Spotlight Case May 2008

1. Spotlight Case May 2008 Diagnosing HIV: It Doesn’t Take a Brain Surgeon

2. Source and Credits • This presentation is based on the May 2008 AHRQ WebM&M Spotlight Case • See the full article at http://webmm.ahrq.gov • CME credit is available • Commentary by: Roger Chou, MD, Oregon Health & Science University • Editor, AHRQ WebM&M: Robert Wachter, MD • Spotlight Editor: Niraj Sehgal, MD, MPH • Managing Editor: Erin Hartman, MS

3. Objectives At the conclusion of this educational activity, participants should be able to: • Describe the current epidemiology of HIV infection • Identify the risk factors for HIV infection • Indicate the challenges associated with HIV screening practices • Review current guidelines for HIV screening

4. Case: Diagnosing HIV A 41-year-old healthy man was admitted after one week of new onset headaches, and a witnessed generalized seizure. On examination, he was neurologically intact with stable vital signs, and the exam was otherwise unremarkable. Laboratory studies were notable for a mild leukopenia and anemia. Imaging revealed a 3 cm left-sided brain mass with surrounding edema.

5. Case: Diagnosing HIV (2) The radiologist reported the findings to be concerning for a malignant rather than infectious process. The patient was single, with no children, and had emigrated from Mexico 8 years earlier. He was started on steroids and transferred to a referral facility for neurosurgical biopsy and possible excision.

6. Case: Diagnosing HIV (3) Upon arrival to the referral facility, the patient remained neurologically stable and underwent left-sided craniotomy and brain biopsy. Unexpectedly, pathology revealed toxoplasma cysts, confirming a diagnosis of cerebral toxoplasmosis, for which therapy was initiated. This diagnosis prompted an HIV test that returned positive.

7. HIV Infection • Estimated to affect more than 1 millionin the United States • About ¼ of infected persons may be unaware of their infection status See Notes for references.

8. Acquired Immunodeficiency Syndrome • Without treatment, median time from HIV seroconversion to developing AIDS is 8-11 years • Many persons with HIV infection not diagnosed until after an opportunistic infection, such as toxoplasmosis or pneumocystis • About ¼ of patients are simultaneously diagnosed with HIV and AIDS • About 40% of newly diagnosed meet criteria for AIDS within 1 year See Notes for references.

9. Most Common Risk Factors for HIV • In men • Male-to-male sexual contact (60%) • Injection drug use (16%) • Heterosexual contact with person known to have or be at high risk for HIV (17%) • In women • High-risk heterosexual contact (76%) • Injection drug use (21%) • Providers must take complete and targeted history to fully understand patient’s risk factors for HIV infection See Notes for references.

10. Risk Factor Assessment • Failure to take a thorough history, particularlyfor sensitive questions, may result in the failureto order an HIV test • Risk factor assessment is crucial because clinical diagnosis of acute HIV infection is challenging • Symptoms are short-lived, non-specific, and often atypical • Following resolution of acute HIV infection, patients often experience prolonged, relatively asymptomatic phase until they become severely immunocompromised See Notes for references.

11. Risk Factor Assessment (cont.) • Clinicians should view every health care encounter as potential opportunity to inquire about HIV risk factors • About 40% of persons reporting an HIV risk factor have never been tested • Even in settings with good access to health care, high-risk behaviors often remain undetected or fail to lead to testing • Important to test those who report risk factors, given high yield of testing in such persons • Another high-yield strategy is to routinely test persons evaluated in higher-prevalence settings See Notes for references.

12. Case (cont.): Diagnosing HIV The patient's clinical status deteriorated steadily following surgery. He developed worsening neurological status, required mechanical ventilation for airway protection, and developed a number of infectious complications that ultimately led to his death after a 5-week hospitalization.

13. Issues in Present Case • Difficult to know whether identifying HIV infection at time of admission would have led to a change in overall outcome • However, with described imaging findings, earlier knowledge of HIV infection could have led to immediate toxoplasmosis antibody testing, which may have prevented an unnecessary brain biopsy

14. Issues in Present Case (cont.) • Toxoplasmosis typically occurs only after the CD4 count has dropped below 100 cells/mm3 • Thus, there is a good chance patient had been infected with HIV for a decade or more • Although patient is described as previously healthy, he probably had previous encounters with the health care system following seroconversion See Notes for references.

