OVERVIEW

CASE REPORTS

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Lamivudine	134678-17-4	C8-H11-N3-O3-S

ANNOTATED BIBLIOGRAPHY

References updated: 18 April 2019

• Nunez M. Hepatotoxicity of antiviral agents. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 505-18.

  (Review of hepatotoxicity of antiviral agents).
• Flexner C. Antiretroviral agents and treatment of HIV infection. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 1623-63.

  (Textbook of pharmacology and therapeutics).
• Acosta EP. Antiviral agents (nonretroviral). In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 1105-18.

  (Textbook of pharmacology and therapeutics).
• Freiman JP, Helfert KE, Hamrell MR, Stein DS. Hepatomegaly with severe steatosis in HIV-seropositive patients. AIDS 1993; 7; 379-85. [PubMed: 8471200]

  (Reports of 6 fatal and 2 nonfatal cases of hepatomegaly and steatosis in patients with HIV on zidovudine for 3-12 months).
• Chattha G, Arieff AI, Cumings G, Tierney LM Jr. Lactic acidosis complicating the acquired immunodeficiency syndrome. Ann Intern Med 1993; 118: 37-9. [PubMed: 8416156]

  (Report of 7 patients with HIV infection who developed lactic acidosis of unknown cause, presenting with nausea, anorexia and weight loss followed by dyspnea, stupor and death [in 4]; 4 on zidovudine, 1 ganciclovir and 1 clofazimine; initial arterial pH 7.09-7.27, lactate 10.4-17.4 mmol/L).
• McKenzie R, Fried MW, Sallie R, Conjeevaram H, Di Bisceglie AM, Park Y, Savarese B, et al. Hepatic failure and lactic acidosis due to fialuridine (FIAU), an investigational nucleoside analogue for chronic hepatitis B. N Engl J Med 1995; 333: 1099-105. [PubMed: 7565947]

  (Description of syndrome of lactic acidosis, hepatic failure and pancreatitis arising after 8-11 weeks of fialuridine treatment in 15 patients with chronic hepatitis B; among 7 patients affected, 5 died of intractable lactic acidosis and 2 survived, but required emergency liver transplantation).
• Lewis W, Dalakas MC. Mitochondrial toxicity of antiviral drugs. Nature Med 1995; 1: 417-23. [PubMed: 7585087]

  (Review of mechanisms for mitochondrial injury by nucleoside analogues including inhibition of mitochondrial DNA polymerase gamma).
• Styrt B, Freiman JP. Hepatotoxicity of antiviral agents. Gastroenterol Clin North Am 1995; 24: 839-52. [PubMed: 8749901]

  (Early review of liver toxicity of antiviral agents; covering the first four nucleoside analogues used for HIV infection: zidovudine, didanosine, zalcitabine and stavudine).
• Honkoop P, de Man RA, Heijtink RA, Schalm SW. Hepatitis B reactivation after lamivudine. Lancet 1995; 346: 1156-7. [PubMed: 7475613]

  (29 year old with chronic hepatitis B developed flare of hepatitis starting 4 weeks after 6 month course of lamivudine, with jaundice [peak bilirubin 7 mg/dL, ALT 3290 U/L] and high levels of HBV DNA, having rebounded after therapy).
• Lenzo NP, Garas BA, French MA. Hepatic steatosis and lactic acidosis associated with stavudine treatment in an HIV patient: a case report. AIDS 1997; 11: 1294-6. [PubMed: 9256950]

  (32 year old with HIV developed lactic acidosis and hepatic steatosis 6 months after starting stavudine [plus zidovudine and lamivudine] with bilirubin 1.6 mg/dL and ALT 67 U/L, rapid resolution with stopping stavudine).
• Schiano T, Lissoos T, Ahmed A, Siano C, Zaitman D, Cohn G, Ehrenpreis E. Lamivudine-stavudine-induced liver failure in hepatitis B cirrhosis. Am J Gastroenterol 1997; 92: 1563-4. [PubMed: 9317091]

