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Updated September 20, 2006

Case 4: Resistance to Nelfinavir

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A 27-year-old woman with a baseline CD4 count of 294 cells/mm3 and HIV RNA of 52,000 copies/mL initiates antiretroviral therapy with a regimen of stavudine (Zerit) plus lamivudine (Epivir) plus nelfinavir (Viracept). She has excellent early success with this regimen and within 4 months her HIV RNA decreases to less than 50 copies/ml and her CD4 count rises to 310 cells/mm3. About 1 year later she has several months of depression and has significant trouble with adherence. Her HIV RNA becomes detectable at 1256 copies/ml and a repeat 4 weeks later shows a value of 2043 copies/ml. A genotype shows a M184V mutation in reverse transcriptase and a D30N mutation in the protease.

Which of the following is TRUE regarding resistance to nelfinavir?

A The D30N mutation will cause cross-resistance to atazanavir (Reyataz) and saquinavir (Invirase), but not to lopinavir-ritonavir (Kaletra).
B The development of the D30N mutation with early virologic failure is unusual in a patient taking a nelfinavir-based regimen. The L90M mutation is usually the most common initial protease inhibitor mutation to occur in this setting.
C Assuming that problems with adherence have been adequately addressed, this patient would have greater than 50% chance of achieving an HIV RNA value less than 50 copies/ml with a carefully designed subsequent regimen.
D Because of the unique resistance profile of nelfinavir, the 2006 DHHS antiretroviral therapy guidelines have ranked it as the preferred protease inhibitor to use in combination antiretroviral therapy in patients who have a CD4 count between 200-350 cells/mm3.