The protease inhibitor (PI) ritonavir (Norvir) is commonly used in dual-PI combinations as a booster because ritonavir significantly raises the level of other PIs and prolongs the time they remain at high levels in the blood. This has led to the creation of twice- or even once-daily PI-based regimens. However, ritonavir is not always well tolerated. And, according to Italian researchers, there is also the theoretical risk that by exposing HIV to two simultaneous PIs, the virus may more easily develop resistance to PIs, limiting future treatment options.
A possible alternative to the boosting effect of ritonavir is the use of the anti-ulcer drug cimetidine (Tagamet). This drug was tested as a potential immune booster in PHAs in the late 1980s and early 1990s. Unfortunately, trials with cimetidine produced little evidence that this drug delayed the appearance of AIDS.
Now researchers in Italy and the UK are testing cimetidine again, this time as a possible booster for the PI saquinavir (Fortovase). The rationale for this stems from the fact that cimetidine impairs the activity of certain liver enzymes that help break down saquinavir. By reducing the effectiveness of these enzymes, cimetidine could prolong the time saquinavir remains in the blood.
Researchers in Turino, Italy, recruited 12 healthy, HIV negative subjects (4 females, 8 males) for a four-week study. For the first 13 days, subjects received saquinavir 1,200 mg three times daily. After this, the dose was reduced to 1,200 mg twice daily, and cimetidine was added at a dose of 400 mg twice daily.
On average, when cimetidine was used, the amount of saquinavir that entered the blood increased by 120%. Moreover, levels of saquinavir remained higher for longer when it was taken with cimetidine than when it was taken without.
The next step is to conduct studies of cimetidine and saquinavir in HIV positive people to confirm these findings and to study the long-term results and side effects.
REFERENCE
Boffito M, Trentini L, Raiteri R, et al. Pharmacoenhancement of saquinavir by cimetidine: an alternative booster to ritonavir? 3rd International Workshop on Clinical Pharmacology of HIV Therapy, 11-13 April 2002, Washington DC. Abstract 2.8.
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