Uses
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Treatment of HIV Infection
Lamivudine is used in conjunction with other antiretroviral agents for treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults, adolescents, and pediatric patients 3 months of age or older.
Lamivudine usually is used in multiple-drug regimens that include another HIV nucleoside reverse transcriptase inhibitor (NRTI) (dual NRTIs) and an HIV integrase strand transferase inhibitor (INSTI), HIV nonnucleoside reverse transcriptase inhibitor (NNRTI), or HIV protease inhibitor (PI) in INSTI-, NNRTI-, or PI-based regimens.
If the dual NRTI option of lamivudine and zidovudine is used in conjunction with other antiretrovirals for treatment of HIV-1 infection, a fixed-combination preparation containing both drugs (lamivudine/zidovudine; Combivir) is commercially available and can be used in adults, adolescents, and pediatric patients weighing 30 kg or more to decrease pill burden and improve adherence.
If the dual NRTI option of lamivudine and abacavir is used in conjunction with other antiretrovirals for treatment of HIV-1 infection, a fixed-combination preparation containing both drugs (abacavir/lamivudine; Epzicom) is commercially available and can be used in adults to decrease pill burden and improve adherence. Abacavir/lamivudine must be used in conjunction with other antiretrovirals for treatment of HIV-1 infection and should be used with a drug from another class (not another NRTI).
Lamivudine has been used in triple NRTI regimens (i.e., single-class NRTI regimens) that include lamivudine and 2 other NRTIs. A fixed-combination preparation containing abacavir, lamivudine, and zidovudine (abacavir/lamivudine/zidovudine; Trizivir) is commercially available and can be used in adults and adolescents weighing 40 kg or more to provide a triple NRTI regimen and to decrease pill burden and improve adherence.
(See All-NRTI Regimens under Treatment of HIV Infection: Antiretroviral-naive Adults and Adolescents, in Uses.) The most appropriate antiretroviral regimen cannot be defined for each clinical scenario and selection of specific antiretroviral agents for use in such regimens should be individualized based on information regarding antiretroviral potency, potential rate of development of resistance, known toxicities, and potential for pharmacokinetic interactions as well as virologic, immunologic, and clinical characteristics of the individual patient. For information on the general principles and guidelines for use of antiretroviral therapy, including specific recommendations for initial therapy in antiretroviral-naive patients and recommendations for changing antiretroviral regimens,
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Antiretroviral-naive Adults and Adolescents
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Dual NRTI Options
For initial treatment regimens in HIV-infected adults and adolescents, the US Department of Health and Human Services (HHS) Panel on Antiretroviral Guidelines for Adults and Adolescents states that tenofovir disoproxil fumarate (tenofovir DF) and emtricitabine (or lamivudine) is the recommended dual NRTI option for use in most INSTI-, NNRTI-, and PI-based regimens recommended for initial treatment. These experts state that abacavir and lamivudine (or emtricitabine) also is a recommended dual NRTI option for use in some initial treatment regimens in antiretroviral-naive adults and adolescents, but should be used only in those who are negative for human leukocyte antigen (HLA)-B*5701. These recommendations are based on safety and efficacy data from clinical trials, long-term clinical experience, and availability of fixed-combination preparations containing NRTIs.
The HHS panel states that recommended regimens for initial treatment in antiretroviral-naive adults and adolescents that can be used regardless of baseline plasma HIV RNA levels or CD4 T-cell counts include the dual NRTI option of tenofovir DF and emtricitabine (or lamivudine) in conjunction with efavirenz, ritonavir-boosted atazanavir, ritonavir-boosted darunavir, dolutegravir, or raltegravir. In addition, the dual NRTI option of abacavir and lamivudine (or emtricitabine) in conjunction with dolutegravir is a recommended regimen that can be used for initial treatment in antiretroviral-naive adults and adolescents regardless of baseline plasma HIV RNA levels or CD4 T-cell counts in those who are negative for HLA-B*5701.
