Prevalence of multiple dideoxynucleoside analogue resistance (MddNR) in a multicenter cohort of HIV-1 - Infected Italian patients with virologic failure

Claudia Balotta, Michela Violin, Laura Monno, Patrizia Bagnarelli, Chiara Riva, Guido Facchi, Alberto Berlusconi, Monica Lippi, Stefano Rusconi, Massimo Clementi, Massimo Galli, Gioacchino Angarano, Mauro Moroni

Research output: Contribution to journalArticle

Abstract

We evaluated the prevalence of both Q151M and 6-bp insert at position 69 of RT region responsible for multiple dideoxynucleoside analogue-resistant (MddNR) HIV-1 variants in 177 patients who failed to respond to combination therapy. Patients had received protease inhibitors (PI) and/or nonnucleoside reverse transcriptase inhibitors (NNRTIs) after a long-term experience with nucleoside reverse transcriptase inhibitors (NRTIs) (including zidovudine monotherapy). Two of 177 patients (1.1%) showed the specific complex of Q151M mutation, while 4 (2.3%) had the 69 6-bp insert. Mutations that belong to the 151 set in the absence of the pivotal Q151M substitution were detected in as many as 3.9% of the patients. One patient exhibited a 69S [VG] insert that has not been previously phenotypically characterized. This HIV-1 isolate had high levels of resistance to all NRTIs except stavudine. MddNR is an emerging problem after sequential therapy with this class of compounds among HIV-1-infected patients. Either didanosine (ddI) or zidovudine (ZDV) monotherapy allowed the emergence of MddNR variants containing Q151M complex. Monotherapy with ZDV and ddI or subsequent treatments with various NRTI combinations were the common background in the patients with the 69 insert. The overall prevalence of MddNR (3.4%) in Italy is comparable with that observed in several other European countries (3.4%-6.5%). These data suggest that patients failed by NRTI regimens should be analyzed for the presence of both patterns of MddNR.

Original languageEnglish
Pages (from-to)232-240
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Volume24
Issue number3
Publication statusPublished - Jul 1 2000

Keywords

  • Antiretroviral drug failure
  • Multiple dideoxynucleoside analogue-resistant HIV-1 variants
  • Q151M complex
  • RT 69 insert

ASJC Scopus subject areas

  • Virology
  • Immunology

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    Balotta, C., Violin, M., Monno, L., Bagnarelli, P., Riva, C., Facchi, G., Berlusconi, A., Lippi, M., Rusconi, S., Clementi, M., Galli, M., Angarano, G., & Moroni, M. (2000). Prevalence of multiple dideoxynucleoside analogue resistance (MddNR) in a multicenter cohort of HIV-1 - Infected Italian patients with virologic failure. Journal of Acquired Immune Deficiency Syndromes, 24(3), 232-240.