CE/CME

HIV Infection: What Primary Care Providers Need to Know

Clinician Reviews. 2014 May;24(5):38-48

References

1. Daar ES, Little S, Pitt J, et al. Diagnosis of primary HIV-1 infection: Los Angeles county primary HIV infection recruitment network. Ann Intern Med. 2001;134:25-29.

2. Hightow-Weidman LB, Golin CE, Green K, et al. Identifying people with acute HIV infection: demographic features, risk factors, and use of health care among individuals with AHI in North Carolina. AIDS Behav. 2009;13:1075-1083.

3. Richey LE, Halperin J. Acute human immunodeficiency virus infection. Am J Med Sci. 2013;345(2):136-142.

4. Weintraub AC, Giner J, Menezes P, et al. Infrequent diagnosis of primary human immunodeficiency virus infection: missed opportunities in acute care settings. Arch Intern Med. 2003;163:2097-2100.

5. Marks G, Crepaz N, Senterfitt JW, Janssen RS. Meta-analysis of high-risk sexual behavior in persons aware and unaware they are infected with HIV in the United States: implications for HIV prevention programs.
J Acquir Immune Defic Syndr. 2005;39:446-453.

6. CDC. Estimated HIV incidence among adults and adolescents in the United States, 2007–2010. www.cdc.gov/hiv/topics/surveillance/resourc es/reports/#supplemental. Accessed April 15, 2014.

7. CDC. National HIV prevention progress report, 2013. www.cdc.gov/hiv/pdf/policies_NationalProgressReport.pdf. Published December 2013. Accessed April 15, 2014.

8. CDC. Draft recommendations: diagnostic laboratory testing for HIV infection in the United States. www.cdc.gov/hiv/pdf/policies_Draft_HIV_Testing_Alg_Rec_508.2.pdf. Accessed April 15, 2014.

9. Kuhar DT, Henderson DK, Struble KA, et al. Updated US Public Health Service guidelines for the management of occupational exposures to human immunodeficiency virus and recommendations for postexposure prophylaxis. Infect Control Hosp Epidemiol. 2013;34:875-892.

10. Pinkerton SD, Martin JN, Roland ME, et al. Cost-effectiveness of HIV postexposure prophylaxis following sexual or injection drug exposure in 96 metropolitan areas in the United States. AIDS. 2004;18:2065-2073.

11. CDC. Update to interim guidance for preexposure prophylaxis (PrEP) for the prevention of HIV infection: PrEP for injecting drug users. MMWR. 2013;62:463-465.

12. Bell DM. Occupational risk of human immunodeficiency virus infection in healthcare workers: an overview. Am J Med. 1997;102(suppl 5B):9-15.

13. CDC. Interim guidance for clinicians considering the use of preexposure prophylaxis for the prevention of HIV infection in heterosexually active adults. MMWR. 2012;61:586-589.

14. CDC. Interim guidance: preexposure prophylaxis for the prevention of HIV infection in men who have sex with men. MMWR. 2011;60:65-68.

15. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed April 15, 2014.

16. Kitahata MM, Gange SJ, Abraham AG, et al. Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med. 2009; 360:1815-1826.

17. Castel AD, Magnus M, Peterson J, et al. Implementing a novel citywide rapid HIV testing campaign in Washington, DC: findings and lessons learned. Public Health Rep. 2012;127:422-431.

18. CDC. HIV in the United States: stages of care. www.cdc.gov/hiv/pdf/research_mmp_StagesofCare.pdf. Accessed April 15, 2014.

19. Gardner EM, McLees MP, Steiner JF, et al. The spectrum of engagement in HIV care and its relevance to test-and-treat strategies for prevention of HIV infection. Clin Infect Dis. 2011;52:793-800.

20. Mugavero MJ, Westfall AO, Zinski A, et al. Retention in Care (RIC) Study Group. Measuring retention in HIV care: the elusive gold standard.
J Acquir Immune Defic Syndr. 2012;61:574-580.

21. Fleishman JA, Yehia BR, Moore RD, et al. Establishment, retention, and loss to follow-up in outpatient HIV care. J Acquir Immune Defic Syndr. 2012;60:249-259.

22. Rebeiro P, Althoff KN, Buchacz K, et al. Retention among North American HIV-infected persons in clinical care, 2000-2008. J Acquir Immune Defic Syndr. 2013;62:356-362.

23. American Association for the Study of Liver Diseases. Recommendations for testing, managing, and treating hepatitis C. www.hcvguidelines.org/. Accessed April 15, 2014.

24. Aberg JA, Gallant JE, Ghanem KG, et al. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2014;58:e1-e34.

25. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365:493-505.

26. Panel on Antiretroviral Guidelines for Adults and Adolescents. Recommendation on integrase inhibitor use in antiretroviral treatment-naive HIV-infected individuals from the HHS panel on antiretroviral guidelines for adults and adolescents. http://aidsinfo.nih.gov/contentfiles/upload/AdultARV_INSTIRecommendations.pdf. Updated 2013. Accessed April 15, 2014.

27. Chesney MA. The elusive gold standard: future perspectives for HIV adherence assessment and intervention. J Acquir Immune Defic Syndr. 2006;43(suppl 1):S149-155.

SCREENING AND PREVENTION
When discussing many disease processes, prevention is relegated to the end of the discussion—but with HIV, prevention must be a primary concern for patients and providers. HIV prevention includes two critical strategies: finding previously undiagnosed cases of the infection and preventing transmission through treatment of those with the disease, safer sex practices, or prophylactic antiretroviral therapy for those at highest risk. (Chemoprophylaxis for those who have had a potential exposure is referred to as postexposure prophylaxis, or PEP. Chemoprophylaxis for those at high risk for exposure is termed pre-exposure prophylaxis, or PrEP.)

