Drug levels and HIV

July 2001     View PDF     En español

Drug interactions

Many anti-HIV drugs and therapies used to prevent or treat opportunistic infections are metabolized by the same enzyme in the body. This means that there are many possible drug interactions. As a result, it becomes more important to talk about this issue with your doctor or pharmacist about all the meds you’re taking, including over-the-counter herbs and vitamins. More information on drug interactions is available through Project Inform’s Infoline.

One of the most discussed issues on drug interactions in the past few years has been using ritonavir to boost the levels of other protease inhibitors. This approach can result in less frequent dosing and a reduced daily dose. This is achieved in one of two ways: A] ritonavir can greatly increase the Cmax of lopinavir and saquinavir without significantly changing the rate at which the other drug is eliminated from the body, or B] ritonavir can slow down the rate of indinavir, nelfinavir and amprenavir from being eliminated from the body without greatly changing the Cmax.

Dark line – lopinavir or saquinavir taken alone
Gold line – results when taking drug with ritonavir

 

Dark line – indinavir, nelfinavir or amprenavir taken alone
Gold line – results when taking drug with ritonavir

 

Early results suggest that ritonavir is able to boost the levels of two protease inhibitors at the same time, indicating that this may possibly be a useful strategy for third line therapy.

Boosting drug levels, however, may make interpreting resistance results more challenging because the higher drug levels may “overpower” some of the drug-resistant viruses. Currently, most people consider a four times decrease in sensitivity to a drug to mean low level resistance while anything over a ten-times decrease means high level resistance. This is generally considered acceptable because blood levels of a drug are usually only four to eight times higher than what is simply needed to block HIV from reproducing.

However, ritonavir boosts the drug levels of some protease inhibitors upward of 15 times or higher and so these standard 4–10 times changes for resistance tests may become irrelevant. In other words, you may “overpower” some of these resistant viruses by using ritonavir and another protease inhibitor even though your test results indicate you may be resistant to one or more of these drugs. As a result, it may be important to factor in drug levels when evaluating results from your tests.

ATHENA study

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