While antiretroviral therapy (ART) has made treating HIV dramatically simpler, more effective, and safer than in the past, the medications also present unique challenges for internists in the primary care setting who must stay up to date on risks and drug interactions.
At the same time, internists are poised to take a bigger role in identifying patients at risk and administering preexposure prophylaxis (PrEP). Last year, the U.S. Preventive Services Task Force (USPSTF) issued a grade A recommendation for clinicians to prescribe PrEP with ART for high-risk HIV-negative patients.
“As internists, we should be taking detailed sexual histories and offering PrEP to patients at risk,” said HIV specialist Donna Sweet, MD, MACP, professor of medicine at the University of Kansas School of Medicine in Wichita. “Many physicians are operating on the principle that if a patient wants or needs PrEP they will ask, but that leaves a lot of people out because there are many patients who do not perceive themselves as at risk even though they meet the criteria.”
Screening and prevention
According to the USPSTF, an estimated 1.1 million people are currently living with HIV in the United States, and 38,281 new diagnoses were made in 2017. Although the incidence of HIV has been on a modest decline over the past decade, rates have increased among certain groups, such as adults in their late 20s, and the disease disproportionately affects certain populations, including African Americans and Hispanics.
The actual prevalence of HIV is likely much greater than estimated, experts say, because only about half of U.S. adults have ever been tested. The CDC recommends screening at least once between ages 13 and 64 years for people who don't have risk factors and more frequently in those who do. However, HIV testing is not yet a routine part of preventive care partly due to lack of insurance coverage, inconsistent clinician training, and resistance to adding more screening requirements to the typical 15- to 20-minute office visit.
In Utah, for example, there is a fairly low HIV incidence rate (120 to 170 new cases annually) but only about one-quarter of the population has ever been tested, said infectious diseases specialist and ACP Member Adam Spivak, MD, assistant professor at the University of Utah School of Medicine in Salt Lake City, who runs a free HIV prevention clinic.
“Testing is one of the most important things primary care physicians can do now around HIV care,” he said. “It should be a routine part of medical care considering that the test is highly accurate, and the disease can be effectively prevented with PrEP.”
The USPSTF found convincing evidence that PrEP substantially decreases the risk of HIV infection in those at highest risk, including men who have sex with men, people who use injection drugs, and heterosexually active adults, with few side effects. It can also serve as a “gateway” for these patients to seek medical care and establish a relationship with primary care physicians, increasing opportunities for other types of screening and for addressing comorbid conditions, according to Vidya Sundareshan, MD, FACP, an infectious diseases subspecialist at SIU Medicine in Springfield, Ill.
However, only about a tenth of eligible patients are using PrEP, according to the most recent CDC estimates.
“We have two very effective modes of prevention: encouraging all existing patients with HIV to stay on their medications and encouraging primary care physicians to integrate PrEP into their practices,” said infectious diseases specialist Sara Bares, MD, assistant professor at the University of Nebraska Medical Center in Omaha. “Unfortunately, there is still some stigma among primary care physicians and fear of opening up that conversation.”
A recent survey suggests that lack of education and training may underlie those fears, causing slow adoption of preventive strategies in the primary care setting. The survey of general internists found that 85% preferred patients to receive PrEP care within their practice, rather than be referred elsewhere, and felt that all clinicians should be trained to deliver it. However, many cited a lack of education and clinical guidelines and protocols for PrEP implementation as significant barriers. The findings were published online in October 2019 by Preventive Medicine Reports.
Simple changes can lead to improvement, the authors noted, such as giving clinicians better access to existing clinical guidelines and strategies through integration with the electronic health record, for example, and having a designated on-site PrEP specialist.
The lack of universal health coverage has kept HIV rates steady despite the availability of excellent testing and treatment, said Carrie Horwitch, MD, MACP, an internist who specializes in HIV and AIDS care at Virginia Mason Medical Center in Seattle. She noted that system-wide changes are needed to make HIV care a routine part of primary care.
At Virginia Mason, preventive HIV screening is included on a standard health maintenance checklist along with all other CDC-recommended screenings, said Dr. Horwitch. The group also trains all of its physicians and advanced practice clinicians in how to administer PrEP and has integrated standard templates with best practices and current CDC recommendations into its electronic health record.
Internal medicine is the perfect setting for PrEP, she said. “Our patients are coming to us for routine health care and many of them don't know they are at risk. It's very rewarding to be able to get these patients into care when we have such effective tools for prevention and treatment.”
Patients should be started on ART immediately, or as soon as possible, after an HIV diagnosis in order to prevent the development of opportunistic infections and fatal malignancies, according to the most recent recommendations from the International Antiviral Society-USA (IAS-USA) Panel, published in the July 24/31, 2018, JAMA. In stark contrast to the early days of HIV in the 1980s and 1990s, when patients took up to 20 pills at different times during the day, most patients now take one pill daily.
Speed is of paramount importance once a patient has been diagnosed with the virus, said Dr. Sweet, but unfortunately many patients do not come into the clinic right away. For patients who may need to be treated for opportunistic infections at presentation and whose CD4 cell counts have dropped below 50 cells/µL, IAS-USA recommends starting ART within two weeks of diagnosis. For all others, start as soon as possible, Dr. Sweet said.
Initial therapy typically includes a combination of integrase strand transfer inhibitors plus two nucleoside reverse transcriptase inhibitors, according to the recommendations. After the HIV RNA level falls below 50 copies/mL, monitoring is recommended every three months until the virus is suppressed for at least a year, after which it can switch to every six months. Measurement of CD4 cell counts should be done every six months until they remain above 250 cells/µL for at least a year with concomitant viral suppression.
