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-classexperienced 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/mu L (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.

Dolutegravir (DTG)-containing regimens after receiving raltegravir (RAL) or elvitegravir (EVG): Durability and virological response in a large Italian HIV drug resistance network (ARCA) / S. Rusconi, F. Adorni, P. Tau, V. Borghi, M. Pecorari, R. Maserati, D. Francisci, L. Monno, G. Punzi, P. Meraviglia, S. Paolucci, A. Di Biagio, B. Bruzzone, A. Mancon, V. Micheli, M. Zazzi. - In: JOURNAL OF CLINICAL VIROLOGY. - ISSN 1386-6532. - 105(2018 Aug), pp. 112-117. [10.1016/j.jcv.2018.06.012]

Dolutegravir (DTG)-containing regimens after receiving raltegravir (RAL) or elvitegravir (EVG): Durability and virological response in a large Italian HIV drug resistance network (ARCA)

S. Rusconi
Primo
;
A. Mancon;
2018

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-classexperienced 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/mu L (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.
Dolutegravir; drug resistance; genotype; Human immunodeficiency virus Type 1; durability; virological response
Settore MED/17 - Malattie Infettive
ago-2018
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/580091
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