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

Condition(s) targeted: HIV Infections

Intervention: Ritonavir-boosted lopinavir and raltegravir (Drug); Ritonavir-boosted lopinavir and 2N(t)RTI (Drug)

Phase: Phase 4

Status: Not yet recruiting

Sponsored by: The National Centre in HIV Epidemiology and Clinical Research

Official(s) and/or principal investigator(s):
David A Cooper, MD, Study Chair, Affiliation: The National Centre in HIV Epidemiology and Clinical Research
Brian Gazzard, MD, Study Chair, Affiliation: St. Stephen's Trust
Mark A Boyd, MD, Study Director, Affiliation: The National Centre in HIV Epidemiology and Clinical Research

Overall contact:
Mark A Boyd, MD, Phone: 61293850900, Email: mboyd@nchecr.unsw.edu.au

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.

Official title: A Randomised Open-label Study Comparing the Safety and Efficacy of Ritonavir Boosted Lopinavir and 2-3N(t)RTI Backbone Versus Ritonavir Boosted Lopinavir and Raltegravir in Participants Virologically Failing First-line NNRTI/2N(t)RTI Therapy

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Primary outcome: The primary outcome measure of this study is a comparison of the virological efficacy of the two strategies as measured by the proportion of participants with HIV RNA < 200 copies/mL 48 weeks after randomization.

Secondary outcome: A number of secondary outcome measures will be examined in this protocol by randomised treatment arm including virological, immunological, safety and antiretroviral therapy endpoints. Exploratory endpoints include clinical, metabolic, drug resistance.

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.

Minimum age: 16 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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 at least 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 (at least 7 days apart) HIV RNA results of greater then 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:

- absolute neutrophil count (ANC) < 500 cells/microlitres

- hemoglobin < 7. 0 g/decilitres

- platelet count < 50,000 cells/microlitres

- ALT great than 5 x 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, and St. John's wort)

6. Intercurrent illness requiring hospitalization

7. Active opportunistic disease not under adequate control in the opinion of the site Principal Investigator

8. Participants with current alcohol or illicit substance abuse that in the opinion of the site Principal Investigator might adversely affect participation in the study

9. Participants deemed by the site Principal Investigator unlikely to be able to remain in follow-up for the protocol-defined period

Mark A Boyd, MD, Phone: 61293850900, Email: mboyd@nchecr.unsw.edu.au

Hospital Central, Mendoza 5500, Argentina

Hospital General de Agudos 'Teodoro Alvarez', Buenos Aires 1406, Argentina

Hospital Italiano, Buenos Aires, Argentina

Hospital J.M. Ramos Mejia, Buenos Aires, Argentina

Hospital Prof. Alejandro Posadas, Buenos Aires, Argentina

Hospital Rawson, Cordoba, Argentina

FUNCEI, Buenos Aires, Argentina

Hospital San Borja-Arriaran, Santiago, Chile

Hospital de la Universidad Catolica Pontificia, Santiago, Chile

DiTan Hospital, Beijing, China

PUMCH, Beijing, China

Beijing You An Hospital, Beijing, China

Guangzhou No 8 Hospital, Guangzhou, China

Shanghai Public Health Centre, Shanghai, China

Hopital Saint-Louis, Paris, France

J W Goethe Universitat, Frankfurt, Germany

Medical Group Practice, Berlin, Germany

YRG Care, Chennai, India

Mater Misericordiae-Dublin, Dublin, Ireland

University of Malaysia, Kuala Lumpur, Malaysia

Penang Hospital, Kuala Lumpur, Malaysia

Instituto Nacional de Ciencias Medicas y Nutricion "Salvado Zubiran", Mexico D.F., Mexico

Hospital General de Guadalajara, Guadalajara, Mexico

Hospital General de Leon, Leon, Mexico

Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru

IMPACTA/Hospital Dos de Mayo, Lima, Peru

Hospital Almenara, Lima, Peru

Via Libre, Lima, Peru

Tan Tock Seng Hospital, Singapore 308433, Singapore

Josha Research, Bloemfontein, South Africa

Soweto, Soweto, South Africa

National Taiwan University Hospital, Taipei, Taiwan

St Mary's Hospital, London W2 1NY, United Kingdom

Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

Hospital de Infecciosas FJ Muniz, Capital Federal, 1282 Buenos Aires, Argentina

Auckland Hospital, Grafton, Auckland 1, New Zealand

Queen Elizabeth Hospital, Hong Kong, Kowloon, Hong Kong

Chelsea and Westminster Hospital, Fulham, London SW10 9NH, United Kingdom

Hospital Interzonal General de Agudos, Oscar Alende, Buenos Aires, Mar del Plata Provincia 1900, Argentina

Albion Street Centre, Sydney, New South Wales 2010, Australia

Liverpool Hospital, Liverpool, New South Wales 2170, Australia

St Vincent's Hospital, Sydney, New South Wales 2010, Australia

Jos University Teaching Hospital (JUTH), Jos, Plateau State, Nigeria

Plateau State Specialist Hospital, Jos, Plateau State, Nigeria

Evangel Hospital (ECWA), Jos, Plateau State, Nigeria

CAICI, Buenos Aires, Rosario Provincia de Sante Fe 2000, Argentina

The Alfred Hospital, Melbourne, Victoria 3004, Australia

Centre Clinic, Melbourne, Victoria 3182, Australia

Starting date: September 2009
Ending date: August 2012
Last updated: August 6, 2009