Dolutegravir (DTG)-containing regimens after receiving raltegravir (RAL) or elvitegravir (EVG)

Durability and virological response in a large Italian HIV drug resistance network (ARCA)

on behalf of ARCA (Antiviral Response Cohort Analysis)

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)112-117
Number of pages6
JournalJournal of Clinical Virology
Volume105
DOIs
Publication statusPublished - Aug 1 2018

Fingerprint

Drug Resistance
HIV
HIV-1
RNA
JTK 303
dolutegravir
Raltegravir Potassium
HIV Integrase Inhibitors
Antiviral Agents
Cohort Studies
Logistic Models
Observation
Databases
Viruses
Mutation

Keywords

  • Dolutegravir
  • Drug resistance
  • Durability
  • Genotype
  • Human immunodeficiency virus type 1
  • Virological response

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Dolutegravir (DTG)-containing regimens after receiving raltegravir (RAL) or elvitegravir (EVG) : Durability and virological response in a large Italian HIV drug resistance network (ARCA). / on behalf of ARCA (Antiviral Response Cohort Analysis).

In: Journal of Clinical Virology, Vol. 105, 01.08.2018, p. 112-117.

Research output: Contribution to journalArticle

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title = "Dolutegravir (DTG)-containing regimens after receiving raltegravir (RAL) or elvitegravir (EVG): Durability and virological response in a large Italian HIV drug resistance network (ARCA)",
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.",
keywords = "Dolutegravir, Drug resistance, Durability, Genotype, Human immunodeficiency virus type 1, Virological response",
author = "{on behalf of ARCA (Antiviral Response Cohort Analysis)} and S. Rusconi and F. Adorni and P. Tau and V. Borghi and M. Pecorari and R. Maserati and D. Francisci and L. Monno and G. Punzi and P. Meraviglia and S. Paolucci and {Di Biagio}, A. and B. Bruzzone and A. Mancon and V. Micheli and M. Zazzi",
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T1 - Dolutegravir (DTG)-containing regimens after receiving raltegravir (RAL) or elvitegravir (EVG)

T2 - Durability and virological response in a large Italian HIV drug resistance network (ARCA)

AU - on behalf of ARCA (Antiviral Response Cohort Analysis)

AU - Rusconi, S.

AU - Adorni, F.

AU - Tau, P.

AU - Borghi, V.

AU - Pecorari, M.

AU - Maserati, R.

AU - Francisci, D.

AU - Monno, L.

AU - Punzi, G.

AU - Meraviglia, P.

AU - Paolucci, S.

AU - Di Biagio, A.

AU - Bruzzone, B.

AU - Mancon, A.

AU - Micheli, V.

AU - Zazzi, M.

PY - 2018/8/1

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N2 - 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.

AB - 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.

KW - Dolutegravir

KW - Drug resistance

KW - Durability

KW - Genotype

KW - Human immunodeficiency virus type 1

KW - Virological response

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