15. Benefits of Screening for HIV • May identify infected persons at earlier stages of disease • May reduce morbidity and mortality by starting patients on appropriate therapies before they develop a serious infection or advanced immunodeficiency • May reduce secondary transmission, as persons aware of their HIV-positive serostatus may engage in fewer risky behaviors than those unaware of their status See Notes for references.

16. Challenges in Screening • No direct evidence showing benefits of routine screening or early identification of HIV infection on morbidity/mortality and transmission rates • Evidence of decreases in HIV-related morbidity and mortality are primarily from studies of patients with more advanced disease • Although screening asymptomatic patients with no identifiable risk factors would detect additional persons with HIV, the overall number of new infections identified would be limited See Notes for references.

17. Cost-effectiveness of Routine HIV Screening • When potential benefits from reduced secondary transmission are factored in: • Routine screening is cost-effective (<$50,000 per quality-adjusted life-year [QALY] gained) • Remains cost-effective even when prevalence of undiagnosed HIV was at or substantially below that in general population (~ 0.2%) • Without secondary transmission benefits: • Routine screening is not cost-effective (>$50,000 per QALY) in low-prevalence settings • Remains cost-effective in higher-prevalence (>1%) settings See Notes for references.

18. Centers for Disease Control and Prevention (CDC) Guidelines • New CDC guidelines in 2006 • Recommends routine HIV screening for all persons 13 to 64 years • Unless prevalence of HIV in that setting documented to be <0.1% • Streamlined counseling using “opt-out” approach • Patients should be informed that HIV testing will be performed unless they decline (opt-out of) testing, without requiring specific signed consent for HIV testing • This opt-out approach is similar to recommendations for routine screening in the prenatal setting • By streamlining consent process and eliminating need for risk assessment, this recommendation is theoretically less burdensome on clinicians and easier to put into practice See Notes for references.

19. Opt-Out Testing • Studies that assess routine opt-out testing in low-risk and low-prevalence settings are not yet available • Even in higher-prevalence settings, substantial proportion of patients decline testing • Challenges • Need to insure that testing remains truly voluntary and informed, as well as confidential • Higher proportions of false-positives in low-prevalence settings • Continued stigmatization of persons with HIV infection • Current laws or policies in some states mandate specific informed consent or extensive pretest counseling See Notes for references.

20. US Preventive Services Task Force (USPSTF) Recommendations • In low-risk, low-prevalence settings, USPSTF found that potential benefits of routine screening appear small relative to potential burdens/harms (labeling, anxiety, false-positives) • Strongly recommends for screening in persons reporting high-risk behaviors and in high-prevalence settings • Task Force does not recommend for or against routine screening See Notes for references.

21. Screening Pitfalls • HIV screening can take place during any health care encounter, including primary care, urgent or emergency care, and inpatient visits • 40%-60% of HIV-infected persons do not regularly see a provider outside of the emergency department • Studies of routine testing in urgent care centers found that up to ¼ of positive patients didn’t receive results • To realize maximum potential benefits of any HIV screening program, patients must be informed of test results and linked to appropriate follow-up care See Notes for references.

22. Take-Home Points • About ¼ of HIV-infected persons are unaware of status • A substantial proportion of HIV-infected persons are diagnosed late in the course of disease or when they present with an opportunistic infection • Patients with clinical presentations consistent with an HIV-related infection or cancer should be tested for HIV • Routine screening of patients could reduce the proportion of HIV-infected persons unaware of their status and potentially reduce secondary transmission, morbidity, and mortality

23. Take-Home Points (cont.) • Screening will have higher yield in persons reporting risk factors and in higher prevalence settings, but may be cost-effective even in very low prevalence settings if presumed secondary transmission benefits are factored in • Effective screening strategies require protocols for notifying patients of initial and confirmatory results and linking infected patients to HIV follow-up care