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Comorbidities and HIV Care
Crossroads: The Intersection of Comorbidities and HIV Care

Released: March 16, 2026

Sharon R. Lewin
Sharon R. Lewin, AO, FRACP, PhD
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Key Takeaways
  • Studies of cardiovascular risk and cognitive impairment among people living with HIV highlight the importance of managing comorbidities in the context of HIV care and for long-term health.
  • Studies on STI management indicate that single-dose benzathine penicillin G is just as effective as 3 doses for secondary syphilis and indicate promise for 2 novel treatments for gonorrhea.

The average age of people living with HIV is increasing, primarily due to the efficacy and availability of modern antiretroviral therapy (ART). In fact, nearly half of all Australian people living with HIV are older than 50 years of age, and non–AIDS-related mortality is now the major cause of death among people living with HIV in Australia.

With this in mind, management of HIV-related comorbidities is a top priority among Australian HIV healthcare professionals (HCPs). Many abstracts presented at CROI 2026 sought to address these comorbidities and are highly relevant to the concerns of this region.

REPRIEVE: Cardiovascular Events
People with HIV are at increased risk of major adverse cardiovascular events (MACE), compared to the general population. As people living with HIV grow older, understanding and addressing this risk is a key priority in HIV care. The REPRIEVE trial investigated whether pitavastatin could prevent MACE among people living with HIV.

There were 2 new analyses of the REPRIEVE study presented at CROI 2026. In the statin arm, an analysis showed the potential for circulating biomarkers to predict MACE risk (abstract 117). Investigators looked at a number of inflammatory, lipid, and cardiac research biomarkers at baseline and found that multiple biomarkers were predictive of MACE, including IL-6, high-sensitivity C-reactive protein, N-terminal prohormone of brain natriuretic peptide, high-sensitivity cardiac troponin T, and lipid biomarkers. High levels of each could predict MACE. Although there are currently no interventions to modulate these biomarkers, this constellation of biomarkers could be useful for identifying people who are at high risk of MACE.

The other interesting analysis from REPRIEVE, within the same treatment arm, assessed whether the use of pitavastatin in people with low to moderate cardiac risk altered incident hypertension (abstract 118).  Pitavastatin reduced the risk of developing hypertension, and incident hypertension was strongly associated with higher MACE risk, independent of statin use. This is a good reminder of the benefits of statins.

Cognitive Impairment
As people living with HIV age, age-related cognitive conditions are also becoming a more prevalent concern, particularly as mild, chronic cognitive impairment affects up to 50% of people living with HIV.

There was an interesting study on cognitive impairment in people living with HIV presented at CROI from the HIV Netherlands Australia Thailand Research Collaboration, HIV-NAT (abstract 453). This study looked specifically at correlations between metabolic dysfunction–associated steatohepatitis (MASH) and dementia. People with MASH at baseline had a higher risk of accelerated cognitive decline over a 6-year follow-up period. These results are a reminder to identify and manage MASH early.

Sexually Transmitted Infections
Among the many excellent plenary talks, I thought Jeanne Marrazzo’s was very important. She showed graphs of declining sexually transmitted infection (STI) incidence reported by the United States Centers for Disease Control and Prevention (CDC) and hypothesized that these changes could be because of inadequate sampling. The recent changes at the CDC may be affecting data collection, so Australian HCPs should be mindful when considering reports based on recent epidemiologic data from the US.

She also provided updates on STI management: A study recently published in The New England Journal of Medicine reported that single-dose benzathine penicillin G is as good as 3 doses for secondary syphilis. In addition, she highlighted 2 novel treatments for gonorrhea, zoliflodacin and gepotidacin, that are currently in development.

HIV Cure Studies
There also were interesting studies on HIV cure, which is a topic that many people living with HIV ask other HCPs and me about. The RIO trial (abstract 134) examined broadly neutralizing antibodies (bNAbs) plus ART followed by analytical ART interruption, to determine whether viral control would be sustained after bNAb levels had waned. Investigators reported that after treatment interruption, bNAbs were associated with delayed viral rebound in over half of participants.

Studies of PD-1 blockade also reported modified viral rebound kinetics after ART discontinuation. One preclinical study reported at CROI evaluated PD-1 and IL-10 blockade in rhesus macaques (abstract 173), while a phase II global clinical trial assessed a low dose of an unlicensed investigational anti–PD-1 antibody, budigalimab, with and without trosunilimab, an antibody targeting α4β7 (abstract 140). I am a coinvestigator in this industry-sponsored study. I was part of an analysis of immune-related adverse events (irAEs) in this study, which found an overall incidence of irAEs of approximately 7% among people living with HIV treated with these antibodies, vs approximately 40% among those with cancer, who are treated with higher doses of budigalimab. However, the presence of 3 grade 3 irAEs suggests that this treatment can be potentially toxic even at low doses (abstract 390). Low-dose PD-1 blockade is also being investigated in an Australian clinical trial called NIVO-LD, that is interrupting ART in the presence of the anti-PD-1 antibody, nivolumab (abstract 369).

Taken together, these studies indicate that immune-modifying interventions such as bnAbs and anti-PD1 can alter viral kinetics after stopping ART. Although a long way from sustained viral control to levels <20 copies/mL off ART, these studies are an exciting first step to demonstrating that ART-free viral control can be achieved following an intervention in some people.

Your Thoughts
How do age-related and HIV-related comorbidities intersect for your patients living with HIV? How do you address these issues in the context of HIV care? Leave a comment to join the discussion!

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