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Has Pretreatment Genotyping Improved Therapy? Answers From Germany
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6th European HIV Drug Resistance Workshop
March 26-28, 2008
Budapest, Hungary
Mark Mascolini
Following pretreatment genotyping advice helped refine selection of first-line regimens in the German HIV-Seroconverter Cohort [1]. Almost one third of prescribed antiretrovirals were probably inactive when clinicians strayed from genotype-based expert advice in picking a first-line regimen. Only 12.5% of prescribed drugs were judged inactive when a clinician followed expert advice. Although the cohort is large, however, these results rest on findings in only 44 people with resistant virus who were treated after genotyping.
German Seroconverter Cohort researchers genotyped everyone with a known seroconversion date from 1997 through 2007. In the whole cohort 1036 people had no resistance mutations when first genotyped and 143 did. Nucleoside-induced mutations proved most common, affecting 5.8%, followed by nonnucleoside mutations in 2.8% and protease inhibitor (PI) mutations in 2.2%. Only 1.5% had virus resistant to two drugs.
Among 44 cohort members who started antiretrovirals with one or more resistance mutations, 28 (group 1) did so without benefit of genotype-based expert advice and 16 (group 2) did. Almost everyone in both groups had early HIV infection (CDC stage A); 1 person in group 1 had CDC stage B disease. CD4 count averages were also similar in the two groups--424 in group 1 and 473 in group 2. But group 1 had a higher viral load than group 2 (219,366 copies versus 57,805 copies).
Nucleoside mutations were the most common in both groups, affecting 15 of 28 (54%) in group 1 and 8 of 16 (50%) in group 2, followed by PI mutations in 10 of 28 group 1 patients (36%) and 6 of 16 group 2 patients (38%) and nonnucleoside mutations in 8 of 28 group 1 patients (29%) and 3 of 16 group 2 patients (19%).
First-line regimens had to be changed after a median 122 days in group 1 versus 142 days in group 2. According to the Stanford genotype interpreting system, 8 of 27 antiretrovirals prescribed for group 1 (30%) were inactive, compared with 2 of 16 prescribed for group 2 (12.5%).
Despite prescription of more inappropriate drugs by clinicians who ignored expert advice, the two groups had equivalent virologic responses, probably because most of these people had only a single mutation.
Reference
1. Bartmeyer B, Kuecherer C, Werning J, et al. The impact of genotypic resistance testing on the composition of first line therapy in the German HIV-Seroconverter Cohort. Wait and see vs. hit hard and early? 6th European HIV Drug Resistance Workshop. March 26-28, 2008. Budapest. Abstract 93.
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