The month of December is dedicated to raising awareness of the risk posed by the AIDS epidemic, a disease that affects more than 40 million people worldwide. In Brazil and around the world, we see that many people infected with HIV have managed to preserve their health and reach an older age, and it is necessary that treatment follows these changes.
Antiretroviral drugs, introduced in 1996 by the National STD/AIDS Program of the Ministry of Health, ensured longevity for the first generation of people living with HIV. The result is that aging people find themselves facing new health care challenges.
A study led by Unesp researchers, in partnership with the Center for Global Health at Georgetown University, USA, showed that people aged 50 or older with HIV had better clinical outcomes and quality of life when treated with simplified antiretroviral treatment (ART) regimens. The research results will be published in the scientific journal Brazil Journal of Medical and Biological Research.
The research analyzed 1,018 patients treated in the Unified Health System (SUS) between 2020 and 2023. The oldest group, aged 50 years or older, represented 56.6% of the total sample, while the youngest (18 to 49 years old), 43.4%. According to the results of the study, almost 90% of those aged 50 and over had an undetectable viral load, compared to 83.3% of younger people, and a rate of virological failure (when the virus multiplies again in the blood) four times lower (2.5% compared to 10.1%).
Those aged 50 and over also showed better immunological recovery, measured by the number of CD4 T lymphocytes, cells essential to the body’s defense and direct targets of HIV. Only 7% of patients over 50 had less than 350 cells/mm³, compared to 13.3% of younger patients, indicating a more robust immune response and less vulnerability to infections. “The variable most associated with these results was precisely the simplified medication regimen,” the authors commented.
The data used in the study were obtained from the Specialized Service for Infectious Diseases Domingos Alves Meira (SAEI-DAM), Botucatu Medical School (FMB), a reference center that has been monitoring people living with HIV for more than two decades.
According to infectious disease specialist Alexandre Naime Barbosa, research coordinator, this is the first service in the country where the majority of patients are over 50 years old. “The HIV virus, previously associated with young people, has become a chronic disease that requires a geriatric perspective. The aging of the epidemic is already changing the profile of care: people are followed for many years, maintain compliance with treatment and live with other age-related diseases, such as hypertension, diabetes and atherosclerosis, which appear earlier due to a state of chronic inflammation caused by the infection, even when it is controlled”, explains Naime, professor at the Botucatu Faculty of Medicine.
The survey adopted the 50-year mark to define “older people living with HIV”. Indeed, even under effective treatment, HIV maintains the body in a continuous state of inflammation and immune activation, leading to premature wear and tear of the immune system and promoting the early onset of chronic diseases, such as hypertension, diabetes and cardiovascular problems. The prolonged use of antiretrovirals and the risks of interactions between drugs also contribute to this accelerated cellular aging.
Potent drug combinations
Researchers studied the effects of two simplified treatment regimen combinations: lamivudine + dolutegravir (3TC+DTG) and lamivudine + darunavir/ritonavir (3TC+DRV/r), used more frequently by older patients.
Analysis of the results revealed that the use of these treatment regimens and the prolonged duration of treatment – more than 11 years – were strongly associated with sustained viral suppression, when the virus remains permanently undetectable. Lamivudine (3TC) works by blocking the reverse transcriptase enzyme, responsible for converting the RNA of the AIDS virus into DNA inside the human cell – a fundamental step for the invader’s replication. By replacing a DNA base, lamivudine interrupts the copying of viral genetic material and prevents new viral particles from forming. Dolutegravir (DTG) acts at another point in the cycle: it inhibits the integrase enzyme, which the virus uses to “stick” its DNA to the genetic code of the host cell. Without this integration, the HIV virus cannot multiply or produce new copies of itself.
In addition to being potent, dolutegravir has a high genetic barrier, meaning the virus has a harder time developing resistance. Darunavir (DRV) is an inhibitor of protease, an enzyme necessary for the assembly of proteins that form new viral particles. It stops HIV from maturing, making it unable to infect other cells. Darunavir is administered with ritonavir (r), which does not act directly against the virus, but enhances the effect of darunavir by delaying its metabolism in the liver and prolonging its action in the blood.
The most striking change from traditional treatment is the withdrawal of tenofovir (TDF), one of the historic pillars of antiretroviral therapy (ART) in Brazil since the late 1990s. Tenofovir, like lamivudine, blocks the reverse transcriptase enzyme, preventing the virus from copying its RNA into DNA – an essential step for HIV to multiply. The drug remains essential for newly diagnosed people who need to quickly reduce their viral load, as well as for cases of resistance to other drugs. But with prolonged use, tenofovir can cause effects on the kidneys and bones, which is of particular concern to patients over 50 years old.
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