Emergence of HIV-1 drug resistance in previously untreated patients initiating combination antiretroviral treatment: a comparison of different regimen types.
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.
von Wyl
Viktor
V
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Rämistr 100, CH-8091 Zurich, Switzerland. huldrych.guenthard@usz.ch
Yerly
Sabine
S
Böni
Jürg
J
Bürgisser
Philippe
P
Klimkait
Thomas
T
Battegay
Manuel
M
Furrer
Hansjakob
H
Telenti
Amalio
A
Hirschel
Bernard
B
Vernazza
Pietro L
PL
Bernasconi
Enos
E
Rickenbach
Martin
M
Perrin
Luc
L
Ledergerber
Bruno
B
Günthard
Huldrych F
HF
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D016001:Confidence Intervals; D024921:Drug Resistance, Multiple, Viral; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000032:analysis; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use*; D013557:Switzerland / Q000453:epidemiology; D016896:Treatment Outcome
D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019438:Ritonavir