A ROBUST TRIAL vs TAF-CONTAINING REGIMENS

VO:

INTRODUCTION
 

DOVATO dolutegravir 50 mg/lamivudine 300 mg tablets

 

Please see full Important Safety Information, including Boxed Warning, for DOVATO throughout this video.

 

Please see accompanying full Prescribing Information, including Boxed Warning, for DOVATO.

 

KIM NEZIANYA:

Hi there. I’m Kim Nezianya, a Medical Science Liaison in the South Texas region. I’d like to introduce my co-presenter for this video, Dr Martinez.

 

DR MARTINEZ:

Hi, I’m Dr Dora Martinez, Regional Medical Director at ViiV Healthcare. I work with and advocate for underserved people living with HIV. I am passionate about helping these populations, and my experience with my patients gives me added perspective. I’m excited to bring that perspective into today’s conversation as I share the 196-week long-term data for DOVATO from the TANGO trial.

 

KIM NEZIANYA:

Thanks, Dr Martinez. I’m excited to have you walk through these long-term results for today. Let’s get right into it.

 

DR MARTINEZ:

Today, we’ll review the TANGO study design and baseline characteristics, efficacy, resistance, and drug-related adverse events. Before we get started, let’s review the Indication and Important Safety Information for DOVATO.

 

VO:

INDICATION

DOVATO is indicated as a complete regimen to treat HIV-1 infection in adults with no antiretroviral treatment history or to replace a regimen in those who are virologically suppressed on a stable regimen with no history of treatment failure or known resistance to the components of DOVATO.

 

IMPORTANT SAFETY INFORMATION

DOVATO contains a Boxed Warning for patients who are co-infected with hepatitis B virus. All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating DOVATO. Emergence of HBV resistance has been reported with lamivudine-containing regimens. If DOVATO is used in patients with HBV co-infection, additional treatment should be considered for the appropriate treatment of chronic HBV, or use an alternative regimen. Additionally, if you are using DOVATO in an HBV co-infected patient and discontinue treatment, severe acute exacerbation of their hepatitis B may occur. Closely monitor hepatic function.

 

Contraindications

DOVATO is contraindicated in patients who have had a prior hypersensitivity reaction to dolutegravir or lamivudine or in patients who are receiving dofetilide.

 

Additional Important Safety Information for DOVATO will be presented later in this video.

 

Please see accompanying full Prescribing Information, including Boxed Warning, for DOVATO.

 

KIM NEZIANYA:

So, Dr Martinez, can you give us a quick refresher on the TANGO study and how it was set up?

 

DR MARTINEZ: 

Sure. TANGO evaluated the efficacy and safety of a switch to DOVATO in virologically suppressed adults versus remaining on a tenofovir alafenamide (TAF)-containing regimen.

 

DR MARTINEZ:

This is a Phase 3, randomized, multicenter, noninferiority switch study with 741 patients combined. Today, we will be discussing the data through 196 weeks. The primary endpoint was the proportion of patients with HIV-1 RNA ≥50 copies/mL at Week 48, using the FDA Snapshot analysis with a 4% noninferiority margin. Proportion of patients with HIV-1 RNA <50 copies/mL at Weeks 48, 96, and 144 were prespecified secondary endpoints. Week 196 was an exploratory endpoint. At Week 148, patients in the TAF-containing regimen cohort switched to DOVATO if their HIV-1 RNA was <50 copies/mL.

 

The initial TAF-containing regimens included TAF and emtricitabine plus a third agent. 79.6%, or 296 patients, included an INSTI in their initial regimen; 66%, or 249 patients, were on boosted elvitegravir with cobicistat; 12.9%, or 48 patients, included an NNRTI; 10%, or 41 patients, were on a dolutegravir-based regimen; and 7.5%, or 28 patients, included a PI.

 

DR MARTINEZ:

Baseline characteristics were similar between the 2 arms. 

 

Additionally, 39% of trial participants had no documented historical genotype at baseline.

 

KIM NEZIANYA:

Now, the main focus of TANGO was to see how DOVATO performed versus TAF-containing regimens. And the primary endpoint for this study was the proportion of patients with HIV-1 RNA ≥50 copies/mL at 48 weeks.

 

DR MARTINEZ:

That’s right. At 48 weeks, DOVATO demonstrated noninferiority with no increased rate of Snapshot virologic failure versus those who remained on TAF-containing regimens, with <1% of patients having HIV-1 RNA ≥50 copies/mL across both treatment arms at 48 weeks. At 96 weeks, DOVATO also demonstrated noninferiority with <1% of patients in the DOVATO arm and 1% of patients in the TAF-containing regimens arm having a viral load of ≥50 copies/mL.

 

KIM NEZIANYA:

So, what about from Week 96 to Week 144? Did we see similar results for DOVATO versus TAF-containing regimens?

 

DR MARTINEZ:

Efficacy results at 144 weeks were consistent, showing noninferiority with <1% of patients in the DOVATO arm and 1% of patients in the TAF-containing regimens arm having HIV-1 RNA ≥50 copies/mL.

 

DOVATO also demonstrated maintenance of virologic suppression versus TAF-containing regimens, with 86% and 82% suppression for the DOVATO arm and TAF-containing regimens arm, respectively.

