ViiV Healthcare’s Two Drug Regimen Shows Promising Results in HIV-1 Patients
By T. Chakraborty, Ph.D.
Around 38 million people worldwide live with Acquired Immunodeficiency Syndrome (AIDS), with approximately 1.7 million diagnosed last year. To date, there are no treatments against Human Immunodeficiency Virus (HIV), but various anti-retroviral therapies have been used to slow disease progression. One of the major challenges of long-term treatment is the development of resistance due to mutation in the viral genome. Hence, pharmaceutical companies have come up with combination therapies.
ViiV Healthcare, a specialist for HIV treatments, owned partly by GSK and Pfizer, announced the results from a long-term trial using their two-drug regimen (2DR) compared to the widely used three-drug approach.  Kimberly Smith, 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.” 
HIV is a retrovirus containing RNA as the genetic material. Once the virus injects it inside the host cell, it uses the reverse transcriptase enzyme to reverse transcribe the RNA and then integrates the resulting DNA into the host genome. Scientists have targeted different steps of this process to inhibit the viral transduction. Dovato is a combination of two drugs, namely, dolutegravir, an integrase inhibitor inhibiting the integration of the viral genome to the host genome, and lamivudine, a nucleoside reverse transcriptase inhibitor. 
GEMINI 1 & 2 Clinical Trials
GEMINI 1 and 2 are parallel, blinded, randomized, non-inferiority Phase III clinical trials that tested the efficacy of the two-drug regimen of dolutegravir plus lamivudine (Dovato) compared to a 3-drug regimen of dolutegravir plus TDF/FTC in HIV patients. This study’s primary endpoint was to analyze the proportion of patients with HIV-1 RNA plasma <50c/mL at Week 48 under both treatment regimens, while secondary endpoints included analyzing the proportion of patients with HIV-1 RNA plasma <50c/mL up to Week 144.
Of the 716 patients receiving the two-drug regimen, 584 patients (82%) showed an HIV-1 RNA plasma at less than 50c/mL as compared to 84% (599 out of 717) in the 3-drug regimen till week 144. This shows that over a period of 3 years, the two-drug regimen is comparable to the three-drug regimen. Further, only one patient developed resistance towards the two-drug regimen before discontinuing. This shows that this regimen is not susceptible to the development of treatment resistance over a period of 3 years. The most common adverse events being headache, nausea, diarrhea, insomnia, fatigue, and anxiety.
Pedro Cahn, the principal investigator for the GEMINI study, said, “These long-term data confirm that dolutegravir-based 2-drug regimens have a rightful place in the HIV treatment compendium. Dolutegravir plus lamivudine demonstrates long-term non-inferior efficacy compared to dolutegravir plus TDF/FTC with benefits beyond viral suppression. While overall adverse event rates were similar across the study arms, we saw fewer drug-related adverse events with dolutegravir plus lamivudine. Clinicians who wanted proof that a dolutegravir-based 2-drug-regimen works long-term in treatment-naïve adults with HIV now have evidence to show that it does.” 
The major competitor for Dovato will be Gilead Sciences’ blockbuster drug Biktarvy, which is a combination of three drugs. Compared to total revenue of $476 million from these drugs by Viiv Healthcare, Biktarvy generated a revenue of more than $3 billion in the first half of 2020. Though acceptance of the two drug-regimen is higher in Europe, it is still not widely accepted in the US. Considering this new data, it will be interesting to see if Viiv Healthcare’s Dovato can cut into Biktarvy’s revenue. 
Editor: Rajaneesh K. Gopinath, Ph.D.
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