Tenofovir DF and emtricitabine (or lamivudine) is the preferred dual NRTI option for antiretroviral regimens used in HIV-infected patients coinfected with hepatitis B virus (HBV). All 3 of these NRTIs (tenofovir DF, emtricitabine, lamivudine) have activity against both HIV and HBV, and regimens that contain only 1 of these 3 antiretrovirals are not recommended in HIV-infected patients coinfected with HBV.
When the dual NRTI option of abacavir and lamivudine is used, the fixed-combination preparation containing both drugs (abacavir/lamivudine; Epzicom) can be used in adults. Abacavir/lamivudine must be used in conjunction with other antiretrovirals for treatment of HIV-1 infection and should be used with a drug from a different class (not another NRTI).
The dual NRTI option of zidovudine and lamivudine is no longer recommended for initial treatment regimens in nonpregnant antiretroviral-naive adults and adolescents because it has greater toxicity than the dual NRTI options of tenofovir DF and emtricitabine or abacavir and lamivudine and requires twice-daily dosing. However, the dual NRTI option of zidovudine and lamivudine is one of several preferred dual NRTI options for initial treatment regimens in antiretroviral-naive pregnant women
(see Pregnancy under Cautions: Pregnancy, Fertility, and Lactation) and for initial treatment regimens in pediatric patients(see Pediatric Patients under Uses: Treatment of HIV Infection) . When the dual NRTI option of lamivudine and zidovudine is used in conjunction with other antiretrovirals, the fixed-combination preparation containing both drugs (lamivudine/zidovudine; Combivir) can be used in adults and adolescents weighing 30 kg or more.A dual NRTI option of didanosine and lamivudine (or emtricitabine) is not recommended for initial antiretroviral regimens because of inferior virologic efficacy and limited clinical trial experience in antiretroviral-naive patients.
A dual NRTI option of stavudine and lamivudine is not recommended for initial antiretroviral regimens because of reported toxicities.
Lamivudine and emtricitabine should not be used concomitantly at any time since the drugs have similar resistance profiles and minimal additive antiretroviral activity.
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All-NRTI Regimens
Lamivudine has been included in NRTI regimens that include 3 or 4 NRTIs (without any drugs from another class). However, triple and quadruple NRTI regimens are not usually recommended for treatment of HIV-1 infection in antiretroviral-naive adults or adolescents because such regimens have inferior virologic efficacy or have not been adequately studied. In addition, regimens that only include NRTIs are not usually recommended in antiretroviral-experienced patients.
(See Antiretroviral-experienced Adults and Adolescents under Uses: Treatment of HIV Infection.) Lamivudine has been used in a triple NRTI regimen that includes abacavir, lamivudine, and zidovudine. The fixed-combination preparation containing these 3 NRTIs (abacavir/lamivudine/zidovudine; Trizivir) can be used in adults and adolescents weighing 40 kg or more. Abacavir/lamivudine/zidovudine is intended only for regimens that require all 3 drugs, and clinicians should consider that data are limited regarding use of this fixed-combination preparation in patients with baseline viral loads exceeding 100,000 copies/mL. Although a triple NRTI regimen of abacavir, lamivudine, and zidovudine offers the advantages of fewer drug interactions, low pill burden, and ease of administration (because of the commercially available fixed-combination preparation), and spares patients from potential adverse effects associated with PIs and NNRTIs, there is evidence that triple NRTI regimens have inferior virologic efficacy. Therefore, experts state that a triple NRTI regimen that includes abacavir, lamivudine, and zidovudine is not recommended for initial therapy in antiretroviral-naive adults and adolescents and should be used only when other regimens cannot be used.
A triple NRTI regimen of lamivudine, zidovudine, and tenofovir DF has been used and has been shown to have antiretroviral activity; however, this regimen should be used only when other regimens cannot be used.
A triple NRTI regimen of abacavir, lamivudine, and tenofovir DF is not recommended at any time in antiretroviral-naive or antiretroviral-experienced patients because of a high rate of virologic failure. Interim analysis of a randomized, open-label study evaluating efficacy of a once-daily regimen of abacavir, lamivudine, and tenofovir DF compared with an NNRTI-based once-daily regimen of efavirenz, abacavir, and lamivudine in treatment-naive patients (ESS30009) indicated a high rate of early virologic nonresponse in those receiving the triple NRTI regimen (almost 50%). Based on these results, the abacavir, lamivudine, and tenofovir DF arm of the study was terminated. A high rate of virologic nonresponse also was reported in a pilot study evaluating this triple NRTI regimen. Several possible reasons for the poor response to this regimen have been proposed, but the ESS30009 investigators suggest that the most likely cause is a low genetic barrier to resistance because of synergistic selection from all 3 NRTIs for 2 specific resistance mutations (M184V and K65R).
