Regimen Switch to Dolutegravir/Lamivudine Fixed Dose Combination From Current Antiretroviral Regimen in HIV-1 Infected and Virologically Suppressed Adults (SALSA)

NCT04021290 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 208090
• Study Type: interventional
• Target: 493
• Locations: 17 countries
• Sites: 119

Brief Summary

The aim of this study is to determine if virologically suppressed Human Immunodeficiency Virus (HIV) Type 1 infected adults on a current antiretroviral regimen (CAR) (including 2 nucleoside reverse transcriptase inhibitors \[NRTIs\] plus a third agent) remain suppressed upon switching to dolutegravir/lamivudine (DTG/3TC) fixed dose combination (FDC). The main objective of the study is to demonstrate the non-inferior antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 48 weeks in virologically suppressed adults living with HIV-1. The study will also evaluate information regarding the safety and health related quality of life. The study will include Screening Phase (up to 28 days), a Randomization Phase (up to Week 52) and a Continuation Phase (post Week 52). The Continuation Phase is not applicable for participants in Sweden and Denmark. Approximately 490 participants will be randomized in 1:1 ratio to receive DTG/3TC FDC once daily for up to 52 weeks or continue their CAR for 52 weeks. Participants in the DTG/3TC FDC arm who successfully complete up to 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in Continuation Phase.

Conditions

HIV Infections

Keywords

Current antiretroviral regimen (CAR); HIV-1; Long-term antiviral activity; Dolutegravir/lamivudine; Fixed dose combination

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) >=50 Copies/Milliliter (c/mL) as Per Food and Drug Administration (FDA) Snapshot Category at Week 48

  Number of participants with plasma HIV 1 RNA \>=50 c/mL were evaluated using FDA snapshot algorithm at Week 48 to demonstrate the non-inferior antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 48 weeks. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL ), along with study drug discontinuation status. Participants with plasma HIV 1 RNA \>=50 c/mL were termed as subjects with virologic failure. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.

  Week 48

Secondary Outcomes (26)

• Number of Participants With Plasma HIV-1 RNA <50 c/mL Using the FDA Snapshot Algorithm at Week 48

  Week 48

• Number of Participants With Plasma HIV-1 RNA >=50 c/mL as Per FDA Snapshot Category at Week 24

  Week 24

• Number of Participants With Plasma HIV-1 RNA <50 c/mL Using the FDA Snapshot Algorithm at Week 24

  Week 24

• Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count for Week 24

  Baseline (Day 1) and Week 24

• Change From Baseline in CD4+ Cell Count for Week 48

  Baseline (Day 1) and Week 48

Study Arms (2)

Participants receiving DTG/3TC FDC

EXPERIMENTAL

Eligible participants will be randomized to receive 50 milligrams (mg)/300 mg DTG/3TC FDC therapy from Day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.

Drug: DTG/3TC FDC

Participants receiving CAR

ACTIVE COMPARATOR

Eligible participants will continue to receive CAR from Day 1 up to 52 weeks.

Drug: CAR

Interventions

DTG/3TC FDC DRUG

DTG/3TC FDC will be available as white, oval, film-coated tablets at a unit dose strength of 50 mg/300 mg. Participants will take DTG/3TC once daily via oral route.

Participants receiving DTG/3TC FDC

CAR DRUG

Participants who are randomized to the CAR arm will continue to take the current treatment until Week 52. CAR will include 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.

Participants receiving CAR

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible participants must be able to understand and comply with protocol requirements, instructions, and restrictions; participant must be likely to complete the study as planned; participants should be considered appropriate candidates for participation in an investigative clinical trial with oral medication (example given \[e.g.\] no active problematic substance abuse, acute major organ disease, or potential long-term work assignments out of the country).
• Participant should be aged 18 years or older (or older, if required by local regulatory agencies), at the time of signing the informed consent.
• Participants living with HIV.
• Documented evidence of at least two plasma HIV-1 RNA measurements \<50 c/mL in the 12 months prior to Screening: one within the 6 to 12 month window, and one within 6 months prior to Screening.
• Plasma HIV-1 RNA \<50 c/mL at Screening.
• Participant must be on uninterrupted current regimen (either the initial or second Combination antiretroviral therapy \[cART\] regimen) for at least 3 months prior to Screening.
• i) Any prior switch, defined as a change of a single drug or multiple drugs simultaneously, must have occurred due to tolerability and/or safety concerns or access to medications, or convenience/simplification and must not have been done for suspected or established treatment failure. The following switches, if they are the only switches, would not be considered a change in regimen. a) A switch from a PI boosted with ritonavir (RTV) to the same PI boosted with cobicistat is allowed (and vice versa). b) A switch from 3TC to emtricitabine (FTC) (and vice versa). c) A switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) (and vice versa).
• ii) Acceptable stable cART regimens prior to Screening include 2 NRTIs plus a) INI (either the initial or second cART regimen) b) NNRTI (either the initial or second cART regimen) c) Boosted PI (or atazanavir \[ATV\] unboosted) (either the initial or second PI-based cART regimen).
• A male or female participant.
• Participant must be capable of giving signed informed consent.
• Participants enrolled in France must be affiliated to, or a beneficiary of, a social security category.

