Effects of Two Anti-HIV Drug Combinations on the Immune Systems of HIV-Infected Patients Who Have Never Received Anti-HIV Drugs

A Randomized, Open-Label, Pilot Treatment Trial Evaluating Cellular Dynamics and Immune Restoration in Treatment-Naive HIV-Infected Subjects Receiving Either the Protease Inhibitor LPV/r or the Nucleoside Analogue Reverse Transcriptase Inhibitors d4T/3TC/Abacavir With the Non-Nucleoside Reverse Transcriptase Inhibitor Nevirapine

This study will compare an anti-HIV drug combination of protease inhibitor plus a nonnucleoside reverse transcriptase inhibitor (NNRTI) to one that includes three nucleoside reverse transcriptase inhibitors (NRTIs) plus an NNRTI. NNRTIs, NRTIs, and protease inhibitors are all types of anti-HIV drugs that block the virus in some way.

This study will try to find out if a treatment regimen containing a protease inhibitor plus an NNRTI has a different effect on the rise of CD4 cells compared to a treatment made up of three NRTIs plus an NNRTI. CD4 cells are cells of the immune system that fight infection. This study will also try to see if the combination of drugs used in this study is safe to use in HIV-positive patients.

This study is designed to further define the dynamics and the mechanisms of the CD4 cell rise seen following administration of potent antiretroviral therapy. It will ascertain if treatment regimens containing nucleoside reverse transcriptase inhibitors (NRTIs) with a nonnucleoside reverse transcriptase inhibitor (NNRTI) have different effects on CD4 dynamics than regimens composed of a protease inhibitor with an NNRTI.

Patients are randomized to one of the two treatment arms listed below. They are stratified based on CD4 count and whether they choose to participate in substudy A5036s.

Arm A (protease inhibitor plus NNRTI regimen): At Day 0 (entry), patients begin taking LPV/RTV. At Day 3, patients add NVP, once daily for 2 weeks and then twice daily for the remainder of the study.

Arm B (triple reverse transcriptase inhibitors plus NNRTI regimen): At Day 0 (entry), patients begin taking 3TC plus d4T plus ABC. At Day 3, patients add NVP, once daily for 2 weeks and then twice daily for the remainder of the study.

HIV RNA analysis is performed at Weeks 4 and 5. If the mean is at least 1.0 log10 lower than the baseline HIV RNA, the patient may continue on study treatment. If the mean is not at least 1.0 log10 lower, however, patients are discontinued from the study by no later than Week 8. After 8 weeks of treatment, patients may change antiretroviral medications with permission of the protocol chair or vice chairs. Regular clinical evaluations are conducted. Blood is drawn to determine HIV RNA quantification, absolute CD4 and CD8 counts, immunological evaluations, telomere assays, and part is stored for future testing. Skin testing and return visits for delayed-type hypersensitivity to standard recall antigens are done on three occasions. Patients remain on the study for 48 weeks. Substudy A5036s evaluates viral dynamics during study treatment. Serial plasma samples are collected during the first 24 hours of treatment and at Day 3 and Week 4. Plasma HIV measurements are performed to differentiate between infectious and non-infectious particle production.

Inclusion Criteria

Patients may be eligible for this study if they:

• Are 18 years of age or older.
• Are HIV-positive.
• Have a CD4 count of 500 cells/mm3 or less.
• Have a viral load greater than 5,000 and less than 100,000 copies/ml.
• Are willing to use barrier methods of birth control (such as condoms) during the study and for 12 weeks after stopping treatment.
• Will most likely respond well to nevirapine. This is determined by the results of a test.

Exclusion Criteria

Patients will not be eligible for this study if they:

• Have ever taken any anti-HIV drugs. (Seven days or less of treatment will be allowed if it was received more than 30 days before study entry.)
• Have pancreatitis (an inflamed pancreas) or hepatitis within 2 weeks of study entry.
• Are pregnant or breast-feeding.
• Actively abuse drugs or alcohol which their doctor feels would interfere with the ability to fulfill study requirements.
• Have taken any medications within 14 days of study entry that would interfere with the study drugs.
• Are receiving or need to receive chemotherapy.