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

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 bPI-mono 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+ 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 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.