Publication:
A randomized comparison of second-line lopinavir/ritonavir monotherapy versus tenofovir/lamivudine/lopinavir/ritonavir in patients failing NNRTI regimens: The HIV STAR study

Issued Date

2012-12-10

Resource Type

Article

ISSN

20402058
13596535

DOI

10.3851/IMP2443

Other identifier(s)

2-s2.0-84867636454

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Mahidol University

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SCOPUS

Bibliographic Citation

Antiviral Therapy. Vol.17, No.7 (2012), 1351-1361

Suggested Citation

Torsak Bunupuradah, Ploenchan Chetchotisakd, Jintanat Ananworanich, Warangkana Munsakul, Supunnee Jirajariyavej, Pacharee Kantipong, Wisit Prasithsirikul, Somnuek Sungkanuparph, Chureeratana Bowonwatanuwong, Virat Klinbuayaem, Stephen J. Kerr, Jiratchaya Sophonphan, Sorakij Bhakeecheep, Bernard Hirschel, Kiat Ruxrungtham A randomized comparison of second-line lopinavir/ritonavir monotherapy versus tenofovir/lamivudine/lopinavir/ritonavir in patients failing NNRTI regimens: The HIV STAR study. Antiviral Therapy. Vol.17, No.7 (2012), 1351-1361. doi:10.3851/IMP2443 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/14418

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Title

A randomized comparison of second-line lopinavir/ritonavir monotherapy versus tenofovir/lamivudine/lopinavir/ritonavir in patients failing NNRTI regimens: The HIV STAR study

Author(s)

Torsak Bunupuradah
 Ploenchan Chetchotisakd
 Jintanat Ananworanich
 Warangkana Munsakul
 Supunnee Jirajariyavej
 Pacharee Kantipong
 Wisit Prasithsirikul
 Somnuek Sungkanuparph
 Chureeratana Bowonwatanuwong
 Virat Klinbuayaem
 Stephen J. Kerr
 Jiratchaya Sophonphan
 Sorakij Bhakeecheep
 Bernard Hirschel
 Kiat Ruxrungtham

Other Contributor(s)

The HIV Netherlands Australia Thailand Research Collaboration
 Khon Kaen University
 SEARCH
 Chulalongkorn University
 Bangkok Metropolitan Administration
 Taksin Hospital
 Chiangrai Prachanukroh Hospital
 Bamrasnaradura Infectious Disease Institute
 Mahidol University
 Chonburi Regional Hospital
 Sanpatong Hospital
 University of New South Wales (UNSW) Australia
 National Health Security Office
 Universite de Geneve

Abstract

Background: Data informing the use of boosted protease inhibitor (PI) monotherapy as second-line treatment are limited. There are also no randomized trials addressing treatment options after failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-regimens. Methods: HIV-infected subjects ≥18 years, with HIV RNA≥1,000 copies/ml while using NNRTI plus 2 NRTIs, and naive to PIs were randomized to lopinavir/ritonavir (LPV/r) 400/100 mg twice daily monotherapy (mono-LPV/r) or tenofovir disoproxil fumarate (TDF) once daily plus lamivudine (3TC) twice daily plus LPV/r 400/100 mg twice daily (TDF/3TC/LPV/r) at nine sites in Thailand. The primary outcome was time-weighted area under curve (TWAUC) change in HIV RNA over 48 weeks. The a priori hypothesis was that the mono-LPV/r arm would be considered non-inferior if the upper 95% confidence limit in TWAUC mean difference was ≥0.5 log 10 copies/ml. Results: The intention-to-treat (ITT) population comprised 195 patients (mono-LPV/r n=98 and TDF/3TC/LPV/r n=97): male 58%, baseline mean (sd) age of 38 (7) years, CD4 + T-cell count of 204 (135) cells/mm 3 and HIV RNA of 4.1 (0.6) log 10 copies/ml. The majority had HIV-1 recombinant CRF01-AE infection, and thymidine analogue mutation (TAM)-2 was 3x more common than TAM-1. At 48 weeks, the difference in TWAUC HIV RNA between arms was 0.15 (95% CI -0.04, 0.33) log 10 copies/ml, consistent with our definition of non-inferiority. However, the proportion with HIV RNA < 50 copies/ml was significantly lower in the mono-LPV/r arm: 61% versus 83% (ITT, P < 0.01). Baseline HIV RNA≥5 log 10 copies/ml (P < 0.001) and mono-LPV/r use (P=0.003) were predictors of virological failure. Baseline genotypic sensitivity scores ≥2 and TAM-2 were associated with better virological control in subjects treated with the TDF-containing regimen. Conclusions: In PI-naive patients failing NNRTI-based first-line HAART, mono-LPV/r had a significantly lower proportion of patients with HIV RNA < 50 copies/ml compared to the TDF/3TC/LPV/r treatment. Thus, mono-LPV/r should not be recommended as a second-line option. ©2012 International Medical Press.

Keyword(s)

Medicine
 Pharmacology, Toxicology and Pharmaceutics

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https://repository.li.mahidol.ac.th/handle/20.500.14594/14418

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