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Published in: Journal of Medical Case Reports 1/2009

Open Access 01-12-2009 | Case report

Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature

Authors: Ennio Polilli, Giustino Parruti, Luana Cosentino, Federica Sozio, Annalisa Saracino, Augusta Consorte, Gioacchino Angarano, Francesco Di Masi, Elena Mazzotta, Paolo Fazii

Published in: Journal of Medical Case Reports | Issue 1/2009

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Abstract

Introduction

Selection of the K103N mutation is associated with moderately reduced in vitro fitness of HIV. Strains bearing K103N in vivo tend to persist, even in the absence of additional drug pressure, as minority quasispecies, often undetectable in genotyping resistance testing assays, performed at standard conditions. Here, we report on the rapid and long lasting selection of a K103N bearing strain as the dominant quasispecies after very short exposure to efavirenz in vivo.

Case presentation

A 55-year-old Caucasian man was switched to efavirenz, zidovudine and lamivudine in February 2003, while on viral suppression in his first-line highly active anti-retroviral treatment regimen. One month later, he reported inconsistent adherence and his viremia level was 5700 c/mL. He did not attend further checkups until September 2005, when his viral load was 181,000 c/mL. The patient reported interrupting his medications approximately three weeks after simplification. The genotyping resistance testing assay was performed both on HIV RNA and HIV DNA from plasma, yielding an identical pattern with the isolate presence of the K103N mutation in the prevalent strain.

