Dolutegravir: Clinical and Laboratory Safety in Integrase Inhibitor–Naive Patients

Curtis, Lloyd; Nichols, Garrett; Stainsby, Chris; Lim, Jessica; Aylott, Alicia; Wynne, Brian; Clark, Andrew; Bloch, Mark; Maechler, Gudrun; Martin-Carpenter, Louise; Raffi, François; Min, Sherene

doi:10.1310/hct1505-199

“…This was also shown for dolutegravir, which caused grade 2 --3 ALT elevations in 16% of co-infected patients versus 3% in non-coinfected [63]. In treatment-naive co-infected patients, the incidence of grade 2 --4 liver enzyme elevations was highest with efavirenz and raltegravir, intermediate with dolutegravir and the lowest with darunavir/ritonavir.…”

Section: Safetymentioning

confidence: 54%

“…The hepatic safety profile of dolutegravir was in general similar to the profile of raltegravir and other comparator drugs [63]. The hepatic safety of dolutegravir in HIV and HBV/HCV co-infected patients is discussed in more detail in section 6.1.…”

Section: Safetymentioning

confidence: 80%

“…The incidence of CPK elevations (grade 3 --4) during the use of dolutegravir (5%), efavirenz (5%), raltegravir (4%) or darunavir/ritonavir (4%) was similar [63]. In the treatment-experienced patients in the SAILING study, grade 3 --4 CPK elevations developed in 2 and 1% with the use of dolutegravir and raltegravir, respectively [63]. Furthermore, dolutegravir does not affect cardiac repolarization, since a single supratherapeutic dose of 250 mg did not show any relevant QT-interval prolongation [67].…”

Section: Safetymentioning

confidence: 89%

“…The incidence of CPK elevations (grade 3 --4) during the use of dolutegravir (5%), efavirenz (5%), raltegravir (4%) or darunavir/ritonavir (4%) was similar [63]. In the treatment-experienced patients in the SAILING study, grade 3 --4 CPK elevations developed in 2 and 1% with the use of dolutegravir and raltegravir, respectively [63].…”

Section: Safetymentioning

confidence: 99%

“…An integrated safety analysis by Curtis et al informed more on clinical and laboratory safety of dolutegravir, including CPK elevations [63]. The incidence of CPK elevations (grade 3 --4) during the use of dolutegravir (5%), efavirenz (5%), raltegravir (4%) or darunavir/ritonavir (4%) was similar [63].…”

Section: Safetymentioning

confidence: 99%

See 3 more Smart Citations

Clinical pharmacokinetics and pharmacodynamics of dolutegravir used as a single tablet regimen for the treatment of HIV-1 infection

Bollen

¹

,

Reiss

²

,

Schapiro

³

et al. 2015

Expert Opinion on Drug Safety

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The dolutegravir/abacavir/lamivudine regimen is highly effective in achieving sustained suppression of HIV-1 RNA plasma concentrations. The STR has a favorable safety profile and a low potential for drug interactions, which will contribute to a prominent role in therapy. As this STR contains abacavir as backbone component, the use requires patients to be HLA-B*5701 negative, with good hepatic function. Other first-line treatment combinations are preferred for patients with hepatitis B co-infection or with a high cardiovascular risk.

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Dolutegravir‐induced acquired sideroblastic anemia in a HIV positive patient: A challenging hematologic complication

Dhonju,

Gautam,

Dahal

et al. 2023

Clinical Case Reports

2

0

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Abacavir Hypersensitivity Reaction Reporting Rates During a Decade of HLA‐B*5701 Screening as a Risk‐Mitigation Measure

Stainsby

¹

,

Perger

²

,

et al. 2018

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Introduction Human leukocyte antigen (HLA) ‐B*5701 screening identifies patients at increased risk for abacavir ( ABC ) hypersensitivity reaction ( HSR ). Screening was adopted in GlaxoSmithKline and ViiV Healthcare clinical trials in 2007 and human immunodeficiency virus treatment guidelines in 2008. Company meta‐analyses of trials pre– HLA ‐B*5701 screening reported HSR rates of 4–8%. We analyzed the effectiveness of HLA ‐B*5701 screening on reducing HSR rates using clinical trial, Observational Pharmaco‐Epidemiology Research & Analysis ( OPERA ) cohort, and spontaneous reporting data. Methods A meta‐analysis examined 12 trials in 3063 HLA ‐B*5701–negative patients receiving an ABC ‐containing regimen from April 9, 2007, to September 22, 2015. Potential cases were identified using prespecified Medical Dictionary for Regulatory Activities (Med DRA ) preferred terms ( drug hypersensitivity, hypersensitivity, anaphylactic reaction, anaphylaxis ) and adjudicated against a Company ABC HSR case definition. Investigator‐diagnosed cases were identified and rates were calculated. In the OPERA cohort, 9619 patients initiating their first ABC ‐containing regimen from January 1, 1999, to January 1, 2016, were identified. Patients were observed from regimen start until the earliest‐following censoring event: ABC discontinuation, loss to follow‐up, death, or study end (July 31, 2016). OPERA physicians evaluated events against OPERA definitions for definite/probable cases of ABC HSR ; rates were calculated pre‐ and post‐2008. The Company case definition was used to identify spontaneously reported cases for four marketed ABC ‐containing products; reporting rates were calculated using estimated exposure from sales data, through December 31, 2016. Results Suspected ABC HSR rates were 1.3% or less in the meta‐analysis. In the OPERA cohort, the rate was 0.4% among patients initiating ABC post‐2008 versus 1.3% pre‐2008 (p<0.0001). Spontaneous reporting rates were low post‐2008 (54 to 22 cases per 100,000 patient‐years exposure [ PYE ]) versus pre‐2008 (618 to 55 cases per 100,000 PYE ). Conclusions Clinically suspected ABC HSR rates were 1.3% or less in HLA ‐B*5701–negative patients. Recognizing their limitations, data from t...

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Dolutegravir: Clinical and Laboratory Safety in Integrase Inhibitor–Naive Patients

Abstract: The safety profile for DTG 50 mg once daily in INI-naive individuals was comparable to RAL- and DRV/r-containing regimens and generally favorable compared with EFV-containing regimens.

Cited by 44 publications

References 8 publications

Clinical pharmacokinetics and pharmacodynamics of dolutegravir used as a single tablet regimen for the treatment of HIV-1 infection

Clinical pharmacokinetics and pharmacodynamics of dolutegravir used as a single tablet regimen for the treatment of HIV-1 infection

Dolutegravir‐induced acquired sideroblastic anemia in a HIV positive patient: A challenging hematologic complication

Abacavir Hypersensitivity Reaction Reporting Rates During a Decade of HLA‐B*5701 Screening as a Risk‐Mitigation Measure

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