A Trial of 2 Options for Second Line Combination Antiretroviral Therapy Following Virological Failure of a Standard Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI)+2N(t)RTI First Line Regimen
- Conditions
- HIV Infections
- Interventions
- Registration Number
- NCT00931463
- Lead Sponsor
- Kirby Institute
- Brief Summary
The investigators hypothesize that following virological failure of a standard NNRTI+2N(T)RTI regimen second-line antiretroviral therapy consisting of ritonavir-boosted lopinavir and 2N(T)RTIs will offer comparable efficacy to that provided by ritonavir-boosted lopinavir and raltegravir.
The study will be conducted for 96-weeks with the primary endpoint analyzed after 48-weeks.
The primary endpoint is virological: a comparison of virological suppression in plasma \< 200 copies/mL between the randomized arms after 48 weeks.
Secondary and exploratory endpoints include virological, immunological, safety, clinical, metabolic, drug adherence, drug resistance and quality of life.
- Detailed Description
In HIV-infected subjects who have virologically failed first-line antiretroviral therapy comprising 2N(t)RTI + 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 2-3N(t)RTIs.
Eligible patients will be randomised to one of two arms:
I. ritonavir boosted lopinavir (LPV/r) 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3N(t)RTIs
II. ritonavir boosted lopinavir (LPV/r) 200mg/50mg 4 tabs once daily or 2 tabs twice daily + raltegravir 400 mg twice daily
The primary objective of this study is to compare the virological efficacy of the two strategies as measured by the proportion of participants with HIV RNA \< 200 copies/mL 48 weeks after randomisation.
Secondary objectives include virological, immunological, safety and antiretroviral therapy endpoints.
Exploratory endpoints include clinical, metabolic, drug resistance, medication adherence and quality of life endpoints.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 558
- HIV-1 positive by licensed diagnostic test
- Aged 16 years or older (or minimum age as determined by local regulations or as legal requirements dictate)
- Have received first antiretroviral regimen consisting of an NNRTI plus 2N(t)RTIs for at least 24 weeks
- No change in antiretroviral therapy within 12 weeks prior to screening
- Failed first-line NNRTI + 2N(t)RTI combination therapy according to virological criteria defined by two consecutive (at least 7 days apart) HIV RNA results of greater then 500 copies/mL
- No prior or current exposure to HIV protease inhibitors and/or HIV integrase inhibitors
- Able to provide written informed consent
-
The following laboratory variables:
- absolute neutrophil count (ANC) < 500 cells/microlitres
- hemoglobin < 7.0 g/decilitres
- platelet count < 50,000 cells/microlitres
- ALT great than 5 x ULN
-
Pregnant or nursing mothers
-
Participants with active viral hepatitis B infection defined by the presence in serum of hepatitis B surface antigen
-
Use of immunomodulators within 30 days prior to screening
-
Use of any prohibited medications (rifampicin, midazolam, triazolam, cisapride, pimozide, amiodarone, dihydroergotamine, ergotamine, ergonovine, methylergonovine, astemizole, terfenadine, vardenafil, and St. John's wort)
-
Intercurrent illness requiring hospitalization
-
Active opportunistic disease not under adequate control in the opinion of the site Principal Investigator
-
Participants with current alcohol or illicit substance abuse that in the opinion of the site Principal Investigator might adversely affect participation in the study
-
Participants deemed by the site Principal Investigator unlikely to be able to remain in follow-up for the protocol-defined period
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ritonavir-boosted lopinavir and 2N(t)RTI Ritonavir-boosted lopinavir This is the current standard of care for second line therapy following failure of standard first-line NNRTI+2N(t)RTIs according to WHO guidelines. Ritonavir-boosted lopinavir and raltegravir Ritonavir-boosted lopinavir This is an experimental arm which is likely to be fully active in the presence of N(t)RTI mutations and which preliminary evidence suggests should be potent and durable. Ritonavir-boosted lopinavir and 2N(t)RTI 2N(t)RTI This is the current standard of care for second line therapy following failure of standard first-line NNRTI+2N(t)RTIs according to WHO guidelines. Ritonavir-boosted lopinavir and raltegravir raltegravir This is an experimental arm which is likely to be fully active in the presence of N(t)RTI mutations and which preliminary evidence suggests should be potent and durable.
