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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00966160
• Other study ID #: HIV-1999-LRE
• Status: Completed
• Phase: Phase 3
• First received: August 25, 2009
• Last updated: September 28, 2009
• Start date: January 1999
• Est. completion date: December 2008

Study information

• Verified date: August 2009
• Source: University of Cologne
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 215
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Immunologic Deficiency Syndromes

Intervention

Drug:
• 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
• 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

Locations

Country	Name	City	State
Germany	Medical Clinic I and Department of Pharmacology, University of Cologne	Cologne

Sponsors (1)

Lead Sponsor	Collaborator
University of Cologne

Country where clinical trial is conducted

Germany, 

References & Publications (3)

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

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in changes of CD4 cell count between PI and NNRTI groups		420 weeks	No
Secondary	Evolution of CD4 cell counts		420 weeks	No
Secondary	Molecular, biochemical and functional markers of CD4 cell apoptosis		420 weeks	No