HIV InfectionsNCT00023218
Effect of a Change in HIV Therapy on Liver Steatosis, Inflammation, and Fibrosis
A study testing Lopinavir/Ritonavir and Efavirenz in people with HIV Infections and Hepatitis C, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.
Trial summary
The purpose of this study is to look at how 2 different anti-HIV drug treatments affect the liver. The use of anti-HIV drugs like the nucleoside reverse transcriptase inhibitors (NRTIs) may be linked to liver problems like fatty changes, scarring, abnormal liver function tests (LFTs), and lactic acidemia (an increase… Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- HIV Infections, Hepatitis C
- What is being tested?
- Lopinavir/Ritonavir and Efavirenz
- How many people
- 0 participants
- Where
- 3 sitesUnited States
- Study dates
- Start not givento not given
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients may be eligible for this study if they:
- Have a higher than normal level of lactic acid and liver enzymes in blood within 45 days prior to study entry.
- Are HIV infected.
- Have been receiving an anti-HIV drug combination containing an NRTI for more than 12 months continuously before entering the study.
- Have an HIV viral load (amount of HIV in the blood) of less than 200 copies/ml within 70 days prior to study entry.
- Have a negative pregnancy test within 45 days prior to study entry.
- Agree to use 2 approved methods of birth control while participating in sexual activity that could lead to pregnancy, while receiving study medications and for 6 weeks after stopping the medications, both men and women and their partners, if able to have children.
- Are at least 13 years of age.
Who cannot join
- Patients will not be eligible for this study if they:
- Have hepatitis B according to certain lab tests.
- Have known causes for liver disease other than HCV or anti-HIV therapy.
- Regularly and excessively use alcohol.
- Are unwilling to restrict alcohol use to the amount allowed during the study.
- Have untreated endocrine disease such as diabetes and Cushing's disease. Diabetes that is under good control, stable hypothyroidism on replacement therapy, and stable hypogonadism on replacement therapy will be allowed.
Show all 23Show fewer
- Receive prednisone within 1 month of study entry or high levels of prednisone (greater than 10 mg/day) within 90 days of study entry.
- Have had poorly controlled congestive heart failure within the last 12 months.
- Have signs and symptoms of abnormal liver function.
- Are unwilling to have a liver biopsy.
- Have a swollen abdomen due to accumulated fluid.
- Are suspected of having liver cancer.
- Are pregnant and breast-feeding.
- Abuse drugs.
- Have a serious illness within 14 days prior to entry.
- Have an AIDS-related (opportunistic) infection or illness at the time of study entry.
- Have HIV resistance to certain anti-HIV drugs.
- Have a history of failing treatment with PI-containing drugs (not due to side effects of the drug).
- Have previously received NNRTI medications (except for current drug combination that is successful).
- Have used certain drugs within 30 days prior to study entry.
- Are allergic to any of the study drugs.
- Are receiving or may need to receive treatment for hepatitis C during the study.
- Have previously enrolled in A5116.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Univ of Hawaii
Honolulu, Hawaii, 96816
Beth Israel Med Ctr
New York, New York, 10003
Tripler Army Med Ctr
Tripler AMC, Hawaii, 96859
About this study
Official title: Effect of Change to a Nucleoside Reverse Transcriptase Inhibitor (NRTI)-Sparing Regimen of Efavirenz (EFV) and Lopinavir/Ritonavir (LPV/r) on Liver Histology in HIV-1-Infected Individuals With Lactic Acidemia and Persistent Alanine Aminotransferase (ALT) Elevations on NRTI-Containing Antiretroviral Therapy
The purpose of this study is to look at how 2 different anti-HIV drug treatments affect the liver.
The use of anti-HIV drugs like the nucleoside reverse transcriptase inhibitors (NRTIs) may be linked to liver problems like fatty changes, scarring, abnormal liver function tests (LFTs), and lactic acidemia (an increase in lactic acid in the blood). Increased liver enzymes may mean liver damage. The way that the liver changes in people with abnormal LFTs and lactic acidemia is not completely understood.
