Side Effects of Truvada
Truvada (emtricitabine/tenofovir disoproxil fumarate) is generally well-tolerated, with the most common side effects being gastrointestinal symptoms (nausea, diarrhea, vomiting), headache, fatigue, and dizziness, while the most clinically significant concerns are renal toxicity and bone mineral density loss. 1
Most Common Side Effects (Occurring in ≥5% of Patients)
Gastrointestinal Effects
- Nausea (9% of patients), diarrhea (9%), and vomiting (2-5%) are the most frequently reported gastrointestinal side effects 1
- Flatulence and dyspepsia occur in 3-4% of patients 1
- These symptoms are typically mild to moderate and rarely lead to discontinuation (<1% discontinuation rate due to GI effects) 1
Neurological Effects
- Headache (5-6%), dizziness (8%), and insomnia (5%) are common neurological complaints 1
- Depression occurs in approximately 9% of patients 1
- Fatigue affects 9% of patients 1
Other Common Effects
- Upper respiratory tract infections (8%), sinusitis (8%), and nasopharyngitis (5%) 1
- Rash events occur in approximately 7% of patients 1
Serious and Clinically Significant Side Effects
Renal Toxicity
- Tenofovir disoproxil fumarate requires surveillance of glomerular filtration rate and dosing adjustment when creatinine clearance falls below 50 mL/min 2
- The drug should be avoided when creatinine clearance is less than 30 mL/min 2
- Renal biomarkers show more favorable profiles with tenofovir alafenamide compared to tenofovir disoproxil fumarate 3, 4
Bone Mineral Density Loss
- Significant mean percentage decrease in bone mineral density at the lumbar spine (-2.2% ± 3.9) through 144 weeks 1
- Hip bone density decreased by -2.8% ± 3.5 1
- The majority of BMD reduction occurs in the first 24-48 weeks and then stabilizes 1
- 28% of tenofovir disoproxil fumarate-treated patients lost at least 5% of BMD at the spine or 7% at the hip 1
- Biochemical markers of bone metabolism (bone-specific alkaline phosphatase, osteocalcin, C-telopeptide) increase significantly 1
Metabolic Effects
- Fasting cholesterol elevations >240 mg/dL occur in 19-22% of patients 1
- Fasting triglyceride elevations >750 mg/dL occur in 1-4% of patients 1
- The lipid profile is more favorable with tenofovir compared to thymidine analogs 2
Laboratory Abnormalities (Grade 3-4)
Common Laboratory Changes
- Creatine kinase elevation (>990 U/L in males, >845 U/L in females): 9-12% 1
- Serum amylase elevation (>175 U/L): 8-9% 1
- AST elevation: 3-5% 1
- ALT elevation: 2-4% 1
- Hematuria (>75-100 RBC/HPF): 3-7% 1
- Neutropenia (<750/mm³): 3% 1
Mitochondrial Toxicity (Class Effect of NRTIs)
Although less common with newer NRTIs, potential manifestations include:
Important Clinical Considerations
Drug Interactions Leading to Increased Tenofovir Exposure
- When combined with pharmacokinetic enhancers (ritonavir or cobicistat) in antiretroviral regimens, tenofovir concentrations increase, requiring caution and frequent renal monitoring 5
- This interaction is not mitigated by staggering administration by 12 hours 5
Comparative Safety Profile
- Tenofovir alafenamide formulations (in Descovy) demonstrate superior bone and renal safety compared to tenofovir disoproxil fumarate while maintaining equivalent efficacy 3, 4
- However, tenofovir alafenamide is associated with more weight gain (median 1.7 kg vs 0.5 kg at 96 weeks) 4
Discontinuation Rates
- Overall discontinuation due to adverse events is low: 1-2% of patients 1, 3
- Both regimens are well tolerated with minimal treatment-limiting adverse effects 3
Special Populations
Hepatitis B Co-infection
- Severe acute exacerbations of hepatitis B may occur upon discontinuation in patients with HIV/HBV co-infection, requiring close monitoring 6
- Both emtricitabine and tenofovir have activity against hepatitis B virus 5
Pregnancy and Breastfeeding
- Daily tenofovir disoproxil fumarate/emtricitabine is recommended for at-risk individuals who are pregnant or breastfeeding 5