A quadruple NRTI regimen of abacavir, lamivudine, tenofovir DF, and zidovudine is not recommended for initial therapy in antiretroviral-naive HIV-infected adults and adolescents because of inferior virologic efficacy. In an open-label pilot study, a quadruple NRTI regimen was compared with an NNRTI-based regimen of efavirenz with lamivudine and zidovudine, and both regimens had similar efficacy and tolerability. However, a larger, open-label study comparing a similar quadruple NRTI regimen (abacavir, emtricitabine, tenofovir DF, zidovudine) with a standard NNRTI- or PI-based regimen found that substantially fewer patients receiving the quadruple NRTI regimen achieved HIV-1 RNA levels below 200 copies/mL.
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NNRTI-based Regimens
The comparative efficacy of a once- or twice-daily lamivudine regimen used in conjunction with zidovudine in an NNRTI-based regimen was evaluated in a 48-week double-blind, randomized study (EPV20001) in 554 antiretroviral-naive adults (79% male, 50% Caucasian, median age 35 years, baseline CD4 T-cell count 69-1089/mm [median 362/mm], median baseline plasma HIV-1 RNA level 4.66 log10 copies/mL). Patients were randomized to receive efavirenz (600 mg once daily) with zidovudine (300 mg twice daily) and either lamivudine 300 mg once daily or lamivudine 150 mg twice daily. Plasma HIV-1 RNA levels were less than 50 copies/mL through week 48 in 61% of patients receiving the once-daily lamivudine regimen and in 63% of those receiving the twice-daily lamivudine regimen. At week 48, the median increase in CD4 T-cell count was 144 cells/mm or 146 cells/mm in those receiving the once- or twice-daily lamivudine regimen, respectively. The virologic failure rate was 8% in both groups.
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Antiretroviral-experienced Adults and Adolescents
Although monotherapy or 2-drug regimens that include only NRTIs no longer are recommended for treatment of HIV infection, early studies evaluating the safety and efficacy of lamivudine in antiretroviral-experienced (previously-treated) patients used such regimens. These studies showed that patients who received lamivudine (150 or 300 mg every 12 hours) in conjunction with zidovudine (200 mg 3 times daily) for 24 weeks experienced greater increases in CD4 T-cell counts than those who received zidovudine monotherapy (200 mg 3 times daily) or zidovudine (200 mg 3 times daily) in conjunction with zalcitabine (0.75 mg 3 times daily; no longer commercially available in the US).
Lamivudine has been evaluated in a randomized, double-blind study (study NUCB3007; CAESAR study) in 1816 HIV-infected patients (baseline CD4 T-cell count 25-250/mm [median 122/mm], 84% nucleoside-experienced, 16% treatment-naive). Oral lamivudine (with or without an NNRTI) was added to the patient's existing regimen (i.e., monotherapy with zidovudine [62%], a 2-drug regimen of zidovudine and didanosine or zalcitabine [38%]) and efficacy was assessed by disease progression or death over the following 12 months. The 12-month cumulative incidence of disease progression or death was 8.9-9.6% in patients randomized to receive lamivudine (with or without an NNRTI) in conjunction with their existing regimen and 19.6% in patients randomized to receive placebo in conjunction with their existing regimen. The 12-month cumulative mortality was 2.6-3 or 5.9% in patients randomized to receive lamivudine (with or without an NNRTI) or placebo, respectively, in conjunction with their existing regimen.
Based on interim analysis of a study evaluating a triple NRTI regimen of abacavir, lamivudine, and tenofovir DF that indicated a high rate of early virologic nonresponse in antiretroviral-naive patients receiving this regimen, a triple NRTI regimen of abacavir, lamivudine, and tenofovir DF is not recommended in either antiretroviral-naive or antiretroviral-experienced patients.
