Antiretroviral Therapy for Advanced HIV Disease in South Africa

April 29, 2013 updated by: Michael Polis, M.D., National Institutes of Health Clinical Center (CC)

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

1771

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • South Africa
      • Centurion, South Africa
        • South African Military Health Services (SAMHS)
      • Eastaern Cape, South Africa
        • Umtata Sickbay
      • Free State, South Africa
        • 3 Military Hospital
      • Gauteng, South Africa
        • 1 Military Hospital
      • Kwazulu-Natal, South Africa
        • Mtubatuba SIckbay
      • Limpopo, South Africa
        • Phalaborwa Sickbay
      • Western Cape, South Africa
        • 2 Military Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • 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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • AZT
Drug: Didanosine
<60 kg/125 mg twice daily or >60kg/200 mg twice daily
Other Names:
  • DDI
Drug: Efavirenz
600 mg once daily
Other Names:
  • 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 Names:
  • AZT
Drug: Didanosine
<60 kg/125 mg twice daily or >60kg/200 mg twice daily
Other Names:
  • DDI
Drug: Lopinavir/Ritonavir
r/LPV 400mg/100mg twice daily
Other Names:
  • 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: Efavirenz
600 mg once daily
Other Names:
  • EFV
Drug: Stavudine
40 mg once daily
Other Names:
  • D4T
Drug: Lamivudine
300 mg once daily
Other Names:
  • 3TC
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: Lopinavir/Ritonavir
r/LPV 400mg/100mg twice daily
Other Names:
  • Kaletra
Drug: Stavudine
40 mg once daily
Other Names:
  • D4T
Drug: Lamivudine
300 mg once daily
Other Names:
  • 3TC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Progression of disease, AIDS, or death in treatment naive patients with advanced HIV diagnosis will be evaluated in the four randomly assigned regimens.
January 2004 until March 31 2008

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serious Adverse Events
Time Frame: January 2004 until March 31, 2008
Safety outcomes in four different randomly assigned regimens
January 2004 until March 31, 2008

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institutes of Health Clinical Center (CC)

Investigators

  • Principal Investigator: Michael Polis, MD, National Institute of Allergy and Infectious Diseases (NIAID)
  • Principal Investigator: Andrew Ratsela, MD, SAMHS

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2004

Primary Completion (Actual)

March 1, 2008

Study Completion (Actual)

August 1, 2008

Study Registration Dates

First Submitted

June 19, 2006

First Submitted That Met QC Criteria

June 19, 2006

First Posted (Estimate)

June 21, 2006

Study Record Updates

Last Update Posted (Estimate)

May 21, 2013

Last Update Submitted That Met QC Criteria

April 29, 2013

Last Verified

April 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 999904094
  • 04-I-N094 (Registry Identifier: NCT00342355)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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