Universität zu Köln

Neogi, Ujjwal ORCID: 0000-0002-0844-3338, Haggblom, Amanda, Singh, Kamalendra, Rogers, Leonard C., Rao, Shwetha D., Amogne, Wondwossen, Schuelter, Eugen, Zazzi, Maurizio ORCID: 0000-0002-0344-6281, Arnold, Eddy, Sarafianos, Stefan G. and Sonnerborg, Anders ORCID: 0000-0001-8928-3374 (2016). Factors influencing the efficacy of rilpivirine in HIV-1 subtype C in low- and middle-income countries. J. Antimicrob. Chemother., 71 (2). S. 367 - 372. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2091

Full text not available from this repository.

Abstract

The use of the NNRTI rilpivirine in low- and middle-income countries (LMICs) is under debate. The main objective of this study was to provide further clinical insights and biochemical evidence on the usefulness of rilpivirine in LMICs. Rilpivirine resistance was assessed in 5340 therapy-naive and 13aEuroS750 first-generation NNRTI-failed patients from Europe and therapy-naive HIV-1 subtype C (HIV-1C)-infected individuals from India (naEuroS=aEuroS617) and Ethiopia (naEuroS=aEuroS127). Rilpivirine inhibition and binding affinity assays were performed using patient-derived HIV-1C reverse transcriptases (RTs). Primary rilpivirine resistance was rare, but the proportion of patients with > 100aEuroS000 HIV-1 RNA copies/mL pre-ART was high in patients from India and Ethiopia, limiting the usefulness of rilpivirine as a first-line drug in LMICs. In patients failing first-line NNRTI treatments, cross-resistance patterns suggested that 73% of the patients could benefit from switching to rilpivirine-based therapy. In vitro inhibition assays showed similar to 2-fold higher rilpivirine IC50 for HIV-1C RT than HIV-1B RT. Pre-steady-state determination of rilpivirine-binding affinities revealed 3.7-fold lower rilpivirine binding to HIV-1C than HIV-1B RT. Structural analysis indicated that naturally occurring polymorphisms close to the NNRTI-binding pocket may reduce rilpivirine binding, leading to lower susceptibility of HIV-1C to rilpivirine. Our clinical and biochemical findings indicate that the usefulness of rilpivirine has limitations in HIV-1C-dominated epidemics in LMICs, but the drug could still be beneficial in patients failing first-line therapy if genotypic resistance testing is performed.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Neogi, Ujjwal UNSPECIFIED orcid.org/0000-0002-0844-3338 UNSPECIFIED Haggblom, Amanda UNSPECIFIED UNSPECIFIED UNSPECIFIED Singh, Kamalendra UNSPECIFIED UNSPECIFIED UNSPECIFIED Rogers, Leonard C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rao, Shwetha D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Amogne, Wondwossen UNSPECIFIED UNSPECIFIED UNSPECIFIED Schuelter, Eugen UNSPECIFIED UNSPECIFIED UNSPECIFIED Zazzi, Maurizio UNSPECIFIED orcid.org/0000-0002-0344-6281 UNSPECIFIED Arnold, Eddy UNSPECIFIED UNSPECIFIED UNSPECIFIED Sarafianos, Stefan G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sonnerborg, Anders UNSPECIFIED orcid.org/0000-0001-8928-3374 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-286395
DOI:	10.1093/jac/dkv359
Journal or Publication Title:	J. Antimicrob. Chemother.
Volume:	71
Number:	2
Page Range:	S. 367 - 372
Date:	2016
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2091
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RESISTANCE-ASSOCIATED MUTATIONS; REVERSE-TRANSCRIPTASE INHIBITORS; FAILING ANTIRETROVIRAL THERAPY; DRUG-RESISTANCE; SUSCEPTIBILITY; EMTRICITABINE; INDIVIDUALS; PREVALENCE; EFAVIRENZ; TENOFOVIR Multiple languages Infectious Diseases; Microbiology; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28639