(See All NRTI Regimens under Treatment of HIV Infection: Antiretroviral-naive Adults and Adolescents, in Uses.)
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Pediatric Patients
Lamivudine is used in conjunction with other antiretroviral agents for treatment of HIV-1 infection in children 3 months of age or older.
For initial treatment of HIV-infected pediatric patients, the HHS Panel on Antiretroviral Therapy and Medical Management of HIV-infected Children recommends a PI or NNRTI and 2 NRTIs (dual NRTIs). These experts state that the preferred dual NRTI options for initial treatment regimens in pediatric patients are zidovudine and either lamivudine or emtricitabine (can be used in pediatric patients of any age) or abacavir and either lamivudine or emtricitabine (can be used in those 3 months of age or older who are negative for HLA-B*5701).
For adolescents at Tanner stage 4 or 5, the preferred dual NRTI options for initial treatment regimens are abacavir and either lamivudine or emtricitabine (only in those negative for HLA-B*5701), tenofovir DF and either lamivudine or emtricitabine, or zidovudine and either lamivudine or emtricitabine. Tenofovir DF and either lamivudine or emtricitabine is considered an alternative (not a preferred) dual NRTI option for initial treatment regimens in children and adolescents at Tanner stage 3, but should be used only in special circumstances in prepubertal children 2 years of age or older and adolescents at Tanner stage 1 or 2.
When the dual NRTI option of lamivudine and zidovudine is used, the fixed-combination preparation containing both drugs (lamivudine/zidovudine; Combivir) can be used in pediatric patients weighing 30 kg or more.
Didanosine and lamivudine (or emtricitabine) is an alternative (not a preferred) dual NRTI option for initial treatment regimens in children 2 weeks of age or older.
Because of a high incidence of toxicity, a dual NRTI option of stavudine and lamivudine (or emtricitabine) should be used in initial treatment regimens in children only in special circumstances.
Emtricitabine and lamivudine should not be used concomitantly at any time since the drugs have similar resistance profiles and minimal additive antiretroviral activity.
Antiretroviral regimens containing only NRTIs are not recommended for initial treatment in antiretroviral-naive pediatric patients because of inferior virologic efficacy.
A triple NRTI regimen that includes abacavir, tenofovir DF, and either lamivudine or emtricitabine or a triple NRTI regimen that includes tenofovir DF, didanosine, and either lamivudine or emtricitabine should not be used at any time in pediatric patients because of the high rate of early virologic failure reported in antiretroviral-naive adults.
For further information on treatment of HIV infection in pediatric patients,
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Prevention of Perinatal HIV Transmission
Lamivudine has been used in some antepartum, intrapartum, and neonatal antiretroviral prophylaxis regimens used for prevention of perinatal HIV transmission.
In the US, multiple-drug antiretroviral regimens are considered the standard of care for treatment of HIV infection in pregnant women and for prevention of perinatal HIV transmission. The HHS Panel on Treatment of HIV-infected Pregnant Women and Prevention of Perinatal Transmission states that all pregnant HIV-infected women in the US should receive multiple-drug antiretroviral therapy, regardless of the woman's plasma HIV-1 RNA level or CD4 T-cell count. In addition, to decrease the risk of perinatal HIV transmission, the HHS panel states that pregnant HIV-infected women with plasma HIV-1 RNA levels exceeding 1000 copies/mL (or with unknown HIV-1 RNA levels) near the time of delivery should receive an intrapartum IV zidovudine prophylaxis regimen and all neonates born to HIV-infected women (HIV-exposed neonates) should receive an oral or IV zidovudine prophylaxis regimen. In certain situations (e.g., infant born to a woman who did not receive antepartum or intrapartum antiretrovirals or received only intrapartum antiretrovirals), a 3-dose nevirapine prophylaxis regimen is recommended in the neonate in addition to the usual neonatal zidovudine prophylaxis regimen. Combined antepartum, intrapartum, and neonatal antiretroviral prophylaxis is recommended since this strategy reduces perinatal HIV transmission by several mechanisms, including lowering maternal antepartum viral load and providing pre- and postexposure prophylaxis in the infant. Maternal and neonatal regimens recommended for prevention of perinatal HIV transmission in the US may differ from those used in other countries (e.g., resource-limited countries).
