Antiretroviral Therapy for Advanced HIV Disease in South Africa
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
2 other identifiers
interventional
1,771
1 country
7
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4 hiv
Started Jan 2004
Longer than P75 for phase_4 hiv
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2004
CompletedFirst Submitted
Initial submission to the registry
June 19, 2006
CompletedFirst Posted
Study publicly available on registry
June 21, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2008
CompletedResults Posted
Study results publicly available
April 16, 2013
CompletedMay 21, 2013
April 1, 2013
4.2 years
June 19, 2006
September 14, 2009
April 29, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression to AIDS or Death in tx naïve Pts With Adv HIV dx in the Four Randomly Assigned Regimens.
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 Outcomes (1)
Serious Adverse Events
January 2004 until March 31, 2008
Study Arms (4)
AZT+DDI+EFV
ACTIVE COMPARATORZidovudine,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)
AZT+DDI+r/LPV
ACTIVE COMPARATORZidovudine,Didanosine,Lopinavir/Ritonavir(AZT 600 mg once daily,DDI 100 mg twice daily,r/LPV 400mg/100mg twice daily)
d4T+3TC+EFV
ACTIVE COMPARATORStavudine,Lamivudine,Efavirenz(d4T 40 mg twice daily,3TC 300 mg once daily,EFV 600 mg once daily)
d4T+3TC+r/LPV
ACTIVE COMPARATORStavudine,Lamivudine,Lopinavir/Ritonavir(d4T 40m mg twice daily,3TC 300 mg once daily,r/LPV 400mg/100mg twice daily)
Interventions
\<60 kg/125 mg twice daily or \>60kg/200 mg twice daily
r/LPV 400mg/100mg twice daily
Eligibility Criteria
You may qualify if:
- 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 5 times upper limit of normal (ULN).
- 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.
You may not qualify if:
- 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).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (7)
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
Related Publications (6)
Rabkin M, El-Sadr W, Katzenstein DA, Mukherjee J, Masur H, Mugyenyi P, Munderi P, Darbyshire J. Antiretroviral treatment in resource-poor settings: clinical research priorities. Lancet. 2002 Nov 9;360(9344):1503-5. doi: 10.1016/S0140-6736(02)11478-4. No abstract available.
PMID: 12433534BACKGROUNDHammer SM, Squires KE, Hughes MD, Grimes JM, Demeter LM, Currier JS, Eron JJ Jr, Feinberg JE, Balfour HH Jr, Deyton LR, Chodakewitz JA, Fischl MA. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N Engl J Med. 1997 Sep 11;337(11):725-33. doi: 10.1056/NEJM199709113371101.
PMID: 9287227BACKGROUNDCameron DW, Heath-Chiozzi M, Danner S, Cohen C, Kravcik S, Maurath C, Sun E, Henry D, Rode R, Potthoff A, Leonard J. Randomised placebo-controlled trial of ritonavir in advanced HIV-1 disease. The Advanced HIV Disease Ritonavir Study Group. Lancet. 1998 Feb 21;351(9102):543-9. doi: 10.1016/s0140-6736(97)04161-5.
PMID: 9492772BACKGROUNDLedwaba L, Tavel JA, Khabo P, Maja P, Qin J, Sangweni P, Liu X, Follmann D, Metcalf JA, Orsega S, Baseler B, Neaton JD, Lane HC; Project Phidisa Biomarkers Team. Pre-ART levels of inflammation and coagulation markers are strong predictors of death in a South African cohort with advanced HIV disease. PLoS One. 2012;7(3):e24243. doi: 10.1371/journal.pone.0024243. Epub 2012 Mar 20.
PMID: 22448211DERIVEDMatthews GV, Manzini P, Hu Z, Khabo P, Maja P, Matchaba G, Sangweni P, Metcalf J, Pool N, Orsega S, Emery S; PHIDISA II study team. Impact of lamivudine on HIV and hepatitis B virus-related outcomes in HIV/hepatitis B virus individuals in a randomized clinical trial of antiretroviral therapy in southern Africa. AIDS. 2011 Sep 10;25(14):1727-35. doi: 10.1097/QAD.0b013e328349bbf3.
PMID: 21716078DERIVEDPhidisa II Writing Team for Project Phidisa; Ratsela A, Polis M, Dhlomo S, Emery S, Grandits G, Khabo P, Khanyile T, Komati S, Neaton JD, Naidoo LC, Magongoa D, Qolohle D. A randomized factorial trial comparing 4 treatment regimens in treatment-naive HIV-infected persons with AIDS and/or a CD4 cell count <200 cells/muL in South Africa. J Infect Dis. 2010 Nov 15;202(10):1529-37. doi: 10.1086/656718. Epub 2010 Oct 13.
PMID: 20942650DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Michael A Polis, MD, MPH
- Organization
- National Institute of Allergy and Infectious Diseases, Dvision of Clinical Research
Study Officials
- PRINCIPAL INVESTIGATOR
Michael Polis, MD
National Institute of Allergy and Infectious Diseases (NIAID)
- PRINCIPAL INVESTIGATOR
Andrew Ratsela, MD
SAMHS
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- FACTORIAL
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Michael Polis
Study Record Dates
First Submitted
June 19, 2006
First Posted
June 21, 2006
Study Start
January 1, 2004
Primary Completion
March 1, 2008
Study Completion
August 1, 2008
Last Updated
May 21, 2013
Results First Posted
April 16, 2013
Record last verified: 2013-04