Clinical Experience with Non-Nucleoside Reverse Transcriptase Inhibitors: L-697,661 and Nevirapine
The four currently approved antiretrovirals all competitively inhibit the reverse transcriptase (RT) enzyme of HIV by acting as nucleoside analogs, causing chain termination when they are incorporated into viral CDNA during the process of reverse transcription.1 Zidovudine (AZT) delays the progression of HIV infection and improves mortality when given to symptomatic immunodeficient patients.2 Each of the other approved agents (didanosine, zalcitibine, and stavudine) has potent in vitro antiviral effects and provides a therapeutic alternative when patients are intolerant of zidovudine or have disease progression despite zidovudine.1 However, the benefit of prolonged monotherapy with currently available drugs is of limited durability,4 at least in part due to the selection of viral strains containing mutations in the RT gene that confer resistance to the therapies.3 There are also significant toxicities associated with these compounds, although the profile of adverse effects is different for each of the four drugs.1,5 Obviously, there is an urgent need to identify novel approaches to suppress HIV replication and prevent the manifestations of AIDS.
Keywords34th Interscience Reverse Transcriptase Enzyme Reverse Transcriptase Gene High Therapeutic Index Nevirapine Therapy
Unable to display preview. Download preview PDF.
- 3.Richman DD. Viral resistance to antiretroviral therapy. In: Broder S, Merigan TC, Bolognesi D, eds. Textbook of AIDS medicine. Baltimore: Williams and Wilkins, 1994: 795–80.Google Scholar
- 5.Saag MS. Nucleoside analogues: adverse effects. Hosp Prac 1992; 27 (suppl 2): 26–36.Google Scholar
- 6.Miyasaka T, Tanaka H, Baba M, et al. A novel lead for specific anti-HIV-1 agents: 1-[2hydroxyethoxymethyl]-6-(phenylthio)thymine. J Med Chem 1989; 32: 2507.Google Scholar
- 18.Cheeseman SH. Nevirapine alone and in combination with AZT: safety and activity[Abstract MoB0053]. Presented at the combined VIII International Conference on AIDS/HIV and the STD World Congress, Amsterdam, The Netherlands, 1992.Google Scholar
- 19.Saag M, Johnson V, Wei X, et al. Clinical, pharmacokinetic, and virologic results in adults treated with nevirapine in combination with AZT/ddC, AZT/ddl, or ddI alone: final report of the BI1009 study. [Abstract M16]. Presented at the 34th Interscience Conference on Antimicrobial Agents and Chemotherapy, Orlando, FL, 1994.Google Scholar
- 22.Kilby JM, Taylor M, Wei X. In situ expression and functional analysis of HIV-1 reverse transcriptase (RT) in patients treated with nevirapine, AZT, and ddI. [Abstract I216]. Presented at the 34th Interscience Conference on Antimicrobial Agents and Chemotherapy, Orlando, FL, 1994.Google Scholar