Lamivudine is a component of several preferred dual NRTI options that are used in conjunction with other antiretrovirals for treatment of HIV-1 infection in pregnant women
(see Pregnancy under Cautions: Pregnancy, Fertility, and Lactation) . Although lamivudine has been included in some intrapartum antiretroviral regimens and also has been used in some neonatal prophylaxis regimens for prevention of perinatal HIV transmission, higher rates of hematologic toxicity have been reported in infants receiving a prophylaxis regimen of zidovudine and lamivudine compared with those receiving zidovudine alone or zidovudine in conjunction with nevirapine. The HHS panel states that, for US patients, decisions to include any additional antiretrovirals for prophylaxis with the recommended intrapartum and neonatal zidovudine prophylaxis regimens should be made in consultation with a pediatric HIV specialist (preferably before delivery) and should be accompanied by maternal counseling regarding the potential risks and benefits. These experts also state that, because safety and dosage data are not available, use of antiretrovirals other than zidovudine and nevirapine cannot be recommended for prophylaxis in premature HIV-exposed neonates.For information on the risk of perinatal transmission of HIV and some additional information regarding recommendations for use of antiretroviral agents for prevention of perinatal HIV transmission, In addition, clinicians can consult the National Perinatal HIV Hotline at 888-448-8765 for information regarding antiretroviral treatment of pregnant HIV-infected women and their infants and prevention of perinatal HIV transmission.
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Postexposure Prophylaxis following Occupational Exposure to HIV
Lamivudine is used in conjunction with other antiretrovirals for postexposure prophylaxis of HIV infection following occupational exposure (PEP) in health-care workers and other individuals exposed via percutaneous injury (e.g., needlestick, cut with sharp object) or mucous membrane or nonintact skin (e.g., chapped, abraded, dermatitis) contact with blood, tissue, or other body fluids that might contain HIV.
The US Public Health Service (USPHS) states that the preferred regimen for PEP following an occupational exposure to HIV is a 3-drug regimen of raltegravir used in conjunction with emtricitabine and tenofovir DF (may be administered as the fixed combination emtricitabine/tenofovir DF; Truvada). These experts recommend several alternative regimens that include an INSTI, NNRTI, or PI and 2 NRTIs (dual NRTIs). The preferred dual NRTI option for use in PEP regimens is emtricitabine and tenofovir DF (may be administered as emtricitabine/tenofovir DF; Truvada); alternative dual NRTIs are tenofovir DF and lamivudine, zidovudine and lamivudine (may be administered as the fixed combination lamivudine/zidovudine; Combivir), or zidovudine and emtricitabine.
Because management of occupational exposures to HIV is complex and evolving, consultation with an infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or the National Clinicians' Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) is recommended whenever possible. However, initiation of PEP should not be delayed while waiting for expert consultation.
For information on types of occupational exposure to HIV and associated risk of infection, management of occupational exposure to HIV, efficacy and safety of postexposure chemoprophylaxis, and recommendations regarding postexposure prophylaxis,
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Postexposure Prophylaxis following Nonoccupational Exposure to HIV
Lamivudine is used in conjunction with other antiretrovirals for postexposure prophylaxis of HIV infection following nonoccupational exposure (nPEP) in individuals exposed to blood, genital secretions, or other potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission.
For additional information on nonoccupational exposure to HIV and recommendations regarding postexposure prophylaxis,
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Chronic Hepatitis B Virus Infection
Lamivudine is used for treatment of chronic hepatitis B virus (HBV) infection associated with evidence of HBV replication and active liver inflammation.
The American Association for the Study of Liver Diseases (AASLD) states that lamivudine is not considered a preferred antiviral for long-term treatment of chronic HBV because a high rate of lamivudine resistance has been reported with such treatment. The manufacturer states that lamivudine should be considered for treatment of chronic HBV infection only when alternative antiviral agents associated with a higher genetic barrier to resistance are not available or appropriate.
