Virological findings from the SARA trial ofboosted protease inhibitor monotherapy
Polly Clayden, HIV i-Base
There is currently an interest in using boosted protease inhibitor monotherapy as a maintenance strategy in resource rich countries.
A pilot substudy of the DART trial, Second-line Anti-Retroviral therapy in Africa (SARA), randomised 192 patients who had received 24 weeks of lopinavir/ritonavir-based (LPV/r) second-line combination therapy to either continue on this combination or to receive LPV/r maintenance monotherapy. Prior to the switch, DART patients had taken first line therapy for a median of 4.4 years.
Data were presented as a late breaker poster at IAS 2010 suggesting few differences between the two groups in CD4 increases or adverse events in the short term.  At week 24 the mean CD4 gain was 48 vs 42 cells/mm3 in the combination and monotherapy arms respectively. For those completing 72 weeks the gains were 159 vs 153 cells/mm3.
No real-time virology was performed in DART but plasma samples were stored from: time at switch to second line, time of SARA randomisation, 24-weeks after SARA randomisation and latest time point (35-107 weeks after SARA randomisation).
Dave Yirrel presented results at Glasgow 2010 from a retrospective analysis of viral load, measured by Roche Amplicor v1.5 on the stored samples. In addition, genotype resistance was assessed on samples with viral load >1000 copies/mL at 24 weeks. Analyses were intent to treat. 
The median CD4 counts overall were 86 cells/mm3 at switch to second line and 245 cells/mm3 at SARA randomisation. The majority of patients (86%) had received a triple nucleoside first line regimen and the remainder two nucleosides and an NNRTI. At SARA randomisation 22% were receiving LPV/r + 2/3 NRTIs, 15% LPV/r + NNRTI and 62% LPV/r + NNRTI + NRTI. Of those with viral load measurements 135/173 (77%) had viral load <50 copies/mL.
The investigators found a higher proportion with undetectable viral load among patients on combination therapy compared to monotherapy at week 24, p=0.007. They reported 77% (70/91) vs 60% (66/94) had viral loads <50 copies/mL and 94% vs 84% had viral load <1000 copies/mL.
Among the small number of patients for whom 96-week data were available for analysis, the proportion with rebound to >200 copies/mL was greater in the monotherapy than combination therapy arm: 50% vs 20% (n=7 per arm). This difference was similar among those with rebound >1000 copies/mL: 40% vs 10% (n=7 in the monotherapy and , n=8 in the combination therapy arms).
Genotype results from the patients with viral load >1000 copies/mL at 24 weeks showed 0/5 patients with major protease inhibitor mutations of those in the combination therapy arm and 4/16 (of 19 patients with rebound to 1000 copies/mL) in the monotherapy arm.
The investigators concluded that, over the relatively short period of follow up (median 60 weeks) since SARA randomisation, there was an increase in low level viraemia with monotherapy compared to combination therapy, but no evidence of systematic increase in viral load after loss of suppression.
The EARNEST trial due to start next year will provide data on the long-term effectiveness of PI maintanance monotherapy in this setting. 
Neither the numbers involved, nor the duration of the trial make it possible to make any definite conclusion from these data. But it does seem that boosted PI monotherapy may not be a viable option in settings without access to viral load monitoring.
- Gilks CF et al. Boosted protease inhibitor monotherapy as maintenance Second-line Anti-Retroviral therapy in Africa: a randomised controlled trial (SARA). 18th International AIDS Conference. 18-23 July, 2010. Vienna. Poster abstract LBPE16.
- Pillay et al. Virological findings from the SARA trial: boosted PI monotherapy as maintenance second-line ART in Africa. 10th International Congress on Drug Therapy in HIV Infection, November 7-11. Glasgow. Oral abstract O20. Published in Journal of the International AIDS Society 2010 13(Suppl 4). O214.
- Europe – Africa Research Network for Evaluation of Second-line Therapy (EARNEST) study.