Raltegravir-based Antiretroviral Versus Maintaining Any Other Antiretroviral Therapy in HIV Mono-infected Patients

NCT02210715 | Completed Phase 4 DMC

• 1 other identifier: switchMerck
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

People infected with HIV are living longer thanks to the use of antiretroviral therapy (cART). In aging HIV persons, other factors are associated with early death. One of the major factors is liver disease, which can be due to liver infections or reasons such as fatty liver. Fatty liver in the general population is a serious problem, affecting 30% of Canadian population. A specific type of fatty liver characterized by much inflammation, named nonalcoholic steatohepatitis (NASH) can lead to cirrhosis and death. Persons living with HIV can be at increased risk of NASH because of toxic effect of certain types of cART on the liver, obesity and other metabolic factors (for example diabetes). Some scientific data suggest that newer cART are associated with less fatty liver and liver damage. However, NASH has not been studied in detail in persons living with HIV. One reason for the lack of research is one of the only ways to detect liver disease is to undergo liver biopsy which can be painful and has complications. Recently, a new non-invasive technology (Fibroscan) has been developed which can tell doctors how much a liver is damaged and how much fat it contains without pain or complications. Moreover, a simple test measuring a specific protein in the blood, the cytokeratin 18 (CK-18), can help the diagnosis of NASH. We will study the effect of switching cART to newer types of HIV medication in patients with a non-invasive diagnosis of NASH done by Fibroscan and cytokeratin 18. We expect that switching older cART to less hepatotoxic drugs will lead to improvement of liver damage, fatty liver and NASH diagnosed by Fibroscan and cytokeratin 18. To evaluate this approach we plan to recruit 58 consenting HIV mono infected patients with non-invasive diagnosis of NASH and/or fatty liver with liver damage. Participants will undergo Fibroscan, a blood test for cytokeratin 18, a complete physical examination and laboratory tests every 3 months for 12 months, then at 18 and 24 months. The effect of the switching of HIV medications will be recorded. We anticipate that the current study will provide evidence for reduction of inflammation and liver damage with newer cART for treatment of HIV infection.

Conditions

HIV; Fatty Liver; Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• improvement of fatty liver or liver fibrosis

  Difference in Fibroscan/CAP measurement from baseline to 24 months

  24 months

Secondary Outcomes (3)

• Difference in serum CK-18 levels

  24 months

• Difference in transaminases levels

  24 months

• Difference in metabolic markers

  24 months

Study Arms (2)

switch to Isentress

EXPERIMENTAL

28 subjects will be prescribed Raltegravir at the standard dose of 400 mg p.o. b.i.d. for 24 months.

Drug: Isentress.

Continue usual antiretroviral therapy

ACTIVE COMPARATOR

28 subjects will continue with their normal cART treatment, as prescribed by their treating physician.

Other: Continue usual antiretroviral therapy

Interventions

Isentress. DRUG

28 subjects will change from their normal cART treatment to Raltegravir, which will be given at the standard dose of 400 mg p.o. b.i.d. for 24 months.

Also known as: Raltegravir

switch to Isentress

Continue usual antiretroviral therapy OTHER

28 subjects will continue with their normal cART treatment, as prescribed by their treating physician.

Continue usual antiretroviral therapy

Eligibility Criteria

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

You may qualify if:

• years or older
• Confirmed positive serology for HIV mono-infection
• Valid Fibroscan/CAP results
• Able to provide informed consent (available in French or English)
• Receiving any approved antiretroviral regimen that does not contain integrase-inhibitor
• Evidence of fatty liver (CAP\>237.8dB/m) AND/OR evidence of significant liver fibrosis (Fibroscan \> 8KPa)
• HIV viral suppression (\<50 copies/mL) for at least 6 months
• No prior evidence of resistance to raltegravir or co-administered nucleoside backbone

You may not qualify if:

• Clinical evidence of decompensated liver disease at entry (e.g. ascites, bleeding esophageal varices, hepatic encephalopathy, or hepatoma/ hepatocellular carcinoma).
• Co-infection with hepatitis C virus (HCV) or hepatitis C virus (HBV) (presence of serum HCV-Ab or HBsAg);
• Alpha-fetoprotein (AFP) greater than or equal to 200 ng/mL at screening.
• Known or suspected Wilson's disease, alpha-1-antitrypsin deficiency, celiac disease or other cause of chronic liver disease.
• Chronic renal insufficiency (eGFR \< 20 mL/min) at screening.
• Pregnancy and planned pregnancy (not using adequate contraception).
• Women who are breastfeeding.
• Active opportunistic infection (except oral thrush) or neoplasm (except Kaposi's sarcoma, skin cancer, or cancer of the cervix or anus, unless known or suspected liver metastasis).

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

McGill University Health Center

Montreal, Quebec, Canada

Location

MeSH Terms

Conditions

Fatty Liver; Non-alcoholic Fatty Liver Disease

Interventions

Raltegravir Potassium

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Giada Sebastiani, MD

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Giada Sebastiani MD

Study Record Dates

• First Submitted: August 5, 2014
• First Posted: August 7, 2014
• Study Start: March 1, 2015
• Primary Completion: January 30, 2019
• Study Completion: January 30, 2023
• Last Updated: October 19, 2023

Record last verified: 2023-10

Locations

CA (1)