Medical Microbiology and Immunology

, Volume 202, Issue 3, pp 251–255

Molecular epidemiology of HIV in a cohort of men having sex with men from Istanbul

  • Dilek Alpsar
  • Ali Agacfidan
  • Nadine Lübke
  • Jens Verheyen
  • Haluk Eraksoy
  • Atahan Çağatay
  • Emel Bozkaya
  • Rolf Kaiser
  • Baki Akgül
Rapid Communication

Abstract

In Turkey, the first HIV/AIDS case was reported in 1985. Since then the number of persons with HIV infection has increased, HIV is getting a public health problem. The aim of this study was to determine HIV-1 subtype diversity, drug resistance and gag cleavage site mutations among 20 HIV-infected men having sex with men from Istanbul, Turkey. The most prevalent subtype was found to be subtype B (50 %), but also the non-B subtypes A1, C and CRF02_AG, CRF03_AB and CRF06_cpx were found. Resistance-associated mutations were found in 6 patients (30 %) with 2/6 patients being therapy-experienced and 4/6 therapy-naïve at the time-point of analysis. In these patients, the nucleoside reverse transcriptase inhibitor (NRTI)-associated resistance mutations M41L, T215C, V75I, T69N, the non-NRTI associated mutations V106I, E138A, K103N and the protease inhibitor associated mutations Q58E and V82I were detected. Two virus strains also presented Gag cleavage site mutations. With increasing numbers of HIV-infected Turkish patients that require anti-retroviral treatment, HIV-1 drug-resistance testing is strongly recommended in order to choose the most active drug combination for therapy to achieve better clinical outcomes.

Keywords

HIV-1 Antiretroviral drug resistance Epidemiology Ethnic group 

Supplementary material

430_2012_285_MOESM1_ESM.doc (71 kb)
Supplementary material 1 (DOC 71 kb)