Safety and efficacy of lamivudine for treatment of chronic HBV infection have not been established in patients with decompensated liver disease, liver transplant recipients, HBV-infected patients coinfected with HIV (
see HIV-infected Individuals under Uses: Chronic Hepatitis B Virus Infection ), HBV-infected patients coinfected with hepatitis C virus (HCV) or hepatitis D virus (HDV), or pediatric patients younger than 2 years of age.The goal of antiviral therapy in patients with chronic HBV infection is to achieve sustained suppression of HBV replication and remission of liver disease. The long-term goal of therapy is to prevent cirrhosis, hepatic failure, and hepatocellular carcinoma. Currently available therapies for chronic HBV infection (e.g., interferon alfa, peginterferon alfa, adefovir, entecavir, lamivudine, telbivudine, tenofovir) do not eradicate HBV and may have only limited long-term efficacy. Decisions on the appropriate time to initiate therapy and which drug to use should take into consideration the patient's age, severity of liver disease, likelihood of response, safety and efficacy of the drug, potential for selection of resistant HBV strains, potential for adverse reactions, costs, patient's pregnancy potential, and patient and provider preferences.
The AASLD states that treatment of HBV infection is indicated if the risk of liver-related morbidity and mortality in the near future (5-10 years) and the likelihood of achieving sustained HBV suppression during continued treatment are high. Treatment also is indicated if the risk of liver-related morbidity and mortality in the foreseeable future (10-20 years) and the likelihood of achieving sustained HBV suppression after a defined course of therapy are high. These experts state that treatment is not indicated if both the risk of liver-related morbidity or mortality in the next 20 years and the likelihood of achieving sustained HBV suppression after a defined course of treatment are low.
Treatment of chronic HBV infection is complex and rapidly evolving. Specialized references should be consulted for specific information regarding the evaluation and management of individuals with chronic HBV infection, including information on the choice of treatment regimens.
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Adults
Safety and efficacy of lamivudine for treatment of HBV infection were evaluated in 3 controlled studies in adults 16 years of age or older with compensated chronic HBV infection (serum HBsAg positive for at least 6 months) accompanied by evidence of HBV replication (positive for serum hepatitis B e antigen [HBeAg] and positive for serum HBV DNA as measured by a research solution hybridization assay) and persistently elevated serum ALT concentrations and/or chronic inflammation on liver biopsy compatible with a diagnosis of chronic viral hepatitis. Lamivudine treatment in patients with chronic HBV infection has been associated with histologic improvement on liver biopsy, decreases in HBV DNA, normalization of serum ALT concentrations, and HBeAg seroconversion (loss of HBeAg and development of antibody to HBeAg).
In a controlled study in Chinese patients with chronic HBV infection who received lamivudine 100 mg once daily, lamivudine 25 mg once daily, or placebo for 12 months, hepatic necroinflammatory activity improved in 56, 49, or 25% and deteriorated in 7, 8, or 26% of patients, respectively. Therapy with lamivudine 100 mg daily was associated with a reduction in the progression of fibrosis compared with placebo. At 12 months, HBeAg seroconversion occurred in 16, 13, or 4%, respectively, of patients receiving lamivudine 100 mg daily, 25 mg daily, or placebo. Therapy with lamivudine 100 mg daily was associated with a rapid and sustained reduction in HBV DNA (97% reduction at week 2, 98% reduction at week 52 compared with baseline) and sustained serum ALT response in 72% of patients; therapy with lamivudine 25 mg daily or placebo was associated with a 93 or 54% reduction in HBV DNA at week 52 and sustained ALT response in 65 or 24% of patients, respectively. In this study, therapy with lamivudine 100 mg daily was more effective than lamivudine 25 mg daily or placebo.
While therapy with lamivudine is associated with histologic improvement in most patients and is well tolerated, the optimum duration of therapy, the durability of HBeAg seroconversions occurring during treatment, and the relationship between treatment response and long-term outcomes such as hepatocellular carcinoma or decompensated cirrhosis remain to be determined. There is some evidence that efficacy of lamivudine may not be sustained during continued therapy. Results from 52-week studies in adults indicate that HBV DNA levels decrease to below the limits of detection in the majority of lamivudine-treated patients early in the course of treatment; however, assay-detectable HBV DNA reappears during treatment in approximately one-third of those who had an initial response. Strains of HBV with resistance to lamivudine have emerged during therapy with the drug, especially during long-term treatment.
