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AIDS Treatment Evolves


 

This is the first of a two-part series on care of the HIV/AIDS patient. Part 2 will address the public health and counseling aspects of HIV management, as well as the care of children with HIV.

It’s been a little more than a quarter-century since acquired immune deficiency syndrome (AIDS) was first identified. Since 1981, many facets of our understanding and management of HIV/AIDS have changed.

In some populations, HIV (when well-controlled) has been transformed to a chronic disease state, with few episodes of the AIDS-defining conditions (opportunistic infections, Kaposi’s sarcoma, wasting syndromes) seen in the early years of the epidemic. However, when treating underserved and indigent populations, hospitalists may still encounter the common symptoms of advanced disease in their HIV-positive patients.

What are the common presenting scenarios of HIV/AIDS seen by hospitalists in the current era of highly active antiretroviral therapy (HAART), and how does antiretroviral therapy affect hospitalists’ management of these patients? The Hospitalist recently interviewed HIV/AIDS specialists and practicing hospitalists to learn find out.

The Differential Diagnosis: Think Broadly

The Centers for Disease Control and Prevention estimates 1.04 million to 1.19 million people live with HIV/AIDS in the United States. The CDC also estimates approximately 40,000 people become infected with HIV each year.1

The conditions that bring HIV-positive patients to the hospital run the gamut. There is a broad range of presenting symptoms, noted Sigall K. Bell, MD, the Division of Infectious Diseases and General Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center in Boston. “The differential diagnoses for patients who are HIV-infected—depending on their immunological status—can be dramatically expanded compared to HIV-negative patients,” says Dr. Bell. “For any given presenting symptom, one needs to think about whether the person’s HIV itself, an opportunistic infection secondary to the HIV, or HIV medication effects are playing into potential explanations for the presenting symptoms.”

Even the demographics of the hospital’s catchment area can be associated with patients’ problems. “The types of problems seen in hospitalized HIV-infected patients largely depends on the degree of access to care that people have,” says HIV and infectious disease specialist Harry Hollander, MD, program director for the University of California, San Francisco Internal Medicine Residency Program, and professor of Clinical Medicine at UCSF. In areas where care systems are not robust, explains Dr. Hollander, people admitted to the hospital will most likely have the same problems seen at the beginning of the epidemic.

If hospitalists are practicing in areas with highly developed systems of care and good penetration of care, people with HIV are just as likely to be admitted to the hospital with problems completely unrelated to their HIV status. In the pre-antiretroviral era, according to Dr. Hollander, hospital physicians typically saw three or four common types of presentations in these patients. “My biggest message these days,” he says, “is to think broadly about the problems these patients present with, and to generate parallel thinking about HIV-related causes as well as causes not related to HIV. Many patients with well-controlled HIV are more likely to wind up in the hospital because of other routine medical problems. If you only consider the HIV status, you may be missing other important, related and treatable conditions.”

Thomas Baudendistel, MD, who is associate residency program director at California Pacific Medical Center, a community-based hospital in San Francisco operated by Sutter Health, confirms that as HIV patients are getting healthier, “their immune systems are being kept intact [with CD4 counts in the normal range] for longer periods of time. We don’t see issues of HIV-related conditions in hospitalization as much as we did 20, 10, or even five years ago. The life-threatening opportunistic infections, although still there, have receded as cause for hospitalization. When an HIV patient gets admitted, it’s just as likely to be a noninfectious condition, such as lymphoma, or hematologic complications. Or, the patients may be old enough to have heart disease or COPD.”

Dr. Sabharwal

Other hospitalists practice in areas where the opposite is true. Aman D. Sabharwal, MD, is associate medical director, Inpatient and Hospitalist Services for Jackson Health Systems and practices primarily at Jackson Memorial Hospital, which serves a large indigent population in south Florida. While he agrees that some HIV patients are being well-managed because of advances in antiretroviral therapy, these are not the patients seen by hospitalists in his group.

“A majority of our HIV-positive patients come in for illnesses or opportunistic infections that are due to their HIV,” he says. “Most of these patients are either noncompliant with their medications or have low CD4 counts. Generally, the acute issue for which they are admitted is generally unrelated to the medication itself—it is probably due more so to the lack of medication.”