You may not qualify if:

• Women who are pregnant or breastfeeding or plan to become pregnant or breastfeed during the study.
• Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
• Participants with unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Participants with the evidence of Hepatitis B virus (HBV) infection based on the results of testing at Screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antigen antibody (anti-HBs) and HBV deoxyribonucleic acid (DNA) as follows: Participants positive for HBsAg are excluded; Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded. Participant's positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not excluded. Anti-HBc must be either total anti-HBc or anti-HBc immunoglobulin G (IgG), and not anti-HBc Immunoglobulin M (IgM). Participants with a documented history of chronic HBV and current undetectable HBV DNA while on a TAF/TDF regimen are excluded.
• Participants with anticipated need for any hepatitis C virus (HCV) therapy during the randomized phase of the study, or anticipated need for HCV therapy with a potential for adverse drug-drug interactions with DTG or 3TC.
• Participants with untreated syphilis infection (positive rapid plasma reagin \[RPR\] at Screening without clear documentation of treatment). Participants who are at least 7 days post completed treatment are eligible.
• Participants with history or presence of allergy intolerance to the study interventions or their components or drugs of their class.
• Participants with ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia.
• Participants who in the investigator's judgment, poses a significant suicidality risk.
• Participants with any pre-existing physical or mental condition which, in the opinion of the Investigator, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.
• Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the study interventions or render the participant unable to take oral medication.
• Use of any regimen consisting of single or dual ART (peri-partum treatment with single dose nevirapine is allowed).
• Participants with current use of stavudine, didanosine, or nelfinavir.
• Participants receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication.
• Participants receiving treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.

Sponsors & Collaborators

• ViiV Healthcare: lead
• GlaxoSmithKline: collaborator
• PPD Development, LP: collaborator

Study Sites (119)

GSK Investigational Site

Los Angeles, California, 90033, United States

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GSK Investigational Site

Newport Beach, California, 92663, United States

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GSK Investigational Site

San Francisco, California, 94110, United States

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GSK Investigational Site

New Haven, Connecticut, 06510, United States

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GSK Investigational Site

Washington D.C., District of Columbia, 20007, United States

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GSK Investigational Site

Washington D.C., District of Columbia, 20017, United States

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GSK Investigational Site

Pensacola, Florida, 32503, United States

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GSK Investigational Site

West Palm Beach, Florida, 33407, United States

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GSK Investigational Site

Atlanta, Georgia, 30309, United States

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GSK Investigational Site

Savannah, Georgia, 31401, United States

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GSK Investigational Site

Kansas City, Kansas, 66160, United States

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GSK Investigational Site

St Louis, Missouri, 63108, United States

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GSK Investigational Site

Hillsborough, New Jersey, 08844, United States

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GSK Investigational Site

Tulsa, Oklahoma, 74127, United States

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GSK Investigational Site

Morgantown, West Virginia, 26506, United States

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GSK Investigational Site

Milwaukee, Wisconsin, 53226, United States

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GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1425AWK, Argentina

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GSK Investigational Site

Ciudad de Buenos Aires, Buenos Aires, C1202ABB, Argentina

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GSK Investigational Site

Rosario, Santa Fe Province, S2000PBJ, Argentina

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Buenos Aires, 1405, Argentina

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GSK Investigational Site

Antwerp, 2000, Belgium

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GSK Investigational Site

Brussels, 1000, Belgium

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GSK Investigational Site

Ghent, 9000, Belgium

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GSK Investigational Site

Salvador, Estado de Bahia, 40110-060, Brazil

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GSK Investigational Site

Curitiba, Paraná, 80060-900, Brazil

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GSK Investigational Site

Campinas, São Paulo, 13015-080, Brazil

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GSK Investigational Site

Manaus, 69040-000, Brazil

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GSK Investigational Site

Rio de Janeiro, 21040-360, Brazil

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GSK Investigational Site

São Paulo, 01246-090, Brazil

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GSK Investigational Site

São Paulo, 04039-032, Brazil

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GSK Investigational Site

Vancouver, British Columbia, V6Z 2T1, Canada

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GSK Investigational Site

Winnipeg, Manitoba, R3A 1R9, Canada

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GSK Investigational Site

Ottawa, Ontario, K1H 8L6, Canada

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Toronto, Ontario, M5G 2N2, Canada

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Montreal, Quebec, H2L 4E9, Canada

