HIV
Conditions
Keywords
Protease Inhibitors, Reverse Transcriptase Inhibitors, AIDS, Opportunistic Infections, Resource-Poor
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.
Interventions
DRUGZidovudine
600 mg once daily
DRUGStavudine
40 mg once daily
DRUGDidanosine
\<60 kg/125 mg twice daily or \>60kg/200 mg twice daily
DRUGLamivudine
300 mg once daily
DRUGEfavirenz
600 mg once daily
DRUGLopinavir/Ritonavir
r/LPV 400mg/100mg twice daily
Sponsors
National Institutes of Health Clinical Center (CC)
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to No maximum
Healthy volunteers
No
Inclusion 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression to AIDS or Death in tx naïve Pts With Adv HIV dx in the Four Randomly Assigned Regimens. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serious Adverse Events | January 2004 until March 31, 2008 | Safety outcomes in four different randomly assigned regimens |
Countries
South Africa
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AZT+ddI+EFV Zidovudine + Didanosine+Efavirenz | 444 |
| AZT + ddI + r/LPV Zidovudine + Didanosine + Lopinavir \[LPV\] co-formulated with ritonavir \[RTV\] | 440 |
| d4T + 3TC + EFV Stavudine + Lamivudine + efavirenz | 444 |
| d4T + 3TC + r/LPV Stavudine + Lamivudine + lopinavir/ritonavir | 443 |
| Total | 1,771 |
Baseline characteristics
| Characteristic | AZT+ddI+EFV | AZT + ddI + r/LPV | d4T + 3TC + EFV | d4T + 3TC + r/LPV | Total |
|---|---|---|---|---|---|
| Age Continuous | 35.3 years STANDARD_DEVIATION 5.4 | 35.3 years STANDARD_DEVIATION 5.4 | 35.5 years STANDARD_DEVIATION 5.5 | 35.6 years STANDARD_DEVIATION 5.5 | 35.4 years STANDARD_DEVIATION 5.4 |
| Region of Enrollment South Africa | 444 participants | 440 participants | 444 participants | 443 participants | 1771.0 participants |
| Sex: Female, Male Female | 146 Participants | 135 Participants | 144 Participants | 142 Participants | 567.0 Participants |
| Sex: Female, Male Male | 298 Participants | 305 Participants | 300 Participants | 301 Participants | 1204.0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 444 | 0 / 440 | 0 / 444 | 0 / 443 |
| serious Total, serious adverse events | 96 / 444 | 85 / 440 | 72 / 444 | 71 / 443 |
Outcome results
Primary
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.
Time frame: January 2004 until March 31 2008
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZT+ddI+EFV | Progression to AIDS or Death in tx naïve Pts With Adv HIV dx in the Four Randomly Assigned Regimens. | 93 participants |
| AZT + ddI + r/LPV | Progression to AIDS or Death in tx naïve Pts With Adv HIV dx in the Four Randomly Assigned Regimens. | 77 participants |
| d4T + 3TC + EFV | Progression to AIDS or Death in tx naïve Pts With Adv HIV dx in the Four Randomly Assigned Regimens. | 70 participants |
| d4T + 3TC + r/LPV | Progression to AIDS or Death in tx naïve Pts With Adv HIV dx in the Four Randomly Assigned Regimens. | 80 participants |
Secondary
Serious Adverse Events
Safety outcomes in four different randomly assigned regimens
Time frame: January 2004 until March 31, 2008
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZT+ddI+EFV | Serious Adverse Events | 73 participant |
| AZT + ddI + r/LPV | Serious Adverse Events | 69 participant |
| d4T + 3TC + EFV | Serious Adverse Events | 64 participant |
| d4T + 3TC + r/LPV | Serious Adverse Events | 60 participant |