HIV Management — The Evolving Role of the Primary Care Physician

Sax, Paul E., MD
Clinical Director of the Division of Infectious Diseases
Brigham and Women's Hospital
Professor of Medicine
Harvard Medical School
Boston, MA
Also by this Author 

The recommendation for universal screening of adolescents and adults aged 15 to 65 years for HIV infection, issued by the United States Preventive Services Task Force (USPSTF) in April 2013,1 highlights the growing role for primary care physicians (PCPs) in HIV care. The effectiveness of standardized regimens for many patients, and the growing number of HIV patients, are two other significant factors leading to an expanded role for PCPs in managing HIV.

Dr. Paul Sax, Clinical Director, Division of Infectious Disease, Brigham and Women’s Hospital, and Professor of Medicine at Harvard Medical School, reviews the role PCPs should play in HIV screening and diagnosis, and discusses the rationale for co-management of patients by PCPs and HIV infectious disease specialists.

Increasing Diagnosis Rates – The Move to Universal Screening

“One major point everyone should understand,” stresses Dr. Sax, “is that patients can only access life-saving and life-prolonging HIV therapy if they are diagnosed - and that is easier said than done. Twenty percent (20%) or so of Americans with HIV are unaware they are infected, because they’ve never been tested.2 And so a major impetus that has been going on since 2006 has been to broadly expand screening for HIV infection in all healthcare settings, not just in primary care physician offices, but also in walk-in centers, emergency rooms, OB/Gyn offices and so on.”

The Centers for Disease Control and Prevention (CDC) and U.S. Preventive Services Task Force (USPSTF) now both recommend one-time HIV screening for all Americans 15 to 65, and an annual test for high-risk individuals. The CDC recommendations were issued in 2006, but the USPSTF only published its revised guideline in April 2013.1, 3 Dr. Sax feels this consensus between the USPSTF and the CDC will likely lead to broader adoption of the recommendations. “In general, when the USPSTF makes a recommendation it has very significant policy implications for quality measures and reimbursement,” he notes.

Applying the Guidelines in Practice

Dr. Sax suggests it’s important that patients don’t feel they’re being assessed for risk , as they may then resist being tested. “The best approach is to say that, as part of routine healthcare, we recommend everyone has a one-time HIV test,” he says. “When people hear that they usually agree and there are no issues - they don’t feel there’s any kind of value judgment being applied to them. If a clinician were to start with extensive queries about potential risk factors, that could make people feel defensive.” This approach is facilitated by changes in laws, which in the past required written consent for HIV testing. Currently, all but two states, Nebraska and New York, have laws consistent with the CDC recommendation that a separate written consent is not necessary for HIV testing.4

Initial Testing

The most common test performed for diagnosing HIV is a blood test - a standard enzyme-linked immunosorbent assay or an ELISA. “These are very inexpensive tests, which screens for HIV antibodies,” says Dr. Sax. “They’re highly accurate, with sensitivity and specificity of 99.5%, and results are available within 1 to 2 days – often faster.1If those tests come back negative they essentially rule out HIV infection that’s been present for at least a month. If the test is positive, a second test – usually an HIV Western blot-based assay - is performed to confirm the result.” The ELISA and the Western blot are usually combined in one package, when a clinician orders HIV testing: if the ELISA is positive it’s automatically referred for testing with the Western blot.

In addition to the standard testing outlined above there is a rapid test performed at point of care. “A rapid test can be performed both on blood, by a finger stick, or on saliva,” explains Dr. Sax. “If that test is positive, the clinician will move ahead with the standard procedure. If that test is negative the physician doesn’t need to send any further testing in most cases.”

One limitation to the standard approach is in cases where there is recently acquired HIV. In the sub-set of people who have acquired infection very recently - within the past month - the antibody test may not be fully positive or is often negative. If it’s positive the Western blot will often be negative. In these instances the physician needs to order an HIV viral load test. “The reason this is important,” notes Dr. Sax, “is that sometimes people choose to get tested for HIV infection, because of recent exposure. It’s also important if people have symptoms associated with recently acquired HIV infection. When people acquire HIV they develop a syndrome that’s similar to mononucleosis, so if a clinician is evaluating someone with a mononucleosis-like syndrome, and they suspect HIV, they should order the appropriate test.”  The FDA approved test for this purpose is an RNA Qualitative assay.  However, a quantitative HIV RNA test -- often called "viral load" -- is much more widely available since it is used for HIV monitoring.  This also can be used for diagnosis of recently acquired HIV infection, although it is not FDA approved for this indication.

A “4th generation” HIV diagnostic assay, which simultaneously detects both antigen and antibodies for HIV, is also available. This test can be useful in extending diagnosis in earlier, acute phase infection with HIV, prior to the emergence of antibodies produced by the infected patient, effectively reducing the window between initial infection and the detection of infection based on formation of detectable antibodies. The median detection time using this test has been shown to be 7 days earlier (range 0 to 20 days) compared to 3rd generation ELISA tests to which they were compared.5, 6  The 4th generation tests have demonstrated high sensitivity for both early and established infections, and high specificity in a low HIV prevalence population. Additionally, an algorithm using this test identified HIV-2 infections that would otherwise have been misclassified as HIV-1 infections by the HIV-1 Western blot.6

Baseline Testing and Referral

Following a positive diagnosis Dr. Sax recommends that physicians order baseline testing, so results are available in time for the referral visit. “When I’m contacted by primary care physicians with a new diagnosis I advise them to do the baseline laboratory tests so I can review them. Results are available in about 7 to 10 business days.”