Conclusion

Persistence of the K103N mutation as a majority quasispecies may ensue after a very short exposure to efavirenz. Our case would therefore suggest that the presence of the K103N mutation should always be ruled out by genotyping resistance testing assays, even after minimal exposures to efavirenz.
Literature
1.
go back to reference Maggiolo F, Ravasio L, Ripamonti D, Gregis G, Quinzan G, Arici C, Airoldi M, Suter F: Similar adherence rates favor different virologic outcomes for patients treated with nonnucleoside analogues or protease inhibitors. Clin Infect Dis. 2005, 40: 158-163. 10.1086/426595.CrossRefPubMed Maggiolo F, Ravasio L, Ripamonti D, Gregis G, Quinzan G, Arici C, Airoldi M, Suter F: Similar adherence rates favor different virologic outcomes for patients treated with nonnucleoside analogues or protease inhibitors. Clin Infect Dis. 2005, 40: 158-163. 10.1086/426595.CrossRefPubMed
2.
go back to reference Bangsberg DR, Acosta EP, Gupta R, Guzman D, Riley ED, Harrigan PR, Parkin N, Deeks SG: Adherence-resistance relationships for protease and non-nucleoside reverse transcriptase inhibitors explained by virological fitness. AIDS. 2006, 20: 223-231. 10.1097/01.aids.0000199825.34241.49.CrossRefPubMed Bangsberg DR, Acosta EP, Gupta R, Guzman D, Riley ED, Harrigan PR, Parkin N, Deeks SG: Adherence-resistance relationships for protease and non-nucleoside reverse transcriptase inhibitors explained by virological fitness. AIDS. 2006, 20: 223-231. 10.1097/01.aids.0000199825.34241.49.CrossRefPubMed
3.
go back to reference Delaugerre C, Rohban R, Simon A, Mouroux M, Tricot C, Agher R, Huraux JM, Katlama C, Calvez V: Resistance profile and cross-resistance of HIV-1 among patients failing a non-nucleoside reverse transcriptase inhibitor-containing regimen. J Med Virol. 2001, 65: 445-448. 10.1002/jmv.2055.CrossRefPubMed Delaugerre C, Rohban R, Simon A, Mouroux M, Tricot C, Agher R, Huraux JM, Katlama C, Calvez V: Resistance profile and cross-resistance of HIV-1 among patients failing a non-nucleoside reverse transcriptase inhibitor-containing regimen. J Med Virol. 2001, 65: 445-448. 10.1002/jmv.2055.CrossRefPubMed
4.
go back to reference Bacheler L, Jeffrey S, Hanna G, D'Aquila R, Wallace L, Logue K, Cordova B, Hertogs K, Larder B, Buckery R, Baker D, Gallagher K, Scarnati H, Tritch R, Rizzo C: Genotypic correlates of phenotypic resistance to efavirenz in virus isolates from patients failing nonnucleoside reverse transcriptase inhibitor therapy. J Virol. 2001, 75: 4999-5008. 10.1128/JVI.75.11.4999-5008.2001.CrossRefPubMedPubMedCentral Bacheler L, Jeffrey S, Hanna G, D'Aquila R, Wallace L, Logue K, Cordova B, Hertogs K, Larder B, Buckery R, Baker D, Gallagher K, Scarnati H, Tritch R, Rizzo C: Genotypic correlates of phenotypic resistance to efavirenz in virus isolates from patients failing nonnucleoside reverse transcriptase inhibitor therapy. J Virol. 2001, 75: 4999-5008. 10.1128/JVI.75.11.4999-5008.2001.CrossRefPubMedPubMedCentral
5.
go back to reference Collins JA, Thompson MG, Paintsil E, Ricketts M, Gedzior J, Alexander L: Competitive Fitness of Nevirapine-Resistant Human Immunodeficiency Virus Type 1 Mutants. Journal of Virology. 2004, 78: 603-611. 10.1128/JVI.78.2.603-611.2004.CrossRefPubMedPubMedCentral Collins JA, Thompson MG, Paintsil E, Ricketts M, Gedzior J, Alexander L: Competitive Fitness of Nevirapine-Resistant Human Immunodeficiency Virus Type 1 Mutants. Journal of Virology. 2004, 78: 603-611. 10.1128/JVI.78.2.603-611.2004.CrossRefPubMedPubMedCentral
6.
go back to reference Flys T, Donnell D, Mwatha A, Nakabiito C, Musoke P, Mmiro F, Jackson JB, Guai LA, Eshleman SH: Persistence of K103N-contening HIV1 variants after single dose nevirapine for prevention of HIV1 mother to child transmission. J Infect Dis. 2007, 195: 711-715. 10.1086/511433.CrossRefPubMed Flys T, Donnell D, Mwatha A, Nakabiito C, Musoke P, Mmiro F, Jackson JB, Guai LA, Eshleman SH: Persistence of K103N-contening HIV1 variants after single dose nevirapine for prevention of HIV1 mother to child transmission. J Infect Dis. 2007, 195: 711-715. 10.1086/511433.CrossRefPubMed
