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Antiretroviral Therapy for Advanced HIV Disease in South Africa

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Michael Polis, M.D., National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00342355
First received: June 19, 2006
Last updated: April 29, 2013
Last verified: April 2013
  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: Lamivudine
Drug: Efavirenz
Drug: Lopinavir/Ritonavir
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: 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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Progression to AIDS or Death in tx naïve Pts With Adv HIV dx in the Four Randomly Assigned Regimens. [ Time Frame: January 2004 until March 31 2008 ] [ Designated as safety issue: No ]
    Progression of disease, AIDS, or death in treatment naive patients with advanced HIV diagnosis will be evaluated in the four randomly assigned regimens.


Secondary Outcome Measures:
  • Serious Adverse Events [ Time Frame: January 2004 until March 31, 2008 ] [ Designated as safety issue: Yes ]
    Safety outcomes in four different randomly assigned regimens


Enrollment: 1771
Study Start Date: January 2004
Study Completion Date: August 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: AZT+DDI+EFV
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)
Drug: Zidovudine
600 mg once daily
Other Name: AZT
Drug: Didanosine
<60 kg/125 mg twice daily or >60kg/200 mg twice daily
Other Name: DDI
Drug: Efavirenz
600 mg once daily
Other Name: EFV
Active Comparator: AZT+DDI+r/LPV
Zidovudine,Didanosine,Lopinavir/Ritonavir(AZT 600 mg once daily,DDI 100 mg twice daily,r/LPV 400mg/100mg twice daily)
Drug: Zidovudine
600 mg once daily
Other Name: AZT
Drug: Didanosine
<60 kg/125 mg twice daily or >60kg/200 mg twice daily
Other Name: DDI
Drug: Lopinavir/Ritonavir
r/LPV 400mg/100mg twice daily
Other Name: Kaletra
Active Comparator: d4T+3TC+EFV
Stavudine,Lamivudine,Efavirenz(d4T 40 mg twice daily,3TC 300 mg once daily,EFV 600 mg once daily)
Drug: Stavudine
40 mg once daily
Other Name: D4T
Drug: Lamivudine
300 mg once daily
Other Name: 3TC
Drug: Efavirenz
600 mg once daily
Other Name: EFV
Active Comparator: d4T+3TC+r/LPV
Stavudine,Lamivudine,Lopinavir/Ritonavir(d4T 40m mg twice daily,3TC 300 mg once daily,r/LPV 400mg/100mg twice daily)
Drug: Stavudine
40 mg once daily
Other Name: D4T
Drug: Lamivudine
300 mg once daily
Other Name: 3TC
Drug: Lopinavir/Ritonavir
r/LPV 400mg/100mg twice daily
Other Name: Kaletra

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.

  Eligibility

Ages Eligible for Study:   14 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • 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:

  1. Haemoglobin greater than or equal to 9.0g/dL for men and greater than or equal to 8.0g/dL for women.
  2. Absolute neutrophil count greater than or equal to 500 cells/microL.
  3. Platelet count greater than or equal to 25,000/mm(3).
  4. Serum transaminase (ALT or AST) less than or equal to 5 times 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00342355

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
Sponsors and Collaborators
Investigators
Principal Investigator: Michael Polis, MD NIH/NIAID
Principal Investigator: Andrew Ratsela, MD SAMHS
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Michael Polis, M.D., Michael Polis, National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00342355     History of Changes
Other Study ID Numbers: 999904094, 04-I-N094
Study First Received: June 19, 2006
Results First Received: September 14, 2009
Last Updated: April 29, 2013
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:
Didanosine
Efavirenz
Lamivudine
Lopinavir
Reverse Transcriptase Inhibitors
Ritonavir
Stavudine
Zidovudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014