LYCOS RETRIEVER 
Lamivudine: Zidovudine
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Lamivudine is a selective inhibitor of HIV-1 and HIV-2 replication in vitro, including zidovudine-resistant clinical isolates of the human immunodeficiency virus (HIV). Lamivudine is metabolised intracellularly to the active 5'-triphosphate which inhibits the RNA-and DNA-dependant activities of HIV reverse transcriptase by termination of the viral DNA chain. Lamivudine does not interfere with cellular deoxynucleotide metabolism and has little effect on mammalian cell and mitochondrial DNA content. In vitro, lamivudine demonstrates low cytotoxicity to peripheral blood lymphocytes, to established lymphocyte and monocyte-macrophage cell lines, and to a variety of bone marrow progenitor cells. In vitro, lamivudine therefore has a high therapeutic index. Reduced in-vitro sensitivity to lamivudine has been reported for HIV isolated from patients who have received lamivudine therapy before.
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Lamivudine crosses the placenta. The pharmacokinetics of lamivudine during pregnancy are not significantly altered and dosage adjustment is not required. The Perinatal HIV Guidelines Working Group recommends lamivudine for use during pregnancy; the combination of lamivudine with zidovudine is the recommended dual combination NRTI in pregnancy. It may ... be used in combination with zidovudine in HIV-infected women who are in labor, but have had no prior antiretroviral therapy, in order to reduce the maternal-fetal transmission of HIV. Cases of lactic acidosis/hepatic steatosis syndrome have been reported in pregnant women receiving nucleoside analogues. It is not known if pregnancy itself potentiates this known side effect; however, pregnant women may be at increased risk of lactic acidosis and liver damage.
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Lamivudine is administered orally, and it is rapidly absorbed with a bio-availability of over 80%. Some research suggests that lamivudine can cross the blood-brain barrier. Lamivudine is often given in combination with zidovudine, with which it is highly synergistic. Lamivudine treatment has been shown to restore zidovudine sensitivity of previously resistant HIV. Several mutagenicity tests show that lamivudine should not show mutagenic activity in therapeutic doses.
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Lamivudine was approved by the FDA in December of 1995. (106) Compared with other antiretroviral drugs, it is relatively weak when used alone, as viral resistance develops within 1 month; therefore, monotherapy is not recommended with lamivudine. The utility of this drug is its ability to modify viral resistance to zidovudine and produce a synergistic effect when used together with either zidovudine or stavudine, with or without a Protease Inhibitor. (100) In addition to its anti-HIV activity, lamivudine is effective in suppressing hepatitis B replication.(106)
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Lamivudine has been used in combination with zidovudine for prevention of mother-to-child transmission of HIV. Although the safety and efficacy of this two-drug regimen has not been established, it is considered one of several options used in HIV infected women in labor who have received no prior antiretroviral therapy. Lamivudine is ... used in conjunction with zidovudine or, alternatively, with stavudine for postexposure prophylaxis of HIV infection in health care workers and other individuals exposed occupationally to blood, body fluids, or tissues associated with a risk for transmission of HIV.[5]
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Lamivudine and zidovudine may stop your body from making enough blood cells. Tell your doctor if you have or have ever had any blood disorders such as anemia or bone marrow problems. If you experience any of the following symptoms, call your doctor immediately: unusual bleeding or bruising; shortness of breath; pale skin; fever, sore throat, chills, and other signs of infection; or unusual tiredness or weakness. Lamivudine and zidovudine may cause muscle disorders. Tell your doctor if you have or have ever had any disease or swelling of the muscles. If you experience muscle pain or weakness, call your doctor immediately.
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