By William Elliott, MD, FACP, and James Chan, PharmD, PhD

Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.

Drs. Elliott and Chan report no financial relationships relevant to this field of study.

The FDA has approved a new single-tablet, once-daily, triple-drug regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adult and pediatric patients. This combination is comprised of efavirenz (EFV), lamivudine (3TC), and tenofovir disoproxil fumarate (TDF). EFV is a non-nucleoside reverse transcriptase inhibitor. 3TC and TDF are nucleo(t)side reverse transcriptase inhibitors (NRTIs). The combination is the most widely use regimen outside the United States.1 This is marketed as Symfi, a lower-cost, once-a-day option.


EFV/3TC/TDF is indicated as a complete regimen for the treatment of HIV-1 infection in adult and pediatric patients weighing at least 40 kg.2


The recommended dose is one tablet once daily on an empty stomach, preferably at bedtime.2 Each tablet contains 600 mg of EFV, 300 mg of 3TC, and 300 mg of TDF.


EFV/3TC/TDF offers a less expensive, single-tablet, initial treatment option for patients with HIV-1 infections.3


The form of TDF in this combination carries greater potential to reduce bone mineral density and cause renal toxicity than another form of tenofovir (alafenamide) (TAF).3 In a three-year clinical trial, 28% of TDF-treated subjects lost at least 5% of bone mineral density in the spine or 7% at the hip.2 In addition, TAF provides pharmacologically active tenofovir diphosphate at one-tenth the oral dose, 90% lower systemic exposure, and 2.41-fold higher cellular concentration.4

Common (> 10%) adverse reactions associated with EFV/3TC/TDF were headache (14%), pain (13%), diarrhea (11%), depression (11%), rash event (18%), increase in fasting cholesterol > 240 mg/dL (19%), and increase in creatine kinase (12%).2


The efficacy and safety of EFV/3TC/TDF were published in 2004 based on a randomized, double-blind study comparing EFV/3TC/TDF to EFV/3TC and stavudine (d4T).2,5 HIV-1-infected (median RNA, 77,600 copies/mL and 43% > 100,000), treatment-naïve adults were randomized to EFV/3TC/TDF (n = 299) or EFV/3TC/d4T (n = 301). The main efficacy outcome was the proportion of patients with HIV RNA levels < 400 copies/mL at week 48 and secondary efficacy endpoints at weeks 48, 96, and 144. Responders at week 48 were 79% for EFV/3TC/TDF compared to 82% for EFV/3TC/d4T. The corresponding proportions were 68% and 62% for week 144, respectively. EFV/3TC/TDF was associated with less effect on the lipid profile and less lipodystrophy.5


HIV treatment guidelines recommend seven combinations as initial treatment in most patients.6 These are raltegravir/emtricitabine with TDF or TAF, elvitegravir/cobicistat/emtricitabine with TDF or TAF, dolutegravir/abacavir/lamivudine, and dolutegravir/emtricitabine with TDF or TAF. Efavirenz-based regimens have been used widely with excellent virologic activity.6 However, the low genetic barrier to resistance and relatively high central nervous system side effects make it less attractive compared to the first-line recommendations.6 The cost for EFV/3TC/TDF is $1,634 compared to $2,724 for efavirenz, emtricitabine, and TDF. Lamivudine and emtricitabine may be substituted for each other, so these are considered as interchangeable NRTIs.


  1. Mylan. Mylan Introduces Symfi Triple Combo Once-Daily HIV Treatment in the U.S., March 28, 2018. Available at: Accessed April 23, 2018.
  2. Symfi Prescribing Information, Mylan Specialty L.P., March 2018. Available at: Accessed April 23, 2018.
  3. Post FA, Yazdanpanah Y, Schembri G, et al. Efficacy and safety of emtricitabine/tenofovir alafenamide (FTC/TAF) vs. emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) as a backbone for treatment of HIV-1 infection in virologically suppressed adults: Subgroup analysis by third agent of a randomized, double-blind, active-controlled phase 3 trial. HIV Clin Trials 2017;18:135-140.
  4. Podany AT, Bares SH, Havens J, et al. Plasma and intracellular pharmacokinetics of tenofovir in patients switched from tenofovir disoproxil fumarate to tenofovir alafenamide. AIDS 2018;32:761-765.
  5. Gallant JE, Staszewski S, Pozniak AL, et al. Efficacy and safety of tenofovir DF vs. stavudine in combination therapy in antiretroviral-naive patients: A 3-year randomized trial. JAMA 2004;292:191-201.
  6. U.S. Department of Health and Human Services. AIDSinfo. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Updated March 27, 2018. Available at: Accessed April 23, 2018.