Dr. Bell

Dr. Baudendistel reports that he and fellow hospitalists at California Pacific Medical Center are also seeing more immune reconstitution illness, in which the reconstituted immune system exhibits an “overexuberant” reaction, causing unique presentations. For example, patients with low CD4 counts who have clinically silent infection with Mycobacterium Avium Complex, hepatitis B, or a variety of infectious agents may experience a significant boost in their CD4 count with antiretroviral therapy. The resurgent immune system can then mount a response to these previously quiescent pathogens, causing a flare-up of symptoms.

“If the primary site of occult disease is the lungs, a respiratory exacerbation will occur; if in the liver, as in the example of hepatitis B, a significant hepatitis can ensue,” says Dr. Baudendistel.

Call in Consultants: Keep a Low Threshold

As the management of HIV becomes more sophisticated, hospitalists should frequently consult infectious-disease and consulting pharmacy colleagues. “I think the hospitalist is very well-equipped to deal with the acute illnesses that these patients have,” notes Dr. Hollander. “Most hospitalists feel less comfortable with the details of managing the chronic medical regimen—particularly the antiretroviral drugs, which they don’t have an opportunity to prescribe, manage, and monitor over time.”

Dr. Baudendistel concurs: “As a hospitalist, what I face with these patients—especially if they come in with an illness unrelated to HIV—is trying to figure out how a drug I am thinking of prescribing for their heart disease or kidney failure will impact their HAART therapy. Is there going to be some hidden interaction that I’m not aware of because I don’t deal with those medications every day?”

It is precisely when weighing those questions about chronic therapy when hospitalists would be best served to quickly consider consulting either a primary physician or the appropriate consultant about the details of the medication regimen. “In most cases, you’re going to want to continue that regimen during hospitalization for other intercurrent problems,” he says.

When possible, it’s a good idea for the hospitalist to touch base with the primary HIV provider, says Dr. Bell. “There are sometimes subtleties to the care that are not necessarily transmitted in a faxed document or in information the patient brings to the hospital. Those subtleties—about doses of antiretroviral drugs or changes in regimen—can make big differences.”

Hospitalists should inform themselves of the potentially harmful effects of antiretroviral drugs, as well as the potential harm in stopping them. “It takes an awareness of knowing what the potential problems are to know when to utilize a consultant,” says Dr. Bell. “As doctors, we are appropriately aware of the power of medications, and it’s not uncommon when the clinical picture is unclear for physicians to think, ‘First do no harm—let me stop these medications.’ One has to be aware of the fact that stopping a medication doesn’t happen in a vacuum.”

Resources Abound

The field of clinical HIV medicine is characterized by rapid change. In addition to consultancy with infectious disease, HIV and clinical pharmacy specialists, hospitalists can also access a range of information to keep current on advances in HIV/AIDS scientific discovery and clinical practice issues.

  • A summary of information sources: “Keeping Up-To-Date: Sources of Information for the Provider” is available online at http://hab.hrsa.gov/tools/primarycareguide.
  • Information on antiretroviral drugs, their adverse events and interactions: The University of California San Francisco site, HIVInSite. www.hivinsite.ucsf.edu Comprehensive, up-to-date information on all aspects of the disease, including worldwide trends and links to other reputable Web sites is provided at the HIVInSite.
  • Government Web sites: The Centers for Disease Control and Prevention (www.cdc.gov) and the Division of Acquired Immunodeficiency Syndrome at the National Institute of Allergy and Infectious Diseases (www.niaid.nih.gov/daids) also provide a wealth of information.

Nuances of HAART Require Vigilance

“Highly active antiretroviral therapy has resulted in improved immunological status for many HIV-positive patients, but the therapy has also introduced several potential complications and consequences of which hospitalists should be aware,” says Dr. Bell. Most notable among those consequences: the effects of starting and stopping medications.

“It used to be,” says Dr. Baudendistel, “that we would say, ‘The patients are only going to be here in the hospital for a few days; let’s just stop their highly active HIV treatment.’ Now we know that is not a good idea, because stopping treatment can create resistant viruses.”

Dr. Bell explains one such example: Each of the classes of antiretroviral drugs has a different half-life. If a physician stops all antiretroviral therapy at the same time, the nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) may wash out of the system more quickly than does the nonnucleoside reverse transcriptase inhibitor (NNRTI). The result will be NNRTI monotherapy, and drug resistance can occur quickly in that setting, says Dr. Bell. (Note: not all patients are on NNRTIs; some may be on protease inhibitors or fusion inhibitors, which all have potentially adverse events and drug-drug interactions.)

