Background.
Numerous
studies have shown that baseline drug resistance patterns may influence the
outcome of antiretroviral therapy. Therefore, guidelines recommend drug
resistance testing to guide the choice of initial regimen. In addition to
optimizing individual patient management, these baseline resistance data enable
transmitted drug resistance (TDR) to be surveyed for public health purposes.
The SPREAD program systematically collects data to gain insight into TDR
occurring in Europe since 2001.
Methods.
Demographic,
clinical, and virological data from 4140 antiretroviral-naive human
immunodeficiency virus (HIV)–infected individuals from 26 countries who were
newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was
defined using the WHO list for surveillance of drug resistance mutations.
Prevalence of TDR was assessed over time by comparing the results to SPREAD
data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was
predicted using the Stanford HIVdb program version 7.0.
Results.
The
overall prevalence of TDR did not change significantly over time and was 8.3%
(95% confidence interval, 7.2%–9.5%) in 2008–2010. The most frequent indicators
of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%),
followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations
(2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most
predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and
6.5% of patient isolates were predicted to have resistance to regimens
containing efavirenz or rilpivirine, respectively, independent of current NRTI
backbones.
Conclusions.
Although
TDR was highest for NRTIs, the impact of baseline drug resistance patterns on
susceptibility was largest for NNRTIs. The prevalence of TDR assessed by
epidemiological surveys does not clearly indicate to what degree susceptibility
to different drug classes is affected.
Below: Overall weighted prevalence
of transmitted drug resistance in patients with newly diagnosed human
immunodeficiency virus (HIV) in Europe. The error bars indicate the standard
error. Abbreviations: NNRTI, nonnucleoside reverse transcriptase inhibitor;
NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; TDR,
transmitted drug resistance.
Below: Genotypic sensitivity scores
(GSSs) of 8 recommended first-line regimens in patients in Europe newly
diagnosed with human immunodeficiency virus in 2008–2010. Abbreviations: ATV,
atazanavir; DRV, darunavir; EFV, efavirenz; KVX, Kivexa (abacavir +
lamivudine); NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease
inhibitor; RPV, rilpivirine; TVD, Truvada (tenofovir +emtricitabine).
Full article at: http://goo.gl/GF3BXW
By:
1Luxembourg, Institute of Health,
Luxembourg
2Department of Virology, University Medical
Center Utrecht, The Netherlands
3Karolinska Institute, Solna
4Karolinska University Hospital, Stockholm,
Sweden
5National Center of Infectious and
Parasitic Diseases, Sofia, Bulgaria
6Complejo Hospitalario Universitario de Granada, Instituto
de Investigación IBS Granada; on behalf ofCohorte de Adultos de la Red de Investigación en
SIDA, Spain
7Erasmus MC, University Medical Center,
Rotterdam, The Netherlands
8University of Bergen, Norway
9University College Dublin, Ireland
Sorbonne
Paris Cité, Paris, France
11Lithuanian AIDS Center, Vilnius, Lithuania
12Robert Koch Institute, Berlin, Germany
13Hospital of Infectious Diseases, Warsaw,
Poland
14St Elisabeth Hospital, Tilburg, The
Netherlands
15Infectiology Center of Latvia, Riga
16University of Cyprus, Nicosia
17Department of Infectious Diseases,
National Institute for Health and Welfare, Helsinki, Finland
18National Reference Laboratory for HIV/AIDS, National
Institute of Public Health, Prague, CzechRepublic
19National HIV Reference Laboratory, Chaim
Sheba Medical Center, Tel-Hashomer, Israel
20Statens Serum Institut, Copenhagen,
Denmark
21National Institute for Infectious Diseases
“Prof. dr. Matei Bals”, Bucharest, Romania
22National Retrovirus Reference Center,
University of Athens, Greece
23IrsiCaixa Foundation, Badalona, Spain
24Faculty of Medicine, Slovenian HIV/AIDS
Reference Centre, University of Ljubljana, Slovenia
25Medical University Vienna, Austria
26Slovak Medical University, Bratislava,
Slovakia
27Faculty of Medicine, University of
Belgrade, Serbia
28Rega Institute for Medical Research, KU
Leuven, Belgium
29University of Siena, Italy
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