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GSK Investigational Site

Montreal, Quebec, H4A 3J1, Canada

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GSK Investigational Site

Regina, Saskatchewan, S4P 0W5, Canada

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GSK Investigational Site

Guangzhou, Guangdong, 510060, China

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GSK Investigational Site

Beijing, 100015, China

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GSK Investigational Site

Beijing, 100069, China

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GSK Investigational Site

Chongqing, 400000, China

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GSK Investigational Site

Shanghai, 201508, China

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GSK Investigational Site

Aarhus, 8200, Denmark

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GSK Investigational Site

Copenhagen, DK-2100, Denmark

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GSK Investigational Site

Hvidovre, 2650, Denmark

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GSK Investigational Site

Odense C, 5000, Denmark

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GSK Investigational Site

Bobigny, 93000, France

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GSK Investigational Site

Bordeaux, 33075, France

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GSK Investigational Site

Nice, 6202, France

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GSK Investigational Site

Orléans, 45067, France

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GSK Investigational Site

Paris, 75010, France

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GSK Investigational Site

Paris, 75012, France

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GSK Investigational Site

Toulouse, 31059, France

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GSK Investigational Site

Tourcoing, 59208, France

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GSK Investigational Site

Munich, Bavaria, 80335, Germany

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München, Bavaria, 81675, Germany

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GSK Investigational Site

Frankfurt am Main, Hesse, 60596, Germany

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Bonn, North Rhine-Westphalia, 53105, Germany

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Cologne, North Rhine-Westphalia, 50668, Germany

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Cologne, North Rhine-Westphalia, 50674, Germany

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Essen, North Rhine-Westphalia, 45122, Germany

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Hamburg, 20146, Germany

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Hamburg, 20246, Germany

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GSK Investigational Site

München, 80336, Germany

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GSK Investigational Site

Modena, Emilia-Romagna, 41100, Italy

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GSK Investigational Site

Rome, Lazio, 00149, Italy

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GSK Investigational Site

Rome, Lazio, 00168, Italy

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GSK Investigational Site

Milan, Lombardy, 20127, Italy

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GSK Investigational Site

Milan, Lombardy, 20142, Italy

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GSK Investigational Site

Milan, Lombardy, 20157, Italy

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GSK Investigational Site

Pavia, Lombardy, 27100, Italy

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GSK Investigational Site

Bergamo, 24128, Italy

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GSK Investigational Site

Brescia, 25123, Italy

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GSK Investigational Site

Guadalajara, Jalisco, 44160, Mexico

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GSK Investigational Site

Guadalajara, Jalisco, 44280, Mexico

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GSK Investigational Site

Zapopan, Jalisco, 45170, Mexico

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Distrito Federal, 06470, Mexico

