Acquired Immunodeficiency SyndromePhase 3NCT00966160
CD4 Cell Recovery in HIV-1 Patients Comparing 2 Treatment Regimes
A Phase 3 study testing Lopinavir/Ritonavir plus Lamivudine/Zidovudine and Efavirenz plus Lamivudine/Zidovudine in people with Acquired Immunodeficiency Syndrome and HIV Infections, run by University of Cologne at 1 site in Germany.
Trial summary
Therapy guidelines recommend the use of either the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz or a ritonavir-boostered protease inhibitor (PI) plus 2 nucleoside reverse transcriptase inhibitors (NRTI) as first-line treatment regimes of HIV-1 infection. Read more about this study
- Who is it for?
- Ages 20 to 60 years
- Conditions the study is for
- Acquired Immunodeficiency Syndrome, HIV Infections
- What is being tested?
- Lopinavir/Ritonavir plus Lamivudine/Zidovudine and Efavirenz plus Lamivudine/Zidovudine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 215 participants
- Where
- 1 siteGermany
- Study dates
- Jan 1999to Dec 2008
- Phase
- Phase 3
- 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 20 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Recent, non-acute HIV-1 infection
- Caucasians
- BMI between 17.5 and 30 kg/m2
- CD4 count <200 cells/µl
- Plasma viral load >100,000 HIV-1 RNA copies/ml
Who cannot join
- Actual or previous antiretroviral therapy
- Acute illness
- Coinfection with HBV or HCV
- Opportunistic infection (Pneumocystis jiroveci pneumonia, Toxoplasma gondii encephalitis, Mycobacterium ssp. infection, syphilis, cryptosporidiosis, cryptococcosis, aspergillosis, cytomegalovirus infection or progressive multifocal leukoencephalopathy)
- Hepatic or renal disorder
- Severe cardiovascular disease
Show all 16Show fewer
- Hematologic disorder
- Autoimmune disorder
- Diabetes mellitus or other severe endocrine disorder
- Malignancy
- Neurocognitive disorder
- Psychiatric disorder
- Drug or alcohol addiction
- Chronic drug use (except of blood pressure-lowering or lipid-lowering drugs or proton-pump inhibitors)
- Any acute medication within 7 days or vaccination within 30 days prior to entry
- Pregnancy or lactation
Trial locations and contacts
1 site in 1 country.
Germany1 site
Medical Clinic I and Department of Pharmacology, University of Cologne
Cologne
About this study
Official title: Phase 3, Single Center, Controlled, Investigator-blinded, Randomized Matched Pair Design Study of CD4 Cell Recovery in HIV-1 Patients With Sustained Virologic Response Comparing Protease Inhibitor and Non-nucleoside Reverse Transcriptase Inhibitor Based Treatment Regimes
Therapy guidelines recommend the use of either the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz or a ritonavir-boostered protease inhibitor (PI) plus 2 nucleoside reverse transcriptase inhibitors (NRTI) as first-line treatment regimes of HIV-1 infection. Recent clinical studies suggest potential advantages of NNRTI- over PI-based regimes in therapy initiation due to lower rates of virologic failure and less metabolic side-effects. In contrast, PI regimes were claimed to cause greater increases in CD4 cell count than NNRTI regimes, which has been attributed to intrinsic antiapoptotic effects of the PI. However, it is still unclear whether the immunological response to a PI-containing regime is greater than to an NNRTI-containing regime, whether there is a difference in the extent of reduction of apoptosis between PI and NNRTI regimes and whether a difference in apoptosis is associated with a difference in CD4 cell recovery.
We conducted a controlled, long-term, random matched pair design study in HIV-1 infected individuals under sustained virologic suppression to evaluate in head-to-head comparison the clinical effects of a constant PI-based or NNRTI-based regime on CD4 cell recovery and the underlying molecular, biochemical and functional mechanisms.
