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

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.