CD4 Cell Recovery in HIV-1 Patients Comparing 2 Treatment Regimes

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Acquired Immunodeficiency Syndrome, HIV Infections

Intervention / Treatment
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* Drug: Lopinavir/Ritonavir plus Lamivudine/Zidovudine
* Drug: Efavirenz plus Lamivudine/Zidovudine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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 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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PI<br>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 | Drug: Lopinavir/Ritonavir plus Lamivudine/Zidovudine<br>* 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<br>|
| Active Comparator: NNRTI<br>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 | Drug: Efavirenz plus Lamivudine/Zidovudine<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in changes of CD4 cell count between PI and NNRTI groups |  | 420 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of CD4 cell counts |  | 420 weeks | 
| Molecular, biochemical and functional markers of CD4 cell apoptosis |  | 420 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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treatment naive