Antiretroviral Therapy for Advanced HIV Disease in South Africa

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.

• 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 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).