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
Conditions
Interventions
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
Concentr
Sponsors
University Medical Center Hamburg-Eppendorf
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: •Pregnant or lactating subjects •Prior antiretroviral treatment for the last six month •Known hypersensitivity to atazanavir/ritonavir •Documented resistance to any of the study drugs (either genotypic or phenotypic) •Severe hepatic impairment •Hepatic transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) >/= 5 x upper limit of normal (ULN) •Subjects receiving ongoing therapy with any of the medications that are contraindicated with any of the study drugs. Administration of any of these medications must be discontinued at least 14 days prior to the Baseline visit and for the duration of the study period. The full list of disallowed medications can be found in Appendix IV. •Other AIDS-defining events (see Appendix VIII for definition of AIDS-defining events) than PCP or TE present at screening, except for oesophageal candidiasis and Kaposi sarcoma (KS) not requiring systemic chemotherapy. •Prior history of significant renal disease •Any current known clinical or symptomatic laboratory parameter of Grade 4 (see Appendix ). Asymptomatic Grade 4 abnormalities will be permitted at the discretion of the investigator if deemed clinically appropriate (excluding adverse events and laboratory parameters mentioned elsewhere in the inclusion/exclusion criteria). Abnormalities deemed insignificant by the investigator must be discussed with the Medical Monitor prior to enrollment. •Malignancies requiring any systemic therapy within 30 days of baseline •Current alcohol or substance use judged by the investigator to potentially interfere with subject study compliance •Subjects currently taking part in any other clinical trial using an investigational product, with the exception of studies where the treatment studied has been stopped for more than 1 month prior to baseline •Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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.;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. ;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.;Timepoint(s) of evaluation of this end point: Baseline, week 4, 8, 12, 16, 20, 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
Germany
Contacts
Public ContactDr. Silke Schrum
CTC North GmbH & Co. KG
Outcome results
None listed