Understanding What are the long term side effects of Biktarvy?

October 9, 2025 •

4 min read

In recent clinical trials, Biktarvy has demonstrated high efficacy and durable viral suppression, with over 99% of participants achieving viral suppression after 240 weeks. While generally well-tolerated, this lifelong medication requires an understanding of what are the long term side effects of Biktarvy to ensure continued health and well-being for those managing HIV.

Quick Summary

This article examines the long-term safety profile of Biktarvy, detailing potential effects on renal and bone health, weight, liver function, and psychological well-being during years of treatment.

Key Points

Favorable Kidney and Bone Profile: Biktarvy's component tenofovir alafenamide (TAF) is less toxic to the kidneys and bones than older formulations like TDF, leading to smaller impacts on renal function and bone mineral density over time.
Potential for Weight Gain: Some patients on Biktarvy, particularly those with a lower baseline BMI, may experience weight gain. This can be partly attributed to a 'return-to-health' effect, but the mechanism is still under investigation.
Liver Health Monitoring: Patients co-infected with HIV and Hepatitis B must be carefully monitored. A boxed warning exists because discontinuing Biktarvy can cause severe, potentially fatal, worsening of Hepatitis B.
Mental Health Considerations: Though uncommon, psychiatric side effects like depression, anxiety, insomnia, and abnormal dreams have been reported. A history of mental health issues may increase this risk.
Immune Reconstitution Syndrome: When starting Biktarvy, some patients may experience IRIS, an exaggerated immune response to opportunistic infections, as their immune system recovers. This usually happens in the first few months.
High Barrier to Resistance: Long-term studies show that Biktarvy maintains high efficacy with a high barrier to resistance, meaning the virus is less likely to mutate and become resistant to the medication.

Biktarvy is a single-tablet regimen used for treating HIV-1 infection, combining three active ingredients: bictegravir (an integrase inhibitor), emtricitabine (FTC), and tenofovir alafenamide (TAF). While its high effectiveness is well-established, managing HIV is a lifelong commitment, making the long-term side effect profile a critical topic for both patients and healthcare providers. While many mild, temporary side effects like headache and nausea may occur early in treatment, it is important to understand the potential for less common, yet serious, effects that can emerge with prolonged use.

Impact on Kidney and Bone Health

One of the most significant advances in modern ART has been the development of tenofovir alafenamide (TAF), a component of Biktarvy, which has a more favorable long-term safety profile for kidneys and bones compared to its predecessor, tenofovir disoproxil fumarate (TDF). TAF is designed to deliver higher levels of the active drug to HIV-infected cells with significantly lower levels circulating in the bloodstream, thereby reducing exposure to the kidneys and bones.

Long-term studies have shown that patients on TAF-based regimens experience smaller declines in bone mineral density (BMD) and better renal function outcomes compared to those on TDF. A five-year study involving Biktarvy users showed only small declines in hip and spine BMD, reinforcing its safety in this area. However, vigilant monitoring is still essential, especially for individuals with pre-existing conditions like chronic kidney disease.

Monitoring for Renal Function and Bone Density

Kidney Function: Regular assessment of serum creatinine, creatinine clearance, and urine protein is recommended.
Bone Density: For those at risk, regular bone density scans (DEXA scans) may be advised.
Preventative Measures: Maintaining adequate calcium and vitamin D intake is also important for bone health.

Weight Changes and Metabolic Effects

A notable and increasingly discussed long-term side effect of modern ART, including regimens with integrase inhibitors like bictegravir in Biktarvy, is weight gain. The exact mechanism is not fully understood but may be influenced by several factors:

Return-to-Health Effect: For individuals experiencing weight loss and metabolic stress due to uncontrolled HIV, effective ART can lead to a 'return to health' with improved appetite and weight gain.
Metabolic Shifts: Integrase inhibitors may cause metabolic changes that contribute to weight gain or altered fat distribution.
Individual Factors: Variables such as race, sex, baseline weight, and pre-existing conditions can all influence the degree of weight gain.

In some studies, median weight gain over one to two years ranged from 1 to 4 kg, though some patients have experienced more significant changes. This is not uniform across all patients, and weight changes should be managed proactively with a healthcare provider.

Liver Health Considerations

While serious liver problems are rare with Biktarvy, there are important long-term considerations, particularly concerning those with Hepatitis B (HBV) co-infection.

