Universität zu Köln

Rhee, Soo-Yon ORCID: 0000-0002-1231-6542, Boehm, Michael, Tarasova, Olga ORCID: 0000-0002-3723-7832, Di Teodoro, Giulia ORCID: 0000-0002-0418-0067, Abecasis, Ana B., Sonnerborg, Anders, Bailey, Alexander J., Kireev, Dmitry, Zazzi, Maurizio ORCID: 0000-0002-0344-6281 and Shafer, Robert W. (2022). Spectrum of Atazanavir-Selected Protease Inhibitor-Resistance Mutations. Pathogens, 11 (5). BASEL: MDPI. ISSN 2076-0817

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Abstract

Ritonavir-boosted atazanavir is an option for second-line therapy in low- and middle-income countries (LMICs). We analyzed publicly available HIV-1 protease sequences from previously PI-naive patients with virological failure (VF) following treatment with atazanavir. Overall, 1497 patient sequences were identified, including 740 reported in 27 published studies and 757 from datasets assembled for this analysis. A total of 63% of patients received boosted atazanavir. A total of 38% had non-subtype B viruses. A total of 264 (18%) sequences had a PI drug-resistance mutation (DRM) defined as having a Stanford HIV Drug Resistance Database mutation penalty score. Among sequences with a DRM, nine major DRMs had a prevalence >5%: I50L (34%), M46I (33%), V82A (22%), L90M (19%), I54V (16%), N88S (10%), M46L (8%), V32I (6%), and I84V (6%). Common accessory DRMs were L33F (21%), Q58E (16%), K20T (14%), G73S (12%), L10F (10%), F53L (10%), K43T (9%), and L241(6%). A novel nonpolymorphic mutation, L89T occurred in 8.4% of non-subtype B, but in only 0.4% of subtype B sequences. The 264 sequences included 3 (1.1%) interpreted as causing high-level, 14 (5.3%) as causing intermediate, and 27 (10.2%) as causing low-level darunavir resistance. Atazanavir selects for nine major and eight accessory DRMs, and one novel nonpolymorphic mutation occurring primarily in non-B sequences. Atazanavir-selected mutations confer low-levels of darunavir cross resistance. Clinical studies, however, are required to determine the optimal boosted PI to use for second-line and potentially later line therapy in LMICs.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rhee, Soo-Yon UNSPECIFIED orcid.org/0000-0002-1231-6542 UNSPECIFIED Boehm, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Tarasova, Olga UNSPECIFIED orcid.org/0000-0002-3723-7832 UNSPECIFIED Di Teodoro, Giulia UNSPECIFIED orcid.org/0000-0002-0418-0067 UNSPECIFIED Abecasis, Ana B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sonnerborg, Anders UNSPECIFIED UNSPECIFIED UNSPECIFIED Bailey, Alexander J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kireev, Dmitry UNSPECIFIED UNSPECIFIED UNSPECIFIED Zazzi, Maurizio UNSPECIFIED orcid.org/0000-0002-0344-6281 UNSPECIFIED Shafer, Robert W. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-690215
DOI:	10.3390/pathogens11050546
Journal or Publication Title:	Pathogens
Volume:	11
Number:	5
Date:	2022
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2076-0817
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ANTIRETROVIRAL DRUG-RESISTANCE; NAIVE HIV-1-INFECTED PATIENTS; HIV-1 SUBTYPE C; REVERSE-TRANSCRIPTASE; INITIAL TREATMENT; REGIMENS; FAILURE; LOPINAVIR/RITONAVIR; EFAVIRENZ; TENOFOVIR Multiple languages Microbiology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/69021