Read the detailed description
This study provides a unique opportunity to prospectively assess the relationship of lactic acidemia with liver dysfunction and to determine whether lactic acidemia and liver dysfunction are likely to be secondary to NRTI-induced mitochondrial toxicity. If lactic acidemia and hepatic fatty infiltration (steatosis) in this study population are secondary to NRTI-induced mitochondrial toxicity, withdrawal of NRTI medications can be expected to result in partial improvement or resolution of these findings. Furthermore, this study will examine the possible additive ill effects of NRTI-induced mitochondrial toxicity on liver function in individuals coinfected with hepatitis C.
This study is designed both as a stand-alone ACTG protocol providing an NRTI-sparing regimen and as a study coenrollable simultaneously with A5116.
Patients enrolling in A5133 as a stand-alone study: Patients on NRTI-containing regimens with elevated lactates and ALTs are enrolled into a single open-label NRTI-sparing treatment regimen of efavirenz (EFV) plus lopinavir/ritonavir (LPV/r), which are provided by the study. These patients follow virologic failure/toxicity management guidelines as detailed in the protocol.
Patients coenrolling in A5116: Patients are studied on their assigned A5116 antiretroviral regimens with medication as provided by A5116. Those randomized in A5116 to the NRTI-sparing regimen of EFV and LPV/r identical to that offered by A5133 will be assessed together with patients who entered A5133 as a stand-alone study. Individuals assigned in A5116 to the continued NRTI arm of 2NRTIs plus EFV are enrolled into a separate observational arm of A5133. The impact of continued NRTI therapy on liver histology is assessed in this observational arm. Virologic failure/toxicity management is in accordance with the A5116 protocol. The definition of virologic failure in A5116 is identical to the definition used in A5133.
Arm 1 consists of patients assigned to an NRTI-sparing regimen without evidence of HCV coinfection.
Arm 2 consists of patients assigned to an NRTI-sparing regimen with evidence of HCV coinfection.
Arm 3 consists of patients coenrolled in the NRTI-containing arm of A5116 with or without evidence of HCV coinfection.
All patients are evaluated for safety and for virologic and immunologic responses. In addition, individuals undergo liver biopsy and upper abdominal CT scans within 30 days prior to entry and within 30 days prior to week 24. The biopsied tissue is reviewed for evidence of fatty infiltration, inflammation, and fibrosis. The CT scans are assessed for degree of fatty infiltration. If sufficient liver tissue is available, the biopsied tissue will be assessed for other parameters. Plasma, PBMCs, and sera are collected to explore the role of oxidative stress and other parameters in the development of hepatic fatty infiltration (steatosis) and hyperlactatemia. The effect of changes in liver fatty infiltration and plasma lactate on lipoproteins will be explored. Finally, PBMC mtDNA content will be correlated with liver mtDNA content.
- Conditions
- HIV Infections, Hepatitis C
- Being tested
- Lopinavir/Ritonavir, Efavirenz
- Keywords
- Liver, HIV-1, HIV Protease Inhibitors, Ritonavir, Biopsy, Reverse Transcriptase Inhibitors, Anti-HIV Agents, ABT 378, Acidosis, Lactic, efavirenz, Alanine Transaminase
- Medical subject headings
- HIV Infections, Hepatitis C, Acidosis, Lactic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lopinavir/RitonavirDrug
EfavirenzDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Cecilia Shikuma, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00023218
- Sponsor's protocol ID
- ACTG A5133
- Other IDs
- AACTG A5133
- Status last verified
- Jun 2003
- First submitted
- 29 Aug 2001
- Last updated
- 9 Mar 2015
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Change to a Nucleoside Reverse Transcriptase Inhibitor (NRTI)-Sparing Regimen of Efavirenz (EFV) and Lopinavir/Ritonavir (LPV/r) on Liver Histology in HIV-1-Infected Individuals With Lactic Acidemia and Persistent Alanine Aminotransferase (ALT) Elevations on NRTI-Containing Antiretroviral Therapy
- ClinicalTrials.gov ID
- NCT00023218
- Acronym / sponsor ID
- ACTG A5133
- Conditions
- HIV Infections, Hepatitis C
- Keywords
- Liver, HIV-1, HIV Protease Inhibitors, Ritonavir, Biopsy, Reverse Transcriptase Inhibitors, Anti-HIV Agents, ABT 378
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- First posted
- 31 Aug 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to look at how 2 different anti-HIV drug treatments affect the liver.
