PI interactions: lopinavir/rifampicin, saquinavir, atazanavir/tenofovir in pregnancy
Double-dose lopinavir/r insufficient for young children using rifampicin
The effect of doubling the lopinavir/ritonavir dose when given with rifampicin was studied in young children (aged ~0.5-2 years). 
Lopinavir/ritonavir was dosed according to body surface area and was administered twice daily at 460/115 mg/m2 for children receiving rifampicin (n=15) and 230/57.5 mg/m2 for the control group (n=24). Despite the increase in dose, lopinavir AUC, Cmax and Cmin were significantly lower in the rifampicin group (22.29 vs 48.33 mg.h/L, 4.45 vs 7.94 mg/L, 0.63 vs 4.25 mg/L, respectively). 60% of the rifampicin group had sub-therapeutic trough concentrations (<1 mg/L).
Doubling the dose did not overcome the effect of rifampicin and should not be used in young children.There is an urgent need to establish safe, effective and feasible co-treatment for young children with HIV associated TB.
Low dose (50mg) ritonavir may be sufficient to boost saquinavir
This study investigated the possibility of using a lower dose of ritonavir (50 mg) to boost saquinavir concentrations. 
Pharmacokinetics were determined in 18 Thai HIV-positive subjects who received saquinavir (1500 mg twice daily) with ritonavir (100 mg or 50 mg twice daily). Saquinavir pharmacokinetics showed no significant difference when boosted with 100 or 50 mg ritonavir (AUC 27.6 vs 31.0 mg/L.h; Cmax 3.9 vs 4.6 mg/L; Cmin 0.13 vs 0.16 mg/L; median values).
Ritonavir concentrations were significantly higher with the 100 mg dose than with the 50 mg dose.
The lower dose of ritonavir had to be administered as the solution once an acceptable formulation is available, the lower 50 mg dose should be investigated in larger studies and with other protease inhibitors
As this study was in Thai patients, weight may be a factor that needs consideration before this is looked at in other patient groups.
Atazanavir levels reduced with tenofovir in pregnancy
Atazanavir pharmacokinetics were determined in 27 pregnant women receiving atazanavir/ritonavir alone (300/100 mg once daily, n=14) or with tenofovir (300 mg once daily, n=13). 
Median atazanavir AUC and trough concentrations during the third trimester were found to be lower in the presence of tenofovir (32.7 vs 37.5 µg.h/ml, 0.59 vs 0.72 µg/ml, respectively). Atazanavir exposure increased post partum, but was still lower in the presence of tenofovir (AUC 41.9 vs 57.9 µg.h/ml, Ctrough 0.95 vs 1.20 µg/ml). A dose increase of atazanavir/ritonavir to 400/100 mg once daily may be necessary to ensure adequate atazanavir exposure in pregnant women, especially if treatment-experienced or receiving tenofovir.
- McIlleron H, et al. Double dose lopinavir/ritonavir provided insufficient lopinavir exposure in children receiving rifampicin based anti-TB treatment. 16th CROI, Montreal, 2009. Oral abstract 98.
- Van Der Lugt J, et al. A 50 mg boosting dose of ritonavir generates adequate saquinavir plasma concentrations in Thai HIV-infected patients.16th CROI, Montreal, 2009. Abstract 697.
- Mirochnick M, et al. Atazanavir pharmacokinetics with and without tenofovir during pregnancy.16th CROI, Montreal, 2009. Abstract 941.