Changes in Liver Steatosis After Switching to Raltegravir in HIV/HCV Coinfection (STERAL)

Changes in Liver Steatosis After Switching From Efavirenz to Raltegravir Among HIV/HCV-Coinfected Patients Receiving Two Nucleoside Analogs Plus Efavirenz: The Steral Study

Primary Objective:

To compare the impact of switching from efavirenz (EFV) plus two nucleoside analogs to rategravir (RAL) plus two nucleoside analogs versus keeping the same antiretroviral regimen on hepatic steatosis (HS) as measured by the controlled attenuation parameter (CAP) among HIV/HCV-coinfected patient.

Secondary Trial Objective:

1. To compare the proportion of HIV/HCV-coinfected patients with one category decrease in the grade of HS between patients continuing with EFV plus two nucleoside analogs and those switching from EFV plus two nucleoside analogs to RAL plus two nucleoside analogs.
2. To evaluate the proportion of patients who maintain viral control (HIV RNA < 50 copies/mL) after switching.

Design:

Open-label, randomized clinical trial to evaluate safety (phase IV)

Condition:

HIV and HCV coinfection.

Intervention:

Patients on current EFV plus two nucleoside analogs will be randomly assigned to switch EFV to RAL (400mg BID), maintaining nucleoside analogs unchanged, or to continue the current regimen.

Study Overview

• Status: Completed
• Conditions: HIV Infection; HCV Coinfection
• Intervention / Treatment: Drug: Raltegravir; Drug: Efavirenz

Detailed Description

Primary Objective:

To compare the impact of switching from efavirenz (EFV) plus two nucleoside analogs to rategravir (RAL) plus two nucleoside analogs versus keeping the same antiretroviral regimen on hepatic steatosis (HS) as measured by the controlled attenuation parameter (CAP) among HIV/HCV-coinfected patient.

Secondary Trial Objective:

1. To compare the proportion of HIV/HCV-coinfected patients with one category decrease in the grade of HS between patients continuing with EFV plus two nucleoside analogs and those switching from EFV plus two nucleoside analogs to RAL plus two nucleoside analogs.
2. To evaluate the proportion of patients who maintain viral control (HIV RNA < 50 copies/mL) after switching.

Design:

Open-label, randomized clinical trial to evaluate safety (phase IV)

Condition:

HIV and HCV coinfection.

Intervention:

Patients on current EFV plus two nucleoside analogs will be randomly assigned to switch EFV to RAL (400mg BID), maintaining nucleoside analogs unchanged, or to continue the current regimen.

Study population and sample size HIV-infected patients with concomitant coinfection by HCV, as shown by detectable plasma HCV RNA, not candidates for therapy against HCV infection during the 48 week period of the Number of patients to recruit: 96, 48 patients per treatment group should be recruited.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Córdoba, Spain
    • Hospital Universitario Reina Sofia
  • Huelva, Spain
    • Hospital Infanta Elena
  • Jaen, Spain
    • Complejo Hospitalario de Jaén
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Málaga, Spain
    • Hospital Universitario Virgen de la Victoria
  • Málaga, Spain
    • Hospital Regional Universitario Carlos Haya
  • Sevilla, Spain
    • Hospital Universitario Virgen del Rocío
  • Seville, Spain, 41014
    • H.U. Valme
  • Cádiz
    • La Línea de la Concepción, Cádiz, Spain
      • Hospital La Línea

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Each subject must be willing and able to provide written informed consent for the trial.
2. Each subject must be ≥ 18 years of age.
3. Each subject must be male or non-pregnant, non-breastfeeding female
4. Each subject must have diagnosis of HIV infection.
5. Each subject must have concomitant coinfection by HCV as shown by detectable plasma HCV RNA.
6. Each subject must have stable treatment with EFV plus two nucleoside analogs for ≥24 weeks.
7. Each subject must have at least 2 documented plasma HIV RNA <50 copies/ml during the last 24 weeks, as observed in, at least, two clinical visits.
8. Each subject must have HS involving more than 10% of hepatocytes, as determined by a CAP measurement ≥238 dB/m.
9. Each sexually active female subject of child-bearing potential must agree to use a medically accepted method of contraception while receiving protocol-specified medication and for 3 months after stopping the medication.Medically accepted methods of contraception include condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed IUD, inert or copper-containing IUD, hormone releasing IUD, systemic hormonal contraceptive, and surgical sterilization (eg,hysterectomy or tubal ligation).Postmenopausal women are not required to use contraception.Postmenopausal is defined as at least 12 consecutive months without a spontaneous menstrual period.
10. Each sexually active male subject with a female partner(s) of child-bearing potential must also provide written informed consent to provide information regarding any pregnancy.
11. Average daily alcohol intake lower than 50 g for men and 40 g for women.

