NCT00966160

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
215

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Jan 1999

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 1999

Completed
9.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2008

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2008

Completed
9 months until next milestone

First Submitted

Initial submission to the registry

August 25, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

August 26, 2009

Completed
Last Updated

September 29, 2009

Status Verified

August 1, 2009

Enrollment Period

9.9 years

First QC Date

August 25, 2009

Last Update Submit

September 28, 2009

Conditions

Acquired Immunodeficiency SyndromeHIV Infections

Keywords

treatment naive

Outcome Measures

Primary Outcomes (1)

  • Difference in changes of CD4 cell count between PI and NNRTI groups

    420 weeks

Secondary Outcomes (2)

  • Evolution of CD4 cell counts

    420 weeks

  • Molecular, biochemical and functional markers of CD4 cell apoptosis

    420 weeks

Study Arms (2)

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

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

Drug: Efavirenz plus Lamivudine/Zidovudine

Interventions

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

PI
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

NNRTI

Eligibility Criteria

Age20 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Medical Clinic I and Department of Pharmacology, University of Cologne

Cologne, Germany

Location

Related Publications (3)

  • 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.

    PMID: 18480202BACKGROUND

  • 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.

    PMID: 10601505BACKGROUND

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

    PMID: 11049971BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency SyndromeHIV Infections

Interventions

LopinavirRitonavirlamivudine, zidovudine drug combinationefavirenzLamivudineZidovudine

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesSlow Virus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Intervention Hierarchy (Ancestors)

PyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsThiazolesSulfur CompoundsOrganic ChemicalsAzolesZalcitabineDeoxycytidineCytidinePyrimidine NucleosidesDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesDideoxynucleosidesThymidine

Study Officials

  • Dirk Taubert, MD PhD

    Department of Pharmacology, University of Cologne, Germany

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

August 25, 2009

First Posted

August 26, 2009

Study Start

January 1, 1999

Primary Completion

December 1, 2008

Study Completion

December 1, 2008

Last Updated

September 29, 2009

Record last verified: 2009-08

Locations

DE(1)