In a “Special Communication” in the July 21 JAMA theme issue on HIV (2010;304:334-339), Elizabeth Chiao, MD, MPH, Assistant Professor of Medicine Sections of Infectious Diseases and Health Services Research Baylor College of Medicine, and coauthors urge oncologists to implement a plan of routine opt-out testing of all their cancer patients.
Background: In 2006, the Centers for Disease Control and Prevention (CDC) recommended nontargeted testing of all people between the ages of 13 and 64 years for HIV in all health care settings as part of routine medical care, regardless of risk profile and without the need for additional consent. “And that's not really happening,” Dr. Chiao said in an interview. So for now, she said, cancer patients should be a specially targeted group, similar to pregnant women, for HIV testing.
Of the approximately one million HIV-infected individuals in the United States, almost one-quarter are undiagnosed. Of newly diagnosed patients, many are advanced in the course of their infection, a situation attested to by the fact that almost 40% of newly diagnosed cases progress to clinical AIDS within one year, Dr. Chiao and her coauthors note.
She hypothesized that there are also cancer patients with undiagnosed HIV infection. “Being HIV-positive does definitely increase your risk for cancer. The second part of it is that if you have cancer and HIV, getting myelosuppressive chemotherapy will probably impact your immune status, and so if you have untreated HIV you're more likely to have adverse events related to myelosuppression and adverse events from your chemotherapy,” she said, “If they are diagnosed with HIV and get that infection under control before starting chemotherapy, they can actually derive immediate benefit.”
She cautioned that highly active antiretroviral therapy (HAART) may have adverse interactions with chemotherapy and recommended that a cancer patient with HIV be under the care of an oncologist familiar with antiretroviral therapy or at least have an oncologist who collaborates closely with the patient's infectious disease physician.
“Despite the [drug] interactions, the benefits of being on antiretroviral therapy appear to outweigh the risks,” Dr. Chiao said.
Rationale for Testing Cancer Patients for HIV
Patients with HIV are at heightened risk for certain cancers, including AIDS-defining ones (e.g., Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer) as well as non-AIDS-defining ones. The authors cited a study using data derived from the national Veterans Affairs database showing that 15% of all anal cancers were associated with HIV.
Another study, from the pre-HAART era, showed that about 19% of non-Hodgkin lymphoma cases were associated with HIV infection.
Dr. Chiao and her colleagues could find only one study, from the United Kingdom, that defined a rate of HIV testing among cancer patients. Of 113 patients diagnosed with Hodgkin or non-Hodgkin lymphoma, 41% had no HIV test. Even among those patients with aggressive non-Hodgkin lymphoma, an AIDS-defining illness, 37% were not tested. “Even when patients present with malignancies known to be associated with high HIV prevalence, HIV testing is not routinely performed,” the JAMA article said.
Even for non-AIDS-defining malignancies, the authors propose that routine HIV testing and treatment of positives is important for the HIV disease itself, to prevent opportunistic and other infections, and to improve cancer treatment, as well as to prevent transmission of the virus to others.
Moreover, the strongest reason for detecting and treating HIV infection is that the infection raises the risk of morbidity and mortality associated with surgery, radiation, and chemotherapy, Dr. Chiao said.
Whereas before the widespread use of HAART, HIV-infected cancer patients often had much shorter survival, now they may survive their cancers nearly or as long as patients with the same cancers not infected with HIV.
Another possible benefit is that by detecting HIV infection in cancer patients, they may be eligible for clinical trials involving AIDS-related malignancies conducted by the AIDS Malignancy Consortium or other cooperative cancer clinical trials groups.
Dr. Chiao said she is trying to battle the misperception that because cancer is a disease of older people and that older people don't get HIV, then “it's a group that doesn't really need to be tested.”
The reality is that the prevalence of HIV infection is increasing among older individuals, especially as the HIV-infected population ages but also from new HIV infections in that age group. Dr. Chiao cited research showing that in 2006 the rate of new infections was higher in people aged 30 to 49 than in the 13-to-29 age group, and that 37% of all newly diagnosed HIV infections were in people older than 40. A Veterans Affairs health care system study showed the prevalence of HIV among those age 55 to 64 to be 3.5%.
