Primary drug-resistance in HIV-positive patients on initiation of first-line antiretroviral therapy in Germany.
BACKGROUND
Resistance against antiretroviral drugs in previously untreated HIV-infected persons is of growing relevance. The aim of the study is to determine the prevalence of resistance-associated mutations in this patient group.


METHODS
In a prospective multicenter-study in Nordrhein-Westfalen, Germany, genotypic resistance testing was performed in untreated HIV-positive patients before administration of first-line highly active antiretroviral therapy (HAART).


RESULTS
Between January 2001 and August 2002 resistance testing was performed in 184 therapy-naive individuals. HAART was initiated in 143 patients, who were included into the study. 70.6 % were males, mean age was 39 years, mean duration of diagnosis of HIV-infection was 1.5 years. The proportion of cases at CDC stage C was 45.4%, mean CD4-cell count was 199 /ml, mean viral load was 206,855 copies/ml. Resistance-associated mutations were detected in 20 patients (14.0%). 10.5% showed mutations indicating nucleoside reverse transcriptase inhibitor- (NRTI) resistance (M41L, E44D, D67N, T69D/N, L74V, V118I, M184V, L210W, K219Q), 2.8% showed non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance (K103N, V108I, Y181C), and 2.1% showed protease-inhibitor- (PI) associated resistance (V82A, L90M), respectively. Multi-class-resistance was found in 2.1%, mutations indicating revertant variants of resistant strains were found in 4.2% (T215C/E/L/S). 86.7% of the isolates showed secondary mutations in the protease gene. No significant difference in the distribution of the parameters age, sex, duration of HIV diagnosis, CDC stage, CD4-cell count, and viral load, between groups with and without resistance was identified.


CONCLUSIONS
The prevalence of primary resistant virus strains can be estimated at 14% in chronically infected HAART-naive HIV-patients in Germany. The majority of these cases show NRTI-associated resistance. Resistance against NNRTI or PI as well as multi-class-resistance is of low prevalence. No risk factor of predictive value can be identified for the diagnosis of resistance mutations in the individual. In conclusion, routine genotypic resistance testing in untreated HIV-positive patients should be performed before administration of first-line HAART in this region.
Oette
Mark
M
Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Clinic Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany. oettem@med.uni-duesseldorf.de
Kaiser
R
R
Däumer
M
M
Akbari
D
D
Fätkenheuer
G
G
Rockstroh
J K
JK
Stechel
J
J
Rieke
A
A
Mauss
S
S
Schmalöer
D
D
Göbels
K
K
Vogt
C
C
Wettstein
M
M
Häussinger
D
D
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002908:Chronic Disease; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000235:genetics; D015497:HIV-1; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D011237:Predictive Value of Tests; D015995:Prevalence; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D012307:Risk Factors
D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D016333:HIV Protease