{"id":853998,"date":"2022-06-19T18:39:45","date_gmt":"2022-06-20T01:39:45","guid":{"rendered":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/"},"modified":"2022-06-19T18:56:06","modified_gmt":"2022-06-20T01:56:06","slug":"pre-treatment-integrase-inhibitor-resistance-is-uncommon-in-antiretroviral-therapy-naive-individuals-with-hiv-1-subtype-a1-and-d-infections-in-uganda","status":"publish","type":"msr-research-item","link":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/publication\/pre-treatment-integrase-inhibitor-resistance-is-uncommon-in-antiretroviral-therapy-naive-individuals-with-hiv-1-subtype-a1-and-d-infections-in-uganda\/","title":{"rendered":"Pre-treatment integrase inhibitor resistance is uncommon in antiretroviral therapy-naive individuals with HIV-1 subtype A1 and D infections in Uganda."},"content":{"rendered":"<p><strong>OBJECTIVE<\/strong> 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. DESIGN We retrospectively examined HIV-1 integrase sequences from Uganda.<\/p>\n<p><strong>METHODS<\/strong> 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.<\/p>\n<p><strong>RESULTS<\/strong> 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\u221702:01\/05\/14, B\u221744:15, and C\u221704:07 predicted the presence of L74I, a mutation recently observed in association with long-acting INSTI cabotegravir virologic failure.<\/p>\n<p><strong>CONCLUSION<\/strong> 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.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>OBJECTIVE 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 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