Human immunodeficiency virus lamivudine

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. 

Gulick RM, Mellors JW, Havilir D, Eron JJ, et al. 1997. Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. NEJM. 337 734-739. 

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. 

In 1997, it was estimated that 30 million adults were infected with the human immunodeficiency virus (HIV) worldwide, with increments of five people infected every minute. It is estimated that approximately 7% of the population of sub-Saharan Africa has been infected. The incubation of the disease is 7 to 8 years. Currently available drugs for acquired immunodeficiency syndrome (AIDS) and HIV are zidovudine, didanosine, lamivudine, and stavudine. The causative agent for AIDS is generally an HIV virus, which is transmitted by sexual contact, blood and blood products, the use of contaminated drug needles, and from mother to fetus. 

Lamivudine Inhibition of viral DNA polymerase and reverse transcriptase Hepatitis B (chronic cases), human immunodeficiency virus type 1 5-7... 

Henry K, Wallace RJ, Belhnan PC, Norris D, Fisher RL, Ross LL, Liao Q, Shaefer MS TARGET Study Team. Twice-daily triple nucleoside intensification treatment with lamivudine-zidovudine plus abacavir sustains suppression of human immunodeficiency virus type 1 results of the TARGET Study. J Infect Dis 2001 183(4) 571-8. 

Lewis LL, Venzon D, Church J, Farley M, Wheeler S, Keller A, Rubin M, Yuen G, Mueller B, Sloas M, Wood L, Balls F, Shearer GM, Brouwers P, Goldsmith J, Pizzo PA. Lamivudine in children with human immunodeficiency virus infection a phase FII study. The National Cancer Institute Pediatric Branch-Human Immunodeficiency Virus Working Group. J Infect Dis I996 I74(I) I6-25. 

The human immunodeficiency virus type 1 (HIV-1) belongs to the family of positive-stranded, enveloped RNA viruses with a DNA intermediate step (retroviruses). Because of the lack of fidelity of the reverse transcriptase (RT), the replication is error-prone, and the infection is characterized by its quasispecies nature. Antiretroviral treatment with such compounds as zidovudine (AZT), zalcitabine (ddC), didanosine (ddl), stavudine (d4T), and lamivudine (3TC) select for quasispecies variants that are resistant to these compounds (1). The detection of these variants is clinically important because they may affect the outcome of the treatment (2). 

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. 

Hertogs K, Bloor S, De Vroey V, van Den Eynde C, Dehertogh P, van Cauwenberge A, et al. A novel human immunodeficiency virus type 1 reverse transcriptase mutational pattern confers phenotypic lamivudine resistance in the absence of mutation 184V. Antimicrob Agents Chemother 2000 44 568-73. 

Moore, K.H., Yuen, G.J., Hussey, E.K., Pakes, G.E., Eron, J.J., Jr., and Bartlett, J.A. Population pharmacokinetics of lamivudine in adult human immunodeficiency virus-infected patients enrolled in two phase III clinical trials. Antimicrobial Agents and Chemotherapy 1999 43 3025-3029. 

Wang LH, Chittick GE, McDowell JA. Single-dose pharmacokinetics and safety of abacavir (1592U89), zidovudine, and lamivudine administered alone and in combination in adults with human immunodeficiency virus infection. Antimicrob Agents Chemo ier (1999) 43, 1708-... 

Fletcher CV, Yogev Nachman SA, Wiznia A, Pelton S, McIntosh K, Stanley K. Pharmacokinetic characteristics of ritonavir, zidovudine, lamivudine, and stavudine in children with human immunodeficiency virus infection. Pharmacotherapy (2004) 24,453-9. 

As a biologic, INF-a is effective only in a subset of patients, is often poorly tolerated, requires parenteral administration, and is expensive. Hence, there is a need for alternative therapies for chronic hepatitis B. The introduction of lamivudine (2) in 1995, the first oral treatment for chronic HBV, ushered in a new era in the treatment of chronic hepatitis B when safe, effective, and well-tolerated oral medications were made available. It is a nucleoside reverse hanscriptase inhibitor (NRTI) with activity against both human immunodeficiency virus type 1 (HIV-1) and HBV. It has been used for the treatment of chronic hepatitis B at a lower dose than for the treatment of HIV, and it improves the... 

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. 

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