Long-term trends of HIV type 1 drug resistance prevalence among antiretroviral treatment-experienced patients in Switzerland.
BACKGROUND
Accurate quantification of the prevalence of human immunodeficiency virus type 1 (HIV-1) drug resistance in patients who are receiving antiretroviral therapy (ART) is difficult, and results from previous studies vary. We attempted to assess the prevalence and dynamics of resistance in a highly representative patient cohort from Switzerland.


METHODS
On the basis of genotypic resistance test results and clinical data, we grouped patients according to their risk of harboring resistant viruses. Estimates of resistance prevalence were calculated on the basis of either the proportion of individuals with a virologic failure or confirmed drug resistance (lower estimate) or the frequency-weighted average of risk group-specific probabilities for the presence of drug resistance mutations (upper estimate).


RESULTS
Lower and upper estimates of drug resistance prevalence in 8064 ART-exposed patients were 50% and 57% in 1999 and 37% and 45% in 2007, respectively. This decrease was driven by 2 mechanisms: loss to follow-up or death of high-risk patients exposed to mono- or dual-nucleoside reverse-transcriptase inhibitor therapy (lower estimates range from 72% to 75%) and continued enrollment of low-risk patients who were taking combination ART containing boosted protease inhibitors or nonnucleoside reverse-transcriptase inhibitors as first-line therapy (lower estimates range from 7% to 12%). A subset of 4184 participants (52%) had >or= 1 study visit per year during 2002-2007. In this subset, lower and upper estimates increased from 45% to 49% and from 52% to 55%, respectively. Yearly increases in prevalence were becoming smaller in later years.


CONCLUSIONS
Contrary to earlier predictions, in situations of free access to drugs, close monitoring, and rapid introduction of new potent therapies, the emergence of drug-resistant viruses can be minimized at the population level. Moreover, this study demonstrates the necessity of interpreting time trends in the context of evolving cohort populations.
von Wyl
Viktor
V
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, ETH Zurich, Zurich, Switzerland. vowv@usz.uzh.ch
Yerly
Sabine
S
Bürgisser
Philippe
P
Klimkait
Thomas
T
Battegay
Manuel
M
Bernasconi
Enos
E
Cavassini
Matthias
M
Furrer
Hansjakob
H
Hirschel
Bernard
B
Vernazza
Pietro L
PL
Francioli
Patrick
P
Bonhoeffer
Sebastian
S
Ledergerber
Bruno
B
Günthard
Huldrych F
HF
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D013557:Switzerland / Q000453:epidemiology; D055815:Young Adult
D019380:Anti-HIV Agents