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

University of Cologne

Status and phase: Completed; Phase 3

Conditions: HIV Infections; Acquired Immunodeficiency Syndrome

Treatments: Drug: Lopinavir/Ritonavir plus Lamivudine/Zidovudine; Drug: Efavirenz plus Lamivudine/Zidovudine

Study type: Interventional

Funder types: Other

Identifiers

NCT00966160

HIV-1999-LRE

Details and patient eligibility

About

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.

Enrollment: 215 patients

Sex: All

Ages: 20 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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215 participants in 2 patient groups

PI

Active Comparator group

Description:

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

Treatment:

Drug: Lopinavir/Ritonavir plus Lamivudine/Zidovudine

NNRTI

Active Comparator group

Description:

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

Treatment:

Drug: Efavirenz plus Lamivudine/Zidovudine