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

NCT ID: NCT00966160

Last Updated: 2009-09-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 215 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-01-31
• Study Completion Date: 2008-12-31

Brief 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. 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

Keywords

treatment naive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

PI

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

Group Type: ACTIVE_COMPARATOR

Lopinavir/Ritonavir plus Lamivudine/Zidovudine

Intervention Type: DRUG

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

NNRTI

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

Group Type: ACTIVE_COMPARATOR

Efavirenz plus Lamivudine/Zidovudine

Intervention Type: DRUG

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

Interventions

Lopinavir/Ritonavir plus Lamivudine/Zidovudine

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

Intervention Type: DRUG

Efavirenz plus Lamivudine/Zidovudine

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Cologne

OTHER

Sponsor Role: lead

Responsible Party

University of Cologne

Principal Investigators

Dirk Taubert, MD PhD

Role: STUDY_DIRECTOR

Department of Pharmacology, University of Cologne, Germany

Locations

Medical Clinic I and Department of Pharmacology, University of Cologne

Cologne, , Germany

Countries

Germany

References

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.

Reference Type: BACKGROUND

PMID: 18480202 (View on PubMed)

Staszewski 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.

Reference Type: BACKGROUND

PMID: 10601505 (View on PubMed)

Badley AD, Pilon AA, Landay A, Lynch DH. Mechanisms of HIV-associated lymphocyte apoptosis. Blood. 2000 Nov 1;96(9):2951-64.

Reference Type: BACKGROUND

PMID: 11049971 (View on PubMed)

Other Identifiers

HIV-1999-LRE

Identifier Type: -

Identifier Source: org_study_id