Disease relevance of lamivudine

• Lamivudine in the treatment of acute hepatitis B [1].
• Lamivudine for chronic hepatitis B [2].
• Treatment with lamivudine, zidovudine, or both in HIV-positive patients with 200 to 500 CD4+ cells per cubic millimeter. North American HIV Working Party [3].
• Combination therapy was also more effective than lamivudine alone in lowering plasma HIV-1 RNA levels and increasing the percentage of CD4+ cells (P < 0.001 for all comparisons), and these advantages persisted through 52 weeks [3].
• Lamivudine in the treatment of polyarteritis nodosa associated with acute hepatitis B [4].

Psychiatry related information on lamivudine

• Lamivudine was given 150 mg/day for 96 weeks in each group; interferon was administered 10 MU three times a week for 24 weeks in the combination therapy group [5].
• Short-term corticosteroid therapy in combination with lamivudine: A case of déjà vu [6]?
• Prenatal 3TC exposure had rather limited effects on locomotor activity development, and no effect on nociception [7].
• Then patients stopped pyrazinamide and ethambutol and started once-daily antiretroviral therapy (ART) with didanosine, lamivudine, ritonavir (200 mg) and saquinavir (1600 mg) (second PK study, n = 18) [8].
• Sensitive and early detection of emerging hepatitis B virus (HBV) drug resistance may not only help monitor the viral dynamics associated with lamivudine treatment but could also improve therapeutic decision making [9].

High impact information on lamivudine

• Lamivudine for the treatment of chronic hepatitis B [10].
• Self-limited post-treatment elevations in serum alanine aminotransferase were more common in lamivudine recipients: 25 percent had serum alanine aminotransferase levels that were at least three times base-line levels, as compared with 8 percent of placebo recipients (P=0.01) [11].
• The presence of zidovudine-resistance mutations in HIV RNA at base line was strongly predictive of the loss of viral suppression in subjects treated with zidovudine and lamivudine [12].
• CONCLUSIONS: The suppression of plasma HIV RNA after six months of treatment with indinavir, zidovudine, and lamivudine is better sustained by the continuation of these three drugs than by maintenance therapy with either indinavir alone or zidovudine and lamivudine [12].
• Lamivudine was initiated in women at 32 weeks' gestation through delivery at 150 mg twice per day orally; children received lamivudine, 2 mg/kg twice per day for 6 weeks [13].

Chemical compound and disease context of lamivudine

• CONCLUSIONS: In most HIV-infected patients with prior antiretroviral therapy, the combination of indinavir, zidovudine, and lamivudine reduces levels of HIV RNA to less than 500 copies per milliliter for as long as one year [14].
• Safety and efficacy of lamivudine-zidovudine combination therapy in antiretroviral-naive patients. A randomized controlled comparison with zidovudine monotherapy. Lamivudine European HIV Working Group [15].
• CONCLUSIONS: The addition of adefovir dipivoxil to lamivudine in patients with CHB with compensated or decompensated liver disease due to YMDD mutant HBV is associated with virologic and biochemical improvement during 52 weeks of treatment and is well tolerated [16].
• A dose-ranging study of the efficacy and tolerability of entecavir in Lamivudine-refractory chronic hepatitis B patients [17].
• Tenofovir disoproxil fumarate exhibits strong antiviral effect in a patient with lamivudine-resistant severe hepatitis B reactivation [18].

Biological context of lamivudine

• CONCLUSION--In zidovudine-experienced HIV-1-infected patients, combination treatment with lamivudine and zidovudine is well tolerated and provides greater and more sustained increases in CD4+ cell counts and decreases in viral load than continued zidovudine monotherapy [19].
• Effect of trimethoprim on lamivudine bioavailability [20].
• In this study, susceptibility of wild-type and lamivudine-resistant HBV M552I, M552V, and L528M/M552V mutants to other reverse transcriptase inhibitors was investigated by transient transfection of full-length HBV DNA into human hepatoma cells [21].
• METHODS: YMDD genotypes in 740 consecutive samples collected from 116 patients throughout lamivudine treatment were retrospectively analyzed using a matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS)-based genotyping assay, termed restriction fragment mass polymorphism (RFMP) [22].
• BACKGROUND & AIMS: Lamivudine inhibits hepatitis B virus replication [23].

