Long-Term Side Effects of Antiretroviral Therapy

Information about the short-term side effects of antiretroviral therapy (ART) is becoming more available. However, information on the long-term side effects of ART is limited.

Since many HIV drugs are so new, there has not been enough time to see their long-term effects. As people are living longer with HIV and taking ART for longer periods of time, we are starting to learn more about their extended outcomes.

Some common long-term side effects of ART are listed below. While this is not an exhaustive list of all long-term effects, it does highlight some of the most common issues that aging individuals with HIV taking ART might experience.

Long-term side effects of antiretroviral therapy

Bone disease

As we age, our bones naturally thin. When bones become too thin, they are at risk of fracturing. This thinning is called osteopenia or osteoporosis, depending on how severe it is. Although bone thinning and fracture risk increase with age, research suggests this risk is greater for people with HIV taking long-term ART compared to the general population.

This risk appears to be highest with the NRTI (nucleoside reverse transcriptase inhibitor) class of drugs. The most common drug in this class is tenofovir disoproxil. Tenofovir disoproxil is in many different treatment regimens and combination medications.1,2

Kidney and metabolic disorders

Research shows that people living with HIV have a higher risk of developing kidney failure, diabetes, or chronic kidney disease compared to the general population. This may be partly related to aging and partly related to ART-related kidney toxicity.1,2

Kidney and metabolic issues are often associated with NRTIs (especially tenofovir disoproxil and zidovudine). One study found that the longer a person used an NRTI, the greater their risk of getting diabetes.1,2

Other medications that may be associated with an increased risk of developing diabetes or kidney issues after long-term use include atazanavir (a protease inhibitor) and the combination treatment of lopinavir/ritonavir (a protease inhibitor-containing combination).1,2

Brain function issues

Many things can contribute to changes in brain function (part of the central nervous system), including normal aging. However, research shows that people living with HIV, especially older adults, are at a higher risk for brain function issues than the general population.

The ART drug efavirenz may cause slower information processing and more short-term memory compared to other drugs like lopinavir/ritonavir. Efavirenz may also lead to long-term depression or thoughts of suicide. More information is needed on this potential link.1,2

Integrase inhibitors like dolutegravir may also have long-term effects on brain function and mental health.1,2

Cardiovascular disease

Current research shows that the risk of cardiovascular disease (CVD) and serious complications from CVD is higher for older adults with HIV compared to those without HIV. These complications include stroke and heart attack.1,2

Protease inhibitors may play a role in the risk of heart attack. The NRTI drug abacavir has also been tied to an increase in heart attack risk. However, more research is needed to understand this potential link.1,2

Liver disease

People living with HIV may be at an increased risk for many liver conditions. This includes alcoholic and non-alcoholic fatty liver disease. The metabolic issues that may occur because of HIV and its treatment can also impact liver function. These issues may also cause infection with hepatitis B or hepatitis C.1,2

More research is needed to understand if there is a link between ART and liver disease. However, there may be a relationship between liver issues and long-term NRTI use. The drug didanosine was found to cause liver issues and is no longer recommended as a treatment option for HIV. Liver issues can be common, with nearly all classes of HIV drugs potentially increasing risk.1,2

How do I balance the need for treatment with potential long-term effects?

When reading about the risk of these potential long-term side effects, it can be hard to think about treatment. However, advances in HIV knowledge have led to better treatments over time with fewer effects.

While these effects may seem scary, the result of not taking ART can be devastating. HIV that progresses to AIDS as a result of not treating the virus can be fatal. A number of different health issues can lead to death.

Talk to your doctor about side effect concerns

If you are concerned about your risk of developing long-term side effects from ART, talk to your doctor. They can help you determine the risks and benefits of using different drugs.

Consistent treatment with ART can lead to the virus being undetectable in a person’s blood work. When a person is undetectable, it is virtually impossible for them to transmit the virus to others (commonly referred to as undetectable = untransmittable).

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