ViiV HEALTHCARE ANNOUNCES DOLUTEGRAVIR PLUS LAMIVUDINE THREE-YEAR DATA CONFIRMING LONG-TERM VIRAL SUPPRESSION NON-INFERIOR TO A 3-DRUG REGIMEN FOR TREATMENT-NAÏVE ADULTS WITH HIV-1

Kimberly Smith, M.D., MPH, Head of Research & Development at ViiV Healthcare, said: “Globally, the number of people living with HIV aged 50 and over is increasing and that’s testament to the success of antiretroviral therapy, which has transformed HIV into a chronic condition. However, living longer with HIV can mean taking multiple medications for many years, and we know that many people living with HIV have a preference to take as few medicines as possible, as long as their HIV remains under control. The momentum behind 2DRs is growing: Dovato has now shown sustained efficacy and tolerability through three years of treatment, with people able to maintain viral suppression with fewer medicines than a 3-drug regimen.”

Dolutegravir plus lamivudine continued to demonstrate a high genetic barrier to treatment-emergent resistance. The percentage of individuals with protocol-defined confirmed virologic withdrawal (CVW) was 1.7% (12/716) in the dolutegravir plus lamivudine arm and 1.3% (9/717) in the dolutegravir plus TDF/FTC arm.¹ None of these participants developed treatment-emergent resistance mutations. One non-CVW participant receiving dolutegravir plus lamivudine with reported non-adherence to treatment developed M184V and R263R/K resistance mutations before discontinuing the study.¹

Overall adverse event (AE) rates were similar between the study arms, with lower rates of drug-related AEs in participants receiving dolutegravir plus lamivudine compared with those receiving dolutegravir plus TDF/FTC (20% [146/716] vs 27% [192/717], respectively).¹ Four deaths occurred (3/716 for dolutegravir plus lamivudine vs 1/717 for dolutegravir plus TDF/FTC), all of which were considered unrelated to the study drug regimen.¹ The study findings showed potential for long-term bone and renal health outcomes, with post-baseline changes in markers of bone and renal function continuing to favour dolutegravir plus lamivudine compared to dolutegravir plus TDF/FTC through Week 144.¹

Important Safety Information for Dovato
The following safety information is based on the Highlights section of the Prescribing Information for Dovato. Please consult the full Prescribing Information for all the labeled safety information for Dovato.

WARNING: PATIENTS CO-INFECTED WITH HEPATITIS B VIRUS (HBV) AND HUMAN IMMUNODEFICIENCY VIRUS (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

DOSAGE AND ADMINISTRATION

• Prior to or when initiating Dovato, test patients for HBV infection.
• Pregnancy Testing: Perform pregnancy testing before initiation of Dovato in individuals of childbearing potential
• One tablet taken orally once daily with or without food
• The dolutegravir dose (50 mg) in Dovato is insufficient when coadministered with carbamazepine or rifampin. If Dovato is coadministered with carbamazepine or rifampin, take one tablet of Dovato once daily, followed by an additional dolutegravir 50-mg tablet, approximately 12 hours from the dose of Dovato

CONTRAINDICATIONS

• Prior hypersensitivity reaction to dolutegravir or lamivudine
• Coadministration with dofetilide

WARNINGS AND PRECAUTIONS

• Hypersensitivity reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury, have been reported with dolutegravir. Discontinue Dovato immediately if signs or symptoms of hypersensitivity reactions develop, as a delay in stopping treatment may result in a life-threatening reaction
• Hepatotoxicity has been reported in patients receiving a dolutegravir-containing regimen. Patients with underlying hepatitis B or C may be at increased risk for worsening or development of transaminase elevations with Dovato. Monitoring for hepatotoxicity is recommended
• Embryo-fetal toxicity may occur when used at the time of conception and in early pregnancy.  An alternative treatment to Dovato should be considered at the time of conception through the first trimester of pregnancy due to the risk of neural tube defects. Counsel individuals of childbearing potential to use effective contraception
• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues
• Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy

ADVERSE REACTIONS
The most common adverse reactions (all grades) observed in ≥2% (in those receiving Dovato) were headache, nausea, diarrhea, insomnia, fatigue, and anxiety.

DRUG INTERACTIONS

• Dovato is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended
• Refer to the full prescribing information for important drug interactions with Dovato

USE IN SPECIFIC POPULATIONS

• Pregnancy: An alternative treatment to Dovato should be considered at the time of conception through the first trimester due to the risk of neural tube defects
• Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission.
• Females and males of reproductive potential: Pregnancy testing and contraception are recommended in individuals of childbearing potential
• Renal Impairment: Dovato is not recommended in patients with creatinine clearance less than 50 mL/min
• Hepatic Impairment: Dovato is not recommended in patients with severe hepatic impairment (Child-Pugh Score C)

Please refer to the full European Summary of Product Characteristics for Dovato for full prescribing information, including contraindications, special warnings and precautions for use. For the US, please refer to the US Prescribing Information.