Loading ...

Miguel, a 63-year-old Los Angeles teacher, recently marked the 38th anniversary of his diagnosis with HIV. The doctor had told him he would be dead in a couple of years. He lived fearful that each passing one might be his last. 

Miguel started to take AZT (azidothymidine), the first antiretroviral drug used to treat HIV and AIDS, and then moved to a succession of other drugs. While he was on one called Crixivan, he experienced hollowed cheeks and increased fat in his chin, characteristic of early HIV medications. He escaped other early effects: Severe headaches, muscle pain, insomnia, anemia and other blood disorders. “Gay men were talking about it being very harmful to the body,” says Miguel (not his real name, for privacy reasons). “But it was a crapshoot; if you take this terrible thing, at least you have a fighting chance.” 

The drugs saved many millions of lives, but some doctors wondered about long-term effects of the early medications. They saw lipid disturbances and severe neuropathy: Numbness, tingling, and pain in the limbs. Some predicted a future of early heart disease and heart attacks among gay men and others infected by HIV. 

Today it’s known that people with HIV receiving antiviral treatments do tend to have higher rates of certain chronic health conditions. But researchers still aren’t fully sure what causes what. Research has shown that some HIV drugs, particularly the early ones, increase certain risks, but so, too, does low-level persistence of the virus in the body. Sorting out the causes is important to monitoring and treating this group of patients, who now can expect to live a close-to-normal lifespan. 

More than 50 antiretroviral medicines, which keep HIV from replicating and spreading, are approved by the US Food and Drug Administration. They are generally taken as a regimen, combining two or three medications from different drug classes. 

People taking AZT, the first drug to be approved, often found themselves with a condition known as wasting, or involuntary weight loss of 10 percent or more. In contrast, some of today’s drugs appear to cause weight gain, says Kristine Erlandson, an infectious disease specialist at UCHealth University of Colorado Hospital. In a 2024 report of 2624 HIV-positive people, published in Clinical Infectious Diseases, she found that the mean weight gain was almost 8 pounds in the first year of antiretroviral therapy. 

During roughly 9 years of follow-up, about 5 percent of participants were diagnosed with diabetes and 14 percent with metabolic syndrome (a group of conditions including obesity, low levels of “good” or HDL cholesterol, and high blood sugar), and 16 participants had a stroke. While some people have pronounced weight gain on the new HIV drugs, “there are many people on these medications that have a totally normal weight,” Erlandson says. “We don’t know who it will be that gains, or why.” 

More generally, researchers have linked HIV-positive people with a slate of conditions normally associated with advancing years: Cardiovascular disease, cognitive impairment, diabetes, and frailty. “In the early days of the epidemic, people were starting to scream that people with HIV were having premature aging,” says Peter Reiss, a former internal medicine doctor and infectious disease specialist at the Amsterdam University Medical Center. “But there was really no data to back that statement up.” 

To get answers, in 2010 Reiss and colleagues began a study called AGEhIV that followed 1146 people in Amsterdam over about 6 years. Just over half were HIV-positive, and a similar group without HIV made up the rest. 

The scientists found that people with HIV were indeed more likely to have hypertension, heart attacks, osteoporosis, kidney disease, and peripheral artery disease (where arteries in the legs and abdomen narrow, slowing blood flow). Nearly all of the HIV-positive participants were taking HIV medications, with near-undetectable levels of the virus, Reiss says, “so you’re really talking about what is happening in effectively treated HIV.” 

Reiss and colleagues also found a link to cancers not traditionally associated with infection by HIV, such as ones of the stomach, lungs, and blood. Of 38 people who died during the years of the study, 16 succumbed to such cancers, and all but one were in the HIV-positive group. 

Many other population studies have been conducted through the years, and findings generally align: People with HIV appear to have an increased risk of various chronic diseases, as well as an average life expectancy 5-10 years shorter than people who are HIV-negative. 

For example, a 2022 review of 47 reports on antiretroviral therapy reported that having HIV doubled the risk of cardiovascular disease and increased the risk of bone and muscle conditions like sarcopenia (a gradual loss of muscle mass and strength), depression and cancer. And a large US study published in 2020 found that in 2016, people without HIV could expect to live 9 more years on average than people with HIV. They also averaged more than 16 years free of other health conditions than the HIV group. 

In good news, the life expectancy gap was down dramatically, from a 22-year difference in the early 2000s, largely because of modern antiretrovirals and early treatment commencement, scientists think. 

What causes these differences? It’s important to know, because these disproportionate rates of chronic illness harm people’s lives and are costly, noted Anthony Fauci, former director of the National Institute of Allergy and Infectious Diseases, and colleagues in a 2019 opinion article in the journal JAMA. Monthly costs for treating someone with HIV plus cardiovascular disease or chronic kidney disease were $1400 to $5000 more per month than for someone with HIV alone, they wrote. 

Lifestyle is one contributing factor. People with HIV tend to have higher rates of smoking, alcohol use, depression and anxiety, says Reiss. But, he adds, this can’t account for all the increase in early onset of age-related conditions. 

Medication connections, meanwhile, continue to emerge. Abacavir, to name one example, has recently been linked to cardiovascular disease, says Priscilla Hsue, chief of cardiology at UCLA Health. At the 2024 AIDS Conference, researchers reported that people who had taken the drug had a 50 percent greater risk of major cardiovascular problems such as heart attack and stroke, and those currently taking it had a 42 percent higher risk compared to people on other antiretroviral treatments. 

Another possible contributor to chronic diseases is the effects of HIV on the body, even when the infection is well controlled. The virus is still there, activating the immune system and inducing low-level inflammation. 

Knowing that antiretrovirals or HIV-induced inflammation may hasten the onset of conditions like cancer and cardiovascular disease could be a reason to change clinical screening and detection practices of such conditions for people with HIV, Reiss says. He has evidence from the AGEhIV study that much damage is done to the body in the early stages of infection, perhaps before treatment commences. That argues for better screening of people at high risk of having HIV and for early treatment commencement to help mitigate health issues later, he says. 

One encouraging report from a large clinical trial known as REPRIEVE, involving more than 7500 participants, was that taking a statin medication reduced rates of heart attacks, strokes, and other cardiac problems among people with HIV by 35 percent. The five-year trial’s findings, published in 2023, have been incorporated into clinical guidelines for treating people with HIV. 

Miguel, the longtime patient who started with AZT, says the standard message from doctors for people with HIV is to live as healthily as possible to avoid premature aging and related conditions. Today, he is being treated for diabetes and is in remission for anal cancer. He can’t know if HIV or the drugs that sustain him, or neither, caused the conditions, but he does not give it much thought. 

“I have a great marriage, a lovely home; I have dogs and a job that I love,” he says. “The amazing thing is I am still here.”

This article originally appeared in Knowable Magazine on June 10, 2025. Knowable Magazine is an independent journalistic endeavor from Annual Reviews, a nonprofit publisher dedicated to synthesizing and integrating knowledge for the progress of science and the benefit of society. Sign up for Knowable Magazine's newsletter.