Dolutegravir-Rilpivirine Effective for Maintaining HIV Suppression

By Will Boggs MD

January 22, 2018

NEW YORK (Reuters Health) - The recently approved combination of dolutegravir and rilpivirine is effective for maintaining virological suppression in adults with HIV-1, according to results from the SWORD-1 and SWORD-2 noninferiority studies.

"The most interesting and significant finding in SWORD was that the dolutegravir and rilpivirine regimen achieved noninferior viral suppression (viral load <50 copies/mL) at 48 weeks compared with a three- or four-drug regimen,” Dr. Lesley P. Kahl from ViiV Healthcare, Brentford, UK, told Reuters Health by email. “This happened in both the pooled and individual analyses of SWORD 1 and SWORD 2.”

Current treatment guidelines support a three-drug antiretroviral therapy (ART) regimen, but there has been growing support for two-drug regimens to minimize cumulative drug exposure and reduce risks for long-term drug-related toxicities. The primary concern has been whether two-drug regimens lead to treatment-emergent resistance and subsequent virological failure.

Dr. Kahl and colleagues evaluated the efficacy and safety of dolutegravir-rilpivirine compared with continuation of current ART for 48 weeks in 1,028 adults infected with HIV-1.

At the week 48 primary-endpoint analysis, 95% of patients in SWORD-1 and 94% of patients in SWORD-2 maintained viral suppression after switching to dolutegravir-rilpivirine, compared with 96% and 94%, respectively, who remained on their current ART, the researchers report in The Lancet, online January 5.

In the pooled analysis, 95% of participants in both treatment groups maintained viral loads lower than 50 copies/mL, thereby confirming the noninferiority of dolutegravir-rilpivirine.

Adverse events considered to be drug related and those leading to withdrawal from the study were more common among patients switching to dolutegravir-rilpivirine than among those continuing their current ART.

Switching to dolutegravir-rilpivirine had no effect on lipid levels or inflammatory or cardiovascular biomarkers.

Patients switching to dolutegravir-rilpivirine had greater improvements in HIV Treatment Satisfaction Questionnaire total score and Symptom Bother Score, compared with patients continuing their current ART.

“The results from these studies change our understanding of how HIV can be managed,” Dr. Kahl said. “For more than 20 years we thought that three or more drugs were required to maintain virologic suppression, but the SWORD studies provide compelling data that suppression can be maintained with a two-drug regimen of dolutegravir and rilpivirine.”

“This was reflected in updates made to clinical guidelines during 2017, which saw both the U.S. Department for Health and Human Services (DHHS, October 2017) and the European AIDS Society (EACS, October 2017) guidelines recommend a dolutegravir and rilpivirine regimen as a switch option for virologically suppressed patients,” she said.

Dr. Kahl added, “The U.S. FDA approved Juluca (dolutegravir and rilpivirine) on 21st November 2017, as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults who are virologically suppressed (HIV-1 RNA less than 50 copies/mL) on a stable antiretroviral regimen for at least six months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Juluca. Juluca is the smallest single-tablet regimen on the market.”

Dr. Mark A. Boyd from the University of Adelaide, Australia, who coauthored a linked editorial, told Reuters Health by email, "The old adage that ‘you need 3 drugs to control and maintain HIV replication’ is wrong. I think it is perfectly reasonable based on these results to offer people receiving standard triple therapy who have maintained an undetectable plasma viral load for >6 months to switch to the combination of dolutegravir-rilpivirine (DLT-RPV), assuming they fit the same study population criteria as in the SWORD studies.”

He added that it is “important that this study result isn’t seen as meaning that DTG+RPV can be used in people with viral replication - e.g., ART-naive people living with HIV (PLHIV) or people virologically failing their current ART regimen. More research is required in different PLHIV populations to reach that conclusion.”

“It’s also important that clinicians ensure that there has been no prior failure to agents that may confer cross resistance to either DTG or RPV (or that previous genotypic antiretroviral resistance test, GART, results don’t suggest baseline resistance to either of the 2 drugs),” Dr. Boyd said.

Dr. Jose M. Gatell from the University of Barcelona, Spain, who has also evaluated dolutegravir-based regimens but was not involved in the new work, said, "Maintenance treatment is a business for life, quite often for more than 20-40 years. So the lower the number of drugs, the better in terms of convenience, tolerance, and potential drug-drug interactions. Dolutegravir-rilpivirine (in a single pill) is an option. Cabotegravir-rilpivirine (both long-acting injections - once every 1 or 2 months) are being explored in ongoing trials. Dolutegravir-lamivudine (also in a single pill) may be the most attractive option in near future if ongoing trials are positive as expected.”

“Dual therapy is an option in virologically suppressed patients,” he told Reuters Health by email. “Besides virologically suppressed patients, dual therapy may also become an option in antiretroviral-naive patients.”

ViiV Healthcare and Janssen Pharmaceutica NV sponsored the studies, employed eight of the authors and had various relationships with several others and with Dr. Boyd. GSK employed one of the authors.

SOURCES: http://bit.ly/2Diu2Yq and http://bit.ly/2DSqZHz

Lancet 2018.

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