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GSK Investigational Site

Saint Petersburg, 196645, Russia

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GSK Investigational Site

Tolyatti, 445846, Russia

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GSK Investigational Site

Yekaterinburg, 620149, Russia

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GSK Investigational Site

Bloemfontein, 9301, South Africa

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GSK Investigational Site

Cape Town, 7505, South Africa

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GSK Investigational Site

Observatory, Cape Town, 7925, South Africa

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GSK Investigational Site

A Coruña, 15006, Spain

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GSK Investigational Site

Badalona, Barcelona, 8916, Spain

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GSK Investigational Site

Cadiz, 11009, Spain

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GSK Investigational Site

Granada, 18016, Spain

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GSK Investigational Site

Madrid, 28006, Spain

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GSK Investigational Site

Madrid, 28007, Spain

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GSK Investigational Site

Madrid, 28034, Spain

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GSK Investigational Site

Madrid, 28041, Spain

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GSK Investigational Site

Madrid, 28046, Spain

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GSK Investigational Site

Murcia, 30120, Spain

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GSK Investigational Site

Palma de Mallorca, 07198, Spain

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GSK Investigational Site

San Sebastián de los Reyes, 28702, Spain

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GSK Investigational Site

Santa Cruz de Tenerife, 38010, Spain

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GSK Investigational Site

Seville, 41013, Spain

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GSK Investigational Site

Valencia, 46014, Spain

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GSK Investigational Site

Gothenburg, SE-416 85, Sweden

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GSK Investigational Site

Malmo, SE-205 02, Sweden

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GSK Investigational Site

Stockholm, SE-118 83, Sweden

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GSK Investigational Site

Stockholm, SE-14186, Sweden

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GSK Investigational Site

Kaohsiumg, 81362, Taiwan

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GSK Investigational Site

Kaohsiung City, 807, Taiwan

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GSK Investigational Site

New Taipei City, 220, Taiwan

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GSK Investigational Site

Taichung, 404, Taiwan

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GSK Investigational Site

Taipei, 10016, Taiwan

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GSK Investigational Site

Taoyuan District, 330, Taiwan

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GSK Investigational Site

Leeds, Yorkshire, LS9 7TF, United Kingdom

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GSK Investigational Site

Birmingham, B9 5SS, United Kingdom

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GSK Investigational Site

Brighton, BN2 1ES, United Kingdom

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GSK Investigational Site

Bristol, BS10 5NB, United Kingdom

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GSK Investigational Site

Liverpool, L7 8XP, United Kingdom

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GSK Investigational Site

London, SW10 9TH, United Kingdom

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GSK Investigational Site

London, WC1E 6LB, United Kingdom

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GSK Investigational Site

Manchester, M13 0FH, United Kingdom

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GSK Investigational Site

Manchester, M8 5RB, United Kingdom

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GSK Investigational Site

Newcastle upon Tyne, NE7 7DN, United Kingdom

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GSK Investigational Site

Sheffield, S10 2JF, United Kingdom

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Related Publications (5)

• Llibre JM, Brites C, Cheng CY, Osiyemi O, Galera C, Hocqueloux L, Maggiolo F, Degen O, Taylor S, Blair E, Man C, Wynne B, Oyee J, Underwood M, Curtis L, Bontempo G, van Wyk J. Efficacy and Safety of Switching to the 2-Drug Regimen Dolutegravir/Lamivudine Versus Continuing a 3- or 4-Drug Regimen for Maintaining Virologic Suppression in Adults Living With Human Immunodeficiency Virus 1 (HIV-1): Week 48 Results From the Phase 3, Noninferiority SALSA Randomized Trial. Clin Infect Dis. 2023 Feb 18;76(4):720-729. doi: 10.1093/cid/ciac130.

  PMID: 35235656 BACKGROUND

• Kumar P, Clarke AE, Jonsson-Oldenbuttel C, Deltoro MG, Di Giambenedetto S, Brites C, Hocqueloux L, Lu PL, Oyee J, Oglesby A, Wynne B, Jones B, Evitt LA, Fox D, Kisare M, Priest J. Patient-Reported Outcomes After Switching to a 2-Drug Regimen of Fixed-Dose Combination Dolutegravir/Lamivudine: 48-Week Results from the SALSA Study. AIDS Behav. 2025 Jan;29(1):235-245. doi: 10.1007/s10461-024-04479-9. Epub 2024 Sep 3.

  PMID: 39225890 DERIVED

• Scholten S, Cahn P, Portilla J, Bisshop F, Hodder S, Ruane P, Kaplan R, Wynne BR, Man CY, Grove R, Wang R, Jones B, Ait-Khaled M, Kisare M, Okoli C. Dolutegravir/Lamivudine Efficacy and Safety Outcomes in People With HIV-1 With or Without Historical Resistance Results at Screening: 48-Week Pooled Analysis. Open Forum Infect Dis. 2024 Jul 1;11(7):ofae365. doi: 10.1093/ofid/ofae365. eCollection 2024 Jul.

  PMID: 39015350 DERIVED

• Walmsley S, Smith DE, Gorgolas M, Cahn PE, Lutz T, Lacombe K, Kumar PN, Wynne B, Grove R, Bontempo G, Moodley R, Okoli C, Kisare M, Jones B, Clark A, Ait-Khaled M. Efficacy and safety of switching to dolutegravir/lamivudine in virologically suppressed people with HIV-1 aged >/= 50 years: week 48 pooled results from the TANGO and SALSA studies. AIDS Res Ther. 2024 Mar 21;21(1):17. doi: 10.1186/s12981-024-00604-9.

  PMID: 38515183 DERIVED

• Masters MC, Cohn SE. Two-drug HIV regimens: more data still needed. Lancet HIV. 2021 Aug;8(8):e454-e455. doi: 10.1016/S2352-3018(21)00106-5. No abstract available.

  PMID: 34358493 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Automobiles

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Motor Vehicles; Transportation; Technology, Industry, and Agriculture

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a randomized study with parallel group assignment where participants will be randomized into one of the two treatment groups. Participants randomized to DTG/3TC FDC will receive DTG/3TC FDC up to Week 52. Participants randomized to CAR will continue to take their current regimen up to Week 52. Randomization will be stratified by Baseline third agent class (protease inhibitor \[PI\], integrase inhibitor \[INI\], or non-nucleoside reverse transcriptase inhibitor \[NNRTI\]).

Study Record Dates

• First Submitted: July 11, 2019
• First Posted: July 16, 2019
• Study Start: November 11, 2019
• Primary Completion: April 23, 2021
• Study Completion: September 9, 2022
• Last Updated: October 19, 2023
• Results First Posted: July 1, 2022

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

BR (7); BE (3); CA (7); CN (5); DK (4); RU (3); GB (11); ME (4); ZA (3); ES (15); FR (8); DE (10); TW (6); SE (4); IT (9); AR (4); US (16)