Raltegravir non-inferior to nucleoside based regimens in second-line therapy with lopinavir/ritonavir over 96 weeks: a randomised open label study for the treatment of HIV-1 infection.
OBJECTIVE
To determine the durability over 96 weeks of safety and efficacy of lopinavir/ritonavir (LPV/r) and raltegravir (RAL) which was demonstrated to have non-inferior efficacy relative to a regimen of LPV/r with nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) (Control) in primary analysis at 48 weeks.


METHODS
Open label, centrally randomised trial.


METHODS
Recruitment was from 37 primary and secondary care sites from Africa, Asia, Australia, Europe and Latin America.


METHODS
541 HIV-1 infected adults virologically failing first-line non-NRTI + 2N(t)RTI, with no previous exposure to protease inhibitors or integrase strand transfer inhibitors were analysed, 425 completed 96 weeks follow up on randomised therapy.


METHODS
Randomisation was 1:1 to Control or RAL.


METHODS
Differences between the proportion of participants with plasma HIV-1 RNA (VL) <200 copies/mL by intention to treat were compared with a non-inferiority margin of -12%. Differences in biochemical, haematological and metabolic changes were assessed using T-tests.


RESULTS
VL <200 copies/mL at 96 weeks was: RAL 80.4%, Control 76.0% (difference: 4.4 [95%CI -2.6, 11.3]) and met non-inferiority criteria. The RAL arm had a significantly higher mean change (difference Control-RAL; 95%CI) in haemoglobin (-2.9; -5.7, -1.1), total lymphocytes (-0.2; -0.3, -0.0), total cholesterol (-0.5; -0.8, -0.3), HDL cholesterol (-0.1; -0.1, -0.0) and LDL cholesterol (-0.3; -0.5, -0.2).


CONCLUSIONS
At 96 weeks, both RAL and Control maintained efficacy greater than 75% and continued to demonstrate similar safety profiles. These results support the use of a combination LPV/r and RAL regimen as an option following failure of 1st line NNRTI + 2N(t)RTIs.


BACKGROUND
ClinicalTrials.gov NCT00931463.
The Kirby Institute, UNSW Australia, Sydney, Australia.
Janaki
J
Amin
The Kirby Institute, UNSW Australia, Sydney, Australia.
Mark A
MA
Boyd
Y. R. Gaitonde Centre for AIDS Research and Education, Chennai, India.
Nagalingeswaran
N
Kumarasamy
The Kirby Institute, UNSW Australia, Sydney, Australia.
Cecilia L
CL
Moore
Hospital JM Ramos Mejia, Buenos Aires, Argentina.
Marcello H
MH
Losso
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, United States of America.
Chidi A
CA
Nwizu
University of the Witwatersrand and Baragwanath Hospital, Johannesburg, South Africa.
Lerato
L
Mohapi
UNSW Australia, The HIV Netherlands Australia Thailand Research Collaboration, Bangkok, Thailand.
Stephen J
SJ
Kerr
TREAT Asia, amfAR, The Foundation for AIDS Research, Bangkok, Thailand.
Annette H
AH
Sohn
Merck Research Laboratories, Merck Sharp & Dohme, Whitehouse Station, New Jersey, United States of America.
Hedy
H
Teppler
Global Medical Affairs Virology, Abbvie, North Chicago, Illinois, United States of America.
Boris
B
Renjifo
Service des Maladies Infectieuses, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris, Paris, France.
Jean-Michel
JM
Molina
The Kirby Institute, UNSW Australia, Sydney, Australia.
Sean
S
Emery
The Kirby Institute, UNSW Australia, Sydney, Australia.
David A
DA
Cooper
D000328:Adult; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D061466:Lopinavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D000068898:Raltegravir Potassium / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D063127:Secondary Health Care
D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D061466:Lopinavir; D000068898:Raltegravir Potassium; D019438:Ritonavir