The use of anti-HIV drugs like the nucleoside reverse transcriptase inhibitors (NRTIs) may be linked to liver problems like fatty changes, scarring, abnormal liver function tests (LFTs), and lactic acidemia (an increase in lactic acid in the blood). Increased liver enzymes may mean liver damage. The way that the liver changes in people with abnormal LFTs and lactic acidemia is not completely understood.
Detailed description
This study provides a unique opportunity to prospectively assess the relationship of lactic acidemia with liver dysfunction and to determine whether lactic acidemia and liver dysfunction are likely to be secondary to NRTI-induced mitochondrial toxicity. If lactic acidemia and hepatic fatty infiltration (steatosis) in this study population are secondary to NRTI-induced mitochondrial toxicity, withdrawal of NRTI medications can be expected to result in partial improvement or resolution of these findings. Furthermore, this study will examine the possible additive ill effects of NRTI-induced mitochondrial toxicity on liver function in individuals coinfected with hepatitis C.
This study is designed both as a stand-alone ACTG protocol providing an NRTI-sparing regimen and as a study coenrollable simultaneously with A5116.
Patients enrolling in A5133 as a stand-alone study: Patients on NRTI-containing regimens with elevated lactates and ALTs are enrolled into a single open-label NRTI-sparing treatment regimen of efavirenz (EFV) plus lopinavir/ritonavir (LPV/r), which are provided by the study. These patients follow virologic failure/toxicity management guidelines as detailed in the protocol.
Patients coenrolling in A5116: Patients are studied on their assigned A5116 antiretroviral regimens with medication as provided by A5116. Those randomized in A5116 to the NRTI-sparing regimen of EFV and LPV/r identical to that offered by A5133 will be assessed together with patients who entered A5133 as a stand-alone study. Individuals assigned in A5116 to the continued NRTI arm of 2NRTIs plus EFV are enrolled into a separate observational arm of A5133. The impact of continued NRTI therapy on liver histology is assessed in this observational arm. Virologic failure/toxicity management is in accordance with the A5116 protocol. The definition of virologic failure in A5116 is identical to the definition used in A5133.
Arm 1 consists of patients assigned to an NRTI-sparing regimen without evidence of HCV coinfection.
Arm 2 consists of patients assigned to an NRTI-sparing regimen with evidence of HCV coinfection.
Arm 3 consists of patients coenrolled in the NRTI-containing arm of A5116 with or without evidence of HCV coinfection.
All patients are evaluated for safety and for virologic and immunologic responses. In addition, individuals undergo liver biopsy and upper abdominal CT scans within 30 days prior to entry and within 30 days prior to week 24. The biopsied tissue is reviewed for evidence of fatty infiltration, inflammation, and fibrosis. The CT scans are assessed for degree of fatty infiltration. If sufficient liver tissue is available, the biopsied tissue will be assessed for other parameters. Plasma, PBMCs, and sera are collected to explore the role of oxidative stress and other parameters in the development of hepatic fatty infiltration (steatosis) and hyperlactatemia. The effect of changes in liver fatty infiltration and plasma lactate on lipoproteins will be explored. Finally, PBMC mtDNA content will be correlated with liver mtDNA content.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Have a higher than normal level of lactic acid and liver enzymes in blood within 45 days prior to study entry.
- Are HIV infected.
- Have been receiving an anti-HIV drug combination containing an NRTI for more than 12 months continuously before entering the study.
- Have an HIV viral load (amount of HIV in the blood) of less than 200 copies/ml within 70 days prior to study entry.
- Have a negative pregnancy test within 45 days prior to study entry.
Key exclusion criteria (23 listed)
- Have hepatitis B according to certain lab tests.
- Have known causes for liver disease other than HCV or anti-HIV therapy.
- Regularly and excessively use alcohol.
- Are unwilling to restrict alcohol use to the amount allowed during the study.
- Have untreated endocrine disease such as diabetes and Cushing's disease. Diabetes that is under good control, stable hypothyroidism on replacement therapy, and stable hypogonadism on replacement therapy will be allowed.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lopinavir/Ritonavir | Drug | – |
| Efavirenz | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cecilia Shikuma study chair
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lopinavir/Ritonavir and Efavirenz in people with HIV Infections and Hepatitis C, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 9 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2015.