Dolutegravir is a human immunodeficiency virus (HIV) integrase inhibitor, the third in this class of agents that target the viral integrase. Dolutegravir is used only in combination with other antiretroviral agents in the treatment of HIV infection, and it has had limited use. Dolutegravir is associated with a low rate of serum aminotransferase elevations during therapy, but has not been linked to instances of acute, clinically apparent liver injury.


Dolutegravir (doe" loo teg' ra vir) is relatively new antiretroviral drug that targets the HIV integrase, one of the three viral enzymes involved in replication. Dolutegravir blocks the binding site of the HIV integrase and prevents the strand transfer activity and integration of the provirus into the host genome. Dolutegravir has both in vitro and in vivo activity against HIV, and several randomized controlled trials have shown that it can cause significant declines in HIV RNA levels and rises in peripheral CD4 T cell counts. Dolutegravir was approved for use in HIV infection in the United States in 2013 and is currently used in an increasing proportion of antiretroviral regimens. Dolutegravir is available as 50 mg tablets under the brand name Tivicay. The recommended dose regimen is 50 mg twice daily in combination with other classes of antiretroviral agents. A single tablet, fixed dose regimen of dolutegravir [50 mg], abacavir [600 mg] and lamivudine [300 mg] is also available under the name Triumeq, the recommended dose being one tablet daily. While generally well tolerated, dolutegravir therapy may be accompanied by diarrhea, headache, nausea and fever.


In large clinical trials, therapy with dolutegravir was associated with alanine aminotransferase (ALT) elevations of greater than 3 times the upper limit of normal (ULN) in 2% to 5% of patients, but these rates were similar to those in comparator groups receiving matched background optimized antiretroviral therapy without dolutegravir. These elevations were not associated with clinical symptoms and generally did not require dose modification. A few instances of acute liver injury with jaundice were described in the registration trials for dolutegravir which occurred in association with hypersensitivity reactions and resolved with drug discontinuation. The clinical features of these cases were not provided and their association with dolutegravir as opposed to the concurrent antiretroviral agents was not fully established. Since its approval and more wide spread use, however, several case reports of acute hepatitis attributable to dolutegravir have appeared. The latency to onset varried from 1 to 8 months and the pattern of serum enzyme elevations was hepatocellular. Immunoallergic and autoimmune features were not present. At least one published case resulted in acute liver failure and need for liver transplanation. The product label for dolutegravir mentions hepatitis and hepatic failure as potential adverse reactions and states that patients with hepatitis B or C coinfection are susceptible to worsening or flares of hepatitis with initiation of dolutegravir therapy, perhaps as a consequence of immune reconstitution syndrome. Monitoring of liver tests is recommended in patients starting regimens that include dolutegravir.

Likelihood score: D (possible cause of clinically apparent liver injury).

Mechanism of Injury

The mechanism by which dolutegravir might cause liver injury is not known. Dolutegravir is metabolized by the liver, largely by glucuronidation with subsequent urinary clearance. Dolutegravir has little or no effect on microsomal cytochrome P450 enzymes. Reconstitution of immune reactivity by antiretroviral therapy in patients with an underlying chronic hepatitis B or C can be associated with a transient flare of hepatitis. This effect occurs with many potent antiretroviral regimens and is not specific to dolutegravir or the integrase inhibitors.

Outcome and Management

Dolutegravir is associated with a low rate of serum enzyme elevations during therapy and monitoring of liver tests is recommended. Cases of acute hepatitis including fatal instances have been reported. Elevations of serum aminotransferase levels above 5 times the ULN should lead to dose interruptions and permanent discontinuation if they persist or are associated with clinical symptoms or jaundice. Switching to other antiretroviral agents is appropriate iand there does not appear to be cross sensitivity to hepatic injury among the various HIV integrase inhibitors. Dolutegravir has not been linked to cases of chronic cholestasis or vanishing bile duct syndrome.

Drug Class: Antiviral Agents

Other Drugs in the Subclass, Integrase Strand Transfer Inhibitors: Bictegravir, Cabotegravir, Elvitegravir, Raltegravir



Dolutegravir – Tivicay®


Antiviral Agents


Product labeling at DailyMed, National Library of Medicine, NIH



References updated: 10 January 2018

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    (28 year old African woman with HIV infection developed persistent ALT elevations a month after switching from raltegravir/ tenofovir/emtricitabine to dolutegravir/abacavir/lamivudine [ALT 300 U/L], which worsened despite switching back [bilirubin 7.3 mg/dL, ALT 1636 U/L, Alk P 131 U/L, INR 2.14], ultimately requiring liver transplantation for acute liver failure).
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    (47 year old man with HIV developed ALT elevations 8 months after starting dolutegravir/abacavir/lamivudine [bilirubin 0.8 mg/dL, ALT 343 U/L], which worsened with continuing [bilirubin 2.1 mg/dL, ALT 1004 U/L], improving on stopping and switching to elvitegravir/tenofovir/emtricitabine).