dc.contributor.author | Mccluskey, Suzanne M. | |
dc.contributor.author | Kamelian, Kimia | |
dc.contributor.author | Musinguzi, Nicholas | |
dc.contributor.author | Kigozi, Simone | |
dc.contributor.author | II, Yap Boum | |
dc.contributor.author | Bwana, Mwebesa B. | |
dc.contributor.author | Muzoora, Conrad | |
dc.contributor.author | Brumme, Zabrina L. | |
dc.contributor.author | Carrington, Mary | |
dc.contributor.author | Carlson, Jonathan | |
dc.contributor.author | Foley, Brian | |
dc.contributor.author | Hunt, Peter W. | |
dc.contributor.author | Martin, Jeffrey N. | |
dc.contributor.author | Bangsberg, David R. | |
dc.contributor.author | Harrigan, P. Richard | |
dc.contributor.author | Siedner, Mark J. | |
dc.contributor.author | Haberer, Jessica E. | |
dc.contributor.author | Lee, Guinevere Q. | |
dc.date.accessioned | 2022-06-15T08:01:47Z | |
dc.date.available | 2022-06-15T08:01:47Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | Mccluskey, S. M., Kamelian, K., Musinguzi, N., Kigozi, S., Boum 2nd, Y., Bwana, M. B., ... & Lee, G. Q. (2021). Pre-treatment integrase inhibitor resistance is uncommon in ART-naïve individuals with HIV-1 subtype A1 and D infections in Uganda. AIDS (London, England). | en_US |
dc.identifier.uri | http://ir.must.ac.ug/xmlui/handle/123456789/2132 | |
dc.description.abstract | Objective: Dolutegravir (DTG) is now a preferred component of first-line antiretroviral therapy (ART). However, prevalence data on natural resistance to integrase 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-naïve cohort with diverse HIV-1 subtypes.
Design: We retrospectively examined HIV-1 integrase sequences from Uganda.
Methods: Plasma samples were derived from the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort, reflecting enrollment from 2002–2010, 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. HLA typing was performed for all study participants.
Results: Plasma samples from 511 ART-naïve 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.
Conclusion: 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. | en_US |
dc.description.sponsorship | National Institutes of Health (K23 AI143470 and T32 AI007387 to SMM, R21AI150398 to GQL, UM1 CA181255 and P30 AI027763 to JNM, R01 MH054907 to DRB, and K24 MH114732 to JEH). | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | AIDS | en_US |
dc.subject | HIV-1 | en_US |
dc.subject | Integrase strand transfer inhibitors | en_US |
dc.subject | dolutegravir | en_US |
dc.subject | Mutation | en_US |
dc.subject | HIV integrase | en_US |
dc.subject | Sub-Saharan Africa | en_US |
dc.subject | Uganda | en_US |
dc.title | Pre-treatment integrase inhibitor resistance is uncommon in ART-naïve individuals with HIV-1 subtype A1 and D infections in Uganda | en_US |
dc.type | Article | en_US |