What is a serious long-term side effect of antiretroviral therapy?

October 9, 2025 •

2 min read

As of 2024, people on effective antiretroviral therapy (ART) can expect to live a near-normal lifespan, but this longevity has brought increased attention to long-term health complications. This raises the important question of what is a serious long-term side effect of antiretroviral therapy and how it can be managed.

Quick Summary

Chronic conditions such as cardiovascular disease, renal toxicity, and bone density loss are major long-term concerns associated with antiretroviral therapy. Metabolic changes like lipodystrophy and dyslipidemia can also persist, influenced by both older medications and HIV-related inflammation.

Key Points

Cardiovascular Disease (CVD): People with HIV have a higher risk of heart disease and stroke due to a combination of ART-related metabolic issues and chronic inflammation from the virus itself.
Renal Toxicity (Kidney Damage): The older drug tenofovir disoproxil fumarate (TDF) can cause kidney damage, making routine monitoring crucial, while the newer tenofovir alafenamide (TAF) offers a safer alternative.
Bone Mineral Density Loss (Osteoporosis): HIV, combined with certain ART drugs like TDF and boosted protease inhibitors, can lead to reduced bone density and an increased risk of fractures.
Metabolic Changes and Lipodystrophy: Older ART regimens were strongly linked to body fat redistribution (lipoatrophy and lipohypertrophy), as well as dyslipidemia and insulin resistance, though these are less common with newer drugs.
Chronic Inflammation: Persistent low-grade inflammation, even with viral suppression, is a key driver of many long-term health issues in people with HIV, including cardiovascular disease.
Management is Key: Regular medical monitoring, adopting a healthy lifestyle, and using modern ART regimens with better side effect profiles are essential for mitigating long-term risks.

Cardiovascular Complications: A Leading Concern

One significant long-term side effect of ART is an increased risk of cardiovascular disease (CVD). Individuals with HIV have a higher likelihood of experiencing heart attacks, strokes, and heart failure compared to those without HIV. This elevated risk stems from several factors:

Chronic Inflammation: HIV causes persistent low-grade inflammation, even when the virus is suppressed, contributing to atherosclerosis.
Metabolic Issues: Some ART drugs, particularly older ones, can negatively affect cholesterol levels and insulin sensitivity, increasing CVD risk. Newer drugs generally have a better metabolic profile.
Specific Drug Links: While debated, some studies have suggested a link between certain drugs, like abacavir, and increased cardiovascular events, though the benefits of continuous ART are considered to outweigh these potential risks.

Renal and Bone Health Impacts

Long-term ART can also affect the kidneys and bones.

Renal Toxicity

Tenofovir Disoproxil Fumarate (TDF): This common drug can lead to kidney damage, especially with long-term use. Monitoring kidney function is vital, and safer alternatives are available.
Tenofovir Alafenamide (TAF): A newer version of tenofovir, TAF is less likely to cause kidney or bone problems than TDF.

Bone Mineral Density Loss

People with HIV face a higher risk of weakened bones and fractures. Chronic inflammation and ART contribute to this.
TDF and boosted protease inhibitors are particularly linked to bone loss, while switching to TAF can improve bone density.

Metabolic Changes

While less common with newer drugs, metabolic issues like lipodystrophy (fat redistribution) and dyslipidemia (abnormal blood fats) can still occur. Older drugs like stavudine and zidovudine were strongly associated with lipoatrophy, and switching to newer drugs can help. Contemporary ART can still affect lipid and glucose metabolism, increasing the risk of CVD and diabetes.

Managing and Mitigating Long-Term Effects

Proactive management is key. This includes using modern regimens, regular monitoring, adopting a healthy lifestyle, and managing other health issues like high blood pressure and diabetes.

Comparison of Older vs. Newer ART Drug Classes

The full comparison table detailing the risks of older vs. newer ART drug classes for various conditions like lipodystrophy, renal toxicity, bone density loss, dyslipidemia, mitochondrial toxicity, and CVD risk can be found at {Link: Core Concepts - Adverse Effects of Antiretroviral Medications https://www.hiv.uw.edu/go/antiretroviral-therapy/adverse-effects/core-concept/all}.

Conclusion

While serious long-term side effects remain a concern with ART, modern medicine has significantly improved treatment safety profiles. Working closely with healthcare providers, adhering to treatment, and maintaining a healthy lifestyle are key to minimizing long-term side effects and ensuring a long, healthy life with HIV. Further information is available from {Link: clinicalinfo.hiv.gov https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/adverse-effects-antiretroviral-agents}.

Frequently Asked Questions

While modern ART is much safer, long-term side effects can include a higher risk of cardiovascular disease, kidney problems, and bone density loss. The specific risks depend on the medications used and individual health factors.

Some antiretrovirals, most notably the older formulation tenofovir disoproxil fumarate (TDF), have been associated with kidney toxicity over the long term. Newer alternatives like tenofovir alafenamide (TAF) have a much lower risk of causing kidney damage.

Long-term HIV infection and certain antiretroviral drugs, particularly TDF and boosted protease inhibitors, can increase the risk of reduced bone mineral density, leading to osteopenia and osteoporosis.

Lipodystrophy is a condition involving the redistribution of body fat (fat loss in some areas, fat gain in others). It was a significant problem with older ART drugs but is far less common with modern regimens.

Even with successful viral suppression on ART, HIV infection can cause a state of chronic, low-level inflammation. This ongoing inflammation is thought to drive many long-term health complications, including cardiovascular disease.

Managing long-term side effects involves regular monitoring of health indicators (e.g., kidney function, lipids, bone density), choosing modern ART regimens with better safety profiles, and adopting a healthy lifestyle including diet, exercise, and smoking cessation.

Newer ART medications have significantly fewer and less severe side effects than older drugs. While the risk of long-term complications is reduced, lifelong management and monitoring of overall health are still important, especially for conditions influenced by chronic inflammation.