Non-occupational post exposure prevention

When you think you were exposed to HIV within the past three days

May 2007     View PDF     En español

Which NNRTI or protease inhibitor to consider?

Some nPEP sites routinely prescribe only two NRTIs. Others believe that if nPEP is going to be attempted, the best and most potent shot we have is to use three drugs. These 3-drug regimens are the standard of care for people with established HIV infection, and they have proven to be much more potent than 2-drug regimens. For people who choose a more aggressive nPEP regimen, typically they would use two NRTIs and a PI.

In general, NNRTIs are not used in nPEP regimens. While nevirapine (Viramune) is the more widely studied drug in this class, severe rash associated with nevirapine makes it somewhat unpalatable therapy for nPEP. Risk of developing a severe rash may be greater than the actual chance of HIV infection due to an exposure to HIV. The other NNRTI, efavirenz (Sustiva), has been associated with a high level of side effects, especially in its first month of use, and should not be used by pregnant women or nursing mothers because of possible harmful effects to their child. Delavirdine (Rescriptor) is considered the least potent NNRTI. It is not a widely used anti-HIV drug, so an nPEP regimen with an NNRTI as a third drug is highly unusual.

If one added a PI to make a three-drug regimen, the least likely drug to use is full dose ritonavir (Norvir) because it has a high rate of side effects compared to any of the others. In terms of short-term side effects, there’s little reason to choose one vs. another of the other protease inhibitors: ata­zanavir (Reyataz), fosamprenavir (Lexiva), tipranivir (Aptivus), indinavir (Crixivan), saquinavir (Invirase), darun­avir (Prezista), nelfinavir (Viracept) or lopinavir + ritonavir (Kaletra). However, some are considerably easier to use than others. Some require twice daily dosing, such as Kaletra, nelfinavir, fosamprenavir and darunavir. Some of these drugs require a booster of a second drug (low doses of ritonavir) in order to be effective against HIV. It’s unclear if this is also true when used as part of nPEP regimens. One protease inhibitor, atazanavir, can be taken once daily. Another factor to consider is the number of pills that must be taken each time the drug is used. Both Kaletra (because of its potency) and atazanavir (because of its ease of use) are often among the first choices considered for nPEP regimens.

Over the past decade, several anti-HIV drugs have been approved, greatly expanding the options in the fight against AIDS. Some cannot be used with other drugs (including non-HIV drugs), and/or their dose must be adjusted when combining them. For example, if atazanavir is combined with tenofovir (Viread) or a single pill formulation that includes tenofovir (such as Truvada), it must be used with a low dose of the protease inhibitor ritonavir to help boost its potency. The bottom line is that constructing an anti-HIV regimen to use in PEP should be done with the guidance of someone familiar with anti-HIV drugs and how to combine them. The doctor you see might not be an HIV specialist, but professional support is available to help your doctor, through the national PEPline (1-888-448-4911), in selecting and monitoring an nPEP regimen. This line is intended for use by health care professionals only.

In nPEP, where drugs are only taken for 28 days, it’s fair to assume that both 2- and 3-drug regimens are roughly equal or at least adequate. The true differences in these approaches and among the different drugs probably rest in their ability to suppress HIV replication over a long period of time. In the short-term, for a 28-day nPEP regimen, either approach should be adequate.

NNRTIs are generally better tolerated than any of the PIs, which may make them more desirable for nPEP. Moreover, some PIs have more drug interactions than NNRTIs.