Dual Regimens in Trials Show Promise

The Power of Two
Dual regimens show promise in clinical trials
by Chael Needle

At the International AIDS Conference in Amsterdam last July, ViiV Healthcare shared its latest research with attendees. Part of the research focused on regimens that would reduce the medication burden and subsequent drug exposure for individuals living with HIV/AIDS and on lifelong treatment. Reducing the medication burden would potentially help adherence and a reduced drug exposure might mitigate the impact of side effects.

First, promising data emerged from the GEMINI 1 and 2 Phase 3 clinical trials, which were designed to assess the safety and efficacy of a two-drug regimen of dolutegravir (an integrase inhibitor) and lamivudine (an NRTI) compared to a three-drug regimen of dolutegravir and two nucleoside reverse transcriptase inhibitors, tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), in treatment naïve HIV-1 infected adults with baseline viral loads less than 500,000 copies per ml.

Primary endpoint results at forty-eight weeks showed the two-drug regimen’s non-inferiority compared to the three-drug regimen. So, efficacy was found to be similar, and no resistance emerged. In addition, the safety profile for the two-drug regimen was consistent with its components’ product labelling; both regimens were well tolerated. Fewer side effects, including kidney and bone problems, were found in the two-drug combo.

GEMINI principal investigator Pedro Cahn, Fundación Huésped, Buenos Aires, Argentina, shared the overall conclusion that the two-drug regimen was an effective option for HIV-1 treatment. In a prepared statement, he said: “For the last fifteen to twenty years, the standard of care for HIV has revolved around three-drug regimens. Now that we have more potent drugs, the focus is shifting to tolerability and convenience. The GEMINI studies show that we can get the efficacy of three drugs in a two-drug regimen with the tolerability and drug interaction profile of DTG and 3TC. These are important findings for people living with HIV who will spend their lifetime taking drugs to suppress their virus. The studies have the potential to expand the treatment paradigm for first-line therapy of people living with HIV.”

Researchers working on another set of two-drug regimen studies, SWORD 1 and 2, whose earlier results already helped lead to approval of the combination of dolutegravir (ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer Inc. and Shionogi Limited as shareholders) and the NNRTI rilpivirine (Janssen Sciences Ireland UC, part of the Janssen Pharmaceutical Companies of Johnson & Johnson.) under the brand name Juluca, offered 100-week Phase 3 results. The studies are evaluating the safety and efficacy of switching virologically-suppressed people living with HIV who have successfully suppressed their virus from a three or four-drug antiretroviral regimen to a two-drug regimen of dolutegravir and rilpivirine.

Data culled from both the SWORD 1 and SWORD 2 studies showed that eighty-nine percent of participants on the two-drug regimen of dolutegravir and rilpivirine for 100 weeks were able to maintain viral suppression, with a viral load of less than 50 copies/mL.

No new safety findings were added in the second year of the study. Thirty-four participants withdrew because of adverse events through week 100.

Researchers observed a low rate of snapshot virologic non-response, with six participants meeting the confirmed virologic withdrawal criterion.

In the “late switch” arm (participants were not switched to the two-drug regimen until week 52), ninety-three percent of participants maintained viral suppression through week 100. While two participants met the confirmed virologic withdrawal criterion, the safety profile of the late switch group was comparable to the early switch group. Thirty participants experienced serious adverse events and fifteen participants experienced adverse events that resulted in withdrawing from the study.

In a prepared statement, John C. Pottage, Jr., MD, Chief Scientific and Medical Officer, ViiV Healthcare, said, “As we progress further into a new era of HIV treatment, these 100-week data from the SWORD studies add to the growing evidence base for Juluca and two-drug regimens. The results confirm the ability of Juluca to maintain efficacy over a 100-week period and importantly support that the long-term safety profile of this regimen is consistent with the respective labels of the component medicines. This 100-week data should provide physicians with further confidence that they may be able to reduce the number of antiretroviral drugs required to effectively maintain virologic suppression in their patient’s HIV.”

The 148-week data for SWORD is expected in 2019.

Chael Needle is Managing Editor of A&U. Follow him on Twitter @ChaelNeedle.