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Transmitted Drug Resistance 9-10% in Europe
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"Drug-Resistant HIV Stable in Europe"
By Michael Smith, Senior Staff Writer, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.
August 15, 2006
http://www.medpagetoday.com
even before taking any antiretroviral medications there is a chance that they may have drug-resistant HIV.
About 9% of patients who get an HIV infection in Europe will acquire a strain that is already resistant to some medications.
data and conclusions should be considered to be preliminary as they have not yet been reviewed and published in a peer-reviewed publication.
TORONTO, Aug. 15 -- The transmission of drug-resistant HIV appears to be stabilizing, at least in Europe.
But still 9.1% of newly infected HIV patients are already carrying a virus that carries resistance mutations to one of the three main classes of anti-retroviral medications, reported Annemarie Wensing, M.D., of the University Medical Center in Utrecht, Holland, at the 16th International AIDS Conference here.
The so-called SPREAD study, supported by the European Commission, is the first to prospectively analyze how many HIV-positive patients have a drug-resistant HIV infection even before they are treated with any medications, Dr. Wensing said.
An earlier retrospective analysis conducted in Europe, the CATCH study, reported that about one in 10 new infections was resistant, Dr. Wensing said, so the current study shows the rate is roughly stable.
The good news from the SPREAD study, she said, is that for two of the classes -- protease inhibitors and nucleoside reverse transcriptase inhibitors -- the mutations that were found do not appear to confer resistance to the whole class.
On the other hand, while resistance to non-nucleoside reverse transcriptase inhibitors was relatively rare, Dr. Wensing said, the mutations that were found tended to make the virus resistant to the whole class.
Because the non-nucleoside reverse transcriptase inhibitors -- and especially Sustiva (efavirenz) -- form the backbone of many highly active anti-retroviral therapy (HAART) regimens, such "patients have already limited options," she said.
The analysis, of 1,083 newly-infected patients in the years 2002 and 2003, showed:
* 5.4% had virus resistant to nucleoside reverse transcriptase inhibitors.
* 3.0% had virus resistant to protease inhibitors.
* 2.6% had virus resistant to non-nucleoside reverse transcriptase inhibitors.
* 0.7% had virus already resistant to two classes of anti-retroviral drugs.
Interestingly, she said, the resistance to nucleoside reverse transcriptase inhibitors appears to have been declining over time, from just under 14% in 1996 and 1997 -- as reported by the CATCH investigators -- to 5.4% today. The change is probably an effect of changing treatment patterns, she said.
All told, there were 96 cases of virus with mutations associated with resistance, Dr. Wensing said, but 68 -- or 71% -- had only one such mutation.
Resistance was more common in people carrying virus of subtype B, the strain most prevalent in Europe and North America, Dr. Wensing said. The prevalence of resistance in those with subtype B virus was 10.4%, compared with 6.3% for non-subtype B, and the difference was statistically significant at P=0.03.
The study shows that resistance is not inevitable, according to Stefano Vella, M.D., of the Italian national health agency and a former president of the International AIDS Society. "All resistant viruses are the sons of our mistakes," he said -- mistakes such as monotherapy, the use of poor drugs, and complicated regimens that lead to non-adherence.
Resistance "is stabilizing because now we are treating (patients) well," Dr. Vella said in an interview.
ABSTRACT
Transmission of HIV drug resistance in Europe
Wensing A.M, University Medical Center Utrecht, Eijkman Winkler Center, Dept of Virology, Utrecht, Netherlands
Background: In Europe an official European Commission supported programme monitors prospectively the prevalence of baseline HIV drug resistance and the risk factors involved in the spread of resistant HIV in 17 countries. Funding European Comission (QLK2-CT-2001-01344).
Methods: & Population characteristics: Newly diagnosed individuals were recruited prospectively and clinical, demographic and behavioral data were collected. In 2002/2003 a total of 1083 newly diagnosed individuals were included, source of infection was: homo/bisexual (44%), heterosexual contact (42%) or iv-drug use (9%). 34% were from outside Western-Europe. 74% were asymptomatic (CDC class A). 22% had laboratory evidence of recent seroconversion (<1 year). Over 13 subtypes/CRFs were identified, predominantly B 66%, A 9%, C 9%, G 4% and CRF02_AG 4%.
Results:
9.1% (96/1050, CI95% 7.5 - 11.1%) of individuals harbored viruses with drug resistance mutations (IAS-list).
Prevalence was higher in seroconverters than in patients with undefined duration of infection (10.6% vs 8.7, OR =1.2 (0.7-2.2;p=0.37).
The prevalence of NRTI mutations was 5.4%, 1 out of 3 strains harbored more than one NRTI mutation. Most frequently observed were (n): 215Y/F/revertants (37), 41L (13), 219E/Q (10). The prevalence of PI mutations was 3.0%, most frequent observed were: 46I/L (15 ), 90M (13), 82I/F/T/S (8),
The frequency of NNRTI mutations was 2.6%, mostly 103N(11) and 108I(8). Less than 1% was infected with a dual class resistant strain.
Using an extensive list of risk factors no significant correlations were observed, except for individuals infected in a high prevalence country or infected with a non-B subtype virus, who had a significant lower risk of being infected with a strain harboring drug resistance mutations (5.2% vs 10.0, OR=0.49 (0.24-0.99;p=0.046)) and (6.3 vs 10.4, OR= 0.57 (0.35-0.95;p=0.03)).
Conclusions: The SPREAD-programme provides the first representative data on transmission of HIV drug-resistance across Europe. The prevalence of 9% baseline resistance in prospectively identified newly diagnosed patients warrants continuous surveillance.
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