Slide 38 of 76
Notes:
Combining protease inhibitors may be desirable, for a number of different reasons:
To improve adherence. The logistics of taking multiple antiretroviral agents can be very burdensome, and may adversely affect medication adherence. When certain drugs are combined, dosing regimens may be simplified, and often pill burden and/or food restrictions may be minimized. For instance, when indinavir and ritonavir are both used for therapeutic effect, lower dosages of both (I.e., indinavir 400 mg BID and ritonavir 400 mg BID) may be used. In addition, in the presence of ritonavir, indinavir absorption is no longer significantly affected by the presence of food.
To minimize side effects. The standard dosage of ritonavir is 600 mg twice daily. At this dosage, many patients may experience significant toxicity, such as gastrointestinal upset, nausea, diarrhea, flushing, and peri-oral tingling. When ritonavir is combined with saquinavir, a lower dosage may be used, with better tolerance. Another example may be seen when indinavir is coadministered with ritonavir: indinavir peak levels are lower, which may potentially be associated with a reduced risk of nephrolithiasis.
To enhance antiviral activity. Additive or synergistic antiviral effects may be observed when various antiretrovirals are administered together. For instance, ritonavir and saquinavir have demonstrated in vitro synergy against HIV, and long-term viral suppression in protease inhibitor-naïve patients has been demonstrated with this combination.
