Antiretroviral Therapy for Advanced HIV Disease in South Africa
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
HIV |
Drug: Zidovudine Drug: Stavudine Drug: Didanosine Drug: Lamevudine Drug: Efavirenz |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Factorial Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Randomized, Open-Label 2x2 Factorial Study to Compare the Safety and Efficacy of Different Combination Antiretroviral Therapy Regimens in Treatment Naive Patients With Advanced HIV Disease and/or CD4+ Cell Counts Less Than 200 Cells/MicroL |
- The primary objectives of PHIDISA II are 1) to compare the efavirenz (EFV) versus Kaletra (r/LPV) in combination with two nucleoside reverse transcriptase inhibitors for progression to AIDS or death in treatment na ve patients with advanced HIV disease. [ Time Frame: Anticipate will occur until 31st March 2008 ] [ Designated as safety issue: Yes ]
- To compare the 4 different randomly assigned regimens with one another for progression to AIDS or death and a number of secondary efficacy and safety outcomes. [ Time Frame: Anticipate will occur until 31st March 2008 ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 2800 |
| Study Start Date: | January 2004 |
-
Drug: Zidovudine
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.
Eligibility| Ages Eligible for Study: | 14 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
- INCLUSION CRITERIA:
Uniformed SANDF personnel or family members of SANDF personnel who are registered as eligible for health services from the SAMHS.
HIV positive as diagnosed and/or confirmed in PHIDISA I OR documented HIV infection from an accredited source.
CD4+ cell count less than 200 cells/microL (or less than or equal to 14% for patients post-splenectomy) AND/OR any AIDS defining illness currently or historically. Patients with pulmonary tuberculosis must have a CD4+ cell count less than 200 cells/microL. Patients with KS must have a CD4+ cell count less than 200 cells/microL unless their sarcoma is progressive and/or requires chemotherapy.
Antiretroviral treatment naive (less than 7 days cumulative exposure to any antiretroviral drug) or treated for post-exposure prophylaxis without becoming HIV infected at that time.
Laboratory variables as follows:
- Haemoglobin greater than or equal to 9.0g/dL for men and greater than or equal to 8.0g/dL for women.
- Absolute neutrophil count greater than or equal to 500 cells/microL.
- Platelet count greater than or equal to 25,000/mm(3).
Serum transaminase (ALT or AST) less than or equal to 5X upper limit of normal (ULN).
14 years or older.
Likely to be compliant with study procedures and clinical visits in the opinion of the clinical investigator (guidance is provided in the protocol to assist clinicians in making this decision).
Have completed the PHIDISA treatment adherence counseling session.
Provision of written informed consent.
EXCLUSION CRITERIA:
Any history of pancreatitis or serious pathology indicative of increased risk for pancreatitis.
Current requirement for use of a medication that is contra-indicated with the PHIDISA II study drugs. Where possible, alternate therapies should be selected in order to facilitate randomization. Patients entering the study with tuberculosis should defer screening and randomization until successful completion of an induction course of anti-mycobacterium therapy including rifampicin. As appropriate this patient could recommence screening when starting the maintenance regimen of anti-tubercular drugs excluding rifampicin.
Pregnancy (following delivery, such women may be enrolled).
Contacts and Locations| South Africa | |
| South African Military Health Services (SAMHS) | |
| Centurion, South Africa | |
| Umtata Sickbay | |
| Eastaern Cape, South Africa | |
| 3 Military Hospital | |
| Free State, South Africa | |
| 1 Military Hospital | |
| Gauteng, South Africa | |
| Mtubatuba SIckbay | |
| Kwazulu-Natal, South Africa | |
| Phalaborwa Sickbay | |
| Limpopo, South Africa | |
| 2 Military Hospital | |
| Western Cape, South Africa | |
More Information
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Michael A. Polis, M.D./National Institute of Allergy and Infectious Diseases, National Institutes of Health |
| ClinicalTrials.gov Identifier: | NCT00342355 History of Changes |
| Other Study ID Numbers: | 999904094, 04-I-N094 |
| Study First Received: | June 19, 2006 |
| Last Updated: | September 19, 2008 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Institutes of Health Clinical Center (CC):
|
Protease Inhibitors Reverse Transcriptase Inhibitors AIDS Opportunistic Infections Resource-Poor |
Additional relevant MeSH terms:
|
Acquired Immunodeficiency Syndrome HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Slow Virus Diseases Immunologic Deficiency Syndromes Immune System Diseases Didanosine Zidovudine |
Stavudine Reverse Transcriptase Inhibitors Efavirenz Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Therapeutic Uses Anti-HIV Agents |
ClinicalTrials.gov processed this record on March 14, 2013
