von Wyl, V; Yerly, S; Böni, J; Bürgisser, P; Klimkait, T; Battegay, M; Furrer, H; Telenti, A; Hirschel, B; Vernazza, P L; Bernasconi, E; Rickenbach, M; Perrin, L; Ledergerber, B; Günthard, H F; Swiss HIV Cohort Study, (2007). Emergence of HIV-1 drug resistance in previously untreated patients initiating combination antiretroviral treatment: a comparison of different regimen types. Archives of Internal Medicine, 167(16):1782-1790.
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BACKGROUND: Standard first-line combination antiretroviral treatment (cART) against human immunodeficiency virus 1 (HIV-1) contains either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r). Differences between these regimen types in the extent of the emergence of drug resistance on virological failure and the implications for further treatment options have rarely been assessed. METHODS: We investigated virological outcomes in patients from the Swiss HIV Cohort Study initiating cART between January 1, 1999, and December 31, 2005, with an unboosted PI, a PI/r, or an NNRTI and compared genotypic drug resistance patterns among these groups at treatment failure. RESULTS: A total of 489 patients started cART with a PI, 518 with a PI/r, and 805 with an NNRTI. A total of 177 virological failures were observed (108 [22%] PI failures, 24 [5%] PI/r failures, and 45 [6%] NNRTI failures). The failure rate was highest in the PI group (10.3 per 100 person-years; 95% confidence interval [CI], 8.5-12.4). No difference was seen between patients taking a PI/r (2.7; 95% CI, 1.8-4.0) and those taking an NNRTI (2.4; 95% CI, 1.8-3.3). Genotypic test results were available for 142 (80%) of the patients with a virological treatment failure. Resistance mutations were found in 84% (95% CI, 75%-92%) of patients taking a PI, 30% (95% CI, 12%-54%) of patients taking a PI/r, and 66% (95% CI, 49%-80%) of patients taking an NNRTI (P < .001). Multidrug resistance occurred almost exclusively as resistance against lamivudine-emtricitabine and the group-specific third drug and was observed in 17% (95% CI, 9%-26%) of patients taking a PI, 10% (95% CI, 0.1%-32%) of patients taking a PI/r, and 50% (95% CI, 33%-67%) of patients taking an NNRTI (P < .001). CONCLUSIONS: Regimens that contained a PI/r or an NNRTI exhibited similar potency as first-line regimens. However, the use of a PI/r led to less resistance in case of virological failure, preserving more drug options for the future.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Institute of Medical Virology|
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Date:||10 September 2007|
|Deposited On:||11 Feb 2008 12:28|
|Last Modified:||28 Nov 2013 00:58|
|Publisher:||American Medical Association|
|Citations:||Web of Science®. Times Cited: 75|
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