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Title: Drug resistance mutations in HIV-2 patients failing raltegravir and influence on dolutegravir response.
Authors: Requena, Silvia
Treviño, Ana
Cabezas, Teresa
Garcia-Delgado, Rosa
Amengual, María José
Lozano, Ana Belén
Peñaranda, María
Fernández, Juan Manuel
Soriano, Vicente
de Mendoza, Carmen
Spanish HIV-2 Study Group
metadata.dc.subject.mesh: Adult
Amino Acid Substitution
Anti-HIV Agents
Drug Resistance, Viral
HIV Infections
HIV Integrase
HIV Integrase Inhibitors
Heterocyclic Compounds, 3-Ring
Middle Aged
RNA, Viral
Raltegravir Potassium
Treatment Failure
Issue Date: 2017
Abstract: A broader extent of amino acid substitutions in the integrase of HIV-2 compared with HIV-1 might enable greater cross-resistance between raltegravir and dolutegravir in HIV-2 infection. Few studies have examined the virological response to dolutegravir in HIV-2 patients that failed raltegravir. All patients recorded in the HIV-2 Spanish cohort were examined. The integrase coding region was sequenced in viraemic patients. Changes associated with resistance to raltegravir and dolutegravir in HIV-1 were recorded. From 319 HIV-2-infected patients recorded in the HIV-2 Spanish cohort, 53 integrase sequences from 30 individuals were obtained (20 raltegravir naive and 10 raltegravir experienced). Only one secondary mutation (E138A) was found in one of the 20 raltegravir-naive HIV-2 patients. For raltegravir-experienced individuals, the resistance mutation profile in 9 of 10 viraemic patients was as follows: N155H + A153G/S (four); Y143G + A153S (two); Q148R + G140A/S (two); and Y143C + Q91R (one). Of note, all patients with Y143G and N155H developed a rare non-polymorphic mutation at codon 153. Rescue therapy with dolutegravir was given to 5 of these 10 patients. After >6 months on dolutegravir therapy, three patients with baseline N155H experienced viral rebound. In two of them N155H was replaced by Q148K/R and in another by G118R. A wide repertoire of resistance mutations in the integrase gene occur in HIV-2-infected patients failing on raltegravir. Although dolutegravir may allow successful rescue in most HIV-2 raltegravir failures, we report and characterize three cases of dolutegravir resistance in HIV-2 patients, emerging variants Q148K and Q148R and a novel change G118R.
metadata.dc.identifier.doi: 10.1093/jac/dkx090
Appears in Collections:Producción 2020

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