None listed
Conditions
Brief summary
Research Hypothesis: In HIV-infected subjects who have virologically failed first-line antiretroviral therapy comprising 2NRTI + NNRTI a regimen of second-line therapy incorporating ritonavir-boosted lopinavir and raltegravir provides comparable (i.e. non-inferior) antiretroviral efficacy over 48 weeks to a regimen containing ritonavir-boosted lopinavir and 2-3NRTIs. Study Design: This is a Phase IIIb/IV, international, randomised, open label study comparing two regimens of combination antiretroviral therapy in people living with HIV with confirmed virological failure of first-line NNRTI/2 NRTI regimens. The study will run for 96-weeks but the primary analysis will take place at the week 48 time point. Eligible participants will be randomised in equal proportions to one of two regimens of combination ART as follows: I. ritonavir boosted lopinavir (LPV/r) + 2-3NRTIs II. ritonavir boosted lopinavir (LPV/r) + raltegravir Number of Subjects per Group: Approximately 275 eligible subjects will be randomly allocated to each of the two treatment arms giving a study total of 550 participants.
Interventions
This study is a Phase IIIB/IV, randomised, open label comparison of two independent regimens of combination antiretrovirals as second-line therapy following confirmed virological failure of a first-line non-nucleoside and two nucleoside reverse transcriptase inhibitors (NNRTI/2N(t)RTI) combination antiretroviral (ART) regimen. Eligible participants will be randomly allocated to receive one of the two study regimens.
I. ritonavir boosted lopinavir (LPV/r) 200mg/50mg 4 tablets once daily or 2 ta
This study is a Phase IIIB/IV, randomised, open label comparison of two independent regimens of combination antiretrovirals as second-line therapy following confirmed virological failure of a first-line non-nucleoside and two nucleoside reverse transcriptase inhibitors (NNRTI/2N(t)RTI) combination antiretroviral (ART) regimen. Eligible participants will be randomly allocated to receive one of the two study regimens. I. ritonavir boosted lopinavir (LPV/r) 200mg/50mg 4 tablets once daily or 2 tabs twice daily + 2-3N(t)RTIs II. ritonavir boosted lopinavir (LPV/r) 200mg/50mg 4 tablets once daily or 2 tabs twice daily + raltegravir 400 mg 1 tablet twice daily. All treatments will be adminstered orally. The dose of 2-3N(t)RTIs given will be at the treating physician's discretion, according to the local guidelines and the patient's condition.
Sponsors
University of New South Wales/Kirby Institute
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. HIV-1 positive by licensed diagnostic test 2. Aged 16 years or older (or minimum age as determined by local regulations or as legal requirements dictate) 3. Have received first antiretroviral regimen consisting of an NNRTI plus 2N(t)RTIs for = 24 weeks 4. No change in antiretroviral therapy within 12 weeks prior to screening 5. Failed first-line NNRTI + 2N(t)RTI combination therapy according to virological criteria defined by two consecutive (=7 days apart) HIV RNA results of >500 copies/mL 6. No prior or current exposure to HIV protease inhibitors and/or HIV integrase inhibitors 7. Able to provide written informed consent
Exclusion criteria
1. The following laboratory variables a) absolute neutrophil count (ANC) <500 cells/microlitres. b) hemoglobin <7.0 g/dL c) platelet count <50,000 cells/microlitres d) Alanine transaminase (ALT) >5 x upper limit normal (ULN) 2. Pregnant or nursing mothers 3. Participants with active viral hepatitis B infection defined by the presence in serum of hepatitis B surface antigen 4. Use of immunomodulators within 30 days prior to screening 5. Use of any prohibited medications (rifampicin, midazolam, triazolam, cisapride, pimozide, amiodarone, dihydroergotamine, ergotamine, ergonovine, methylergonovine, astemizole, terfenadine, vardenafil, St. John’s wort) 6. Intercurrent illness requiring hospitalisation 7. Active opportunistic disease not under adequate control in the opinion of the investigator 8. Participants with current alcohol or illicit substance abuse that in the opinion of the investigator might adversely affect participation in the study 9. Participants deemed by the investigator unlikely to be able to remain in follow-up for the protocol defined period
Outcome results
None listed