While emergency departments have adopted the practice of routine opt-out testing to some degree, the CDC recommendations have gone largely unheeded, and unknown, elsewhere.
“In all honesty I was not aware that the CDC made that recommendation,” said Gregory Masters, MD, of Medical Oncology Hematology Consultants in Newark, Delaware, and Associate Professor of Medicine at Thomas Jefferson University Medical School.
He said that in his practice, he does HIV tests on patients with identified risk factors, such as a history of intravenous drug use, homosexual contact, or prostitution, as well as on patients with cancers of the cervix, lymphomas, or Kaposi's sarcoma.
Dr. Masters said that based on the evidence presented in the JAMA paper, it looks like cancer patients with HIV do better if they are on HAART. But before testing all cancer patients for HIV and not just ones at higher risk, he said, “You'd want to be able to demonstrate that it really does make a difference, because we're talking about testing a lot of people for a small difference….You'd want to show that it's worthwhile to convince people they should do it.”
He predicted that almost all of his patients would say they do not need an HIV test, but they probably would not resist. “So if I said to them that I routinely get an HIV test on everyone with cancer….I think my patients wouldn't complain about that,” he said. “They've got bigger things to think about, and again, they all don't think that they're at risk.”
Barriers to Routine Opt-Out Testing
Some barriers to routine opt-out testing are falling. The Centers for Medicare and Medicaid Services now allows reimbursement for routine HIV testing. But Dr. Chiao notes that other barriers, such as physician attitudes, logistic problems, and funding issues for the extra time and personnel required, still hinder routine testing.
Dr. Masters wondered if insurance companies will go along with Medicare in paying for HIV tests for all cancer patients. He speculated that they may say that since the patient does not have any risk factors, why is the test indicated?
ASCO President George Sledge, MD, Professor of Medicine at Indiana University Simon Cancer Center, said that ASCO has no policy on routine HIV testing, and he takes a more nuanced approach than universal opt-out testing. He noted that routine testing places a significant cost and time burden on physicians and patients to discuss what the test is, why it is being done, and the opt-out option.
“It makes sense to routinely test in some groups and probably makes sense to not routinely test in others,” he said. “To a certain extent, what we're talking about is making sure the right people get tested.”
For example, he said breast and prostate cancer patients have a lower prevalence of HIV infection than the general public, “especially in rural Indiana,” but patients with Hodgkin lymphoma or anal or hepatic carcinoma are at higher risk of being HIV-positive. “There are well-defined populations of patients which I think are outlined pretty well in Dr. Chiao's paper where it's absolutely rational to do routine HIV testing in an opt-out approach.”
The practice setting may also affect the yield of routine testing. “If your practice is in an area where there's high poverty, you're likely to have a higher rate of infection,” Dr. Chiao said. “Most cancer centers draw from a very wide demographic population.”
Adopting the CDC Recommendation
In an editorial in the same issue of JAMA (2010;304(3):348-349), Roland Merchant, MD, MPH, ScD, and Michael Waxman, MD, both of the Department of Emergency Medicine at Warren Alpert Medical School of Brown University, comment, “It is surprising that a group of patients who are usually meticulously evaluated and monitored may lack a routine assessment that is simple and inexpensive yet could have profound implications for care.”
Since the vast majority of clinicians of all medical specialties have not adopted the CDC-recommended routine nontargeted opt-out testing for HIV in their patients, Drs. Merchant and Waxman suggest that such screening could be implemented in stages, with oncologists being some of the first to do so, with the ultimate goal of making it the usual behavior for all clinicians.
Dr. Chiao agreed, saying, “One of our hopes is that some of the bigger cancer centers will start considering doing this in a systematic fashion, and as that gets adopted, smaller cancer centers and/or individual practitioners may follow suit.” She noted that infectious disease specialist Victor Mulanovich, MD at the University of Texas MD Anderson Cancer Center is trying to set up a systematic opt-out HIV testing program there.
So far, she said oncologists have greeted her proposal of routine opt-out HIV testing of all cancer patients with some indifference versus the situation with infectious disease physicians, “who really think this is a good idea.”