Anatomical context of lamivudine

• Interestingly, lamivudine also enhanced the responses to mitogens and recall antigens, showing that its effect was not limited to HBV-specific T cells [24].
• In hepatocyte cultures infected with pretreatment serum, HBV DNA concentrations were reduced to less than 6% of those in control cultures by addition of lamivudine in concentrations as low as 0.03 mumol/L [25].
• After 1 year of therapy, viral RNA levels in LN of individuals remained detectable but were log10 = 4 lower than in subjects on the triple drug regimen with interruption of therapy or in those treated with ZDV/3TC alone, who had viral loads in their lymph nodes indistinguishable from those expected for untreated patients [26].
• Using these cell lines, we assessed the susceptibility of all four strains of lamivudine-resistant HBV to eleven nucleoside analogues in various stages of clinical development [27].
• Pre-emptive use of lamivudine in bone marrow transplantation with chronic hepatitis B virus infection [28].

Associations of lamivudine with other chemical compounds

• RESULTS: The proportion of patients whose disease progressed to AIDS or death was lower with indinavir, zidovudine, and lamivudine (6 percent) than with zidovudine and lamivudine alone (11 percent; estimated hazard ratio, 0.50; 95 percent confidence interval, 0.33 to 0.76; P=0.001) [29].
• Adefovir dipivoxil is active in vivo and in vitro against wild-type and lamivudine-resistant HBV [30].
• Gel analysis of the reverse transcription products revealed that both 3TC-resistant RT mutants produce significantly shorter cDNA molecules than the wild-type enzyme [Met (wt)>Val>Ile], indicating that 3TC-resistant RT polymerases are less processive enzymes [31].
• Predictors of virologic and clinical outcomes in HIV-1-infected patients receiving concurrent treatment with indinavir, zidovudine, and lamivudine. AIDS Clinical Trials Group Protocol 320 [32].
• Changes in absolute CD4+ cell counts were significantly better for the low-dose and the high-dose lamivudine groups than for the zalcitabine group (median changes at 52 weeks were +42.5 cells/mm3 in the low-dose lamivudine group, +23.33 cells/mm3 in the high-dose lamivudine group, and -29.58 cells/mm3 in the zalcitabine group) [33].

Gene context of lamivudine

• Finally, an increased expression of the MRP5 homologue, ATP-binding cassette C11 (ABCC11) was observed in the CEM 3TC cells [34].
• However, despite a small overexpression of multidrug resistance protein (MRP) 4, additional studies with cells specifically engineered to overexpress MRP4 demonstrated there was no impact on either 3TC accumulation or efflux [34].
• Lamivudine treatment reduced TRAIL-mediated apoptosis and TRAIL-R1/DR4 expression in Hep G2.2.15 cells [35].
• BCH 189 inhibited the proliferation of B and T lymphocytes from normal and HIV+ subjects less than AZT; even if lymphocytes from HIV+ (CDC III) subjects produced higher levels of IL-6 and TNF-alpha, neither BCH 189 nor AZT molecule interfered with cytokine release [36].
• In addition, A-ODNs specific for Hsp60 also inhibit replication of a mutant HBV strain that is resistant to the nucleoside analogue 3TC, which is the main drug used for HBV treatment, and we suggest that A-ODNs directed against Hsp60 are possible reagents as anti-HBV drugs [37].

Analytical, diagnostic and therapeutic context of lamivudine

• INTERVENTION: The study cohort received lamivudine in addition to the standard Pediatric AIDS Clinical Trial Group 076 Study zidovudine prophylaxis regimen [13].
• The emergence of resistant hepatitis B virus (HBV), with mutations in the YMDD motif of the polymerase gene after treatment with lamivudine, is becoming an important clinical problem [21].
• We analyzed the genetic and phenotypic evolution of the viral quasispecies of a patient who received successively lamivudine, add-on adefovir+lamivudine, followed by lamivudine+adefovir+hepatitis B immunoglobulins (HBIg) after orthotopic liver transplantation [38].
• Serum HBV DNA levels were measured prior to lamivudine, at transplantation, and at 12 months posttransplantation [39].
• Preemptive lamivudine in hepatitis B patients undergoing chemotherapy [40].

References