Biktarvy is a single-tablet regimen (STR) that has transformed the management of Human Immunodeficiency Virus (HIV). It combines three active ingredients—bictegravir (an integrase strand transfer inhibitor), emtricitabine, and tenofovir alafenamide (TAF) (both nucleoside reverse transcriptase inhibitors). This combination works to suppress the HIV virus, but as with any lifelong medication, it is important to be aware of the long-term effects. Studies, including Gilead’s BICSTaR, have followed patients for several years to track these effects. While many side effects are mild and resolve early in treatment, others can persist or emerge later.
Long-Term Impact on Kidney Function
One of the most significant concerns with long-term HIV therapy has been kidney health, especially with older formulations of tenofovir. Biktarvy contains tenofovir alafenamide (TAF), a newer version designed to deliver the drug more efficiently to HIV-infected cells and minimize plasma tenofovir levels, thereby reducing the risk of renal toxicity.
Monitoring Kidney Health
Despite the improved safety profile with TAF, healthcare providers will regularly monitor kidney function in patients taking Biktarvy, particularly those with pre-existing renal impairment or other risk factors. This monitoring involves assessing serum creatinine, creatinine clearance, urine glucose, and urine protein. Potential kidney issues to watch for include acute renal failure, proximal renal tubulopathy, and Fanconi syndrome, although these are rare with Biktarvy. Patients taking other nephrotoxic agents, such as high-dose nonsteroidal anti-inflammatory drugs (NSAIDs), are also at increased risk and require careful monitoring.
Effects on Bone Mineral Density
Bone mineral density (BMD) is another area of long-term consideration for people living with HIV, as both the virus and some medications can affect bone health. The TAF component in Biktarvy was also developed to have less impact on bone health compared to its predecessor, tenofovir disoproxil fumarate (TDF).
Clinical Findings on Bone Health
Five-year clinical data from Gilead’s Study 1489 showed only small, stable impacts on hip and spine BMD in patients on Biktarvy. In contrast, studies comparing Biktarvy to older TDF-based regimens demonstrated improved bone mass recovery, particularly for individuals switching from TDF to Biktarvy. These findings suggest Biktarvy is a favorable option for long-term bone health compared to older alternatives.
Weight Gain and Metabolic Changes
Weight gain is a side effect that has been observed in some patients on modern antiretroviral therapy, including Biktarvy. While initial clinical trials did not highlight it, subsequent real-world data and comparative studies have noted a trend.
Theories on Weight Gain
Several hypotheses exist for why this might occur:
- Return to health effect: Some weight gain may be a sign of restored health as the HIV virus is suppressed and the immune system recovers.
- Metabolic changes: The integrase inhibitor (bictegravir) and TAF components may influence metabolism and fat distribution.
- Improved tolerability: Less nausea and stomach upset with newer drugs might lead to an increase in appetite.
Mental Health Side Effects
Though less common, psychiatric side effects like depression have been reported with Biktarvy. While many cases were linked to a pre-existing history of depression, some instances involved suicidal thoughts or actions. Any new or worsening symptoms should be discussed with a healthcare provider immediately.
Important Considerations for Co-infected Patients
Hepatitis B Co-infection
Biktarvy carries a boxed warning, the strongest warning from the FDA, regarding the risk of severe acute exacerbations of hepatitis B upon discontinuation in patients co-infected with HIV and Hepatitis B. It is crucial that these patients do not stop taking Biktarvy without medical supervision. If discontinuation is necessary, liver function must be monitored for several months.
Comparison of Biktarvy to Older HIV Regimens
| Feature | Biktarvy (TAF-based) | Older Regimens (e.g., TDF-based) |
|---|---|---|
| Renal Safety | Lower risk of kidney problems | Higher risk of kidney toxicity and dysfunction |
| Bone Health | Minimal impact on bone mineral density | Associated with greater reductions in bone mineral density |
| Weight Gain | Small-to-moderate weight gain reported, possibly linked to return-to-health or metabolic changes | Some older regimens also linked to weight changes; TAF/INSTI combinations specifically noted |
| Tolerability | Generally well-tolerated, low discontinuation rates due to side effects | May have higher rates of gastrointestinal side effects |
| Efficacy | Highly effective and durable viral suppression | Effective but potentially more toxic, leading to shifts towards modern regimens |
Immune Reconstitution Inflammatory Syndrome (IRIS)
IRIS can occur early in treatment as the recovering immune system starts to fight off previously undetected or treated infections. This can cause symptoms that may appear as new or worsening infections, and should be reported to a doctor.
Conclusion
Long-term use of Biktarvy has been supported by robust clinical data and real-world evidence, which show durable viral suppression and a favorable safety profile compared to older HIV treatments. While serious long-term effects like kidney problems, liver damage, and depression are possible, they are uncommon and can often be managed with proactive monitoring and communication with a healthcare provider. For patients with Hepatitis B co-infection, adhering strictly to the treatment regimen and medical guidance is critical to avoid severe liver complications. The emergence of side effects like weight gain requires further research, but the overall benefits of effective HIV suppression with Biktarvy greatly outweigh these potential risks for most patients.
For additional information and guidelines on HIV treatment, refer to the resources provided by the U.S. government: HIV.gov - Clinical Info
