Switching to 50mg ritonavir dose for selected protease inhibitors

Polly Clayden HIV i-Base

Although not appropriate for LPV (see previous article), a 50mg boosting dose of RTV may be sufficient for selected PIs, argue researchers from the University of Liverpool and Chelsea and Westminster in a letter to the editor published in the December 15 2011 edition of JAIDS.

Lower doses of RTV may be better tolerated, cheaper and easier to co-formulate with PIs than the current dose.

Andrew Hill and colleagues identified four crossover PK studies evaluating 50 vs 100mg of RTV. These included boosting once daily atazanavir (ATV), 300/50 vs 300/100mg and once daily darunavir (DRV) 800/50 vs 800/100mg. The other two studies indentified by the researchers were with saquinavir and amprenavir, which are less commonly used PIs and not preferred options, particularly in resource-limited settings.

These small PK studies – conducted with 13 and 18 participants for ATV and DRV respectively – showed bioequivalent AUC and Cmax concentrations of both drugs using the lower and higher RTV doses. But Cmin concentrations were slightly lower when boosted with the 50 mg dose of RTV. See Table 1: PK parameters of ATV and DRV boosted with 50 and 100mg of RTV.

Table 1: PK parameters of ATV and DRV boosted with 50 and 100mg of RTV
PI (Ref)/dose Cmax mg/L AUC mg.h.L Cmin mg/L
ATV 300/50 mg 5.07 47.1 0.59
ATV 300/100 mg 5.19 50.6 0.79
DRV 800/50 mg 6.14 (1.32) 68.5 (20.5) 1.67 (0.64)
DRV 800/100 mg 6.17 (1.27) 77.2 (23.5) 2.12 (0.80)

Mean PKs of boosted PI (SD)

The researchers explained that the clinical significance of the lower Cmin levels was not known and this would need to be investigated in larger studies including efficacy endpoints. They added that small differences in RTV boosting doses might have different consequences in treatment naïve and experienced patients.

They noted that as RTV is only marketed as a 100 mg tablet, these studies were conducted using the liquid formulation. If a 50mg heat stable tablet of RTV could be manufactured or 50 mg coformulated with either PI, new bioequivalence trials would be needed to ensure the boosting effects were similar to those achieved with the liquid.

A 50mg RTV tablet would also be very useful for paediatric dosing, as the liquid is expensive, impractical (particularly for resource limited settings) and tastes dreadful.

They concluded that if lower doses of RTV are able to achieve bioequivalence there is a strong justification for the development of a 50mg tablet and/or coformulations of RTV with these PIs.


Once again, the 50 mg RTV tablet really would be useful in paediatrics.

The generic companies should be able to make 50 mg tablets and get approval by showing that 2 x 50 mg tablets are bioequivalent to an Abbott 100 mg tablet.


Hill A et al. Should we switch to a 50mg boosting dose of ritonavir for selected protease inhibitors? J Acquir Immune Defic Syndr. Volume 58. Number 5. December 15, 2011.

Links to other websites are current at date of posting but not maintained.