Human immunodeficiency virus nevirapine

Kochar R, Nevah Ml, Lukens FJ, Fallon MB, Machicao VI. Vanishing bile duct syndrome in human immunodeficiency virus nevirapine hepatotoxicity revisited. World J Gastroenterol 2010 16 (26) 3335-8. 

The first lead compounds for non-nucleoside reverse transcriptase (RT) inhibitors (NNRTl) were discovered about 15 years ago (Pauwels et al. 1990 Merluzzi et al. 1990 Goldman et al. 1991 De Clercq 1993 Riibsamen-Waigmann et al. 1997). Since then they have become an important ingredient of the dmg combination schemes that are currently used in the treatment of human immunodeficiency virus type 1 (HlV-1) infections. Starting from the HEPT and TIBO derivatives, numerous classes of compounds have been described as NNRTIs. Four compounds (nevirapine, delavirdine, efavirenz and etravirine) have so far been approved for clinical use and several others are the subject of clinical trials (Balzarini 2004 Stellbrink 2007). 

TC, lamivudine ABC, abacavir APV, amprenavir AST, aspartate aminotransferase ALT, alanine aminotransferase ATV, atazanavir CBC, complete blood cell count D/C, discontinue ddl, didano-sine d4T, stavudine EFV, efavirenz FTC, emtricitabine P1BV, hepatitis B virus F1CV, hepatitis C vims HIV, human immunodeficiency virus IDV, indinavir IV, intravenous LFT, liver function tests LPV/r, lopinavir + ritonavir NNRTI, nonnucleoside reverse transcriptase inhibitor NRTI, nucleoside reverse transcriptase inhibitor NVP, nevirapine PI, protease inhibitor PT, prothrombin time T.bili, total bilirubin TDF, tenofovir disoproxiI fumarate TPV, tipranavir ULN, upper limit of normal ZDV, zidovudine. 

Human health effects, of polychlorinated biphenyls, 13 140-142 Human IgG (hlgG), detection of, 14 155, 156. See also Immunoglobulin G (IgG) Human immunodeficiency virus (HIV). See also HIV entries Nevirapine entries inactivation of, 12 139 lactoferricins and, 18 258... 

Palaniappan C, Fay PJ, Bambara RA. Nevirapine alters the cleavage specificity of ribonuclease H of human immunodeficiency virus 1 reverse transcriptase. J Biol Chem 1995 270 4861-4869. 

Martinez E, Arnaiz JA, Podzamczer D, Dalmau D, et al. 2003. Substitution of nevirapine, efavirenz or abacavir for protease inhibitors in patients with human immunodeficiency virus infection. NEJM. 349 1036-1046. 

The activity of triazepines 220 and 221 against the human immunodeficiency virus 1 (HIV-1) multiplication in acutely infected cells has been studied on the basis of inhibition of virus-induced cytopathogenicity in MT-4 cells. The triazepines 221 having a pyridine ring were found to be less potent than 220. The results of activity studies are given in Table 6. Nevirapine has been used as the reference <2000JHC1539>. 

At the present time, there are at least 14 compounds that have been formally approved for the treatment of human immunodeficiency virus (HIV) infections. There are six nucleoside reverse transcriptase inhibitors (NRTIs) that, after their intracellular conversion to the 5 -triphosphate form, are able to interfere as competitive inhibitors of the normal substrates (dNTPs). These are zidovudine (AZT), didanosine (ddl), zalcitabine (ddC), stavudine (d4T), lamivudine (3TC), and abacavir (ABC). There are three nonnucleoside reverse transcriptase inhibitors (NNRTIs) — nevirapine, delavirdine, and efavirenz — that, as such, directly interact with the reverse transcriptase at a nonsubstrate binding, allosteric site. There are five HIV protease inhibitors (Pis saquinavir, ritonavir, indinavir, nelfinavir, and amprenavir) that block the cleavage of precursor to mature HIV proteins, thus impairing the infectivity of the virus particles produced in the presence of these inhibitors. 

Benson CA, Deeks SG, Brun SC, Gulick RM, Eron JJ, Kessler HA, Murphy RL, Hicks C, King M, Wheeler D, Feinberg J, Stryker R, Sax PE, Riddler S, Thompson M, Real K, Hsu A, Kempf D, Japour AJ, Sun E. Safety and antiviral activity at 48 weeks of lopinavir/ritonavir plus nevirapine and 2 nucleoside reverse-transcriptase inhibitors in human immunodeficiency virus type 1-infected protease inhibitor-experienced patients. J Infect Dis 2002 185(5) 599-607. 

Luzuriaga K, Bryson Y, McSheriy G, Robinson J, Stechenberg B, Scott G, Lamson M, Cort S, Sullivan JL. Pharmacokinetics, safety, and activity of nevirapine in human immunodeficiency virus type 1-infected children. J Infect Dis 1996 174(4) 713-21. 

