Positive Results Demonstrated in Switch to 2-Drug Regimen for HIV-1 Infection

The TANGO study assessed whether adults maintained viral suppression for at least 6 months after switching to the the dolutegravir/lamivudine combination.

The phase 3 TANGO study evaluating a treatment switch for virally suppressed adults with HIV-1 infection has shown positive results.

Study results demonstrated noninferior efficacy for a 2-drug regimen of dolutegravir/lamivudine (Dovato, ViiV Healthcare) when patients were switched from a tenofovir alafenamide fumarate (TAF)-containing regimen of at least 3 drugs.1

ViiV Healthcare announced the results Wednesday by ViiV Healthcare at the 10th International AIDS Society Conference on HIV Science (IAS 2019) in Mexico City, Mexico.1

The study results offer evidence that the 2-drug dolutegravir/lamivudine regimen is as effective as the 3-drug, TAF-containing regimen,

according to Kimberly Smith, MD, head of global research and medical strategy at ViiV Healthcare.1

“With HIV now considered a chronic condition and people living with HIV needing antiretroviral treatments for life, taking fewer medications over a lifetime has become an important consideration for the community,” she said in a statement.1

The FDA approved ViiV Healthcare’s dolutegravir/lamivudine regimen in April, at which time the standard of care was a 3-drug regimen.

The agency's approval provided the option of a 2-drug regiment in a single tablet, thereby eliminating additional toxicity and potential interactions from a third drug, according to Debra Birnkrant, MD, director of the FDA’s Division of Antiviral Products.2

“Having a drug-sparing treatment available that uses fewer drugs is beneficial to patients who may have issues taking multiple medications over a long period of time,” she said in a statement.2

Prior to the FDA approval, the efficacy and safety of dolutegravir/lamivudine were demonstrated in 2 identical, randomized, double-blind, controlled clinical trials in 1433 HIV-infected adults with no prior antiretroviral treatment history, taking 1 tablet taken daily.2

The TANGO phase III, randomized, open-label, active-controlled, multicenter study assessed whether adults living with HIV-1 who had maintained viral suppression for at least 6 months on a TAF-containing regimen of at least 3 drugs, were able to maintain similar rates of viral suppression after switching to the dolutegravir/lamivudine regimen in a fixed-dose combination. The study compared to continuing the TAF-containing regimen and met its primary endpoint for noninferiority based on the proportion of participants with plasma HIV-1 RNA ≥50 copies per milliliter (c/mL) at week 48, based on the FDA snapshot algorithm.1

Results showed that switching to dolutegravir/lamivudine was noninferior to continuing a TAF-containing regimen at week 48 (snapshot virologic failure: <1% vs. <1%; adjusted difference: -0.3% [95% CI: -1.2, 0.7]).1

The proportion of participants with plasma HIV-1 RNA <50 c/mL was high and similar in both arms and demonstrated noninferiority (93.2% of participants in the dolutegravir/lamivudine arm compared with 93.0% in the TAF-containing regimen arm).1

During the TANGO study, the most common adverse effects were nasopharyngitis (12% versus 11%, respectively), upper respiratory tract infections (8% versus 9%, respectively), and diarrhea (8% versus 7%, respectively).1

Common adverse reactions with the dolutegravir/lamivudine also include fatigue, headaches, insomnia, and nausea. In addition, there is a known risk for neural tube defects in babies born to women being treated with dolutegravir.2

ViiV Healthcare’s labeling for the 2-drug regimen includes a boxed warning cautioning patients infected with both hepatitis B and HIV to add additional treatment for their hepatitis B or consider a different drug regimen. Patients with both hepatitis B and HIV who take products containing lamivudine have developed hepatitis B variants associated with resistance to the drug. These patients may have severe liver problems, including liver failure, when they stop taking drugs containing lamivudine.2

In addition to the TANGO study, Viiv Healthcare announced Wednesday at IAS 2019 positive results for a pair of phase 3 studies comparing the 2-drug dolutegravir/lamivudine regimen to a 3-drug regimen of dolutegravir plus 2 nucleoside reverse transcriptase inhibitors (NRTIs), tenofovir disoproxil fumarate/emtricitabine (TDF/FTC).

Week 96 results from the GEMINI 1 and GEMINI 2 studies showed that the dolutegravir/lamivudine regimen continued to offer noninferior efficacy with no cases of treatment emergent resistance in individuals with virologic failure, according to the company.3

About 1.1 million people in the United States are living with HIV, and about 15% of them are unaware that they are infected. Effective treatment is important in reducing the amount of virus in the blood.

A suppressed viral load in people living with HIV prevents disease progression and helps them live healthier, longer lives, according to the FDA.2

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References

  • ViiV Healthcare announces positive week 48 results in first study to evaluate treatment switch from TAF-containing regimen with three or more drugs to 2-drug regimen of dolutegravir/lamivudine for HIV-1 infection [news release]. London, UK; July 24, 2019: Viiv Healthcare. viivhealthcare.com/en-gb/media/press-releases/2019/july/viiv-healthcare-announces-positive-week-48-results-in-first-stud/. Accessed July 24, 2019.
  • FDA approves first two-drug complete regimen for HIV-infected patients who have never received antiretroviral treatment [news release]. Silver Spring, MD; April 8, 2019: FDA website. www.fda.gov/news-events/press-announcements/fda-approves-first-two-drug-complete-regimen-hiv-infected-patients-who-have-never-received. Accessed July 24, 2019.
  • ViiV Healthcare presents GEMINI 1 & 2 studies through week 96 showing 2-drug regimen of dolutegravir plus lamivudine continues to demonstrate high efficacy rates and no cases of treatment emergent resistance [news release]. London, UK; July 24, 2019: Viiv Healthcare. viivhealthcare.com/en-gb/media/press-releases/2019/july/viiv-healthcare-presents-gemini-1---2-studies-through-week-96-sh/. Accessed July 24, 2019.