TABLE 1.
Potential use of protease inhibitors in HAART
| FDA-approved HIV-1 protease inhibitorsa
|
Recommended companion nucleoside inhibitors for triple therapyb | |
|---|---|---|
| Name (synonym) | Company (code) | |
| Saquinavir (Invirase or Fortovase) | Roche (Ro-31-8959) | AZT + ddI |
| Ritonavir (Norvir) | Abbott (ABT-538) | d4T + ddI |
| Indinavir (Crixivan) | Merck (MK-639,L735) | AZT + ddC |
| Nelfinavir (Viracept) | Agouron (AG-1343) | AZT + 3TC |
Some compounds not yet FDA approved but in the pipeline are DMP-450 (analog of DMP-323 but with good oral bioavailability and a low Ki of 0.3 nM), VX-470 (141W94), and KNI-272 (tight-binding transition state analog containing allophenylnorstatine [12]). Recently, amprenavir (Agenerase) was FDA approved, and the information is described in the text.
This table is from a list that was compiled based on recommendations by several pharmaceutical manufacturers at the 1999 ICAAC Meeting in San Francisco. As noted at the July 2000 AIDS World Congress (D. Moodley, personal communication), nevirapine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is recommended alone in one dose during labor, one at birth, and one after birth as a low-cost replacement for the more complex AZT treatment. Also, there is currently some controversy among clinicians as to whether efavirenz (Sustiva), another NNRTI, should be used first before PIs, due to its simplicity of dosage (one pill a day because of its long half-life [40 to 55 h]) and its prevention of problems with lipodystrophy, saving the PIs for a time when RT inhibitors fail. Thus, there is some flux about which HIV drugs are optimal, and we have provided only a potential snapshot in this table.