ed in patients treated with combinationantiretroviral therapy, including DOVATO. During the initial phase of combination antiretroviraltreatment, patients whose immune systems respond may develop an inflammatory response toindolent or residual opportunistic infections (such as Mycobacterium avium infection,cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which maynecessitate further eva luation and treatment.
Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome)have also been reported to occur in the setting of immune reconstitution; however, the time toonset is more variable, and can occur many months after initiation of treatment.
6 ADVERSE REACTIONS
The following adverse reactions are discussed in other sections of the labeling:
• Patients co-infected with HIV-1 and HBV [see Warnings and Precautions (5.1)].
• Hypersensitivity reactions [see Warnings and Precautions (5.2)].
• Hepatotoxicity [see Warnings and Precautions (5.3)].
• Lactic acidosis and severe hepatomegaly with steatosis [see Warnings and Precautions(5.5)].
• Immune reconstitution syndrome [see Warnings and Precautions (5.7)].
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction ratesobserved in the clinical trials of a drug cannot be directly compared with rates in the clinicaltrials of another drug and may not reflect the rates observed in clinical practice.
The safety assessment of DOVATO in HIV-1–infected adults with no antiretroviral treatmenthistory and with a plasma viral load ≤500,000 HIV-1 RNA copies/mL at the screening visit, isbased on the pooled primary Week 48 analyses of data from 2 identical, multicenter, doubleblind,controlled trials, GEMINI-1 and GEMINI-2. A total of 1,433 HIV-1–infected adults withno antiretroviral treatment history were randomized to dolutegravir (TIVICAY) 50 mg pluslamivudine (EPIVIR) 300 mg, as a complete regimen once daily, or TIVICAY 50 mg plus fixeddosecombination tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) (TRUVADA),administered once daily.
The rates of adverse events leading to discontinuation in the pooled analysis were 2% of subjectsin both treatment arms. The most common adverse events leading to discontinuation werepsychiatric disorders: <1% of subjects in both treatment arms.
Adverse reactions (all grades) observed in at least 2% of subjects in either treatment arm of theWeek 48 pooled analysis from GEMINI-1 and GEMINI-2 trials are provided in Table 2.
The adverse reactions observed for TIVICAY plus EPIVIR in the Week 48 analysis of thepooled data from GEMINI-1 and GEMINI-2 were generally consistent with the adverse reactionprofiles and severities for the individual components when administered with other antiretroviralagents.
Table 2. Adverse Reactions (All Grades) Reported in ≥2% of Subjects in Any TreatmentGroup in Adults with No Antiretroviral Treatment History in GEMINI-1 and GEMINI-2
(Week 48 Pooled Analysis)
Adverse Reaction
TIVICAY plus EPIVIR
(n = 716)
TIVICAY plus
TRUVADA
(n = 717)
Headachea
3% 4%
Nausea 2% 5%
Diarrhea 2% 3%
Insomnia 2% 3%
Fatigueb
2% 2%
Dizziness 1% 2%
a The only adverse reaction of Grade 2 or greater occurring in ≥1% of subjects treated withTIVICAY plus EPIVIR was headache |
