When and how to use tipranavir and darunavir

• Published in: The AIDS reader Vol. 17; no. 4; p. 194
• Main Authors: Hoffman, Christopher J, Gallant, Joel E
• Format: Journal Article
• Language: English
• Published: United States MultiMedia Healthcare Inc 01.04.2007
• Subjects: Anti-HIV Agents - administration & dosage; Anti-HIV Agents - therapeutic use; Darunavir; Drug Administration Schedule; Drug Interactions; HIV Infections - drug therapy; Humans; Pyridines - administration & dosage; Pyridines - therapeutic use; Pyrones - administration & dosage; Pyrones - therapeutic use; Sulfonamides - administration & dosage; Sulfonamides - therapeutic use; Viral Load
• ISSN: 1053-0894

The efficacy of ritonavir-boosted tipranavir (TPV/r) in patients with resistance to multiple PIs was demonstrated in the RESIST trials.6,9,10 In these trials, patients with significant PI resistance were randomized to receive either TPV/r or the best available ritonavir-boosted comparator PI; both groups also received an optimized background regimen. After 48 weeks, 22.8% of participants who received TPV/r had HIV RNA levels below 50 copies/mL, compared with 10.2% of participants who received a comparator PI.6 The presence of specific mutations was also correlated with reduced virological suppression. A tipranavir "score" can be determined by calculating the total number of the following mutations present at baseline: 10V, 13V, 20M/R/V, 33F, 35G, 36I, 43T, 46L, 47V, 54A/M/V, 58E, 69K, 74P, 82L/T, 83D, and 84V. At 2 weeks of treatment, patients with a tipranavir score of 7 or less had a median log10 decline in HIV RNA level of greater than 1 log; those with tipranavir scores greater than 7 had minimal response. However, after 24 weeks, subjects with 0 or 1 tipranavir mutation achieved a median 2-log10 decrease in HIV RNA level, compared with a median 0.5- to 1.5-log10 decrease for those with a tipranavir score of 2 to 7.12 Thus tipranavir is considered to have full activity with a score of 0 or 1, intermediate activity with a score between 2 and 7, and minimal activity with higher scores. Other drugs to avoid or use with caution with either TPV/r or DRV/r include the general list of drugs that are metabolized by or induce CYP 3A4. Drugs to avoid coadministering with either TPV/r or DRV/r because of significantly increased or decreased levels of the coadministered drug include ergot alkaloids, terfenadine, astemizole, cisapride, pimozide, midazolam, and triazolam. Drugs to coadminister with caution because of increases or decreases in the coadministered drug levels include atorvastatin, pravastatin, sildenafil, vardenafil, tadalafil, digoxin, and voriconazole. Coadministration of oral contraceptives may result in low estradiol levels leading to failure to prevent pregnancy. TPV/r also significantly increases levels of rifabutin and fluticasone and decreases the level of methadone, and coadministration of TPV/r with fluconazole leads to higher tipranavir levels. Use of metronidazole with TPV/r may cause a disulfiram-like reaction and should be avoided.