7.
go back to reference Joly V, Descamps D, Peytavin G, Touati F, Mentre F, Duval X, Delarue S, Yeni P, Brun-Vezinet F: Evolution of human immunodeficiency virus type 1 (HIV-1) resistance mutations in nonnucleoside reverse transcriptase inhibitors (NNRTIs) in HIV-1-infected patients switched to antiretroviral therapy without NNRTIs. Antimicrob Agents Chemother. 2004, 48: 172-175. 10.1128/AAC.48.1.172-175.2004.CrossRefPubMedPubMedCentral Joly V, Descamps D, Peytavin G, Touati F, Mentre F, Duval X, Delarue S, Yeni P, Brun-Vezinet F: Evolution of human immunodeficiency virus type 1 (HIV-1) resistance mutations in nonnucleoside reverse transcriptase inhibitors (NNRTIs) in HIV-1-infected patients switched to antiretroviral therapy without NNRTIs. Antimicrob Agents Chemother. 2004, 48: 172-175. 10.1128/AAC.48.1.172-175.2004.CrossRefPubMedPubMedCentral
8.
go back to reference Dybul M, Nies-Kraske E, Dewar R, Maldarelli F, Hallahan CW, Daucher M, Piscitelli SC, Ehler L, Weigand A, Palmer S, Metcalf JA, Davey RT, Rock Kress DM, Powers A, Beck I, Frenkel L, Baseler M, Coffin J, Fauci AS: A proof-of-concept study of short-cycle intermittent antiretroviral therapy with a once-daily regimen of didanosine, Lamivudine, and efavirenz for the treatment of chronic HIV infection. J Infect Dis. 2004, 189: 1974-1982. 10.1086/386344.CrossRefPubMed Dybul M, Nies-Kraske E, Dewar R, Maldarelli F, Hallahan CW, Daucher M, Piscitelli SC, Ehler L, Weigand A, Palmer S, Metcalf JA, Davey RT, Rock Kress DM, Powers A, Beck I, Frenkel L, Baseler M, Coffin J, Fauci AS: A proof-of-concept study of short-cycle intermittent antiretroviral therapy with a once-daily regimen of didanosine, Lamivudine, and efavirenz for the treatment of chronic HIV infection. J Infect Dis. 2004, 189: 1974-1982. 10.1086/386344.CrossRefPubMed
9.
go back to reference Weinstock H, Respess R, Heneine W, Petropoulos CJ, Hellmann NS, Luo CC, Pau CP, Woods T, Gwinn M, Kaplan J: Prevalence of mutations associated with reduced antiretroviral drug susceptibility among human immunodeficiency virus type 1 seroconverters in the United States, 1993-1998. J Infect Dis. 2000, 182: 330-333. 10.1086/315686.CrossRefPubMed Weinstock H, Respess R, Heneine W, Petropoulos CJ, Hellmann NS, Luo CC, Pau CP, Woods T, Gwinn M, Kaplan J: Prevalence of mutations associated with reduced antiretroviral drug susceptibility among human immunodeficiency virus type 1 seroconverters in the United States, 1993-1998. J Infect Dis. 2000, 182: 330-333. 10.1086/315686.CrossRefPubMed
10.
go back to reference Imrie A, Beveridge A, Genn W, Vizzard J, Cooper DA: Transmission of human immunodeficiency virus type 1 resistant to nevirapine and zidovudine. Sydney Primary HIV Infection Study Group. J Infect Dis. 1997, 175: 1502-1506. 10.1086/516487.CrossRefPubMed Imrie A, Beveridge A, Genn W, Vizzard J, Cooper DA: Transmission of human immunodeficiency virus type 1 resistant to nevirapine and zidovudine. Sydney Primary HIV Infection Study Group. J Infect Dis. 1997, 175: 1502-1506. 10.1086/516487.CrossRefPubMed
11.
go back to reference Flys T, Nissley DV, Claasen CW, Jones D, Shi C, Guay LA, Musoke P, Mmiro F, Strathern JN, Jackson JB, Eshleman JR, Eshleman SH: Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants with the K103N nevirapine (NVP) resistance mutation in some women and infants after the administration of single-dose NVP: HIVNET 012. J Infect Dis. 2005, 192: 24-29. 10.1086/430742.CrossRefPubMed Flys T, Nissley DV, Claasen CW, Jones D, Shi C, Guay LA, Musoke P, Mmiro F, Strathern JN, Jackson JB, Eshleman JR, Eshleman SH: Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants with the K103N nevirapine (NVP) resistance mutation in some women and infants after the administration of single-dose NVP: HIVNET 012. J Infect Dis. 2005, 192: 24-29. 10.1086/430742.CrossRefPubMed
