Lopinavir/ritonavir monotherapy after 24 weeks of second-line antiretroviral therapy in Africa: a randomized controlled trial (SARA)

Gilks, Charles F., Walker, A. Sarah, Dunn, David T., Gibb, Diana M., Kikaire, Ben, Reid, Andrew, Musana, Hellen, Mambule, Ivan, Kasirye, Ronnie, Robertson, Val, Ssali, Francis, Spyer, Moira, Pillay, Deenan, Yirrell, David and Kaleebu, Pontiano (2012) Lopinavir/ritonavir monotherapy after 24 weeks of second-line antiretroviral therapy in Africa: a randomized controlled trial (SARA). Antiviral Therapy, 17 7: 1363-1373. doi:10.3851/IMP2253

Author Gilks, Charles F.
Walker, A. Sarah
Dunn, David T.
Gibb, Diana M.
Kikaire, Ben
Reid, Andrew
Musana, Hellen
Mambule, Ivan
Kasirye, Ronnie
Robertson, Val
Ssali, Francis
Spyer, Moira
Pillay, Deenan
Yirrell, David
Kaleebu, Pontiano
Title Lopinavir/ritonavir monotherapy after 24 weeks of second-line antiretroviral therapy in Africa: a randomized controlled trial (SARA)
Journal name Antiviral Therapy   Check publisher's open access policy
ISSN 1359-6535
Publication date 2012-01
Year available 2012
Sub-type Article (original research)
DOI 10.3851/IMP2253
Open Access Status
Volume 17
Issue 7
Start page 1363
End page 1373
Total pages 11
Place of publication London, United Kingdom
Publisher International Medical Press
Collection year 2012
Language eng
Formatted abstract
 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/mm3 (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.
Keyword Resource Limited Settings
Public Health Approach
Hiv Infected Patients
Protease Inhibitor
Virological Failure
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Public Health Publications
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Citation counts: TR Web of Science Citation Count  Cited 12 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 13 times in Scopus Article | Citations
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