References

  1. 1.
    Stürmer M, Doerr HW, Gürtler L (2009) Human immunodeficiency virus: 25 years of diagnostic and therapeutic strategies and their impact on hepatitis B and C virus. Med Microbiol Immunol 198(3):147–155PubMedCrossRefGoogle Scholar
  2. 2.
  3. 3.
    Oette M, Kaiser R, Däumer M, Akbari D, Fätkenheuer G, Rockstroh JK, Stechel J, Rieke A, Mauss S, Schmaloer D, Gobels K, Vogt C, Wettstein M, Häussinger D (2004) Primary drug-resistance in HIV-positive patients on initiation of first-line antiretroviral therapy in Germany. Eur J Med Res 9(5):273–278PubMedGoogle Scholar
  4. 4.
    Oette M, Kaiser R, Däumer M, Petch R, Fätkenheuer G, Carls H, Rockstroh JK, Schmaloer D, Stechel J, Feldt T, Pfister H, Häussinger D (2006) Primary HIV drug resistance and efficacy of first-line antiretroviral therapy guided by resistance testing. J Acquir Immune Defic Syndr 41(5):573–581PubMedCrossRefGoogle Scholar
  5. 5.
    Schülter E, Oette M, Balduin M, Reuter S, Rockstroh J, Fätkenheuer G, Esser S, Lengauer T, Agacfidan A, Pfister H, Kaiser R, Akgül B (2011) HIV prevalence and route of transmission in Turkish immigrants living in North-Rhine Westphalia, Germany. Med Microbiol Immunol 200(4):219–223PubMedCrossRefGoogle Scholar
  6. 6.
    Tee KK, Kamarulzaman A, Ng KP (2006) Prevalence and pattern of drug resistance mutations among antiretroviral-treated HIV-1 patients with suboptimal virological response in Malaysia. Med Microbiol Immunol 195(2):107–112PubMedCrossRefGoogle Scholar
  7. 7.
    Sierra S, Kaiser R, Lübke N, Thielen A, Schülter E, Heger E, Däumer M, Reuter S, Esser S, Fätkenheuer G, Pfister H, Oette M, Lengauer T (2011) Prediction of HIV-1 coreceptor usage (tropism) by sequence analysis using a genotypic approach. J Vis Exp (58). pii: 3264. doi:10.3791/3264
  8. 8.
    Verheyen J, Litau E, Sing T, Däumer M, Balduin M, Oette M, Fätkenheuer G, Rockstroh JK, Schuldenzucker U, Hoffmann D, Pfister H, Kaiser R (2006) Compensatory mutations at the HIV cleavage sites p7/p1 and p1/p6-gag in therapy-naive and therapy-experienced patients. Antiviral Ther 11(7):879–887Google Scholar
  9. 9.
    Karaosmanoglu HK, Aydin OA, Nazlican O (2011) Profile of HIV/AIDS patients in a tertiary hospital in Istanbul, Turkey. HIV Clin Trials 12(2):104–108PubMedCrossRefGoogle Scholar
  10. 10.
    Hemelaar J, Gouws E, Ghys PD, Osmanov S (2006) Global and regional distribution of HIV-1 genetic subtypes and recombinants in 2004. AIDS 20(16):W13–W23PubMedCrossRefGoogle Scholar
  11. 11.
    Yilmaz G, Midilli K, Turkoglu S, Bayraktaroglu Z, Kuskucu AM, Ozkan E, Atasever L, Calangu S, Altas K (2006) Genetic subtypes of human immunodeficiency virus type 1 (HIV-1) in Istanbul, Turkey. Int J Infect Dis 10(4):286–290PubMedCrossRefGoogle Scholar
  12. 12.
    Stanojevic M, Alexiev I, Beshkov D, Gokengin D, Mezei M, Minarovits J, Otelea D, Paraschiv S, Poljak M, Zidovec-Lepej S, Paraskevis D (2012) HIV1 molecular epidemiology in the Balkans: a melting pot for high genetic diversity. AIDS Rev 14(1):28–36PubMedGoogle Scholar
  13. 13.
    Gatanaga H, Ode H, Hachiya A, Hayashida T, Sato H, Oka S (2010) Combination of V106I and V179D polymorphic mutations in human immunodeficiency virus type 1 reverse transcriptase confers resistance to efavirenz and nevirapine but not etravirine. Antimicrob Agents Chemother 54(4):1596–1602PubMedCrossRefGoogle Scholar
  14. 14.
    Marcelin AG, Flandre P, Descamps D, Morand-Joubert L, Charpentier C, Izopet J, Trabaud MA, Saoudin H, Delaugerre C, Tamalet C, Cottalorda J, Bouvier-Alias M, Bettinger D, Dos Santos G, Ruffault A, Alloui C, Henquell C, Rogez S, Barin F, Signori-Schmuck A, Vallet S, Masquelier B, Calvez V (2010) Factors associated with virological response to etravirine in nonnucleoside reverse transcriptase inhibitor-experienced HIV-1-infected patients. Antimicrob Agents Chemother 54(1):72–77PubMedCrossRefGoogle Scholar
  15. 15.
    Bellocchi MC, Forbici F, Palombi L, Gori C, Coelho E, Svicher V, D’Arrigo R, Emberti-Gialloreti L, Ceffa S, Erba F, Marazzi MC, Silberstein FC, Perno CF (2005) Subtype analysis and mutations to antiviral drugs in HIV-1-infected patients from Mozambique before initiation of antiretroviral therapy: results from the DREAM programme. J Med Virol 76(4):452–458PubMedCrossRefGoogle Scholar
  16. 16.
    Turner D, Brenner B, Moisi D, Detorio M, Cesaire R, Kurimura T, Mori H, Essex M, Maayan S, Wainberg MA (2004) Nucleotide and amino acid polymorphisms at drug resistance sites in non-B-subtype variants of human immunodeficiency virus type 1. Antimicrob Agents Chemother 48(8):2993–2998PubMedCrossRefGoogle Scholar