Krogstad P, Lee S, Johnson G, Stanley K, McNamara J, Moye J, Jackson JB, Aguayo R, Dieudonne A, Khoury M, Mendez H, Nachman S, Wiznia A, Ballow A, Aweeka F, Rosenblatt HM, Perdue L, Frasia A, Jeremy R, Anderson M, Japour A, Fields C, Farnsworth A, Lewis R, Schnittman S, GigUotti M, Maldonaldo S, Lane B, Hernandez JE, et al. Pediatric AIDS Clinical Trials Group 377 Study Team. Nucleoside-analogue reverse-transcriptase inhibitors plus nevirapine, nehinavir, or ritonavir for pretreated children infected with human immunodeficiency virus type 1. CUn Infect Dis 2002 34(7) 991-1001. 

Successful treatment of human immunodeficiency virus (HIV-1) infection has been achieved through successful implementation of highly active antiretroviral therapy, frequently referred to as HAART. This involves simultaneous administration of both nucleoside and nonnucleoside reverse transcriptase inhibitors and one or more protease inliibitors. The common nucleoside reverse transcriptase inhibitors are the thymidine analogs didanosine (ddl), lamivudine (3TC), and zalcitabine (ddC) and the non-thymidine analogs abacavir (Ziazen), stavudine (d4T), and zidovudine (AZT). The nonnucleoside reverse transcriptase inhibitors include delavirdine, efavirenz, and nevirapine. The protease inhibitors include indinavir, nelfinavir, ritonavir, and saquinavir. Response to therapy is monitored by quantification of HIV-RNA copies (viral load) and CD-4+ T-lymphocyte count. Successful therapy is indicated when viral load is reduced to <50 copies/mL and CD-4+ count >500 per mL. 

Antiviral effect and pharmacokinetic interaction between nevirapine and indinavir in persons infected with human immunodeficiency virus type 1. J. Infect. Dis. 179, 1116-1123. 

Nevirapine (NVP), a nonnucleoside reverse transcriptase inhibitor, is widely used for the treatment of human immunodeficiency virus (HIV) infections. It is the main option for the first-line treatment of HIV-1, together with two nucleoside reverse transcriptase inhibitors, in countries with limited resources. NVP is associated with two serious clinically restrictive side effects skin reactions and hepatotoxicity. Severe, life threatening, and in some cases fatal hepatotoxicity, including fulminant and cholestatic hepatitis, hepatic necrosis, and hepatic failure, has been reported in HIV-infected patients taking NVP (DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents 2008). For this reason, NVP is given a black box warning for hepatotoxicity, and concern has been raised over NVP-based treatment. 

Havlir D, Cheeseman SH, McLaughlin M, Murphy R, Erice A, Spector SA, Greenough TC, Sullivan JL, Hall D, Myers M (1995) High-dose nevirapine safety, pharmacokinetics, and antiviral effect in patients with human immunodeficiency virus infection. J Infect Dis 171 537-545... 

Havlir DV, Eastman S, Gamst A, Richman DD (1996) Nevirapine-resistant human immunodeficiency virus kinetics of replication and estimated prevalence in untreated patients. J Virol... 

Zhou, X.-J. et al., Population pharmacokinetics of nevirapine, zidovudine, and didanosine in human immunodeficiency virus-infected patients, Antimicrob. Agents Chemother., 43(1) 121-128, 1999. 

Veldkamp AI, Harris M, Montaner JSG, Moyle G, Gazzard B, Youle M, Johnson M, Kwakkel-stein MO, Carlier H, van Leeuwen R, Beijnen JH, Lange JT Reiss P, Hoetelmans RMW. The steady-state pharmacokinetics of efavirenz and nevirapine when used in combination in human immunodeficiency virus type 1-infected persons. J InfectDis (2001) 184,37-42. 

Oberdorfer P, Washington CH, Jittamala P. Human immunodeficiency virus-infected boy with Stevens-Johnson syndrome caused by nevirapine. Pediatr Infect Dis J 2008 27(6) 572. 

Simon, VA. Thiam, M.D. Lipford, L.C. Determination of serum levels of thirteen human immunodeficiency virus-suppressing drugs by high-performance hquid chromatography, J.ChromatogrA, 2001,913,447-453. [zalcitabine lamivudine stavudine didanosine zidovudine nevirapine abacavir indinavir delavirdine nelfinavir saquinavir ritonavir efavirenz]... 

SPE LOD 260 ng/mL for lamivudine zalcitabine lamivudine stavudine didanosine zidovudine nevirapine abacavir indinavir deiavirdine nelimavir saquinavir ritonavir efavirenz] Solas, C. Li, Y.-F. Xie, M.-Y. Sommadossi, J.-P. Zhou, X.-J. Intracellular nucleotides of (-)-2, 3 -deoxy-3 -thiacytidine in peripheral blood mononuclear cells of a patient infected with human immunodeficiency virus, Aratimicro6..4 erats Chemother., 1998, 42, 2989-2995. 

Palladino, D.E. Hopkins, J.L. Ingraham, R.H. Warren, T.C. Kapadia, S.R. Van Moffaert, G.J. Grob, P.M. Stevenson, J.M. Cohen, KA. High-performance liquid chromatography and photoaffinity crosslinking to explore the binding environment of nevirapine to reverse transcriptase of human immunodeficiency virus, J.Chromatogr, 1994, 676, 99-112. 

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