Baseline laboratory testing provides a baseline viral load and a baseline CD4 cell count. “The CD4 cell count is absolutely critical because it determines the urgency of starting HIV therapy,” stresses Dr. Sax. “Patients who have more severe immunodeficiency, CD4 less than 200 cells/mm3, and in particular less than 50 cells/mm3, are the ones who really need to be started on treatment sooner rather than later. For someone without symptoms, who has a higher CD4 cell count, there’s less urgency though we still recommend treatment in most of those cases as well.”

Dr. Sax also feels it is useful to obtain the baseline resistance test at this stage. 10 – 15% of those newly diagnosed with HIV in the U.S. have at least some degree of transmitted drug resistance, which needs to be taken into consideration by the specialist when determining the most effective therapy. 7

Co-Management of Patients

Long-term management of HIV patients has evolved significantly in recent years. Until four to five years ago care remained almost exclusively in the domain of HIV specialists – these clinicians could be from a broad range of fields, including infectious diseases, internal medicine, and family practice, with their distinguishing characteristic that they chose to focus on HIV management.  It was important that the bulk of care be done by HIV specialists due to several factors: the complexity of medical regimens, the frequent adjustments that had to be made to treatment, and the significant amount of side effects. “Since then,” notes Dr. Sax, “treatment has become so good, that most people become stable outpatients with a chronic medical condition like many others who are followed by primary care physicians. Most people are taking just one or a few pills a day, they’re very stable, their CD4 cell count has recovered, and their viral load is undetectable.”

“I would say that the vast majority of patients can be co-managed with PCPs, with visits to a specialist and HIV-specific follow-up typically occurring twice a year,” he continues. “Since we’re expecting them to live for decades they’re certainly going to start getting, and are getting, the diseases of aging that PCPs manage routinely.”

Drug-Drug Interactions

In managing conditions of aging in HIV patients, physicians need to be aware of the potential for drug-drug interactions, notes Dr. Sax.  “One of the most commonly used classes of HIV therapeutics are protease inhibitors and these invariably include ritonavir, a pharmacokinetic booster that increases the level of the protease inhibitor it’s combined with. This is a very powerful inhibitor of the cytochrome P450 enzymes in the liver, which creates the potential for multiple drug-drug interactions of commonly used drugs. These include statins, anti-seizure medications, erectile dysfunction drugs, benzodiazepines, and the one most commonly overlooked - inhaled corticosteroids.” Someone receiving a ritonavir boosted protease inhibitor, who starts to use any inhaler that contains fluticasone, is at very high risk of developing excessive systemic levels of fluticasone leading to the development of Cushing’s syndrome. When the drug is stopped they can develop adrenal insufficiency. This can also occur with steroid injections such as those commonly used for back pain. Being aware of these potential interactions, physicians should choose alternative therapies; if the steroid treatment were absolutely required, an HIV specialist may consider changing the antiretroviral regimen.

Striking a Balance Between Specialists and PCPs

Dr. Sax believes a certain tension will inevitably exist in the sharing of care between specialists and PCPs.  “On the one hand you have multiple complex medications that you really wouldn’t expect PCPs to be prescribing – that would be analogous to people administering chemotherapy, or some of the more complex rheumatologic drugs, in primary care. On the other hand, these patients are really quite stable from an HIV perspective. After their therapy is stabilized and they’ve had immune recovery, they literally can continue for decades, so there’s going to be more and more co-management.”

Given the expanded role of PCPs in HIV care it’s clear important effective coordination and communication are established with HIV infectious disease specialists to ensure optimal patient management over the long-term.

References

  1. Screening for HIV: U.S. Preventive Services Task ForceRecommendation Statement. Ann Intern Med 2013;30 Apr.
    http://www.uspreventiveservicestaskforce.org/uspstf13/hiv/hivfinalrs.htm
    Accessed on June 5, 2013.
  2. HIV Testing. Centers for Disease Control and Prevention.
    http://www.cdc.gov/hiv/topics/testing/index.htm. Accessed on June 5, 2013.
  3. Revised Recommendations for HIV Testing of Adults, Adolescents, and Pregnant Women in Health-Care Settings. MMWR September 22, 2006 / 55(RR14);1-17.
    http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5514a1.htm. Accessed on June 5, 2013.
  4. State HIV Testing Laws: Consent and Counseling Requirements.
    http://www.cdc.gov/hiv/law/states/testing.htm Accessed on June 5, 2013.
  5. Fourth Generation HIV Diagnostic Test Approved, permitting earlier detection of infection. U.S. Food and Drug Administration.
    http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm216409.htm Accessed June 11, 2013.
  6. Nasrullah M, Wesolowski L, Meyer WI et al. Performance of a fourth-generation HIV screening assay and an alternative HIV diagnostic testing algorithm. AIDS 2013, 27:731–737
  7. Kozal MJ, Hullsiek KH, Macarthur RD, Berg-Wolf Mv, Peng Get al. The Incidence of HIV drug resistance and its impact on progression of HIV disease among antiretroviral-naïve participants started on three different antiretroviral therapy strategies. HIV Clin Trials. 2007 Nov-Dec;8(6):357-70.