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istering ritonavir Proton pump inhibitors are contraindicated in patients taking atazanavir because atazanavir requires an acidic pH to remain in solution i Tipranavir Tipranavir is the first nonpeptidic PI approved by the US Food and Drug Administration (FDA) Because of its unique structure, it is active against some strains of HIV that are resistant to other PIs It is dosed with ritonavir (two 250 mg capsules of tipranavir with two 100 mg capsules of ritonavir orally twice daily with food) The most common side effects are nausea, vomiting, diarrhea, fatigue, and headache Tipranavir/ritonavir has been also associated with liver damage and should be used very cautiously in patients with underlying liver disease Recent reports of intracranial hemorrhage in patients taking tipranavir-containing regimens have raised additional safety concerns about this potent PI Because it is a sulfa-containing drug, its use should be closely monitored in patients with sulfa allergy j Darunavir Darunavir is the most recently approved PI with impressive antiviral activity in the setting of significant PI resistance The dosage is 600 mg orally twice daily dosed with 100 mg of ritonavir Darunavir appears to be reasonably welltolerated with a safety profile similar to other PIs, such as lopinavir/ritonavir 3 Nonnucleoside reverse transcriptase inhibitors NNRTIs inhibit reverse transcriptase at a site different from that of the nucleoside and nucleotide agents described above All three have shown antiviral activity as measured by HIV viral load and CD4 responses The major advantage of the NNRTIs is that two of them (nevirapine and efavirenz) have potencies comparable to that of PIs with lower pill burden and fewer side effects In particular, they do not appear to cause lipodystrophy; patients with cholesterol and triglyceride elevations who are switched from a PI to an NNRTI may have improvement in their symptoms The resistance patterns of the NNRTIs are distinct from those of the PIs, so their use still leaves open the option for future PI use The NNRTIs can be used with PIs in patients who are difficult to suppress on simpler regimens or when it is difficult to identify at least two agents to which the patient is not resistant Because these agents may cause alterations in the clearance of PIs, dose modifications may be necessary when these two classes of medications are administered concomitantly Resistance to one drug in this class uniformly predicts resistance to other drugs in the class, though second-generation drugs are being developed There is no therapeutic reason for using more than one NNRTI at the same time a Efavirenz The major advantage of efavirenz is that it can be given once daily in a single dose (600 mg orally) The side effects are neurologic, with patients reporting symptoms ranging from lack of concentration and strange dreams to delusions and mania Fortunately, the neurologic side effects of efavirenz subside over time, usually within a month Due to teratogenicity, efavirenz should be avoided in women who wish to conceive or are already pregnant A once-daily fixeddose combination of efavirenz, tenofovir, and emtricitabine in a single pill (Atripla) is available and is probably the best first.

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