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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Lopinavir/ritonavir monotherapy after 24 weeks of second-line antiretroviral therapy in Africa: A randomized controlled trial (SARA)
Antiviral Therapy, Volume 17, No. 7, Year 2012
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Description
Background: Boosted protease inhibitor (bPI) monotherapy (bPImono) potentially has substantial cost, safety and operational benefits. It has never been evaluated as second-line antiretroviral therapy (ART) in Africa. Methods: After 24 weeks of lopinavir/ritonavir-containing second-line therapy, DART participants were randomized to remain on combination therapy (CT), or change to bPImono maintenance (SARA trial; ISRCTN53817258). Joint primary end points were CD4+ T-cell changes 24 weeks later and serious adverse events (SAEs); retrospectively assayed viral load (VL) was a secondary end point. Analyses were intention-to-treat. Results: A total of 192 participants were randomized to CT (n=95) or bPImono (n=97) and followed for median 60 weeks (IQR 45-84). Participants received median 4.0 years (IQR 3.5-4.4) first-line ART. Median CD4+ T-cell count at first-line failure was 86 cells/mm 3 (47-136), increasing to 245 cells/mm3 (173-325) after 24-week induction when 77% had VL<50 copies/ml. Overall, 44 (23%) were receiving second-line therapy with bPI and nucleoside reverse transcriptase inhibitors (NRTI) only, and 148 (77%) with bPI plus non-NRTI (NNRTI) with or without NRTI. At 24 weeks after randomization to CT versus bPImono, mean CD4+ T-cell increase was 42 (CT, n=85) versus 49 cells/mm3 (bPImono, n=88; adjusted difference 13 [95% CI -15, 43], P=0.37; non-inferior compared with predetermined non-inferiority margin [-33]). Virological suppression was greater for CT versus bPImono (trend P=0.009): 77% (70/91) versus 60% (56/94) were <50 copies/ml, and 5% (5) versus 14% (13) were ≥1,000 copies/ml, respectively. A total of 0 (0%) versus 5 (5%) participants had major protease inhibitor mutations and 3 (3%) versus 0 (0%) new NNRTI/NRTI mutations were detected during follow-up. Two participants (1 CT and 1 bPImono) died >24 weeks after randomization, and 5 (2 CT and 3 bPImono) experienced SAEs (P=0.51). Conclusions: bPImono following a 24-week second-line induction was associated with similar CD4+ T-cell response, but increased low-level viraemia, generally without protease inhibitor resistance. Longer-term trials are needed to provide definitive evidence about effectiveness in Africa. ©2012 International Medical Press.
Authors & Co-Authors
Gilks, Charles F.
United Kingdom, London
Imperial College London
Walker, A. Sarah
United Kingdom, London
Mrc Clinical Trials Unit
Dunn, David T.
United Kingdom, London
Mrc Clinical Trials Unit
Gibb, Diana M.
United Kingdom, London
Mrc Clinical Trials Unit
Kikaire, Bernard
Uganda, Entebbe
Mrc
Reid, Andrew
Zimbabwe, Harare
University of Zimbabwe
Musana, Hellen Wambongo
Uganda, Kampala
Joint Clinical Research Center Uganda
Mambule, Ivan Kiggundu
Uganda, Kampala
Infectious Diseases Institute
Kasirye, Ronnie P.
Uganda, Entebbe
Mrc
Robertson, Valerie J.
Zimbabwe, Harare
University of Zimbabwe
Ssali, Francis N.
Uganda, Kampala
Joint Clinical Research Center Uganda
Spyer, Moira J.
United Kingdom, London
Mrc Clinical Trials Unit
Morris, Lynn G.
United Kingdom, London
University College London
Yirrell, David L.
United Kingdom, Dundee
Ninewells Hospital
Kaleebu, Pontiano P.
Uganda, Entebbe
Mrc
Statistics
Citations: 19
Authors: 15
Affiliations: 8
Identifiers
Doi:
10.3851/IMP2253
ISSN:
13596535
e-ISSN:
20402058
Study Design
Randomised Control Trial
Cohort Study
Study Approach
Quantitative