- Conditions
- Acquired Immunodeficiency Syndrome, HIV Infections
- Being tested
- Lopinavir/Ritonavir plus Lamivudine/Zidovudine, Efavirenz plus Lamivudine/Zidovudine
- Keywords
- treatment naive
- Medical subject headings
- Acquired Immunodeficiency Syndrome, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lopinavir/Ritonavir plus Lamivudine/ZidovudineDrug
400 mg lopinavir and 100 mg ritonavir (Kaletra capsules, Abbott Laboratories) twice daily plus 150 mg lamivudine (Epivir tablets, GlaxoSmithKline) and 300 mg zidovudine (Retrovir tablets, GlaxoSmithKline) twice daily over 476 weeks
Efavirenz plus Lamivudine/ZidovudineDrug
600 mg efavirenz (Sustiva tablets, Bristol-Myers Squibb) once daily plus 150 mg lamivudine (Epivir tablets, GlaxoSmithKline) and 300 mg zidovudine (Retrovir tablets, GlaxoSmithKline) twice daily over 476 weeks
| Study group | Role | What they receive |
|---|---|---|
| PI | Active comparator | 400 mg lopinavir and 100 mg ritonavir (Kaletra capsules, Abbott Laboratories) twice daily plus 150 mg lamivudine (Epivir tablets, GlaxoSmithKline) and 300 mg zidovudine (Retrovir tablets, GlaxoSmithKline) twice daily over a 56-week run-in and a 420-week follow-up Receives: Drug: Lopinavir/Ritonavir plus Lamivudine/Zidovudine |
| NNRTI | Active comparator | 600 mg efavirenz (Sustiva tablets, Bristol-Myers Squibb) once daily plus 150 mg lamivudine (Epivir tablets, GlaxoSmithKline) and 300 mg zidovudine (Retrovir tablets, GlaxoSmithKline) twice daily over a 56-week run-in and a 420-week follow-up Receives: Drug: Efavirenz plus Lamivudine/Zidovudine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in changes of CD4 cell count between PI and NNRTI groups
Measured: 420 weeks
Secondary outcomes (2)
Evolution of CD4 cell counts
Measured: 420 weeks
Molecular, biochemical and functional markers of CD4 cell apoptosis
Measured: 420 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2009 (estimated)
- Study startJan 1999
- Primary completionDec 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acquired Immunodeficiency SyndromeStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 215 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cologne
- Sponsor type
- University, hospital or other
- Investigators
- Dirk Taubert, MD PhD, Study director, Department of Pharmacology, University of Cologne, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00966160
- Sponsor's protocol ID
- HIV-1999-LRE
- Status last verified
- Aug 2009
- First submitted
- 25 Aug 2009
- Last updated
- 29 Sep 2009
- Results posted
- No
Publications
Riddler SA, Haubrich R, DiRienzo AG, Peeples L, Powderly WG, Klingman KL, Garren KW, George T, Rooney JF, Brizz B, Lalloo UG, Murphy RL, Swindells S, Havlir D, Mellors JW; AIDS Clinical Trials Group Study A5142 Team. Class-sparing regimens for initial treatment of HIV-1 infection. N Engl J Med. 2008 May 15;358(20):2095-106. doi: 10.1056/NEJMoa074609.
PubMed 18480202Staszewski S, Morales-Ramirez J, Tashima KT, Rachlis A, Skiest D, Stanford J, Stryker R, Johnson P, Labriola DF, Farina D, Manion DJ, Ruiz NM. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team. N Engl J Med. 1999 Dec 16;341(25):1865-73. doi: 10.1056/NEJM199912163412501.
PubMed 10601505Badley AD, Pilon AA, Landay A, Lynch DH. Mechanisms of HIV-associated lymphocyte apoptosis. Blood. 2000 Nov 1;96(9):2951-64.
PubMed 11049971
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3, Single Center, Controlled, Investigator-blinded, Randomized Matched Pair Design Study of CD4 Cell Recovery in HIV-1 Patients With Sustained Virologic Response Comparing Protease Inhibitor and Non-nucleoside Reverse Transcriptase Inhibitor Based Treatment Regimes
- ClinicalTrials.gov ID
- NCT00966160
- Acronym / sponsor ID
- HIV-1999-LRE
- Conditions
- Acquired Immunodeficiency Syndrome, HIV Infections
- Keywords
- treatment naive
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 215 participants (actual)
- Lead sponsor
- University of CologneUniversity, hospital or other
- Study start
- Jan 1999
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 26 Aug 2009 (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.
Therapy guidelines recommend the use of either the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz or a ritonavir-boostered protease inhibitor (PI) plus 2 nucleoside reverse transcriptase inhibitors (NRTI) as first-line treatment regimes of HIV-1 infection. Recent clinical studies suggest potential advantages of NNRTI- over PI-based regimes in therapy initiation due to lower rates of virologic failure and less metabolic side-effects. In contrast, PI regimes were claimed to cause greater increases in CD4 cell count than NNRTI regimes, which has been attributed to intrinsic antiapoptotic effects of the PI. However, it is still unclear whether the immunological response to a PI-containing regime is greater than to an NNRTI-containing regime, whether there is a difference in the extent of reduction of apoptosis between PI and NNRTI regimes and whether a difference in apoptosis is associated with a difference in CD4 cell recovery.
