Pre-treatment integrase inhibitor resistance is uncommon in antiretroviral therapy-naive individuals with HIV-1 subtype A1 and D infections in Uganda.
Journal
AIDS (London, England)
ISSN: 1473-5571
Titre abrégé: AIDS
Pays: England
ID NLM: 8710219
Informations de publication
Date de publication:
01 06 2021
01 06 2021
Historique:
pubmed:
27
2
2021
medline:
20
5
2021
entrez:
26
2
2021
Statut:
ppublish
Résumé
Dolutegravir (DTG) is now a preferred component of first-line antiretroviral therapy (ART). However, prevalence data on natural resistance to integrase inhibitors [integrase strand transfer inhibitors (INSTIs)] in circulating non-subtype B HIV-1 in sub-Saharan Africa is scarce. Our objective is to report prevalence of pre-treatment integrase polymorphisms associated with resistance to INSTIs in an ART-naive cohort with diverse HIV-1 subtypes. We retrospectively examined HIV-1 integrase sequences from Uganda. Plasma samples were derived from the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort, reflecting enrollment from 2002 to 2010, prior to initiation of ART. HIV-1 integrase was amplified using nested-PCR and Sanger-sequenced (HXB2 4230-5093). Stanford HIVdb v8.8 was used to infer clinically significant INSTI-associated mutations. Human leukocyte antigen (HLA) typing was performed for all study participants. Plasma samples from 511 ART-naive individuals (subtype: 48% A1, 39% D) yielded HIV-1 integrase genotyping results. Six out of 511 participants (1.2%) had any major INSTI-associated mutations. Of these, two had E138T (subtype A1), three had E138E/K (subtype D), and one had T66T/I (subtype D). No participants had mutations traditionally associated with high levels of INSTI resistance. HLA genotypes A∗02:01/05/14, B∗44:15, and C∗04:07 predicted the presence of L74I, a mutation recently observed in association with long-acting INSTI cabotegravir virologic failure. We detected no HIV-1 polymorphisms associated with high levels of DTG resistance in Uganda in the pre-DTG era. Our results support widespread implementation of DTG but careful monitoring of patients on INSTI with virologic failure is warranted to determine if unique mutations predict failure for non-B subtypes of HIV-1.
Identifiants
pubmed: 33635845
doi: 10.1097/QAD.0000000000002854
pii: 00002030-202106010-00009
pmc: PMC8102316
mid: NIHMS1680141
doi:
Substances chimiques
HIV Integrase Inhibitors
0
HIV Integrase
EC 2.7.7.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1083-1089Subventions
Organisme : NIAID NIH HHS
ID : T32 AI007387
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH054907
Pays : United States
Organisme : NIMH NIH HHS
ID : K24 MH114732
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA181255
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI027763
Pays : United States
Organisme : NIAID NIH HHS
ID : K23 AI143470
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI150398
Pays : United States
Organisme : CCR NIH HHS
ID : HHSN261200800001C
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : CIHR
ID : PJT-148621
Pays : Canada
Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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