S Rusconi1, F Adorni2, P Tau3, V Borghi4, M Pecorari5, R Maserati6, D Francisci7, L Monno8, G Punzi9, P Meraviglia10, S Paolucci11, A Di Biagio12, B Bruzzone13, A Mancon14, V Micheli14, M Zazzi15. 1. Divisione Malattie Infettive, DIBIC Luigi Sacco, Università degli Studi di Milano, Italy. Electronic address: stefano.rusconi@unimi.it. 2. ITB-CNR, Segrate, MI, Italy. 3. Divisione Malattie Infettive, DIBIC Luigi Sacco, Università degli Studi di Milano, Italy. 4. Clinica Malattie Infettive, Modena, Italy. 5. Laboratorio di Virologia, Modena, Italy. 6. Ambulatorio Clinica Malattie Infettive, Fondazione Policlinico San Matteo, Pavia, Italy. 7. Clinica Malattie Infettive, Terni, Italy. 8. Clinica Malattie Infettive, Bari, Italy. 9. Laboratorio di Virologia, Bari, Italy. 10. Prima divisione di Malattie Infettive, Ospedale Luigi Sacco, Milano, Italy. 11. Laboratorio di Virologia, Fondazione Policlinico San Matteo, Pavia, Italy. 12. Clinica Malattie Infettive, Azienda Ospedaliera Universitaria San Martino, Genova, Italy. 13. Laboratorio di Igiene, Azienda Ospedaliera Universitaria San Martino, Genova, Italy. 14. Laboratorio Microbiologia Clinica - Virologia - Bioterrorismo, Ospedale Luigi Sacco, ASST FBF-Sacco, Milano, Italy. 15. Dipartimento di Biotecnologie Mediche, Università degli Studi di Siena, Italy.
Abstract
BACKGROUND: Dolutegravir (DTG) is a next-generation HIV integrase inhibitor (INI) with an increased genetic barrier to resistance with respect to raltegravir (RAL) or elvitegravir (EVG). Few data are available on the durability of DTG-containing regimens. OBJECTIVES: We aimed at investigating the duration of the DTG-containing regimen, the occurrence of an HIV-1 RNA blip, and factors associated with DTG virological response. STUDY DESIGN: From the Antiviral Response Cohort Analysis database, we selected 89 HIV-1-positive four-class-experienced subjects who started DTG after receiving RAL or EVG. Factors associated with durability and virological response were analysed by logistic regression. RESULTS: After a median duration of 18.8 [0.4-76.2] months, 79/89 (88.8%) subjects were still on DTG. All subjects remaining on DTG at the end of follow-up had undetectable HIV-1 RNA, compared to 5/10 subjects who discontinued DTG. DTG discontinuation was less frequent in patients who had experienced ≥10 regimens (HR 0.11, p = 0.040). The probability of having an HIV-1 RNA positive value at the last follow-up significantly increased in patients with non-B HIV-1 subtype (HR 5.77, p < .001) and significantly decreased in patients with CD4 nadir >200/μL (HR 0.29, p = 0.038), with more than 10 previous regimens (HR 0.27, p = 0.040), and who harbored virus with IN mutations (HR 0.12, p = 0.023) at DTG start. CONCLUSIONS: After previous exposure to first-generation INIs, treatment with DTG showed long durability and did not show virological rebound after virological suppression. Subjects infected with a non-B HIV-1 subtype had a greater risk of having detectable HIV-1 RNA at the last observation.
BACKGROUND:Dolutegravir (DTG) is a next-generation HIV integrase inhibitor (INI) with an increased genetic barrier to resistance with respect to raltegravir (RAL) or elvitegravir (EVG). Few data are available on the durability of DTG-containing regimens. OBJECTIVES: We aimed at investigating the duration of the DTG-containing regimen, the occurrence of an HIV-1 RNA blip, and factors associated with DTG virological response. STUDY DESIGN: From the Antiviral Response Cohort Analysis database, we selected 89 HIV-1-positive four-class-experienced subjects who started DTG after receiving RAL or EVG. Factors associated with durability and virological response were analysed by logistic regression. RESULTS: After a median duration of 18.8 [0.4-76.2] months, 79/89 (88.8%) subjects were still on DTG. All subjects remaining on DTG at the end of follow-up had undetectable HIV-1 RNA, compared to 5/10 subjects who discontinued DTG. DTG discontinuation was less frequent in patients who had experienced ≥10 regimens (HR 0.11, p = 0.040). The probability of having an HIV-1 RNA positive value at the last follow-up significantly increased in patients with non-B HIV-1 subtype (HR 5.77, p < .001) and significantly decreased in patients with CD4 nadir >200/μL (HR 0.29, p = 0.038), with more than 10 previous regimens (HR 0.27, p = 0.040), and who harbored virus with IN mutations (HR 0.12, p = 0.023) at DTG start. CONCLUSIONS: After previous exposure to first-generation INIs, treatment with DTG showed long durability and did not show virological rebound after virological suppression. Subjects infected with a non-B HIV-1 subtype had a greater risk of having detectable HIV-1 RNA at the last observation.
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