  (Patient with HIV-HBV coinfection and cirrhosis developed flare of hepatitis beginning 2 weeks after adding lamivudine to long term stavudine; bilirubin rising to 20.7 mg/dL, ALT 2414 U/L, ascites and pruritus; slowly improving once lamivudine was stopped; HBV DNA level was high, but timing and serial results were not given).
• Zylberberg H, Pialoux G, Carnot F, Landau A, Bréot C, Pol S. Rapidly evolving hepatitis C virus-related cirrhosis in a human immunodeficiency virus-infected patient receiving triple antiretroviral therapy. Clin Infect Dis 1998; 27:1255-8. [PubMed: 9827279]

  (36 year old with HIV-HCV coinfection developed ascites 9 months after starting lamivudine, indinavir and stavudine with bilirubin 2.1 mg/dL, ALT 60 U/L, and Alk P 107 U/L, with subsequent liver failure; biopsy showed nodularity and "cirrhosis").
• Brinkman K, ter Hofstede HJ, Burger DM, Smeitink JAM, Koopmans PP. Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as a common pathway. AIDS 1998; 12: 1735-44. [PubMed: 9792373]

  (Review of mitochondrial function and role of mitochondrial toxicity or depletion in the adverse side effects of nucleoside analogues).
• Bessesen M, Ives D, Condreay L, Lawrence S, Sherman KE. Chronic active hepatitis B exacerbations in human immunodeficiency virus-infected patients following development of resistance to or withdrawal of lamivudine. Clin Infect Dis 1999; 28: 1032-5. [PubMed: 10452630]

  (Five patients with HIV-HBV coinfection had clinically apparent flares of hepatitis [ALT 163-1408 U/L, bilirubin 0.8-9.5 mg/dL] either on lamivudine [n=3; all 3 with lamivudine resistance] or upon withdrawal [n=2; when switched to other antiretrovirals without activity against HBV]; one died).
• Sulkowski MS, Thomas DL, Chaisson RE, Moore RD. Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection. JAMA 2000; 283: 74-80. [PubMed: 10632283]

  (Among 298 patients with HIV infection, ALT elevations above 5 times ULN occurred in 10.4% per year during antiretroviral treatment; factors associated with ALT elevations included ritonavir [27.3%] and coinfection with either HCV or HBV; ALT with bilirubin elevations occurred in 3 patients; 2 on indinavir and all 3 with coinfection).
• Velasco M, Guijarro C. Elevated liver enzymes following initiation of antiretroviral therapy. JAMA 2000; 283: 2526-7. [PubMed: 10815112]

  (Letter in response to Sulkowski et al. [JAMA 2000] pointing out that antiretroviral therapy can cause immune reconstitution and flares of hepatitis B or C which may be misdiagnosed as hepatotoxicity).
• Sulkowski MS, Thomas DL, Chaisson RE, Moore RD. Elevated liver enzymes following initiation of antiretroviral therapy JAMA 2000; 283: 2526-7. [PubMed: 10815113]

  (Reply to Velasco and Guijarro pointing at that the majority of the ALT elevations described could not be attributed to immune reconstitution).
• Johri S, Alkhuja S, Siviglia G, Soni A. Steatosis-lactic acidosis syndrome associated with stavudine and lamivudine therapy. AIDS 2000; 14: 1286. [PubMed: 10894300]

  (Three women with HIV infection developed lactic acidosis and hepatic steatosis 1-8 months after starting stavudine and lamivudine with AST 291, 48 and 119 U/L, severe acidosis, and fatty liver by imaging; two died one of whom had massive hepatomegaly and steatosis on autopsy).
• Lonergan JT, Behling C, Pfander H, Hassanein TI, Mathews WC. Hyperlactatemia and hepatic abnormalities in 10 human immunodeficiency virus-infected patients receiving nucleoside analogue combination regimens. Clin Infect Dis 2000; 31: 162-6. [PubMed: 10913415]

  (Over 6 months, authors identified 10 HIV-infected patients with high lactate levels [2.9-6.2 mmol/L]; all were taking stavudine, 5 didanosine and 7 lamivudine for 4-20 months; 8 with symptoms of abdominal pain, nausea or distension; all with ALT elevations [2-10.7 times ULN], 3 with HBV or HCV; imaging showed fatty liver in 5; all resolved with stopping, lactate levels falling to normal after 16-111 days).
• Bruno R, Sacchi P, Malfitano A, Filice G. YMDD-mutant HBV strain as a cause of liver failure in an HIV-infected patient. Gastroenterology 2001; 121: 1027-8. [PubMed: 11665695]

