A fixed-dose combination (FDC) of three antiretroviral agents for the treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection. It is a complete, once-daily, single-tablet regimen (STR) containing two nucleoside reverse transcriptase inhibitors (NRTIs) - Lamivudine and Tenofovir Disoproxil Fumarate (TDF) - and one non-nucleoside reverse transcriptase inhibitor (NNRTI) - Efavirenz. It is a cornerstone of first-line antiretroviral therapy (ART) in India as per the National AIDS Control Organization (NACO) guidelines.
Adult: One tablet (Lamivudine 300mg + Tenofovir DF 300mg + Efavirenz 400mg) orally, once daily.
Note: Take on an empty stomach, preferably at bedtime, to improve tolerability of Efavirenz-related central nervous system (CNS) side effects (dizziness, drowsiness). Swallow whole with water. Do not crush or chew. Taking with a high-fat meal may increase Efavirenz absorption and side effects.
This combination inhibits the HIV-1 reverse transcriptase enzyme via two distinct mechanisms, preventing the conversion of viral RNA into DNA, thereby halting viral replication. Lamivudine and Tenofovir are nucleos(t)ide analogues that act as competitive substrates, leading to chain termination. Efavirenz binds allosterically to a hydrophobic pocket, causing conformational change and enzyme inhibition.
Pregnancy: Pregnancy Category D (as per US FDA). Efavirenz is teratogenic in primates (neural tube defects) and there are reports of human fetal abnormalities, especially in the first trimester. This FDC is contraindicated in the first trimester of pregnancy and in women of childbearing potential not using effective contraception. For women already on this regimen who become pregnant, switch to an alternative ART regimen as soon as possible. Lamivudine and Tenofovir are Pregnancy Category B.
Driving: Efavirenz can cause dizziness, impaired concentration, and somnolence, especially during the first weeks of therapy. Patients should be advised not to drive or operate heavy machinery if they experience these symptoms.
| Rifampin | Decreases Efavirenz plasma concentrations. In patients ≥50 kg, standard dose may be used. In patients <50 kg, this FDC is not suitable as Efavirenz dose increase is needed. | Major |
| Voriconazole | Contraindicated. Efavirenz significantly decreases voriconazole levels, and voriconazole increases Efavirenz levels. | Contraindicated |
| Clarithromycin | Efavirenz reduces clarithromycin levels; azithromycin is preferred for MAC prophylaxis. | Moderate |
| Anticonvulsants (Carbamazepine, Phenobarbital, Phenytoin) | May decrease Efavirenz levels; therapeutic drug monitoring recommended. | Major |
| Azole Antifungals (Ketoconazole, Itraconazole) | Efavirenz decreases azole levels; dose adjustment of azole may be needed. | Moderate |
| Artemether/Lumefantrine | Efavirenz may decrease lumefantrine levels, potentially reducing antimalarial efficacy. | Moderate |
| Other Nephrotoxic Drugs (Aminoglycosides, IV Pentamidine, NSAIDs high-dose/long-term) | Increased risk of renal impairment with TDF. | Moderate |
| Didanosine (ddI) | Increased risk of ddI-associated adverse effects (pancreatitis, neuropathy) and virologic failure; avoid concomitant use. | Major |
| Methadone | Efavirenz decreases methadone levels, potentially precipitating opioid withdrawal; methadone dose may need increase. | Moderate |
| Oral Contraceptives (Ethinyl Estradiol) | Efavirenz may reduce contraceptive hormone levels; use alternative or additional barrier method. | Moderate |
Same composition (Lamivudine (300mg) + Tenofovir disoproxil fumarate (300mg) + Efavirenz (400mg)), different brands: