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PLoS One. 2015 Feb 27;10(2):e0118228. doi: 10.1371/journal.pone.0118228. eCollection 2015.

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.

Author information

1
The Kirby Institute, UNSW Australia, Sydney, Australia.
2
Y. R. Gaitonde Centre for AIDS Research and Education, Chennai, India.
3
Hospital JM Ramos Mejia, Buenos Aires, Argentina.
4
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, United States of America.
5
University of the Witwatersrand and Baragwanath Hospital, Johannesburg, South Africa.
6
UNSW Australia, The HIV Netherlands Australia Thailand Research Collaboration, Bangkok, Thailand.
7
TREAT Asia, amfAR, The Foundation for AIDS Research, Bangkok, Thailand.
8
Merck Research Laboratories, Merck Sharp & Dohme, Whitehouse Station, New Jersey, United States of America.
9
Global Medical Affairs Virology, Abbvie, North Chicago, Illinois, United States of America.
10
Service des Maladies Infectieuses, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris, Paris, France.

Abstract

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.

DESIGN:

Open label, centrally randomised trial.

SETTING:

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

SUBJECTS:

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.

INTERVENTION:

Randomisation was 1:1 to Control or RAL.

MAIN OUTCOME MEASURES:

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).

CONCLUSION:

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00931463.

PMID:
25723472
PMCID:
PMC4344344
DOI:
10.1371/journal.pone.0118228
[Indexed for MEDLINE]
Free PMC Article

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