Perspective

2-drug HIV regimen maintains virologic suppression at 148 weeks

The first FDA-approved complete two-drug regimen for the treatment of HIV has demonstrated “durable” efficacy and tolerability, and participants have maintained virologic suppression through at least 148 weeks, according to results from the SWORD 1 and 2 studies.

The 3-year results from the SWORD trials were presented at the 25th Annual Conference of the British HIV Association.

The single-tablet regimen containing dolutegravir and rilpivirine, marketed as Juluca (ViiV Healthcare), was approved by the FDA in November 2017 to treat virologically suppressed adults who have been on a stable ART regimen for at least 6 months with no history of treatment failure.

According to a news release, of the 513 study participants who switched from a three- or four-drug ART regimen to dolutegravir/rilpivirine, 84% maintained viral suppression.

Trial participants who were randomly assigned to the “late switch” arm — in which they continued on their current ART regimen until week 52 before switching to the two-drug regimen — demonstrated “comparable virologic suppression, tolerability and resistance to that seen in the early switch group at week 100,” the release said.

According to the data, just 1% of patients who received the two-drug regimen experienced confirmed virologic withdrawals, 5% experienced drug-related grade 2 to 4 adverse events and 6% of patients discontinued the trial due to adverse events. Although no patients in either arm developed resistance to dolutegravir, six patients developed resistance to rilpivirine, according to the release. Bone biomarker improvements were reported in both study arms through week 148.

“With the SWORD data, we now have 3-year data showing the excellent effectiveness and tolerability of Juluca, the first approved dolutegravir-based two-drug regimen,” Chloe Orkin, MBBCh, clinical professor at Queen Mary University of London, said in the release. “Combined with the potential benefits of lowering the number of antiretroviral agents patients take, these data support the strategy of switching virologically suppressed, stable patients to the two-drug regimen of dolutegravir and rilpivirine.”

The regimen also has been approved in the European Union and other countries, and ViiV Healthcare said it has submitted regulatory marketing applications worldwide.

“The SWORD 1 and 2 studies are the first phase 3 HIV studies to show long-term data for switching from three-drug combination to an oral two-drug regimen, and the efficacy, tolerability and barrier to resistance out to 3 years demonstrated in the study provides further reassurance of the suitability of Juluca for many virologically suppressed adults living with HIV,” John C. Pottage, Jr., MD, chief scientific medical officer at ViiV Healthcare, said in the release.

Disclosures: Orkin reports numerous ties to industry. Pottage is employed by ViiV Healthcare.

The first FDA-approved complete two-drug regimen for the treatment of HIV has demonstrated “durable” efficacy and tolerability, and participants have maintained virologic suppression through at least 148 weeks, according to results from the SWORD 1 and 2 studies.

The 3-year results from the SWORD trials were presented at the 25th Annual Conference of the British HIV Association.

The single-tablet regimen containing dolutegravir and rilpivirine, marketed as Juluca (ViiV Healthcare), was approved by the FDA in November 2017 to treat virologically suppressed adults who have been on a stable ART regimen for at least 6 months with no history of treatment failure.

According to a news release, of the 513 study participants who switched from a three- or four-drug ART regimen to dolutegravir/rilpivirine, 84% maintained viral suppression.

Trial participants who were randomly assigned to the “late switch” arm — in which they continued on their current ART regimen until week 52 before switching to the two-drug regimen — demonstrated “comparable virologic suppression, tolerability and resistance to that seen in the early switch group at week 100,” the release said.

According to the data, just 1% of patients who received the two-drug regimen experienced confirmed virologic withdrawals, 5% experienced drug-related grade 2 to 4 adverse events and 6% of patients discontinued the trial due to adverse events. Although no patients in either arm developed resistance to dolutegravir, six patients developed resistance to rilpivirine, according to the release. Bone biomarker improvements were reported in both study arms through week 148.

“With the SWORD data, we now have 3-year data showing the excellent effectiveness and tolerability of Juluca, the first approved dolutegravir-based two-drug regimen,” Chloe Orkin, MBBCh, clinical professor at Queen Mary University of London, said in the release. “Combined with the potential benefits of lowering the number of antiretroviral agents patients take, these data support the strategy of switching virologically suppressed, stable patients to the two-drug regimen of dolutegravir and rilpivirine.”

The regimen also has been approved in the European Union and other countries, and ViiV Healthcare said it has submitted regulatory marketing applications worldwide.

“The SWORD 1 and 2 studies are the first phase 3 HIV studies to show long-term data for switching from three-drug combination to an oral two-drug regimen, and the efficacy, tolerability and barrier to resistance out to 3 years demonstrated in the study provides further reassurance of the suitability of Juluca for many virologically suppressed adults living with HIV,” John C. Pottage, Jr., MD, chief scientific medical officer at ViiV Healthcare, said in the release.

Disclosures: Orkin reports numerous ties to industry. Pottage is employed by ViiV Healthcare.

    Perspective
    Andrew Hill

    Andrew Hill

    In the SWORD 1 and 2 trials, there was no overall safety or efficacy benefit for patients who switched to dolutegravir plus rilpivirine compared with people who stay on their original treatment. There are cheaper generic alternatives to Juluca, such as generic tenofovir/emtricitabine (TDF/FTC) and low-cost generic protease inhibitors or non-nucleosides. It is not clear whether the high price of branded Juluca can be justified, because there is no clear evidence for efficacy or safety benefits.

    Dolutegravir is associated with weight gain and clinical obesity, according to recently reported independent clinical trials and cohort studies. This weight gain is progressive and could have adverse clinical consequences. However, the company ViiV, which developed dolutegravir, has not measured body weight in their 7,000-patient phase 3 trial program for dolutegravir, including the SWORD 1 and 2 trials. We need more information to assess this potential safety concern. This information will be available in July 2019 from more large independent clinical trials of dolutegravir, such as the ADVANCE and NAMSAL trials.

    • Andrew Hill, PhD
    • Senior research fellow, department of pharmacology
      University of Liverpool

    Disclosures: Hill reports serving as a consultant for WHO and the Clinton Foundation.