  17. 17.
    Klabe RM, Bacheler LT, Ala PJ, Erickson-Viitanen S, Meek JL (1998) Resistance to HIV protease inhibitors: a comparison of enzyme inhibition and antiviral potency. Biochemistry 37(24):8735–8742PubMedCrossRefGoogle Scholar
  18. 18.
    Koh Y, Towata T, Ghosh A, Mitsuya H (2007) Selection in vitro of HIV-1 variants highly resistant to Darunavir using a mixture of HIV-1 isolates resistant to multiple PI. In: 14th conference of retroviruses and opportunistic infections, Los Angeles, p Abstract 606Google Scholar
  19. 19.
    Pulido F, Arribas JR, Hill A, Van Delft Y, Moecklinghoff C (2011) Analysis of drug resistance during HIV RNA viraemia in the MONET trial of darunavir/ritonavir monotherapy. Antivir Ther 16(1):59–65PubMedCrossRefGoogle Scholar
  20. 20.
    Scherrer AU, Ledergerber B, von Wyl V, Boni J, Yerly S, Klimkait T, Cellerai C, Furrer H, Calmy A, Cavassini M, Elzi L, Vernazza PL, Bernasconi E, Gunthard HF (2012) Minor protease inhibitor mutations at baseline do not increase the risk for a virological failure in HIV-1 subtype B infected patients. PLoS One 7(6):e37983PubMedCrossRefGoogle Scholar
  21. 21.
    van Maarseveen NM, de Jong D, Boucher CA, Nijhuis M (2006) An increase in viral replicative capacity drives the evolution of protease inhibitor-resistant human immunodeficiency virus type 1 in the absence of drugs. J Acquir Immune Defic Syndr 42(2):162–168PubMedCrossRefGoogle Scholar
  22. 22.
    Verheyen J, Knops E, Kupfer B, Hamouda O, Somogyi S, Schuldenzucker U, Hoffmann D, Kaiser R, Pfister H, Kücherer C (2009) Prevalence of C-terminal gag cleavage site mutations in HIV from therapy-naive patients. J Infect 58(1):61–67PubMedCrossRefGoogle Scholar
  23. 23.
    Srinivas RV, Fridland A (1998) Antiviral activities of 9-R-2-phosphonomethoxypropyl adenine (PMPA) and bis(isopropyloxymethylcarbonyl)PMPA against various drug-resistant human immunodeficiency virus strains. Antimicrob Agents Chemother 42(6):1484–1487PubMedGoogle Scholar
  24. 24.
    Masquelier B, Race E, Tamalet C, Descamps D, Izopet J, Buffet-Janvresse C, Ruffault A, Mohammed AS, Cottalorda J, Schmuck A, Calvez V, Dam E, Fleury H, Brun-Vezinet F (2001) Genotypic and phenotypic resistance patterns of human immunodeficiency virus type 1 variants with insertions or deletions in the reverse transcriptase (RT): multicenter study of patients treated with RT inhibitors. Antimicrob Agents Chemother 45(6):1836–1842PubMedCrossRefGoogle Scholar
  25. 25.
    Coakley EP, Gillis JM, Hammer SM (2000) Phenotypic and genotypic resistance patterns of HIV-1 isolates derived from individuals treated with didanosine and stavudine. AIDS 14(2):F9–F15PubMedCrossRefGoogle Scholar
  26. 26.
    Kellam P, Boucher CA, Larder BA (1992) Fifth mutation in human immunodeficiency virus type 1 reverse transcriptase contributes to the development of high-level resistance to zidovudine. Proc Natl Acad Sci USA 89(5):1934–1938PubMedCrossRefGoogle Scholar
  27. 27.
    Violin M, Cozzi-Lepri A, Velleca R, Vincenti A, D’Elia S, Chiodo F, Ghinelli F, Bertoli A, d’Arminio Monforte A, Perno CF, Moroni M, Balotta C (2004) Risk of failure in patients with 215 HIV-1 revertants starting their first thymidine analog-containing highly active antiretroviral therapy. AIDS 18(2):227–235PubMedCrossRefGoogle Scholar
  28. 28.
    Bacheler LT, Anton ED, Kudish P, Baker D, Bunville J, Krakowski K, Bolling L, Aujay M, Wang XV, Ellis D, Becker MF, Lasut AL, George HJ, Spalding DR, Hollis G, Abremski K (2000) Human immunodeficiency virus type 1 mutations selected in patients failing efavirenz combination therapy. Antimicrob Agents Chemother 44(9):2475–2484PubMedCrossRefGoogle Scholar
  29. 29.
    Sayan M, Aydin O, Mete B, Uzun N, Karaosmanoglu H, Gunduz A, Tabak F (2012) HIV-1 primary drug resistance mutations in antiretroviral therapy-naïve patients in Istanbul, Turkey. J Int AIDS Soc 15(6):18181. doi:10.7448/IAS.15.6.18181 Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Dilek Alpsar
    • 1
  • Ali Agacfidan
    • 1
  • Nadine Lübke
    • 2
  • Jens Verheyen
    • 2
  • Haluk Eraksoy
    • 3
  • Atahan Çağatay
    • 3
  • Emel Bozkaya
    • 1
  • Rolf Kaiser
    • 2
  • Baki Akgül
    • 2
  1. 1.Department of Microbiology and Clinical Microbiology, Istanbul Faculty of MedicineIstanbul UniversityIstanbulTurkey
  2. 2.Institute of VirologyUniversity of CologneKölnGermany
  3. 3.Department of Infectious Diseases, Istanbul Faculty of MedicineIstanbul UniversityIstanbulTurkey

Personalised recommendations