  (38 year old man with HIV-HBV coinfection on long term antiretroviral therapy including lamivudine [~4 years] developed jaundice with bilirubin 7.4 mg/dL, ALT 1658 U/L, normal lactate, INR 4 and HBV DNA of 270,000 copies/mL with lamivudine resistant mutations [rtM201I and rtL180M], progressive liver failure and death).
• Mina J, Moore CB, James IR, Nolan D, Upton RP, McKinnon EJ, Mallal SA. Chronic hyperlactatemia in HIV-infected patients taking antiretroviral therapy. AIDS 2001; 15: 717-23. [PubMed: 11371686]

  (349 patients with HIV infection were screened for lactate levels on multiple occasions; 2 had lactic acidosis and were both symptomatic and on stavudine: 3.9 per 1000 person-years).
• Ormseth EJ, Holtzmuller KC, Goodman ZD, Colonna JO, Batty DS, Sjogren MH. Hepatic decompensation associated with lamivudine: a case report and review of lamivudine-induced hepatotoxicity. Am J Gastroenterol 2001; 96: 1619-22. [PubMed: 11374710]

  (62 year old with HBV related cirrhosis developed severe flare starting 8 weeks after starting lamivudine [ALT rising from 171 to 1500 U/L, bilirubin 3.1 to 11 mg/dL while HBV DNA became undetectable]; variceal hemorrhage and progressive encephalopathy led to emergency liver transplant, after which lamivudine was continued and he remained HBsAg negative).
• Cihlar T, Birkus G, Greenwalt DE, Hitchcock MJM. Tenofovir exhibits low cytotoxicity in various human cell types: comparison with other nucleotide reverse transcriptase inhibitors. Antiviral Research 2002; 54: 37.45. [PubMed: 11888656]

  (In vitro study of nucleoside analogues found that tenofovir and lamivudine were less cytotoxic to several human cell types than zidovudine, stavudine, didanosine and zalcitabine).
• Clark S, Creighton S, Portmann B, Taylor C, Wendon J, Cramp M. Acute liver failure associated with antiretroviral treatment for HIV: a report of six cases. J Hepatol 2002; 36: 295-301. [PubMed: 11830344]

  (6 patients with HIV infection who developed acute liver failure on stavudine [n=5], lamivudine [n=3], didanosine [n=2], saquinavir [n=2], efavirenz [n=2], nevirapine [n=2], or nelfinavir, delaviridine or zidovudine [n=1] for 1-3 months [peak bilirubin 2.7-32 mg/dL, AST 240-8650 U/L, Alk P 122-191 U/L]; 2 with signs of hypersensitivity; two with hepatitis B; 5 died, autopsies showing massive necrosis; one with massive steatosis; likely multiple causes).
• Spengler U, Lichterfeld M, Rockstroh JK. Antiretroviral drug toxicity.a challenge for the hepatologist? J Hepatol 2002; 36: 283-94. [PubMed: 11830343]

  (Review of the diagnosis of drug induced liver disease in patients with HIV on antiretroviral agents, with discussion of mechanisms including mitochondrial toxicity and hypersensitivity reactions).
• Bonnet F, Bonarek M, Morlat P, Mercie P, Dupon M, Gemain MC, Malvy D, et al. Risk factors for lactic acidosis in HIV-1-infected patients treated with nucleoside reverse-transcriptase inhibitors: a case-control study. Clin Infect Dis 2003; 36: 1324-8. [PubMed: 12746780]

  (Case control study of 9 patients [5 women] with HIV infection and lactic acidosis, 6 with hepatomegaly and 5 with jaundice, 8 on stavudine, 7 on didanosine, 6 on zidovudine; 6 died; risk factors were renal insufficiency and low CD4 counts but numbers of cases were few).
• Arenas-Pinto A, Grant AD, Edwards S, Weller IVD. Lactic acidosis in HIV-1 infected patients: a systematic review of published cases. Sex Transm Infect 2003; 79: 340-4. [PMC free article: PMC1744718] [PubMed: 12902594]

  (Review of 217 published cases of lactic acidosis; 53% female, all taking at least one nucleoside for 1-36 months, 61% on stavudine, 33% didanosine, 31% zidovudine, 30% lamivudine; 92% had hepatic steatosis on biopsy or autopsy; 48% died).
• Kontorinis N, Dieterich D. Hepatotoxicity of antiretroviral therapy. AIDS Rev 2003; 5: 36-43. [PubMed: 12875106]

  (Review of hepatotoxicity of antiretroviral drugs; definition of hepatotoxicity in antiretroviral studies; grade 1=1.25-2.5 times, grade 2=2.6-5 times, grade 3=5.1-10 times and grade 4=>10 times normal or baseline ALT values; abacavir and lamivudine are least likely to cause hepatotoxicity).
• Ogedegbe AE, Thomas DL, Diehl AM. Hyperlactataemia syndromes associated with HIV therapy. Lancet Infect Dis 2003; 3: 329-37. [PubMed: 12781504]

  (Review of mechanisms of hyperlactatemia with antiretroviral therapy, occurs mostly with use of nucleoside analogues, stavudine, didanosine and zidovudine, attributed to mitochondrial depletion, but other mechanisms may be involved).
• Ofotokun I, Pomeroy C. Sex differences in adverse reactions to antiretroviral drugs. Top HIV Med 2003; 11: 55-9. [PubMed: 12717043]

  (Review of sex differences in adverse events; higher frequency of mitochondrial toxicity and hypersensitivity in women than men).
• Ogedegbe AO, Sulkowski MS. Antiretroviral-associated liver injury. Clin Liver Dis 2003; 7: 475-99. [PubMed: 12879995]

  (Review of hepatotoxicity of antiretrovirals; ALT elevations above 5 times ULN reported in 7% with zidovudine, 16% didanosine, 9-13% stavudine, <1% lamivudine, tenofovir and abacavir, 3-10% protease inhibitors, 10% nevirapine and 8% efavirenz; recommend monitoring at 4 weeks and then every 12 weeks, stopping if ALT levels are >10 times ULN or if symptoms of liver injury are present, monitoring more closely if ALT levels are elevated).
• Lok AS, Lai CL, Leung N, Yao GB, Cui ZY, Schiff ER, Dienstag JL, et al. Long-term safety of lamivudine treatment in patients with chronic hepatitis B. Gastroenterology 2004; 126:1932-3. [PubMed: 14724824]

  (Analysis of hepatitis flares in 998 patients treated with lamivudine for up to 6 years; during the first year, flares [ALT >3 times normal] were less common during lamivudine [10%] than placebo [19%] therapy, but increased thereafter usually in association with antiviral resistance; 8 patients developed hepatic decompensation and 2 with antiviral resistance died).
• Abrescia N, D.Abbraccio M, Figoni M, Busto A, Maddaloni A, De Marco M. Hepatotoxicity of antiretroviral drugs. Curr Pharm Des 2005; 11: 3697-710. [PubMed: 16305505]

  (Review of hepatotoxicity of antiretrovirals; major syndrome with nucleoside analogues is mitochondrial injury with lactic acidosis and severe hepatomegaly and steatosis).
• Chang TT, Gish RG, de Man R, Gadano A, Sollano J, Chao YC, Lok AS, et al.; BEHoLD AI463022 Study Group. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med 2006; 354: 1001-10. [PubMed: 16525137]

  (Controlled trial comparing entecavir [n=354] to lamivudine [n=355] in patients with HBeAg-positive chronic hepatitis B; on-treatment ALT elevations >5 times normal in 10% of entecavir- vs 17% of lamivudine-treated subjects [entecavir therapy stopped in one patient]; posttreatment elevations in 2% vs 12%).
• Lai CL, Shouval D, Lok AS, Chang TT, Cheinquer H, Goodman Z, DeHertogh D, et al.; BEHoLD AI463027 Study Group. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N Engl J Med 2006; 354: 1011-20. [PubMed: 16525138]

  (Controlled trial comparing entecavir [n=325] to lamivudine [n=313] in patients with HBeAg-negative chronic hepatitis B; on-treatment ALT elevations >5 times normal in 2% of entecavir- vs 3% of lamivudine-treated; posttreatment elevations in 12% vs 29%, no deaths from flares).
• Björnsson E, Olsson R. Suspected drug-induced liver fatalities reported to the WHO database. Dig Liver Dis 2006; 38: 33-8. [PubMed: 16054882]

  (Among 4690 reports of fatal acute liver failure due to medications reported to a WHO data, 80 were attributed to lamivudine which ranked 6th, even though the lamivudine was probably being given for the acute liver failure rather than causing it).
• Lai CL, Gane E, Liaw YF, Hsu CW, Thongsawat S, Wang Y, Chen Y, et al.; Globe Study Group. Telbivudine versus lamivudine in patients with chronic hepatitis B. N Engl J Med 2007; 357: 2576-88. [PubMed: 18094378]

  (Trial of telbivudine [600 mg/day] vs lamivudine [100 mg/day] for 52 weeks in 1370 patients with chronic hepatitis B; ALT >3 times ULN in 3.7% of telbivudine, 6.3% of lamivudine; 1 on lamivudine developed antiviral resistance and liver failure requiring liver transplant).
• Jain MK. Drug-induced liver injury associated with HIV medications. Clin Liver Dis 2007; 11: 615-39, vii-viii. [PubMed: 17723923]

  (Review of hepatotoxicity of antiretroviral medications; ALT elevations occur in 2-18% of patients, but often resolve spontaneously even without dose modification; classes of injury include hypersensitivity [nevirapine, efavirenz, abacavir], mitochondrial injury [stavudine, didanosine, zidovudine], flares of hepatitis B [lamivudine, emtricitabine, tenofovir], flares of hepatitis C [any potent regimen], idiosyncratic injury [ritonavir, nevirapine, efavirenz], cholestatic hepatitis [many agents]).
• Hou J, Yin YK, Xu D, Tan D, Niu J, Zhou X, Wang Y, et al. Telbivudine versus lamivudine in Chinese patients with chronic hepatitis B: Results at 1 year of a randomized, double-blind trial. Hepatology 2008; 47: 447-54. [PubMed: 18080339]

  (Trial of telbivudine vs lamivudine for 52 weeks in 332 patients with hepatitis B; ALT elevations >3 times normal occurred in 9.1% of lamivudine vs 5.4% of telbivudine treated subjects, usually associated with viral breakthrough; none fatal).
• Schiff E, Simsek H, Lee WM, Chao YC, Sette H Jr, Janssen HL, Han SH, et al. Efficacy and safety of entecavir in patients with chronic hepatitis B and advanced hepatic fibrosis or cirrhosis. Am J Gastroenterol 2008; 103: 2776-83. [PubMed: 18721244]

  (Analysis of 245 patients with advanced chronic hepatitis B in 3 clinical trials; on-treatment flares [ALT >10 times normal] occurred in 1 of 120 entecavir- vs 4 of 125 lamivudine-treated patients).
• Hammer SM, Eron JJ Jr, Reiss P, Schooley RT, Thompson MA, Walmsley S, Cahn P, et al.; International AIDS Society-USA. Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel. JAMA 2008; 300: 555-70. [PubMed: 18677028]

  (Recommendations on use of antiviral therapy in adults with HIV infection, including use of recently approved agents: raltegravir, maraviroc and etravirine).
• Inductivo-Yu I, Bonacini M. Highly active antiretroviral therapy-induced liver injury. Current Drug Safety 2008; 3: 4-13. [PubMed: 18690975]

  (Review of drug induced liver injury due to antiretroviral agents).
• Soriano V, Puoti M, Garcia-Gascó Rockstroh JK, Benhamou Y, Barreiro P, McGovern B. Antiretroviral drugs and liver injury. AIDS 2008; 22: 1-13. [PubMed: 18090386]

  (Review of hepatotoxicity of antiretroviral drugs with recommendations on management, stopping therapy if symptoms arise, with overt jaundice [direct bilirubin], evidence of mitochondrial toxicity, ALT >10 times ULN, ALT at lower levels if newly marketed agent; important to rule out other causes; problematic agents include didanosine, stavudine and zidovudine, nevirapine and efavirenz, full dose ritonavir and tipranavir).
• Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J; Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008; 135: 1924-34. [PMC free article: PMC3654244] [PubMed: 18955056]

  (Among 300 cases of drug induced liver disease in the US collected between 2004 and 2008, 7 were attributed to antiretroviral agents, 2 nevirapine, 1 efavirez and 4 miscellaneous combinations but none to lamivudine).
• Fontana RJ. Side effects of long-term oral antiviral therapy for hepatitis B. Hepatology 2009; 49 (5 Suppl): S185-95. [PubMed: 19399802]

