1. Switch to LPV/r monotherapy  Pilot LPV/r  M03-613  LPV/r Mono  KalMo  OK  OK04  KALESOLO  MOST  HIV-NAT 077

2.  Design  Objective –Non inferiority of the monotherapy group in the proportion of patients with HIV-1 RNA < 50 c/mL at W48 without modification of treatment (per-protocol analysis) ; lower limit of two-sided 90% CI for the difference = - 12%, 80% power –Patients lost to follow-up or with no HIV-1 RNA value at W48 were considered as failures (missing = failure) Continuation current triple antiretroviral therapy (CART) LPV/r 400/100 mg bid Randomisation* 1 : 1 Open-label HIV+ ≥ 18 years On stable cART > 3 months No history of prior virologic failure on PI HIV-1 RNA 6 months N = 87 N = 99 W48 KALESOLO Study: Switch to LPV/r monotherapy Meynard JL, JAC 2010;65:2436-44 KALESOLO * Randomisation was stratified by centre, and ongoing treatment (LPV/r, PI other than LPV/r, NNRTI)

3. KALESOLO Study: Switch to LPV/r monotherapy Continuation of cART N = 99 LPV/r monotherapy N = 87 Median age, years4344 Female24%28% CDC stage C28%25% CD4 cell count, median/mm 3 525494 HIV-RNA < 50 c/mL96%94% ARV at inclusion15.728.6 3TC/FTC ZDV TDF ABC ddI 78% 38% 33% 21% 15% 80% 41% 25% 21% 16% NNRTI 25%29% PI: LPV/r ; other PI 33% ; 41%32% ; 39% Discontinuation by W48, n910 (6 re-intensified) Baseline characteristics and patient disposition Meynard JL, JAC 2010;65:2436-44 KALESOLO

4. Virologic outcome at W48 KALESOLO Study: Switch to LPV/r monotherapy cART N = 12 LPV/mono N = 14 HIV-1 RNA > 50 c/mL05 HIV-1 RNA measure missing 50 Change of ARV For virologic failure For adverse event 703703 10 8 1 Meynard JL, JAC 2010;65:2436-44 KALESOLO Therapeutic failure  Non inferiority of LPV/r monotherapy not demonstrated 88 91 88 84 HIV-1 RNA < 50 c/mL 95% CI for the difference = - 12.4 ; 4.5 95% CI for the difference = - 4.5 ; 10.4 HIV-1 RNA < 50 c/mL with re-intensification allowed 0 25 50 75 100 % 99879987N= LPV/r monoContinue cART

5. KALESOLO Study: Switch to LPV/r monotherapy  Multivariate analysis: treatment failure was not associated with adherence to therapy but was associated with older age at baseline  Of samples with HIV-1 RNA > 50 c/mL, 20 genotypes from 14 patients (all in the LPV/r monotherapy group) could be analysed: 1 patient developed major PI resistance mutation, no patient developed mutations conferring resistance to LPV/r  For lipids, fasting total cholesterol changes were significantly higher in the LPV/r monotherapy group (+ 0.42 mmol/L vs + 0.08 mmol/L ; p = 0.04)  None of the 12 serious adverse events were drug-related  Grade 3 to 4 laboratory abnormalities occurred in 3 patients in each group  Diarrhoea was more frequent in the LPV/r monotherapy group (N = 34 vs N = 13 ; p < 0.001) Other outcomes Meynard JL, JAC 2010;65:2436-44 KALESOLO

6. KALESOLO Study: Switch to LPV/r monotherapy  Conclusions –In patients with virologic suppression, by per-protocol analysis, LPV/r monotherapy did not achieve non inferiority versus continuation of current antiretroviral regimen for maintaining HIV-1 RNA < 50 c/mL –The incidence of virologic failure was low and successfully managed by treatment reintensification Meynard JL, JAC 2010;65:2436-44 KALESOLO