype.
References
1. Lapadula G, Sosta E, Gargiulo F, et al. Updated prevalence of genotypic resistance among naive patients: a single center analysis. 5th European HIV Drug Resistance Workshop. March 28-30, 2007. Cascais, Portugal. Abstract 26.
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