Tenofovir Alafenamide and Weight Gain in HIV-1 Patients
Yes, tenofovir alafenamide (TAF) is associated with significant weight gain in patients with HIV-1, with greater weight gain observed compared to tenofovir disoproxil fumarate (TDF)-containing regimens. 1
Evidence of TAF-Associated Weight Gain
- Greater weight gain has been consistently observed with regimens containing TAF compared to those containing TDF in multiple studies 1
- The majority of patients receiving antiretroviral therapy (ART) experience weight changes of less than 5% of body weight, but a minority gain more than 10% of their body weight 1
- Weight gain typically occurs within the first year following initiation or switch to TAF-containing regimens 1
- In patients switching from TDF to TAF, significant weight gain (mean +1.91 kg) and BMI increase (mean +0.61 kg/m²) were observed during the first year 2
Risk Factors for TAF-Associated Weight Gain
- Women and Black individuals are at higher risk for weight gain with TAF-containing regimens 1
- Older patients (>50 years) and those with longer ART history (>10 years) may experience more significant weight gain after switching to TAF 2
- The combination of TAF with integrase strand transfer inhibitors (INSTIs) is associated with the greatest degree of weight gain 3
- Weight gain is not solely a "return to health" phenomenon but appears to be medication-related 1
Mechanism and Reversibility
- Some of the measured weight gain attributed to TAF may reflect the loss of weight-suppressive effects of TDF rather than a direct effect of TAF 3
- TDF and efavirenz are associated with less weight gain as initial therapy and with weight loss when switching to these drugs 1
- The reversibility of TAF-associated weight gain is limited, with return to pre-therapy weight being rarely observed 1
- In the Swiss HIV Cohort Study, weight loss was seen when patients switched from TAF back to TDF 1, 4
Clinical Implications and Management
- Documentation of weight and BMI every 6 months is recommended for individuals initiating or switching to a TAF-based regimen (evidence rating: AIIa) 1
- Despite weight gain concerns, changing regimens solely because of weight gain is not currently recommended due to known toxicities of alternative agents like TDF (evidence rating: BIa) 1
- Lifestyle changes including diet and exercise should be emphasized for patients on TAF-containing regimens (evidence rating: AIII) 1
- Glucagon-like peptide-1 receptor agonists may be effective for weight loss in people with HIV, similar to the general population 1
Monitoring and Considerations
- Patients on TAF-based regimens should have their weight monitored regularly, particularly during the first year of treatment 1
- The combination of TAF with INSTIs (particularly dolutegravir and bictegravir) may lead to more pronounced weight gain than other combinations 3, 5
- Weight gain with TAF may contribute to metabolic complications and increased cardiovascular risk in people with HIV 3
- In one study, patients switching to bictegravir/emtricitabine/TAF experienced a mean weight gain of 1.63 kg (2.5%) after 12 months 5
In clinical practice, while TAF offers benefits in terms of reduced renal and bone toxicity compared to TDF, the weight gain associated with TAF should be carefully considered when selecting ART regimens, particularly for patients already at risk for obesity-related complications or cardiovascular disease 3.