Prevalence of Transmitted Drug-Resistance Mutations and Polymorphisms in HIV-1 Reverse Transcriptase, Protease, and gp41 Sequences Among Recent Seroconverters in Southern Poland.
BACKGROUND Monitoring of drug resistance-related mutations among patients with recent HIV-1 infection offers an opportunity to describe current patterns of transmitted drug resistance (TDR) mutations. MATERIAL AND METHODS Of 298 individuals newly diagnosed from March 2008 to February 2014 in southern Poland, 47 were deemed to have recent HIV-1 infection by the limiting antigen avidity immunoassay. Proviral DNA was amplified and sequenced in the reverse transcriptase, protease, and gp41 coding regions. Mutations were interpreted according to the Stanford Database algorithm and/or the International Antiviral Society USA guidelines. TDR mutations were defined according to the WHO surveillance list. RESULTS Among 47 patients with recent HIV-1 infection only 1 (2%) had evidence of TDR mutation. No major resistance mutations were found, but the frequency of strains with ≥1 accessory resistance-associated mutations was high, at 98%. Accessory mutations were present in 11% of reverse transcriptase, 96% of protease, and 27% of gp41 sequences. Mean number of accessory resistance mutations in the reverse transcriptase and protease sequences was higher in viruses with no compensatory mutations in the gp41 HR2 domain than in strains with such mutations (p=0.031). CONCLUSIONS Despite the low prevalence of strains with TDR mutations, the frequency of accessory mutations was considerable, which may reflect the history of drug pressure among transmitters or natural viral genetic diversity, and may be relevant for future clinical outcomes. The accumulation of the accessory resistance mutations within the pol gene may restrict the occurrence of compensatory mutations related to enfuvirtide resistance or vice versa.
Department of Microbiology and Virology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland.
Joanna
J
Smoleń-Dzirba
Department of Epidemiology, National Institute of Public Health - National Institute of Hygiene, Warsaw, Poland.
Magdalena
M
Rosińska
Department of Microbiology and Virology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland.
Piotr
P
Kruszyński
Department of Biopharmacy, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland.
Jolanta
J
Bratosiewicz-Wąsik
Department of Microbiology and Virology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland.
Robert
R
Wojtyczka
Department of Epidemiology, National Institute of Public Health - National Institute of Hygiene, Warsaw, Poland.
Janusz
J
Janiec
Department of Infectious Diseases, Hepatology, and Acquired Immune Deficiencies, Wrocław Medical University, Wrocław, Poland.
Bartosz
B
Szetela
Outpatient Clinic for AIDS Diagnostics and Therapy, Specialistic Hospital in Chorzów, Chorzów, Poland.
Marek
M
Beniowski
Department of Infectious Diseases, Jagiellonian University Medical College, Cracow, Poland.
Monika
M
Bociąga-Jasik
Department of Infectious Diseases and Hepatology, Medical University of Łódź, Łódź, Poland.
Elżbieta
E
Jabłonowska
Department of Microbiology and Virology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland.
Tomasz J
TJ
Wąsik
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And
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The Cascade Collaboration In EuroCoord
D000328:Adult; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000037:antagonists & inhibitors / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000235:genetics*; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D009154:Mutation; D011044:Poland; D011110:Polymorphism, Genetic; D015995:Prevalence; D011533:Proviruses / Q000235:genetics; D055815:Young Adult
D004279:DNA, Viral; D015700:HIV Envelope Protein gp41; D017320:HIV Protease Inhibitors; C514787:gp41 protein, Human immunodeficiency virus 1; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1