 

KIM NEZIANYA:

At Week 196, what results did we see for DOVATO in the exploratory endpoints?

 

DR MARTINEZ:

Results at 196 weeks showed that DOVATO late-switch patients had similar outcomes to those of early-switch patients at Week 48. 0% of late-switch patients and <1% of early-switch patients had HIV-1 RNA ≥50 copies/mL.

 

DOVATO demonstrated the same rate of virologic suppression between early-switch patients and late-switch patients, with 93% suppression for both cohorts. DOVATO also maintained durable virologic suppression through 196 weeks in early-switch patients.

 

KIM NEZIANYA:

Thanks, Dr Martinez. Efficacy is such an important piece of the story, but we also know that resistance is a key focus for healthcare providers. What did that look like at Week 196?

 

DR MARTINEZ:

Through 196 weeks, there were 0 cases of treatment-emergent resistance.

 

Resistance was evaluated in patients with confirmed virologic withdrawal, which was defined as one assessment with viral load ≥200 copies/mL immediately after a viral load ≥50 copies/mL.

 

One patient met confirmed virologic withdrawal at Week 196, and they were not found to have any treatment-emergent resistance.

 

KIM NEZIANYA:

This is all great information to have. Tolerability is also something else that’s at top of mind for both doctors and their patients. What can you tell us about drug-related adverse events through 144 and 196 weeks?

 

DR MARTINEZ: 

Drug-related adverse events remained consistent with the comparator through 144 weeks.

 

The most common drug-related adverse events, Grades 2 to 5, occurring in ≥0.5% of patients receiving DOVATO were insomnia (1%), depression (<1%), constipation (<1%), weight increased (<1%), and flatulence (<1%).

 

Through Week 196, the most common drug-related adverse events for late-switch DOVATO patients were diarrhea (2%), headache (2%), and insomnia (1%).

 

This brings us to the end of the TANGO 196-week data review. As I summarize, I’d like you to think about the results we walked through today and consider which patients in your practice could benefit from a switch to DOVATO.

 

Let’s go over some key takeaways.

 

Based on 196-week results from the TANGO trial, DOVATO demonstrated powerful, durable efficacy—it was as effective as TAF-containing regimens at 144 weeks—and a high barrier to resistance, based on 0 cases of treatment-emergent resistance through 196 weeks.

 

Think beyond suppression, and consider a regimen with fewer medicines for your patients.

 

KIM NEZIANYA:

Dr Martinez, thank you so much for walking us through the TANGO 196-week results.

 

DR MARTINEZ:

It was my pleasure. It was great to have you here along the way, Kim.

 

To our viewers, I hope you enjoyed this presentation of the TANGO data for DOVATO. For more information on DOVATO for virologically suppressed patients, visit dovatohcp.com. Please continue watching for some additional Important Safety Information.

 

VO:

Warnings and precautions

Hypersensitivity Reactions:

Hypersensitivity reactions have been reported in persons taking dolutegravir-based regimens and were characterized by the symptoms shown here. Discontinue DOVATO immediately if a severe skin or hypersensitivity reaction develops, as a delay may result in a life-threatening reaction. Monitor and appropriately treat the patient.

 

Hepatotoxicity:

Hepatic adverse events, including hepatotoxicity, have been reported in patients taking dolutegravir-based regimens in persons with and without preexisting hepatic disease. Patients with hepatitis B or C co-infection or who have had a history of elevations in their LFTs may be at increased risk of worsening of their liver function. In some cases, increases in LFTs was consistent with IRS or HBV reactivation. Patients should be monitored for hepatotoxicity.

 

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.

 

Lactic Acidosis and Severe Hepatomegaly With Steatosis:

Discontinue DOVATO if laboratory findings suggest lactic acidosis or severe hepatomegaly, including hepatomegaly with steatosis in the absence of marked transaminase elevations.

 

Adverse Reactions or Loss of Virologic Response Due to Drug Interactions with concomitant use of DOVATO may occur.

 

Immune Reconstitution Syndrome, including autoimmune disorders, has been reported with DOVATO.

 

Adverse reactions

The most common adverse reactions reported with DOVATO include headache, nausea, diarrhea, insomnia, fatigue, and anxiety.

 

Drug interactions

Please consult the full Prescribing Information for more information on potentially significant drug interactions. 

 

DOVATO is indicated as a complete regimen. Coadministration with other ARVs for the treatment of HIV-1 is not recommended. Drugs that induce or inhibit CYP3A or UGT1A1 may affect levels of dolutegravir.

 

DOVATO should be administered 2 hours before or 6 hours after polyvalent cations such as antacids, laxatives, and sucralfate.

 

Alternatively, DOVATO and supplements containing calcium or iron can be taken concomitantly if taken with food.

 

Use in specific populations

Pregnancy: There are insufficient data on the use of DOVATO during pregnancy to assess the risk for birth defects and miscarriage.

 

Advise individuals of childbearing potential of the potential risk of neural tube defects.

 

Lactation: It is not recommended breastfeed if you are HIV positive while taking DOVATO.

 

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.

 

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.

 

Hepatic Impairment: DOVATO is not recommended in patients with severe hepatic impairment.

 

Please visit dovatohcp.com to view the full Prescribing Information, including Boxed Warning, for DOVATO.