- Primary Outcome Measures
Name Time Method Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization 48 weeks following randomization
- Secondary Outcome Measures
Name Time Method Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population 48 weeks The per- protocol population includes those participants who fulfil the protocol in the terms of the eligibility, interventions, and outcome assessment
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Non-completer Classed as Failure 48 weeks The non-completer classed as failure analysis will include all randomised participants; participants who meet the following criteria will be defined as failures:
i. week 48 HIV RNA being above each threshold ii. has missing HIV-1 RNA data for any reason iii. stops randomly assigned therapyParticipants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Baseline VL >100,000 Copies Per mL 48 weeks The difference between treatment arms in proportion of participants with plasma HIV RNA \< 200 copies/mL 48 weeks after randomization, per-protocol population: stratified analysis by baseline plasma viral load (less than or equal to 100,000 copies per mL or \>100,000 copies per mL) on those participants who fulfil the protocol in the terms of the eligibility, interventions, and outcome assessment
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, VL Less Than or Equal to 100,000 Copies Per mL 48 weeks The per- protocol population includes those participants who fulfil the protocol in the terms of the eligibility, interventions, and outcome assessment
Trial Locations
- Locations (44)
Albion Street Centre
🇦🇺Sydney, New South Wales, Australia
Instituto Nacional de Ciencias Medicas y Nutricion "Salvado Zubiran"
🇲🇽Mexico City, Mexico
Plateau State Specialist Hospital
🇳🇬Jos, Plateau State, Nigeria
Hospital General de Agudos 'Teodoro Alvarez'
🇦🇷Buenos Aires, Argentina
Hospital Sungai Buloh
🇲🇾Kuala Lumpur, Malaysia
Hospital General de Guadalajara
🇲🇽Guadalajara, Mexico
Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia
🇵🇪Lima, Peru
CAICI
🇦🇷Buenos Aires, Rosario Provincia De Sante Fe, Argentina
Hospital General de Leon
🇲🇽Leon, Mexico
IMPACTA/Hospital Dos de Mayo
🇵🇪Lima, Peru
Hospital de la Universidad Catolica Pontificia
🇨🇱Santiago, Chile
Evangel Hospital (ECWA)
🇳🇬Jos, Plateau State, Nigeria
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Hospital Almenara
🇵🇪Lima, Peru
Chelsea and Westminster Hospital
🇬🇧Fulham, London, United Kingdom
FUNCEI
🇦🇷Buenos Aires, Argentina
Hospital Interzonal General de Agudos, Oscar Alende
🇦🇷Buenos Aires, Mar Del Plata Provincia, Argentina
Hospital Prof. Alejandro Posadas
🇦🇷Buenos Aires, Argentina
Hospital de Infecciosas FJ Muniz
🇦🇷Buenos Aires, Argentina
Hospital Rawson
🇦🇷Cordoba, Argentina
Hospital J.M. Ramos Mejia
🇦🇷Buenos Aires, Argentina
Hospital Central
🇦🇷Mendoza, Argentina
YRG Care
🇮🇳Chennai, India
Institute of Infectious Diseases
🇮🇳Pune, India
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
J W Goethe Universitat
🇩🇪Frankfurt, Germany
Mater Misericordiae-Dublin
🇮🇪Dublin, Ireland
University of Malaysia
🇲🇾Kuala Lumpur, Malaysia
Hospital Pelau Pinang
🇲🇾Kuala Lumpur, Malaysia
Jos University Teaching Hospital (JUTH)
🇳🇬Jos, Plateau State, Nigeria
Tan Tock Seng Hospital
🇸🇬Singapore, Singapore
Via Libre
🇵🇪Lima, Peru
Josha Research
🇿🇦Bloemfontein, South Africa
Desmond Tutu HIV Foundation
🇿🇦Cape Town, South Africa
Chris Hani Baragwanath Hospital
🇿🇦Soweto, South Africa
Hospital Italiano
🇦🇷Buenos Aires, Argentina
St Vincent's Hospital
🇦🇺Sydney, New South Wales, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Hospital San Borja-Arriaran
🇨🇱Santiago, Chile
Hopital Saint-Louis
🇫🇷Paris, France
Centre Clinic
🇦🇺Melbourne, Victoria, Australia
Medical Group Practice
🇩🇪Berlin, Germany
Auckland Hospital
🇳🇿Grafton, Auckland, New Zealand
Queen Elizabeth Hospital
ðŸ‡ðŸ‡°Hong Kong, Kowloon, Hong Kong