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Emergence of HIV-1 Drug Resistance in Previously Untreated Patients Initiating Combination Antiretroviral TreatmentA Comparison of Different Regimen Types
Viktor von Wyl, MSc;
Sabine Yerly, MSc;
Jürg Böni, DVM;
Philippe Bürgisser, PhD;
Thomas Klimkait, PhD;
Manuel Battegay, MD;
Hansjakob Furrer, MD;
Amalio Telenti, MD;
Bernard Hirschel, MD;
Pietro L. Vernazza, MD;
Enos Bernasconi, MD;
Martin Rickenbach, MD;
Luc Perrin, MD;
Bruno Ledergerber, PhD;
Huldrych F. Günthard, MD; for the Swiss HIV Cohort Study
Arch Intern Med. 2007;167(16):1782-1790.
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.
Author Affiliations: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich (Mr von Wyl and Drs Ledergerber and Günthard); Laboratory of Virology and AIDS Center (Ms Yerly and Dr Perrin) and Division of Infectious Diseases (Dr Hirschel), Geneva University Hospital, Geneva; National Center for Retroviruses, University of Zurich, Zurich (Dr Böni); Division of Immunology (Dr Bürgisser), and Institute of Microbiology (Dr Telenti), Lausanne University Hospital, University of Lausanne, Lausanne; Institute for Medical Microbiology (Dr Klimkait) and Division of Infectious Diseases and Hospital Epidemiology (Dr Battegay), University Hospital Basel, University of Basel, Basel; Division of Infectious Diseases, University Hospital Berne, Berne (Dr Furrer); Division of Infectious Diseases, Cantonal Hospital St Gallen, St Gallen (Dr Vernazza); Division of Infectious Diseases, Regional Hospital Lugano, Lugano (Dr Bernasconi); and Swiss HIV Cohort Study Data Center, Lausanne (Dr Rickenbach), Switzerland.
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