Age-Related Comorbidities and Quality-of-Life Issues in Patients Living With HIV

Contagion, Contagion, February 2022 (Vol. 07, No. 1),

For people living with HIV, age-related comorbidities, such as obesity and diabetes, as well as quality-of-life issues remain challenges. Our Peer Exchange panel discusses clinical approaches for this patient population and trying to keep them in good health.

Although treatment options and life expectancy of patients living with HIV have increased in recent years, age-related comorbidities (particularly obesity and diabetes) and quality-of-life issues continue to be of concern, according to panelists in a Contagion® Peer Exchange panel moderated by Grace McComsey, MD FIDSA. The panelists discussed approaches for screening and management of comorbidities, optimizing antiretroviral therapy (ART) regimens based on viral genotype and patient factors, discussing quality-of-life issues with patients, and addressing the relationship between HIV, obesity, and diabetes.

COMORBIDITIES IN PATIENTS WITH HIV

Comorbid diseases and clinical events associated with aging often occur at a younger age in patients living with HIV compared with the general population, and educating patients on screenings and intervals is imperative to ensure these comorbidities are diagnosed early, said Todd Brown, MD, PhD. He added that the higher burden of comorbidities in patients with HIV is in part related to the persistent effects of previous ART, noting that stavudine (Zerit) is commonly associated with lipoatrophy that can persist for several years after discontinuing the medication. Even if HIV infection is well treated, the HIV disease process itself results in increased systemic inflammation that can drive comorbidities, said Brown. “We have this confluence of inflammation related to HIV and inflammation related to aging, which is important in these aging-related comorbidities,” he said.

Brown emphasized the importance of a long-term approach for screening and management of comorbidities and said preventing major clinical events is crucial for aging well. “Over the long term, you think about a patient who’s middle-aged…you’re trying to prevent events so the person can age well, so they can maintain their physical function, their cognitive function, their quality of life,” he said. “What we know is that these events that happen—whether it be myocardial infarction, a stroke, or a fracture— can have major effects on these trajectories. Trying to be proactive and prevent these events is critical in the overall aging process.”

HIV: TREATMENT OPTIMIZATION

John Koethe, MD, said that although viral suppression is the easiest measure of treatment success with HIV infection, durable suppression of the virus that is refractory to breakthrough and resistance using a regimen that fits the patient’s comorbidities and other personal factors is likely a better gauge of success.

“The principal goal of ART has always been the same…to maintain viral suppression or a level of plasma virus below 50 copies/mL, and thus allow CD4 reconstitution and ideally protect us from opportunistic infections within the environment,” said Koethe. “There [are] several routes to getting there, and the 2 things that we need to separate when we think about how we’re going to approach this is, [first], matching the regimen to the preexisting patterns of viral resistance, and then also matching the regimen within that same idea to the likelihood that this [individual] is not going to take it sufficiently and is going to develop viral resistance.”

Koethe said selection of a treatment regimen is guided by the viral genotype and often uses concatenated databases (such as the International AIDS Society) to identify the optimal agent(s) among protease inhibitors (PIs), nonnucleoside reverse transcriptase inhibitors, and nucleoside reverse treatment options and life expectancy of patients living with HIV have increased in recent years, age-related comorbidities (particularly obesity and diabetes) and quality-of-life issues continue to be of concern, according to panelists in a Contagion® Peer Exchange panel moderated by Grace McComsey, MD FIDSA. The panelists discussed approaches for screening and management of comorbidities, optimizing antiretroviral therapy (ART) regimens based on viral genotype and patient factors, discussing quality-of-life issues with patients, and addressing the relationship between HIV, obesity, and diabetes.

COMORBIDITIES IN PATIENTS WITH HIV

Comorbid diseases and clinical events associated with aging often occur at a younger age in patients living with HIV compared with the general population, and educating patients on screenings and intervals is imperative to ensure these comorbidities are diagnosed early, said Todd Brown, MD, PhD. He added that the higher burden of comorbidities in patients with HIV is in part related to the persistent effects of previous ART, noting that stavudine (Zerit) is commonly associated with lipoatrophy that can persist for several years after discontinuing the medication. Even if HIV infection is well treated, the HIV disease process itself results in increased systemic inflammation that can drive comorbidities, said Brown. “We have this confluence of inflammation related to HIV and inflammation related to aging, which is important in these aging-related comorbidities,” he said.

Brown emphasized the importance of a long-term approach for screening and management of comorbidities and said preventing major clinical events is crucial for aging well. “Over the long term, you think about a patient who’s middle-aged…you’re trying to prevent events so the person can age well, so they can maintain their physical function, their cognitive function, their quality of life,” he said. “What we know is that these events that happen—whether it be myocardial infarction, a stroke, or a fracture— can have major effects on these trajectories. Trying to be proactive and prevent these events is critical in the overall aging process.”

HIV: TREATMENT OPTIMIZATION

John Koethe, MD, said that although viral suppression is the easiest measure of treatment success with HIV infection, durable suppression of the virus that is refractory to breakthrough and resistance using a regimen that fits the patient’s comorbidities and other personal factors is likely a better gauge of success.

“The principal goal of ART has always been the same…to maintain viral suppression or a level of plasma virus below 50 copies/mL, and thus allow CD4 reconstitution and ideally protect us from opportunistic infections within the environment,” said Koethe. “There [are] several routes to getting there, and the 2 things that we need to separate when we think about how we’re going to approach this is, [first], matching the regimen to the preexisting patterns of viral resistance, and then also matching the regimen within that same idea to the likelihood that this [individual] is not going to take it sufficiently and is going to develop viral resistance.”

Koethe said selection of a treatment regimen is guided by the viral genotype and often uses concatenated databases (such as the International AIDS Society) to identify the optimal agent(s) among protease inhibitors (PIs), nonnucleoside reverse transcriptase inhibitors, and nucleoside reverse transcriptase inhibitors. Even if a regimen appears appropriate for a patient’s genotype, he said he may adjust it if he predicts that barriers will prevent the patient from adhering to once-per-day or twice-per-day dosing.

“We may select something with a higher barrier to resistance…for example, a boosted protease inhibitor such as darunavir…or it could be a newer-generation integrase inhibitor,” he said. “For somebody who might be extremely adherent, that would probably be less [of] a question.”

Koethe added that tailoring the regimen to minimize adverse or unwanted effects is important and involves considering the patient’s neuropsychiatric profile (including depression), underlying comorbidities (eg, cardiovascular disease, insulin resistance, diabetes or hyperlipidemia, and current overweight or obesity status), and patient preferences for dosing, and Brown emphasized the importance of awareness of potential drug-drug interactions, notably between boosted PIs and statins and those between dolutegravir and metformin.

HIV: ADDRESSING QUALITY-OF-LIFE ISSUES

Issues related to quality of life are important to address and can prevent patients from continuing with care, according to Tavell Kindall, PhD, DNP, APRN, FNP. “In my experience here in New Orleans, there have been some individuals who have been out of care because they felt as though they weren’t treated well,” he said. “When they come to see me, they now have an opportunity to be on the newer medications that weren’t available to them at the time when they [received their diagnosis]. It’s amazing because they say things like, ‘I can’t believe [it]. If they would’ve had this 10, 15 years ago, I would’ve never fallen out of care, because the whole thing was, I don’t want to take anything that will have me sick and making me feel bad.’”

Kindall added that conversations about quality of life should start at the first meeting with the patient, but the provider should expect to take time to get the patient’s full story.

“You must be patient and allow the journey to have patients share things with you, and then that way you can address different things,” he said. “One of the things right now that I have been talking a lot about with patients is, they tell you things like, ‘Look, I’m afraid to tell [individuals] because I don’t know how they’re going to treat me,’ or, ‘What does this mean? Am I going to go to jail if somebody finds out that I have HIV and I didn’t share my status with them?’ Certainly anxiety, depression, if they were present before the diagnosis, [are] likely exacerbated on the other side of it, so that’s always a concern.”

Kindall added that employment, education, and finances are common concerns among patients, and many still believe a diagnosis of HIV infection means imminent death. “I try to address it along the journey, and I share with them right up front, ‘This is a journey. This is a partnership that you and I have together, and we’ll be talking about a lot of things,’” such as housing, transportation, employment, ability to care for oneself, and internalized stigma. “Because of the history of HIV and how [individuals] have been treated, some of those quality-of-life things are challenging,” said Kindall.

RELATIONSHIP BETWEEN HIV, OBESITY, AND DIABETES

According to Osama Hamdy, MD, PhD, individuals living with HIV are 4 to 5 times more likely to develop type 2 diabetes compared with the general population. “When we see any patient with HIV, we must think of diabetes,” he said.

Hamdy said that from a pathophysiologic perspective, the disease process as well as some HIV treatments are responsible for this increase in risk. “Our research, many years ago, showed that once you introduce inflammation in the adipose tissue and you have provocation from TNF-α [tumor necrosis factor α], IL-6, MCP-1 [monocyte chemoattractant protein 1], and all those provocative inflammatory cytokines, you will see all kinds of metabolic problems, including insulin resistance, endothelial dysfunction, and then atherosclerosis,” he said.

Hamdy said medications, particularly older medications, may also contribute to diabetes. He added that patients who started treatment with protease inhibitors between 1997 and 2014 have an approximately 50-fold increase in risk for type 2 diabetes, and patients who used these drugs, even for a short time, are still presenting today because of the longer life span of patients living with HIV.

“Diabetes is something that you should think of all the time when you have anyone with HIV,” he concluded, adding that weight gain and related health issues, such as obstructive sleep apnea, arthritis, and worsening of diabetes, cardiovascular disease, and pulmonary issues introduce a major health burden for patients with HIV and diabetes.

Moderator

Grace McComsey, MD, FIDSA

Professor of Pediatrics and Medicine

Case Western Reserve University

Cleveland, Ohio

Panelists

Todd Brown, MD, PhD

Endocrinologist and Professor of Medicine

Johns Hopkins School of Medicine

Baltimore, MD

Osama Hamdy, MD, PhD

Endocrinologist and Associate Professor of Medicine

Harvard University

Boston, MA

Tavell Kindall, PhD, DNP, APRN, FNP

Infectious Disease Specialist

St Thomas Community Health Center

New Orleans, LA

John Koethe, MD

Associate Professor of Medicine

Division of Infectious Disease at Vanderbilt University Medical Center

Nashville, TN