As another example, if a patient has co-infection with hepatitis B, stopping an NRTI with activity against hepatitis B (such as lamivudine or tenofovir), may cause hepatitis to flare up. Finally, several studies now suggest that the long-term consequences of starting and stopping therapy (structured treatment interruptions) are also detrimental.2

Hospitalists can incorporate into their diagnosis and treatment of these patients other management strategies beyond potential drug-drug interactions and consequences of incurring resistance when stopping antiretroviral medication. For instance:

At California Pacific Medical Center in San Francisco, hospitalists are seeing more immune reconstitution illness. Dr. Sabharwal

At California Pacific Medical Center in San Francisco, hospitalists are seeing more immune reconstitution illness.

  • Screen for other problems that may be attributable to long-term antiretroviral therapy, such as dyslipidemia, diabetes, and osteoporosis if the patient has adhered to HAART.3 Because mounting data suggest an increased incidence of cardiovascular disease, aggressive management of other underlying cardiovascular risk factors is an important part of care.
  • Ensure electronic medication orders do not automatically default to inappropriate doses. For instance, ritonavir, a protease inhibitor, is most commonly used as a booster dose and not at full dose—but electronic pharmacy ordering systems may not reflect this current knowledge.
  • Raise nursing and physician staff awareness to confirm that HAART doses are not missed (e.g., if a patient is off the floor for extended periods of time). Reconcile medication orders and the medication administration record to ensure all ordered medications are given. For example, if there is a delay in accessing one of the patient’s usual medications, it may be harmful to administer just the other two until the third is available. Alternative arrangements would be required.
  • Consider orders allowing patients to use their own supply of medications if the hospital pharmacy is not able to supply the exact drug needed for their specific HAART regimen.

It is also advisable to ask HIV patients about their use of alternative therapies, says Dr. Hollander, because studies have shown that a substantial minority of people with HIV infection do, in fact, take alternative therapies.4 “We also know,” he says, “that some of these therapies cause adverse reactions and toxicities that you would not ordinarily consider, unless you had obtained that history.”

Education, Education, Education

Dr. Bell notes that there is wide variability in adherence to medication and follow-up clinic visits among those infected with HIV. “It’s important for hospitalists to emphasize links to care,” she says. “A hospital visit is an important time to emphasize education, and to make sure that those patients have the appropriate follow-up.”

The role of hospitalist as patient educator takes on more prominence in settings with a larger percentage of more indigent patients. “I think the key is education, education, education,” Dr. Sabharwal asserts.

He and hospitalists in his group make patient counseling a key component in their treatment, from the time they encounter patients until discharge. They emphasize that with today’s therapies, a 60-year-old HIV-positive patient may avoid hospitalization, while those who do not take their medications risk the severe sequelae of AIDS-defining conditions.

“It’s very important that physicians not be in a hurry to go from patient to patient,” he says. “A lot of times what’s lacking is for physicians to take the time to sit down with the patient and go over the severity of the disease in its later stages. We counsel patients every single time.”

Dr. Baudendistel’s counsel to fellow hospitalists is that although they may still be attuned to treating HIV complications, such as PCP or TB, HIV is now a chronic disease. And as such, “It’s not something that the casual generalist can manage independently,” he says. “When I was in training, I was very well-versed in managing HIV disease. With the initial drug treatments and the common opportunistic infections, treatment was pretty straightforward. But now I wouldn’t feel comfortable managing the HIV part of the illness on my own. HIV is a subspecialist disease now, and it is important to have a colleague with HIV expertise with whom they can consult.” TH

Gretchen Henkel is a frequent contributor to The Hospitalist.

References

  1. CDC HIV/AIDS Fact Sheet, “A Glance at the HIV/AIDS Epidemic.” January 2007. Available online at http://www.cdc.gov/hiv. Last accessed April 2007.
  2. Pai NP, Lawrence J, Reingold AL, et al. Structured treatment interruptions (STI) in chronic unsuppressed HIV infection in adults. Cochran Database Syst Rev. 2006 Jul 19;3:CD006148.
  3. Agins BD, Alexander CS, Bartlett JG. Metabolic Complications of Antiretroviral Therapy. A Guide to Primary Care of People with HIV/AIDS, 2004 Ed. Available online at http://hab.hrsa.gov/tools/primarycareguide. Last accessed May 21, 2007.
  4. Wutoh AK, Brown CM, Kumoji EK, et al. Antiretroviral adherence and use of alternative therapies among older HIV-infected adults. J Natl Med Assoc. 2001 Jul-Aug;93(7-8):243-250.

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