(See Resistance: Resistance in HBV.) Development of lamivudine-resistant HBV during treatment with the drug has been associated with decreased treatment responses evidenced by lower rates of HBeAg seroconversion and HBeAg loss and more frequent increases in HBV DNA levels and serum ALT concentrations after an initial response. Progression of HBV infection, including death, has been reported in some patients with lamivudine-resistant HBV.
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Pediatric Patients
Lamivudine is used for treatment of chronic HBV infection in children 2 years of age or older. Safety and efficacy of lamivudine was evaluated in a double-blind clinical study in 286 children and adolescents 2-17 years of age with compensated chronic HBV infection accompanied by evidence of HBV replication (positive serum HBeAg and positive for serum HBV DNA as measured by a research branched DNA [bDNA] assay) and persistently elevated serum ALT concentrations. Loss of HBeAg and reduction of HBV DNA to below the limits of detection of the research assay (evaluated at week 52) occurred in 23% of children who received 52 weeks of lamivudine (3 mg/kg once daily; maximum 100 mg once daily) compared with 13% of those who received placebo. In addition, normalization of serum ALT concentrations was achieved and maintained to week 52 more frequently in patients treated with lamivudine (55%) compared with placebo (13%). As in the controlled studies in adults, most lamivudine-treated pediatric patients had decreases in serum HBV DNA concentrations below the limits of detection early in treatment, but about one-third of subjects with this initial response had reappearance of detectable HBV DNA during treatment. Adolescents (13-17 years of age) showed less evidence of this treatment effect than younger children.
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HIV-infected Individuals
Safety and efficacy of lamivudine for treatment of chronic HBV infection in patients coinfected with HIV have not been established.
HIV-infected patients coinfected with HBV often have higher HBV viral loads and are more likely to have detectable HBeAg, lower rates of HBeAg seroconversion, and an increased risk for and more rapid progression to cirrhosis, end-stage liver disease, and/or hepatocellular carcinoma compared with individuals not infected with HIV. Decisions to initiate HBV treatment in patients coinfected with HIV and HBV and the most appropriate drugs for HBV treatment in such patients depend on various factors, including the possible effects on replication of both HIV and HBV and whether the patient is currently receiving antiretroviral therapy. Specialized references should be consulted for specific information regarding the evaluation and management of chronic HBV infection in HIV-infected patients.
Although lamivudine is active against both HBV and HIV, it should not be used for treatment of chronic HBV infection in HIV-infected individuals who are not currently receiving antiretroviral therapy since dosages used for treatment of HBV infection are lower than those recommended for treatment of HIV infection and use of suboptimal dosages in HIV-infected individuals may allow for the selection of lamivudine-resistant HIV. In addition, emergence of lamivudine-resistant HBV has been reported in HIV-infected individuals who were coinfected with HBV and receiving lamivudine-containing antiretroviral regimens. Although a high rate of emergence of lamivudine-resistant HBV has been reported with long-term lamivudine therapy in HBV-infected patients without HIV infection, there is some evidence that the rate of emergence of HBV resistance may be even higher in HIV-infected individuals who receive the drug. Reactivation of chronic HBV has been reported in some HIV-infected patients who received long-term lamivudine therapy, and fulminant and fatal reactivation of chronic HBV infection as the result of emergence of lamivudine-resistant HBV has been reported.
(See Precautions Related to Treatment of Chronic HBV Infection under Cautions: Precautions and Contraindications.)
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Transplant Recipients
Safety and efficacy of lamivudine have not been established for treatment of HBV infection in organ transplant recipients. There is some evidence that lamivudine appears to reduce the risk of HBV reinfection in orthotopic liver transplant recipients. However, further study is needed to define the role of lamivudine and other therapies for prevention and control of HBV recurrence in transplant recipients.
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