We conducted a controlled, long-term, random matched pair design study in HIV-1 infected individuals under sustained virologic suppression to evaluate in head-to-head comparison the clinical effects of a constant PI-based or NNRTI-based regime on CD4 cell recovery and the underlying molecular, biochemical and functional mechanisms.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PI | Active comparator | Drug: Lopinavir/Ritonavir plus Lamivudine/Zidovudine400 mg lopinavir and 100 mg ritonavir (Kaletra capsules, Abbott Laboratories) twice daily plus 150 mg lamivudine (Epivir tablets, GlaxoSmithKline) and 300 mg zidovudine (Retrovir tablets, GlaxoSmithKline) twice daily over a 56-week run-in and a 420-week follow-up |
| NNRTI | Active comparator | Drug: Efavirenz plus Lamivudine/Zidovudine600 mg efavirenz (Sustiva tablets, Bristol-Myers Squibb) once daily plus 150 mg lamivudine (Epivir tablets, GlaxoSmithKline) and 300 mg zidovudine (Retrovir tablets, GlaxoSmithKline) twice daily over a 56-week run-in and a 420-week follow-up |
Who may qualify
- Ages
- 20 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Recent, non-acute HIV-1 infection
- Caucasians
- BMI between 17.5 and 30 kg/m2
- CD4 count <200 cells/µl
- Plasma viral load >100,000 HIV-1 RNA copies/ml
Key exclusion criteria (16 listed)
- Actual or previous antiretroviral therapy
- Acute illness
- Coinfection with HBV or HCV
- Opportunistic infection (Pneumocystis jiroveci pneumonia, Toxoplasma gondii encephalitis, Mycobacterium ssp. infection, syphilis, cryptosporidiosis, cryptococcosis, aspergillosis, cytomegalovirus infection or progressive multifocal leukoencephalopathy)
- Hepatic or renal disorder
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 plus Lamivudine/Zidovudine400 mg lopinavir and 100 mg ritonavir (Kaletra capsules, Abbott Laboratories) twice daily plus 150 mg lamivudine (Epivir tablets, GlaxoSmithKline) and 300 mg zidovudine (Retrovir tablets, GlaxoSmithKline) twice daily over 476 weeks | Drug | PI |
| Efavirenz plus Lamivudine/Zidovudine600 mg efavirenz (Sustiva tablets, Bristol-Myers Squibb) once daily plus 150 mg lamivudine (Epivir tablets, GlaxoSmithKline) and 300 mg zidovudine (Retrovir tablets, GlaxoSmithKline) twice daily over 476 weeks | Drug | NNRTI |
Primary outcome
Difference in changes of CD4 cell count between PI and NNRTI groups
Time frame: 420 weeks
2 secondary outcomes
Evolution of CD4 cell counts
Time frame: 420 weeks
Molecular, biochemical and functional markers of CD4 cell apoptosis
Time frame: 420 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2009.
- Background: PubMed 18480202Riddler SA, Haubrich R, DiRienzo AG, Peeples L, Powderly WG, Klingman KL, Garren KW, George T, Rooney JF, Brizz B, Lalloo UG, Murphy RL, Swindells S, Havlir D, Mellors JW; AIDS Clinical Trials Group Study A5142 Team. Class-sparing regimens for initial treatment of HIV-1 infection. N Engl J Med. 2008 May 15;358(20):2095-106. doi: 10.1056/NEJMoa074609.
- Background: PubMed 10601505Staszewski S, Morales-Ramirez J, Tashima KT, Rachlis A, Skiest D, Stanford J, Stryker R, Johnson P, Labriola DF, Farina D, Manion DJ, Ruiz NM. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team. N Engl J Med. 1999 Dec 16;341(25):1865-73. doi: 10.1056/NEJM199912163412501.
- Background: PubMed 11049971Badley AD, Pilon AA, Landay A, Lynch DH. Mechanisms of HIV-associated lymphocyte apoptosis. Blood. 2000 Nov 1;96(9):2951-64.
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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.
Dirk Taubert, MD PhD study director
Department of Pharmacology, University of Cologne, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lopinavir/Ritonavir plus Lamivudine/Zidovudine and Efavirenz plus Lamivudine/Zidovudine in people with Acquired Immunodeficiency Syndrome and HIV Infections, run by University of Cologne at 1 site in Germany.
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 5 inclusion and 16 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: finished, as of the sponsor's last update on 29 Sep 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
What does the primary outcome measure?
Difference in changes of CD4 cell count between PI and NNRTI groups (time frame: 420 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00966160, which also lists 3 linked publications.
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 29 Sep 2009.