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

Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

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

J Acquir Immune Defic Syndr. 2000 Jul 1;24(3):232-40. Unique Identifier : AIDSLINE +
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; Institute of Infectious and Tropical Diseases, L. Sacco Hospital,; University of Milan, Milan, Italy. claudia.balotta@unimi.it

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.

Keywords: JOURNAL ARTICLE Acquired Immunodeficiency Syndrome/DRUG THERAPY Adult Aged Amino Acid Sequence Cohort Studies Consensus Sequence Didanosine/THERAPEUTIC USE Dideoxynucleosides/*THERAPEUTIC USE Drug Resistance, Microbial/GENETICS Drug Resistance, Multiple/GENETICS Drug Therapy, Combination Female Human HIV Infections/*DRUG THERAPY/IMMUNOLOGY/VIROLOGY HIV-1/*DRUG EFFECTS/ENZYMOLOGY/GENETICS HIV-1 Reverse Transcriptase/GENETICS Italy/EPIDEMIOLOGY Male Middle Age Molecular Sequence Data Multicenter Studies Mutagenesis, Insertional Mutation Prevalence Protease Inhibitors/THERAPEUTIC USE Reverse Transcriptase Inhibitors/*THERAPEUTIC USE Support, Non-U.S. Gov't Zidovudine/THERAPEUTIC USE

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