Immediate versus deferred antiretroviral therapy in HIV-infected patients presenting with acute AIDS-defining events (IDEAL-Study)

INTERVENTION: Trade Name: Reyataz® 300mg‐Hartkapseln Pharmaceutical Form: Capsule, hard INN or Proposed INN: ATAZANAVIR CAS Number: 198904‐31‐3 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 300‐ Trade Name: Norvir® 100mg‐Filmtabletten Pharmaceutical Form: Coated tablet INN or Proposed INN: RITONAVIR CAS Number: 155213‐67‐5 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ CONDITION: Patients in late stage of HIV‐infection, treatment naive or without ART for the last 6 month with an acute AIDS‐defining illness, namely PCP or TE. ; MedDRA version: 18.0 Level: LLT Classification code 10001509 Term: AIDS System Organ Class: 100000004862 Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] ‐ Therapeutic techniques [E02] PRIMARY OUTCOME: Main Objective: To compare the rates of clinical progression between both groups. Progression is defined as death, all new/relapsing opportunistic infections (OI), and other grade 4 clinical endpoints (evaluated by standardized toxicity tables) within 24 weeks after randomization. Primary end point(s): The primary endpoint is clinical progression including death, all new or relapsing OI, and other G4 clinical endpoint within 24 weeks. For G4 events standardized toxicity grading tables will be used (http://www.ucdmc.ucdavis.edu/clinicaltrials/documents/vaccine_toxicity _grading _table.pdf). For abnormalities not found in the Toxicity Tables, a Grade 4 event will be defined as potentially life‐threatening (extreme limitation in activity, significant assistance required; significant medical intervention/therapy required, hospitalization or hospice care probable). Patients who drop out of study observation before end of week 12 are counted as clinical progression. Secondary Objective: •to evaluate and to compare hospitalization days after completion of initial OI treatment between both groups. ; •to evaluate the incidence of immune reconstitution inflammatory syndrome (IRIS, definition see Objectives) in both groups during the first 24 weeks.; •to evaluate and to compare the virological outcome proportion in both groups. Virological outcome is assessed by HIV‐1 plasma viral load at Week 24 (proportion of patients achieving HIV RNA < 400/<50 copies/mL). For definition of virological failure, see below. ; •to evaluate and to compare the frequency changes in ART regimen for lack of efficacy or of toxicity in both groups.; •to evaluate the quality of life (QOL) and the adherence to the ARV regimen in subjects starting tenofovir, emtricitabine and atazanavir/ritonavir at late stages of HIV‐1‐infection. ; Timepoint(s) of evaluation of this end point: Baseline, week 4, 8, 12, 16, 20, 24 SECONDARY OUTCOME: Secondary end point(s): •Hospitalization days after completion of OI treatment ; ; •Incidence of immune reconstitution inflammatory syndrome (IRIS) as judged by the site investigator compared in the two groups during the first 24 weeks. ; ; •Virological outcome at week 24 (proportion of patients achieving HIV RNA < 400 (<50 copies/mL). ; ; •Immunological outcome at week 24 (CD4 T‐cell counts and change from baseline at week 24 (absolute, relative, CD4/CD8 ratio); ; •Proportion of patients with changes in ARV regimen for lack of efficacy or of toxicity; ; •Quality of life (QOL), including overall self‐reported QOL at Week 24; Timepoint(s) of evaluation of this end point: Baseline, week 4, 8, 12, 16, 20, 24 with a main focus on week 24; INCLUSION CRITERIA: •No prior antiretroviral therapy for at least 6 month and an acute AIDS defining event, namely PCP or TE. •Naïve to antiretroviral therapy. No prior antiretroviral therapy for at least 6 month (patients without evidence for prior virological failure and without evidence of resistance mutation against the planned ART therapy may be allowed)and an and an •Acute AIDS defining event, namely PCP or TE. Prior ART for mother to child transmission (MTCT) prophylaxis is allowed. •Ability to take oral medications •>= 18 years old •Adequate renal function by calculated creatinine clearance < 60 mL/min according to the Cockcroft–Gault formula. •Negative serum pregnancy test (females of childbearing potential only i.e., not surgically sterile or at least 2 years post‐menopausal). •Women of childbearing potential (WOCBP) must be using a highly effective method of contraception to avoid pregnancy throughout the study and