Clinical trial NCT00342355
Conditions: HIV
Keywords: Protease Inhibitors Reverse Transcriptase Inhibitors AIDS Opportunistic Infections Resource-Poor
Sponsor: National Institutes of Health Clinical Center (CC)
Start date: 2004-01-01; Completion date: 2008-08-01
Enrollment: 1771 participants; Allocation: RANDOMIZED; Intervention model: FACTORIAL

Brief summary:
This study will determine how well four different antiretroviral drug therapies work in patients with advanced HIV disease. The trial is part of the South Africa-U.S. Project Phidisa Programme - a collaboration between the South African Military Health Service (SAMHS) of the South African National Defense Force (SANDF), the U.S. Department of Defense, and the U.S. National Institutes of Health - to help prevent HIV transmission among South African military and civilian employees and their families.

Members of the SANDF with HIV infection may be eligible for this study. HIV-infected family members who are 14 years of age and older may also participate. All participants must have a CD4 count of less than 200 or an AIDS-defining illness.

Participants are randomly assigned to one of the following four antiretroviral drug regimens, which require taking 5 pills or more every day:

* AZT (zidovudine) + ddl (didanosine) + EFV (efavirenz)
* AZT (zidovudine) + ddl (didanosine) + r/LPV (lopinavir/ritonavir)
* D4T (stavudine) + 3TC (lamivudine) + EFV (efavirenz)
* D4T (stavudine) + 3TC (lamivudine) + r/LPV (lopinavir/ritonavir)

Patients are followed for up to 6 years. Clinic visits are scheduled once a month for the first 3 months and then once every 3 months for the next five years. Patients undergo a medical history, physical examination, and blood tests at each visit, and complete questionnaires of behavior, quality of life, and force readiness every year.

Detailed description:
This is a randomized, open label 2x2 factorial study of four regimens of initial therapy.

I. AZT + ddl + EFV

II. AZT + ddl + r/LPV

III. D4T + 3TC + EFV

IV. D4T + 3TC + r/LPV

Eligible patients will commence their randomly allocated study drugs as soon as possible after randomization. Episodes of treatment limiting toxicity will be managed in keeping with protocol specified guidelines.

Patients who experience treatment failures (as specified in the protocol) will be managed by changing their regimen to that corresponding to one of the other treatment groups.

Arms: arm 1: Zidovudine,Didanosine,Efavirenz ( Zidovudine 600 mg once daily,Didanosine \<60 kg/125 mg twice daily or \>60kg/200 mg twice daily,Efavirenz 600 mg once daily) arm 2: Zidovudine,Didanosine,Lopinavir/Ritonavir(AZT 600 mg once daily,DDI 100 mg twice daily,r/LPV 400mg/100mg twice daily) arm 3: Stavudine,Lamivudine,Efavirenz(d4T 40 mg twice daily,3TC 300 mg once daily,EFV 600 mg once daily) arm 4: Stavudine,Lamivudine,Lopinavir/Ritonavir(d4T 40m mg twice daily,3TC 300 mg once daily,r/LPV 400mg/100mg twice daily)
Interventions: intervention 1: Zidovudine intervention 2: Stavudine intervention 3: Didanosine intervention 4: Lamivudine intervention 5: Efavirenz intervention 6: Lopinavir/Ritonavir
Intervention descriptions: intervention 1: 600 mg once daily intervention 2: 40 mg once daily intervention 3: \<60 kg/125 mg twice daily or \>60kg/200 mg twice daily intervention 4: 300 mg once daily intervention 5: 600 mg once daily intervention 6: r/LPV 400mg/100mg twice daily

Protocol documents: