Twenty-Five Years of Lamivudine

Current and Future Use for the Treatment of HIV-1 Infection

Romina Quercia, MD, PhD; Carlo-Federico Perno, MD, PhD; Justin Koteff, PharmD; Katy Moore, RPh, PharmD; Cynthia McCoig, MD; Marty St. Clair, BS; Daniel Kuritzkes, MD


J Acquir Immune Defic Syndr. 2018;78(2):125-135. 

In This Article

Abstract and Introduction


Innovation in medicine is a dynamic, complex, and continuous process that cannot be isolated to a single moment in time. Anniversaries offer opportunities to commemorate crucial discoveries of modern medicine, such as penicillin (1928), polio vaccination (inactivated, 1955; oral, 1961), the surface antigen of the hepatitis B virus (1967), monoclonal antibodies (1975), and the first HIV antiretroviral drugs (zidovudine, 1987). The advent of antiretroviral drugs has had a profound effect on the progress of the epidemiology of HIV infection, transforming a terminal, irreversible disease that caused a global health crisis into a treatable but chronic disease. This result has been driven by the success of antiretroviral drug combinations that include nucleoside reverse transcriptase inhibitors such as lamivudine. Lamivudine, an L-enantiomeric analog of cytosine, potently affects HIV replication by inhibiting viral reverse transcriptase enzymes at concentrations without toxicity against human polymerases. Although lamivudine was approved more than 2 decades ago, it remains a key component of first-line therapy for HIV because of its virological efficacy and ability to be partnered with other antiretroviral agents in traditional and novel combination therapies. The prominence of lamivudine in HIV therapy is highlighted by its incorporation in recent innovative treatment strategies, such as single-tablet regimens that address challenges associated with regimen complexity and treatment adherence and 2-drug regimens being developed to mitigate cumulative drug exposure and toxicities. This review summarizes how the pharmacologic and virologic properties of lamivudine have solidified its role in contemporary HIV therapy and continue to support its use in emerging therapies.


Lamivudine (2'-deoxy-3'-thiacytidine, 3TC) is a first-generation nucleoside reverse transcriptase inhibitor (NRTI) that was approved for the treatment of HIV-1 infection in 1995 and hepatitis B virus (HBV) infection in 1998.[1,2] Lamivudine has been evaluated in more than 50 clinical studies registered on involving >25,000 patients. Since 2002, the World Health Organization (WHO) has been recommending treatment regimens for HIV infection, and both 3TC or emtricitabine (FTC) are preferred components of nearly all fixed-dose combinations.[3] Moreover, in the updated 2016 WHO guidelines, 3TC continues to be recommended as part of fixed-dose combinations as first- and second-line antiretroviral therapy (ART) for adults, adolescents, children, and infants.[3] In addition, WHO recommends that patients coinfected with HIV and HBV use a first-line ART combination containing tenofovir disoproxil fumarate (TDF) plus 3TC or FTC. The WHO guidelines are consistent with those recommended by the International Antiviral Society,[4] European AIDS Clinical Society,[5] and the US Department of Health and Human Services.[6–8] HIV treatment has evolved to include single-tablet regimens containing potent 3- or 4-drug combinations, and 3TC has remained a well-established component in many combination strategies as HIV treatment continues to evolve.