Journal Article

HIV-1 Reverse Transcriptase Connection Domain Mutations: Dynamics of Emergence and Implications for Success of Combination Antiretroviral Therapy

Viktor von Wyl, Maryam Ehteshami, Lisa M. Demeter, Philippe Bürgisser, Monique Nijhuis, Jori Symons, Sabine Yerly, Jürg Böni, Thomas Klimkait, Rob Schuurman, Bruno Ledergerber, Matthias Götte and Huldrych F. Günthard

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 51, issue 5, pages 620-628
Published in print September 2010 | ISSN: 1058-4838
Published online September 2010 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/655764
HIV-1 Reverse Transcriptase Connection Domain Mutations: Dynamics of Emergence and Implications for Success of Combination Antiretroviral Therapy

More Like This

Show all results sharing these subjects:

  • Infectious Diseases
  • Immunology
  • Public Health and Epidemiology
  • Microbiology

GO

Show Summary Details

Preview

Background. Factors promoting the emergence of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) connection domain mutations and their effect on antiretroviral therapy (ART) are still largely undetermined.We investigated this matter by analyzing genotypic resistance tests covering 400 amino acid positions in the RT of HIV-1 subtype B viruses and corresponding treatment histories and laboratory measurements.

Methods. The emergence of connection domain mutations was studied in 334 patients receiving monotherapy or dual therapy with thymidine analogues at the time of the genotypic resistance test. Response to subsequent combination ART (cART) was analyzed using Cox regression for 291 patients receiving unboosted protease inhibitors. Response was defined by ever reaching an HIV RNA level <50 copies/mL during the first cART.

Results. The connection domain mutations N348I, R356K, R358K, A360V, and A371V were more frequently observed in ART-exposed than ART-naive patients, of which only N348I and A360V were nonpolymorphic (with a prevalence of <1.5% in untreated patients). N348I correlated with M184V and predominantly occurred in patients receiving lamivudine and zidovudine concomitantly. A360V was not associated with specific drug combinations and was found to emerge later than M184V or thymidine analogue mutations. Nonpolymorphic connection domain mutations were rarely detected in the absence of established drug resistance mutations in ART-exposed individuals (prevalence, <1%). None of the 5 connection domain mutations associated with treatment showed a statistically significant effect on response to cART.

Conclusions. Despite their frequent emergence, connection domain mutations did not show large detrimental effects on response to cART. Currently, routine implementation of connection domain sequencing seems unnecessary for developed health care settings.

Journal Article.  4980 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.