INDICATION

DOVATO is indicated as a complete regimen to treat HIV-1 infection in adults with no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable ARV regimen with no history of treatment failure and no known resistance to any component of DOVATO.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: PATIENTS CO-INFECTED WITH HEPATITIS B VIRUS (HBV) AND HIV-1: EMERGENCE OF LAMIVUDINE-RESISTANT HBV AND EXACERBATIONS OF HBV

All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating DOVATO. Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens has been reported. If DOVATO is used in patients co-infected with HIV-1 and HBV, additional treatment should be considered for appropriate treatment of chronic HBV; otherwise, consider an alternative regimen.

Severe acute exacerbations of HBV have been reported in patients who are co-infected with HIV-1 and HBV and have discontinued lamivudine, a component of DOVATO. Closely monitor hepatic function in these patients and, if appropriate, initiate anti-HBV treatment.

Contraindications

• Do not use DOVATO in patients with previous hypersensitivity reaction to dolutegravir or lamivudine

• Do not use DOVATO in patients receiving dofetilide

Warnings and precautions Hypersensitivity Reactions:

• Hypersensitivity reactions have been reported with dolutegravir and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury

• Discontinue DOVATO immediately if signs or symptoms of severe skin or hypersensitivity reactions develop, as a delay in stopping treatment may result in a life-threatening reaction. Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated

Hepatotoxicity:

• Hepatic adverse events have been reported, including cases of hepatic toxicity (elevated serum liver biochemistries, hepatitis, and acute liver failure), in patients receiving a dolutegravir- containing regimen without pre-existing hepatic disease or other identifiable risk factors

• Patients with underlying hepatitis B or C or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations with use of DOVATO. In some cases, the elevations in transaminases were consistent with immune reconstitution syndrome or hepatitis B reactivation, particularly in the setting where anti-hepatitis therapy was withdrawn

• Monitoring for hepatotoxicity is recommended

Embryo Fetal Toxicity:

• Assess the risks and benefits of DOVATO and discuss with the patient to determine if an alternative treatment should be considered at the time of conception through the first trimester of pregnancy due to the risk of neural tube defects

• Pregnancy testing is recommended before initiation of DOVATO. Individuals of childbearing potential should be counseled on the consistent use of effective contraception

Lactic Acidosis and Severe Hepatomegaly With Steatosis:

Fatal cases have been reported with the use of nucleoside analogs, including lamivudine. Discontinue DOVATO if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.

Adverse Reactions or Loss of Virologic Response Due to Drug Interactions with concomitant use of DOVATO and other drugs may occur (see Contraindications and Drug interactions).

Immune Reconstitution Syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported with the use of DOVATO.

Adverse reactions

The most common adverse reactions (incidence ≥2%, all grades) with DOVATO were headache (3%), nausea (2%), diarrhea (2%), insomnia (2%), fatigue (2%), and anxiety (2%).

Drug interactions

• Consult full Prescribing Information for DOVATO for more information on potentially significant drug interactions

• DOVATO is a complete regimen. Coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended

• Drugs that induce or inhibit CYP3A or UGT1A1 may affect the plasma concentrations of dolutegravir

• Administer DOVATO 2 hours before or 6 hours after taking polyvalent cation-containing antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. Alternatively, DOVATO and supplements containing calcium or iron can be taken with food

Studied in a Robust Phase 3 Clinical Trial: TANGO1

TRIAL DESIGN


• TANGO is an ongoing, Phase 3, randomized, open-label, noninferiority trial in virologically suppressed (HIV-1 RNA <50 copies/mL) adults with HIV-1 in which all participants were on a TAF-containing regimen and stable for >6 months

• Designed to evaluate the efficacy and safety of DOVATO, a 2-drug regimen, compared with a 3- to 4-drug TAF-containing regimen. From Week 148 onward, all participants switched to DOVATO, a once-daily DTG 50-mg/3TC 300-mg tablet


SELECT ELIGIBILITY CRITERIA

• Participants had no history of virologic failure, no documented NRTI or INSTI resistance, no severe hepatic impairment (Child-Pugh class C), and were HBV negative


TANGO BASELINE CHARACTERISTICS

• At baseline across both treatment arms, 98% had CD4+ T-cell count ≥200 cells/mm3


IMPORTANT SAFETY INFORMATION (cont’d) Use in specific populations

Pregnancy: There are insufficient human data on the use of DOVATO during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage. An Antiretroviral Pregnancy Registry has been established. Advise individuals of childbearing potential of the potential risk of neural tube defects. Assess the risks and benefits of DOVATO and discuss with the patient to determine if an alternative treatment should be considered at the time of conception through the first trimester of pregnancy or if pregnancy is confirmed in the first trimester


Powerful Results With Durable Virologic Suppression

TANGO—NONINFERIOR VIROLOGIC RESPONSE IN VIROLOGICALLY SUPPRESSED ADULTS1,2*

*–8% noninferiority margin for secondary endpoint. CI=confidence interval


As effective long term as a TAF-containing regimen

IMPORTANT SAFETY INFORMATION (cont’d) Use in specific populations (cont’d)

• Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission, developing viral resistance in HIV-positive infants, and adverse reactions in a breastfed infant

• Females and Males of Reproductive Potential: Pregnancy testing is recommended before initiation of DOVATO. Counsel individuals of childbearing potential taking DOVATO on the consistent use of effective contraception


A High Barrier to Resistance Through 144 Weeks1,2

0 cases of treatment-emergent resistance in virologically suppressed adults

No participants in the DOVATO arm had confirmed virologic withdrawal (HIV-1 RNA ≥50 copies/mL followed by a second consecutive HIV-1 RNA ≥200 copies/mL). Therefore, no participants were evaluated for treatment-emergent resistance.


Drug-Related Adverse Events and Discontinuation Rates Through 144 Weeks2

1 participant was excluded for receiving a TDF-containing regimen instead of a TAF-containing regimen. AE=adverse event; TDF=tenofovir disoproxil fumarate.


IMPORTANT SAFETY INFORMATION (cont’d) Use in specific populations (cont’d)

• Renal Impairment: DOVATO is not recommended for patients with creatinine clearance <30 mL/min. Patients with a sustained creatinine clearance between 30 and 49 mL/min should be monitored for hematologic toxicities, which may require a dosage adjustment of lamivudine as an individual component

• Hepatic Impairment: DOVATO is not recommended in patients with severe hepatic impairment (Child-Pugh Score C)