12.
go back to reference Taylor S, Boffito M, Khoo S, Smit E, Back D: Stopping antiretroviral therapy. AIDS. 2007, 21: 1673-1682. 10.1097/QAD.0b013e3281c61394.CrossRefPubMed Taylor S, Boffito M, Khoo S, Smit E, Back D: Stopping antiretroviral therapy. AIDS. 2007, 21: 1673-1682. 10.1097/QAD.0b013e3281c61394.CrossRefPubMed
13.
go back to reference Palmer S, Boltz V, Maldarelli F, Gray G, McIntyre J, Mellors J, Morris L, Coffin J: Selection and persistence of non-nucleoside reverse transcriptase inhibitor-resistant HIV-1 in patients starting and stopping non-nucleoside therapy. AIDS. 2006, 20: 701-710. 10.1097/01.aids.0000216370.69066.7f.CrossRefPubMed Palmer S, Boltz V, Maldarelli F, Gray G, McIntyre J, Mellors J, Morris L, Coffin J: Selection and persistence of non-nucleoside reverse transcriptase inhibitor-resistant HIV-1 in patients starting and stopping non-nucleoside therapy. AIDS. 2006, 20: 701-710. 10.1097/01.aids.0000216370.69066.7f.CrossRefPubMed
14.
go back to reference Capetti AF, Gabrisa AI, Drago L, Vigevania G: Can a K103N HIV strain stably overcome the wild type in the absence of non-nucleoside reverse transcriptase inhibitor selective pressure?. AIDS. 2005, 19: 633-640. 10.1097/01.aids.0000163943.31682.c8.CrossRefPubMed Capetti AF, Gabrisa AI, Drago L, Vigevania G: Can a K103N HIV strain stably overcome the wild type in the absence of non-nucleoside reverse transcriptase inhibitor selective pressure?. AIDS. 2005, 19: 633-640. 10.1097/01.aids.0000163943.31682.c8.CrossRefPubMed
15.
go back to reference Sluis-Cremer N, Temiz AN, Bahar I: Conformational changes in HIV1 Reverse Trascriptase induced by Non Nucleoside Reverse Transciptase Inhibitor Binding. Curr HIV Res. 2004, 2: 323-332. 10.2174/1570162043351093.CrossRefPubMedPubMedCentral Sluis-Cremer N, Temiz AN, Bahar I: Conformational changes in HIV1 Reverse Trascriptase induced by Non Nucleoside Reverse Transciptase Inhibitor Binding. Curr HIV Res. 2004, 2: 323-332. 10.2174/1570162043351093.CrossRefPubMedPubMedCentral
16.
go back to reference Hatano H, Hunt P, Weidler J, Coakley E, Hoh R, Liegler T, McCulloch C, Martin J, Deeks SG: Repeated measures analysis of plasma HIV-1 RNA levels in HIV-infected patients remaining on a stable partially suppressive regimen. 4th IAS conference on HIV22-25-2007, Sydney, Australia. Hatano H, Hunt P, Weidler J, Coakley E, Hoh R, Liegler T, McCulloch C, Martin J, Deeks SG: Repeated measures analysis of plasma HIV-1 RNA levels in HIV-infected patients remaining on a stable partially suppressive regimen. 4th IAS conference on HIV22-25-2007, Sydney, Australia.
17.
go back to reference Fox Z, Phillips A, Cohen C, Neuhaus J, Baxter J, Emery S, Hirschel B, Hullsiek KH, Stephan C, Lundgren J, SMART Study Group: Viral resuppression and detection of drug resistance following interruption of a suppressive non-nucleoside reverse transcriptase inhibitor-based regimen. AIDS. 2008, 22: 2279-2289. 10.1097/QAD.0b013e328311d16f.CrossRefPubMedPubMedCentral Fox Z, Phillips A, Cohen C, Neuhaus J, Baxter J, Emery S, Hirschel B, Hullsiek KH, Stephan C, Lundgren J, SMART Study Group: Viral resuppression and detection of drug resistance following interruption of a suppressive non-nucleoside reverse transcriptase inhibitor-based regimen. AIDS. 2008, 22: 2279-2289. 10.1097/QAD.0b013e328311d16f.CrossRefPubMedPubMedCentral
Metadata
Title
Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature
Authors
Ennio Polilli
Giustino Parruti
Luana Cosentino
Federica Sozio
Annalisa Saracino
Augusta Consorte
Gioacchino Angarano
Francesco Di Masi
Elena Mazzotta
Paolo Fazii
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Journal of Medical Case Reports / Issue 1/2009
Electronic ISSN: 1752-1947
DOI
https://doi.org/10.4076/1752-1947-3-9132

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