Boxed Warning: The FDA has issued a boxed warning for Biktarvy regarding the risk of severe, and potentially fatal, worsening of hepatitis B when the medication is discontinued.
Mandatory Testing: Due to this risk, individuals are typically tested for HBV before starting treatment.
Ongoing Monitoring: Patients co-infected with HBV who need to stop Biktarvy are closely monitored for several months to manage any potential worsening of liver disease.

Potential Mental and Neurological Effects

Neurological and psychiatric side effects have been reported with Biktarvy, though they occur in a small percentage of patients. Post-marketing reports have included depression, anxiety, insomnia, and abnormal dreams. Serious psychiatric events, including suicidal ideation, are rare and have primarily been linked to individuals with a pre-existing history of mental health conditions.

It is important to discuss any changes in mood, thought patterns, or sleep with a healthcare provider. While older HIV drugs were more commonly associated with neurological side effects, newer regimens like Biktarvy have a better overall profile, but monitoring remains important.

Immune Reconstitution Inflammatory Syndrome (IRIS)

IRIS is a possible complication when starting ART, including Biktarvy, especially in those with advanced HIV. It is not a direct drug side effect but rather a result of the recovering immune system reacting to previously hidden or treated infections. IRIS can cause symptoms like fever, swollen lymph nodes, or a worsening of existing infection symptoms. It is most common in the early months of treatment, but the potential exists for delayed onset in some cases.

Long-Term Viral Resistance

One of the most critical aspects of long-term HIV management is preventing viral resistance, which can render treatment ineffective. Studies on Biktarvy have shown a high barrier to resistance, with no reported treatment-emergent resistance over five years of follow-up in treatment-naive individuals. This durability is crucial for maintaining effective, long-term viral suppression.

Comparing Tenofovir Alafenamide (TAF) and Tenofovir Disoproxil Fumarate (TDF)


Feature	TAF (in Biktarvy)	TDF (in older regimens)
Plasma Tenofovir Levels	Significantly lower, reducing systemic exposure.	Higher, leading to greater systemic exposure.
Kidney Impact	More favorable renal safety profile. Smaller or no decline in eGFR over time.	Associated with a higher risk of nephrotoxicity and decline in renal function.
Bone Impact	Minor or negligible decline in bone mineral density (BMD) over time.	Can lead to a greater reduction in BMD, increasing fracture risk.

Conclusion

In summary, Biktarvy represents a significant advancement in HIV treatment, offering high efficacy and a generally favorable safety profile over the long term. Key long-term side effect considerations include monitoring for kidney and bone health, managing potential weight gain, vigilance for liver health, especially in those with Hepatitis B, and awareness of possible mental and neurological effects. The drug's high barrier to resistance further solidifies its role as a durable, long-term treatment option. As with any chronic medication, consistent communication with your healthcare provider and regular monitoring are essential to ensure the best possible outcomes. For more information, the National Institutes of Health offers a comprehensive resource on Biktarvy.

Frequently Asked Questions

Biktarvy contains tenofovir alafenamide (TAF), which has a much more favorable renal safety profile compared to older HIV medications containing TDF. While kidney problems are a potential serious side effect, long-term data indicates that TAF-based regimens cause smaller changes in kidney function. Regular monitoring of kidney health is still recommended.

Weight gain is a possible long-term side effect reported since Biktarvy's approval. While the exact cause isn't fully clear, it may be linked to a 'return-to-health' effect as the immune system improves. The extent of weight gain varies among individuals.

Biktarvy carries a boxed warning regarding the risk of worsened Hepatitis B if the medication is stopped, particularly in those with co-infection. Regular monitoring of liver function tests is crucial for patients with a history of liver problems or HBV.

Although rare, long-term use of Biktarvy has been linked to potential psychiatric side effects, including depression and sleep disturbances, especially in individuals with a pre-existing history of mental health conditions. Any changes in mood or sleep patterns should be reported to a doctor.

No, long-term studies have shown that Biktarvy has a high barrier to resistance, with minimal treatment-emergent resistance reported over extended periods. This helps ensure the regimen remains effective for long-term viral suppression.

Compared to older tenofovir formulations, Biktarvy has a better bone safety profile due to its TAF component. Long-term studies show only minimal impact on bone mineral density. However, patients with a history of bone density issues should be monitored.

If weight gain is a concern, a doctor can help determine the cause. Recommendations might include lifestyle modifications such as diet and exercise. Discussing any concerns with your healthcare provider is the best approach.

Studies focusing on older adults have shown Biktarvy is generally effective and well-tolerated in this population, with outcomes regarding bone density and renal safety similar to younger patients. However, older individuals may be at a higher baseline risk for some conditions, requiring careful monitoring.