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 language | English |
|---|---|
| Pages (from-to) | 112-117 |
| Number of pages | 6 |
| Journal | Journal of Clinical Virology |
| Volume | 105 |
| DOIs | |
| Publication status | Published - Aug 1 2018 |
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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 journal › Article
}
TY - JOUR
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
Y1 - 2018/8/1
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
UR - http://www.scopus.com/inward/record.url?scp=85048946304&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85048946304&partnerID=8YFLogxK
U2 - 10.1016/j.jcv.2018.06.012
DO - 10.1016/j.jcv.2018.06.012
M3 - Article
VL - 105
SP - 112
EP - 117
JO - Journal of Clinical Virology
JF - Journal of Clinical Virology
SN - 1386-6532
ER -