Tenofovir-Emtricitabine

• HIV Treatment
• HIV Pre-Exposure Prophylaxis (PrEP)
• HIV Prevention

Tenofovir-emtricitabine is a fixed-dose combination of two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) used for HIV treatment and pre-exposure prophylaxis (PrEP). The combination (Truvada) is a cornerstone of HIV prevention and treatment regimens.

Mechanism of Action

Both drugs target HIV reverse transcriptase:

Tenofovir disoproxil fumarate (TDF):

• Nucleotide analog (adenosine analog)
• Phosphorylated to active form tenofovir diphosphate
• Competitive inhibitor of HIV reverse transcriptase
• Chain terminator of viral DNA synthesis

Emtricitabine (FTC):

• Nucleoside analog (cytosine analog)
• Phosphorylated intracellularly to active triphosphate
• Competitive inhibitor of HIV reverse transcriptase
• Chain terminator of viral DNA synthesis

Together they provide synergistic antiviral activity with non-overlapping resistance profiles.

Available Formulations

• Truvada: Tenofovir DF 300 mg/emtricitabine 200 mg tablets
• Descovy (TAF-based): Tenofovir alafenamide 25 mg/emtricitabine 200 mg (different formulation with improved renal and bone safety)

Medical Uses

FDA-Approved Indications:

• HIV-1 infection (in combination with other antiretrovirals)
• Pre-exposure prophylaxis (PrEP) to reduce risk of sexually acquired HIV-1
• PrEP for HIV-1 from injection drug use (Descovy not approved for this)

Dosing Guidelines

HIV Treatment:

• One tablet (TDF 300 mg/FTC 200 mg) once daily as part of complete regimen

HIV PrEP:

• One tablet once daily
• For receptive vaginal sex: Maximum protection reached after approximately 20 days of daily use
• For receptive anal sex: Maximum protection reached after approximately 7 days of daily use

Renal Adjustment (TDF/FTC):

• CrCl 30-49 mL/min: One tablet every 48 hours
• CrCl <30 or hemodialysis: Not recommended

Important Safety Information

Boxed Warnings:

• Lactic acidosis and severe hepatomegaly with steatosis: Fatal cases reported
• Post-treatment hepatitis B exacerbation: Test for HBV before initiating; monitor closely if discontinued
• PrEP only for HIV-negative individuals: Document negative HIV status before and during PrEP

Contraindications:

• Not recommended for PrEP in patients with unknown or positive HIV status

Warnings and Precautions:

• Nephrotoxicity and bone mineral density loss (TDF)
• Immune reconstitution syndrome
• Redistribution/accumulation of body fat

Drug Interactions

• Nephrotoxic drugs: Avoid combination (increased toxicity risk)
• Adefovir: Avoid concurrent use
• Didanosine: Increases didanosine levels; not recommended together
• Atazanavir: Increases tenofovir levels; monitor for toxicity
• Lopinavir/ritonavir: Increases tenofovir levels

Special Populations

• Hepatic Impairment: No dose adjustment for TDF; caution with hepatitis B coinfection
• Renal Impairment: Adjust dosing interval; consider TAF-based formulation
• Pregnancy: Preferred NRTI backbone in pregnancy (extensive safety data)
• Lactation: TDF enters breast milk; in developed countries, avoid breastfeeding if HIV-positive
• Adolescents (≥35 kg): Same dosing as adults
• Bone Health: Monitor BMD in patients at risk for osteoporosis