Viral load is the most important predictor of mortality and outcomes, said Dr. Bares. Patients tend to do well if they have an undetectable viral load, even if their CD4 cell count drops below normal levels.
Internists should consider consulting an infectious diseases or HIV specialist if a patient does not achieve virologic suppression, she added. A specialist can help figure out the root cause and modify the patient's drug regimen if necessary. Similarly, comanagement with a specialist should be considered for patients who develop complicated opportunistic infections, such as cryptococcal meningitis.
Although current HIV regimens are much less toxic than in the past, some patients experience negative side effects. For example, tenofovir has been associated with kidney dysfunction, and a recent analysis of clinical trials reported that weight gain is common among patients initiating ART. Findings published in the October 2019 Clinical Infectious Diseases suggest that clinicians should counsel patients about weight management strategies.
“Warning patients at the outset about potential weight gain allows them to get ahead of it,” said Dr. Sweet. “Physicians can also think about modifying the drug regimen if excessive weight gain occurs in the first months of therapy.”
Internists must also be concerned with managing patients' comorbidities and anticipating potentially adverse medication interactions, experts say.
“Over half of people living with HIV are older than 50, and many are entering the geriatric population,” said Dr. Spivak. “Patients may be taking several other types of medications to treat conditions like diabetes, heart disease, and neurocognitive disorders.”
Controlling cardiovascular risk factors is particularly important in this patient population, said cardiologist Matthew Feinstein, MD, assistant professor of medicine at Northwestern University Feinberg School of Medicine in Chicago and lead author of a recent American Heart Association (AHA) statement on managing cardiovascular disease in patients with HIV, published in the July 9, 2019, Circulation. Compared with the general population, people living with HIV have significantly higher rates of myocardial infarction, heart failure, and stroke due to chronic inflammation and immune dysregulation.
The first step in managing risks should always be ensuring that patients are taking their HIV medications continuously (as opposed to intermittently, guided by CD4 cell counts), as studies have shown that uninterrupted therapy protects against cardiovascular events, he said.
In addition, it's useful to know patients' histories with HIV in order to accurately assess risks, he added. Patients diagnosed after developing AIDS-related opportunistic infections, for example, are at higher risk for cardiovascular events than those who started therapy soon after a diagnosis of HIV infection.
Considering the high risk for cardiovascular disease in patients with HIV, the AHA and the American College of Cardiology recommend always considering statin therapy. However, certain statins—particularly simvastatin and lovastatin—should be avoided because they share the same metabolic pathway as many antiretrovirals, leading to high statin concentrations that can cause muscle injury and kidney damage, said ACP Member James Riddell IV, MD, an infectious diseases and HIV/AIDS specialist at the University of Michigan in Ann Arbor. Other statins that are metabolized by different enzymes—such as atorvastatin and rosuvastatin—can be considered at lower doses.
Nonstatin strategies should also be used to lower cardiovascular risks, said Dr. Feinstein. For example, patients should be counseled about quitting smoking, which is prevalent among those with HIV.
Dr. Riddell, who wrote an editorial accompanying the IAS-USA recommendations, also noted several other potential interactions with ART that might be encountered in the primary care setting:
- Corticosteroid injections. These drugs are metabolized by the liver using the same pathway as that used by protease inhibitors. Patients taking both can develop dysfunctional cortisol levels, triggering adrenal dysfunction and Cushing's syndrome. Patients with diabetes who receive a steroid joint injection for osteoarthritis, for example, might experience unusually high glucose levels. However, one inhalable steroid, beclomethasone, has been shown to be effective without causing adrenal suppression.
- Proton-pump inhibitors. Certain antiretroviral medications, such as rilpivirine, require an acidic stomach to be absorbed properly and therefore should not be used with proton-pump inhibitors used to treat heartburn and gastroesophageal reflux disease, which are common among patients with HIV.
- Calcium. Medications that boost the level of calcium in blood, including calcium carbonate to treat acid reflux or osteopenia, may reduce the effectiveness of integrase inhibitors.
“Many HIV drugs are metabolized in the liver and either induce or are metabolized by the cytochrome p450 system. As a result, they may interact with statins and other drugs metabolized through the same system,” said Dr. Riddell. “Medication interactions are one of the biggest considerations for primary care physicians when managing HIV and other comorbid conditions.”
Immunization is also an important piece of optimal care for patients with HIV, said Dr. Sundareshan. The CDC recommends that patients with HIV infection and CD4 cell counts below 200 cells/mm3 talk to their physicians about annual influenza vaccine, Tdap vaccine, pneumococcal vaccine, meningococcal vaccine, and hepatitis B vaccine, as well as the human papillomavirus vaccine (HPV) series if they are up to 45 years of age. Those with CD4 cell counts of 200 cells/mm3 and higher should also discuss the MMR vaccine if they were born in or after 1957 and the varicella vaccine if they were born in or after 1980, according to the CDC.
In general, given recent advances in testing, prevention, and treatment, general internists are perfectly positioned to manage patients across the continuum of HIV care, said Dr. Horwitch.
“Internists take care of a lot of patients with multiple long-term chronic conditions, and HIV infection is now quite easily managed with safe, effective medications—we actually have better outcomes with HIV compared with some other conditions in terms of death and morbidity,” she said. “If we can get people identified, into treatment, and taking the right medications, they can live long, normal lives.”