Is Dolutegravir Alone Enough to Control HIV?

A potent antiretroviral medication -- the integrase inhibitor dolutegravir (Tivicay) -- may be able to suppress HIV when used with just one other well-tolerated drug, and may be able to keep viral load undetectable when used alone, according to studies presented at the 15th European AIDS Conference last month in Barcelona.

As people with HIV continue to face a lifetime of treatment, researchers have tried to find antiretroviral therapy (ART) regimens that are better tolerated, simpler, and easier to take. New options for people with strains of the virus that are drug-resistant and for those who cannot tolerate the side effects of commonly used regimens continue to be a priority.

Combination ART typically includes drugs that target more than one step of the HIV lifecycle, which helps prevent the virus from developing drug resistance (mutating in a way that makes it resistant to one or more HIV medications). Researchers have tried to simplify treatment by cutting down the number of drugs, but this has usually led to low effectiveness. While using a single powerful drug would reduce pill burden, cost, and possibly side effects, prior studies of protease inhibitor monotherapy were mostly disappointing.

But ViiV Healthcare's dolutegravir, which prevents HIV from integrating its genetic material into a host cell's chromosomes, is very potent -- suppressing viral load by an unprecedented 2.5 log in an early 10-day monotherapy study -- has a high barrier to resistance, and may have some unique properties that make it suitable for simplified treatment.

Dolutegravir + Lamivudine

Pedro Cahn, M.D., Ph.D. (Credit: Liz Highleyman)
Pedro Cahn, M.D., Ph.D.
Liz Highleyman

Pedro Cahn, M.D., Ph.D., from Fundación HUÉSPED in Buenos Aires presented results from the PADDLE study, which evaluated a two-drug regimen of dolutegravir plus lamivudine (Epivir) for first-time treatment.

Lamivudine is an inexpensive, well-tolerated nucleoside reverse transcriptase inhibitor (NRTI) with minimal side effects and no known drug interactions. However, it has a low barrier to resistance, which means it's more effective when used in combination with another class of HIV medication.

This pilot study enrolled 20 previously untreated people with low baseline viral load and no known NRTI resistance mutations. All but one were men and the median age was 34 years. At baseline the median CD4 count was approximately 400 cells/mm3 and the median viral load was just over 24,000 copies, though four participants had viral loads over 100,000 copies.

All participants were treated with 50 mg of dolutegravir plus 300 mg of lamivudine once-daily for 48 weeks. Viral load declined rapidly after starting treatment, falling by a median of 2.54 log by day 14. Everyone -- including the four people with baseline viral loads over 100,000 -- reduced their viral loads to under 400 copies after three weeks and under 50 copies after eight weeks onward. CD4 counts rose by approximately 200 cells/mm3. Treatment was well-tolerated with no serious adverse events or laboratory abnormalities.

This dual regimen could offer lower cost, reduced toxicity, and smaller pill burden, Cahn said. He added that follow-up in this study will continue through 96 weeks, and a larger randomized clinical trial is now in preparation.

Dolutegravir Monotherapy

Two other studies presented simplified treatment even further, using once-daily dolutegravir alone as maintenance therapy for people who achieved viral suppression on more complex regimens. Both trials enrolled heavily treatment-experienced patients, many of whom had extensive drug resistance or could not to take standard ART regimens for various reasons.

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