  (Review of side effects of nucleoside analogues used to treat chronic hepatitis B).
• Ferrajolo C, Capuano A, Verhamme KM, Schuemie M, Rossi F, Stricker BH, Sturkenboom MC. Drug-induced hepatic injury in children: a case/non-case study of suspected adverse drug reactions in VigiBase. Br J Clin Pharmacol 2010; 70: 721-8. [PMC free article: PMC2997312] [PubMed: 21039766]

  (Worldwide pharmacovigilance database contained 9036 hepatic adverse drug reactions in children, 3 antiretroviral agents were among the top 40 cases, including zidovudine [8th, 106 cases], lamivudine [26th, 45 cases] and nevirapine [36th, 37 cases]).
• Reuben A, Koch DG, Lee WM; Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology 2010; 52: 2065-76. [PMC free article: PMC3992250] [PubMed: 20949552]

  (Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 were attributed to drug induced liver injury and 4 to antiretroviral agents, including 3 to combinations with stavudine and 1 to abacavir, but none were attributed to lamivudine).
• Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology 2013 ; 144: 1419-25. [PubMed: 23419359]

  (In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, but none were attributed to lamivudine or other antivral agents used to treat hepatitis B).
• Hernández N, Bessone F, Sánchez A, di Pace M, Brahm J, Zapata R, A Chirino R, et al. Profile of idiosyncratic drug induced liver injury in Latin America. An analysis of published reports. Ann Hepatol 2014; 13: 231-9. [PubMed: 24552865]

  (Systematic review of literature of drug induced liver injury in Latin American countries published from 1996 to 2012 identified 176 cases, two of which were attributed to lamivudine but both in combination with zidovudine to treat HIV infection).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, 12 [1.3%] were attributed to antiretroviral agents but none were due to lamivudine or agents being used to treat hepatitis B).
• Lee KS, Kweon YO, Um SH, Kim BH, Lim YS, Paik SW, Heo J, et al. Efficacy and safety of entecavir versus lamivudine over 5 years of treatment: A randomized controlled trial in Korean patients with hepatitis B e antigen-negative chronic hepatitis B. Clin Mol Hepatol 2017; 23: 331-9. [PMC free article: PMC5760004] [PubMed: 28946736]

  (Among 120 Korean patients with chronic hepatitis B treated with lamivudine or entecavir for at least 2 years, virologic responses were less common with lamivudine [48% vs 95%] while breakthough was more frequent [43% vs 1%]; serious adverse events were rare and were unrelated to therapy).
• Pan CQ, Yi W, Liu M, Wan G, Hu YH, Zhou MF. Lamivudine therapy during the second vs the third trimester for preventing transmission of chronic hepatitis B. J Viral Hepat 2017; 24: 246-52. [PubMed: 28025872]

  (Among 160 HBsAg positive expectant mothers with high levels of HBV DNA who were treated with lamivudine starting in the 2nd or 3rd trimester of pregnancy, none had evidence of transmission of hepatitis B to their newborns, while ALT flares occurred in 3% during pregnancy and 9% postpartum when lamivudine was stopped, but none had severe hepatitis or acute liver failure).
• Triumeq--a 3 drug combination for HIV. Med Lett Drugs Ther 2015; 57 (1459): 7-8. [PubMed: 25555073]

  (Concise review of the clinical effiacy, safety and costs of the fixed dose combination of lamivudine, abacavir and dolutegravir as a single tablet regimen for HIV infection; mentions common adverse events of insomnia, headahce and fatigue and that ALT and AST elevations can occur in patients with HBV or HCV coinfection).
• Cahn P, Madero JS, Arribas JR, Antinori A, Ortiz R, Clarke AE, Hung CC, Et al.; GEMINI Study Team. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials. Lancet 2019; 393 (10167): 143-55. [PubMed: 30420123]

  (Among 1441 patients with HIV infection enrolled in two controlled trials comparing 2-drug [dolutegravir and lamivudine] to 3-drug [dolutegravir, tenofovir, emtricitabine] regimens, virologic response rates were similar [91% vs 93%] while drug related adverse events were less frequent with the 2-drug regimen [18% vs 24%], but serious events were similar in frequency [1% vs 1%].