Drug Resistance

In the context of HIV, the development of "resistance" refers to a decrease in a medication's power to fight the HIV virus. This is brought on by genetic changes within the virus called "mutations," which happen while the virus is making copies of itself.

A genetic mutation doesn't change the way your medication works, it changes the way the virus looks to the medication. If the virus has changed a lot, the medication will not be able to recognize the virus to work the way it should, and the virus will no longer be vulnerable or "susceptible" to the medication—this is drug resistance.

So, if the amount of HIV in the blood is not kept low and in control, the possibility of drug resistance increases greatly, and this can limit future treatment options.

A study of KALETRA in combination therapy has shown that it might help reduce the chance of HIV developing resistance and may help keep future treatment options open. In a clinical study*, a group of patients was treated with a KALETRA regimen. Another group of patients in the same study was treated with an HIV medicine called Viracept® (nelfinavir mesylate) in their regimen. Both groups were also given the nucleosides Epivir® and Zerit®. Certain patients from both groups were tested to see if their HIV developed resistance^† from 24 to 48 weeks of therapy. The results of these tests showed that of the patients who were tested for resistance:

• None (0%) taking the KALETRA regimen had HIV that developed resistance to KALETRA*
• Twenty-five patients (33%) taking Viracept® had HIV that developed resistance to Viracept
• Fewer patients on a KALETRA-based regimen developed resistance to Epivir than did those on a Viracept-based regimen.^‡ Of those tested, 15 patients (41%) on a KALETRA-based regimen had resistance to Epivir, and 62 patients (82%) of those tested on the Viracept-based regimen also developed resistance to Epivir.

Selection or resistance to KALETRA in patients new to therapy have not been characterized.

• Resistance to KALETRA has emerged in patients treated with other protease inhibitors prior to KALETRA therapy

* In the clinical study, 326 patients took KALETRA and 327 patients took Viracept in combination with Epivir and Zerit. After 48 weeks of therapy 67% of patients on the KALETRA regimen vs. 52% of patients on the Viracept regimen achieved an undetectable viral load. Of the patients taking KALETRA, 58 had detectable viral loads (more than 400 copies per milliliter of blood). Of the patients taking nelfinavir, 102 had detectable viral loads. Patients from both groups were given a genotypic test ("gee-no-tip-ick": identifies specific changes in HIV copies) to find out if they had detectable viral loads because their HIV developed resistance. Of the 48 KALETRA patients with detectable viral loads, 37 were available for testing. Of the 102 nelfinavir patients with detectable viral loads, 76 were available for testing.

† In the clinical study, HIV was considered to be resistant when it had certain changes, called mutations. For KALETRA, these changes were primary or active site mutations (positions 8, 30, 32, 46, 47, 48, 50, 82, 84, or 90 in protease). For nelfinavir, these changes were the D30N and/or L90M mutation in HIV protease.

‡ Epivir resistance defined as the presence of the M 184 I, V, or T mutation in reverse transcriptase.

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