Clinical trial NCT00966160: CD4 Cell Recovery in HIV-1 Patients Comparing 2 Treatment Regimes
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acquired Immunodeficiency Syndrome
HIV Infections
Keywords: treatment naive
Lead sponsor: University of Cologne
Sponsor class: OTHER
First posted: 2009-08-26
Enrollment: 215
Sex: ALL
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Difference in changes of CD4 cell count between PI and NNRTI groups
timeFrame: 420 weeks
Secondary outcomes:
measure: Evolution of CD4 cell counts
timeFrame: 420 weeks
measure: Molecular, biochemical and functional markers of CD4 cell apoptosis
timeFrame: 420 weeks
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: Medical Clinic I and Department of Pharmacology, University of Cologne
Study officials:
affiliation: Department of Pharmacology, University of Cologne, Germany
name: Dirk Taubert, MD PhD
role: STUDY_DIRECTOR
References:
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.
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. doi: 10.1056/NEJM199912163412501.
citation: Badley AD, Pilon AA, Landay A, Lynch DH. Mechanisms of HIV-associated lymphocyte apoptosis. Blood. 2000 Nov 1;96(9):2951-64.