Exclusion Criteria:

1. The subject has an allergy/sensitivity to investigational product or its/their excipients.
2. The female subject is nursing.
3. The female subject is pregnant or intending to become pregnant.
4. History of ARV failure or documented resistance.
5. Baseline resistance to EFV or to any of the nucleoside analogues inhibitors in the regimen.
6. The subject has any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with the trial evaluations or optimal participation in the trial.
7. The subject has active AIDS-defining event (CDC-C) within 24 weeks before screening.
8. The subject is candidate for therapy against HCV infection during the 48 week trial period in the opinion of the investigator.
9. The subject has a history of malignant neoplasia.
10. Active illicit drug use or any other condition that may compromise the study drug adherence in the opinion of the investigators.
11. The subject has used any investigational drugs within 30 days of Baseline.
12. A subject who has participated in any other clinical trial within 30 days,inclusive, of signing the informed consent form of the current trial.
13. The subject or a family member is among the personnel of the investigational or SPONSOR staff directly involved with this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Raltegravir; Patients on current EFV plus two nucleoside analogs will be randomly assigned to switch EFV to RAL (400mg BID), maintaining nucleoside analogs unchanged, or to continue the current regimen.	Drug: Raltegravir; Patients on current EFV plus two nucleoside analogs will be randomly assigned to switch EFV to RAL (400mg BID), maintaining nucleoside analogs unchanged, or to continue the current regimen.; Other Names: Issentres
Active Comparator: Efavirenz; Patients on current EFV plus two nucleoside analogs will be randomly assigned to switch EFV to RAL (400mg BID), maintaining nucleoside analogs unchanged, or to continue the current regimen.	Drug: Efavirenz; Patients on current EFV plus two nucleoside analogs will be randomly assigned to switch EFV to RAL (400mg BID), maintaining nucleoside analogs unchanged, or to continue the current regimen.; Other Names: Sustiva

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To compare the impact of switching from EFV plus two nucleoside analogs to RAL plus two nucleoside analogs versus keeping the same antiretroviral regimen on HS as measured by CAP among HIV/HCV-coinfected patients.	48 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the proportion of patients who maintain viral control (HIV RNA < 50 copies/mL) after switching.	48 weeks

Collaborators and Investigators

• Sponsor: Juan Macías

Publications and helpful links

General Publications

• Macias J, Mancebo M, Merino D, Tellez F, Montes-Ramirez ML, Pulido F, Rivero-Juarez A, Raffo M, Perez-Perez M, Merchante N, Cotarelo M, Pineda JA; Spanish AIDS Research Network-HEP09 Study Group. Changes in Liver Steatosis After Switching From Efavirenz to Raltegravir Among Human Immunodeficiency Virus-Infected Patients With Nonalcoholic Fatty Liver Disease. Clin Infect Dis. 2017 Sep 15;65(6):1012-1019. doi: 10.1093/cid/cix467.

Helpful Links

• Abstract presented at CROI 2017. Poster available to download
• CROI webcast. THEMED DISCUSSION: OBESITY AND FATTY LIVER DISEASE

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2014
• Primary Completion (Actual): January 17, 2017
• Study Completion (Actual): January 17, 2017

Study Registration Dates

• First Submitted: July 12, 2013
• First Submitted That Met QC Criteria: July 15, 2013
• First Posted (Estimate): July 16, 2013

Study Record Updates

• Last Update Posted (Actual): July 25, 2017
• Last Update Submitted That Met QC Criteria: July 24, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Liver Diseases; Fatty Liver; Coinfection; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Integrase Inhibitors; Integrase Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Raltegravir Potassium; Efavirenz
• Other Study ID Numbers: STERAL/50410

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No