Guidelines published by the CDC in 2006 recommended that clinicians include HIV screening as a routine part of medical care for all patients and that barriers to routine HIV testing be removed. Since then, the estimated proportion of people infected with HIV who are unaware of their HIV-positive status has dropped from about 25% to 16%.^5-7 In applying these recommendations to a primary care setting, the practitioner simply adds an HIV antibody test to the standard panel given to new patients. In addition, established patients who have not previously been tested should be advised to have a baseline HIV test regardless of risk.

Clinicians should offer HIV testing on an opt-out basis and inform patients that the test is recommended; patients can refuse the test should they choose to do so. Patients at higher risk for HIV should undergo retesting annually—or more frequently if indicated. Routine testing need not be accompanied by prevention counseling or special consent. While counseling on safer sex or other risk reduction strategies is always appropriate, it should not be seen as an impediment to routine screening.

Newer fourth-generation immunofluorescence assays (IA) detect both HIV-1 and HIV-2 earlier after infection because they are able to detect the HIV viral capsid protein p24 as well as HIV antibodies. If the initial assay is positive, subsequent confirmatory testing with a discrimination assay will distinguish between the two types of HIV. Because the newer IA tests detect antibody much earlier, using the discrimination assay as the confirmatory test rather than a Western blot has become commonplace, although either test may be used. Home testing for HIV is also available. Patients who obtain a positive result are instructed to have the result confirmed by their health care provider.

Neither rapid tests nor home tests will pick up new infections during initial infection (known as the window period prior to the development of detectable antibodies) but they can be very helpful in screening programs since the patient need not return for a second visit to obtain results. Whatever test is initially used, it is important to confirm its results with a second test; for instance, the first test might be a fourth-generation IA (either a rapid test or traditional), confirmed by a discrimination assay or Western blot. If the confirmatory test is negative or indeterminate, an HIV RNA (viral load) test should be considered.⁸HIV RNA should also be used whenever a new infection is suspected.

PRE- AND POSTEXPOSURE PROPHYLAXIS
PEP to prevent HIV seroconversion following a possible or confirmed HIV exposure is now well accepted, whether the exposure is occupational or not.^9,10 Clinicians should start PEP as soon as possible after exposure, preferably within two hours, but no later than 72 hours after exposure. Do not delay treatment even if the source's or exposed patient’s HIV status or other factors are unknown. Treatment can always be discontinued or modified when further information becomes available.

The most recent update issued by the US Public Health Service includes a change to prior guidelines. They now recommend that all potentially exposed individuals receive a three-drug combination of tenofovir 300 mg orally once daily, emtricitabine 200 mg orally once daily (coformulated as Truvada), and raltegravir 400 mg orally twice daily. Patients should be instructed to continue antiretroviral medications for four weeks. Raltegravir, an integrase inhibitor, has replaced previously recommended drugs used in a three-drug regimen because of its lower incidence of adverse effects as compared to older antiretrovirals. Alternative regimens may be used for a variety of reasons, but the need for an alternative should generally spur expert consultation.

The use of three drugs in all cases is based both on a better understanding of the pathophysiology of HIV and on the availability of medications that are better tolerated. Expert consultation is always helpful in cases of PEP, but particularly in those complicated by pregnancy or breastfeeding, known or suspected drug resistance in the source patient, unknown HIV status of the source patient, delayed report of exposure (> 72 hours), or significant medical illness of the exposed patient. In addition, any toxicity experienced should spur expert consultation. If local expert resources are unavailable, immediate assistance can be obtained through the National Clinicians' Postexposure Prophylaxis Hotline (PEPline) at (888) 448-4911.

Whenever possible, the source patient should undergo testing if his or her HIV status is unknown. If the exposed patient chooses to receive PEP, it is helpful to evaluate the source patient’s history of medication resistance, which should be done by a clinician with HIV expertise. In all cases, the likelihood of HIV conversion after an exposure is low, ranging from approximately 0.3% for a percutaneous exposure to 0.09% for a mucous membrane exposure.^11,12

Clinicians should test the exposed patient for HIV and hepatitis B and C, and women should have a pregnancy test performed. For patients being treated, renal and hepatic function should be evaluated and hematology tests done to monitor for adverse reactions to therapy at baseline, two weeks, and completion of treatment. The exposed patient must be advised to take precautions to avoid any potential for transmission of HIV: use barrier contraception and avoid blood or tissue donation or breastfeeding until after the final follow-up visit. Initial follow-up should occur within 72 hours to reevaluate the need for therapy and reinforce the need for adherence if therapy is continued. Clinicians should also assess the patient regarding his or her emotional as well as physical well-being and access to resources to aid in coping with the event. If a fourth-generation test is used, follow-up HIV testing should be done at six weeks and four months after exposure. Otherwise, follow-up HIV testing should occur at six weeks, 12 weeks, and six months.

PrEP using tenofovir 300 mg orally once daily and emtricitabine 200 mg orally once daily is recommended in interim CDC guidelines for those at particularly high risk for HIV exposure, such as homosexual or heterosexual partners of HIV-positive individuals or injection drug users. For PrEP to be effective, medication adherence is critical. Because PrEP involves daily therapy, patients should be carefully selected and expert consultation is advised.^13,14 All patients on PrEP require regular follow-up and HIV testing. On follow-up, side effects and continued risk should be evaluated. PrEP should be considered part of a broader prevention strategy that includes condom use, prevention and treatment of other sexually transmitted infections, and frequent reassessment of risk. There are often significant difficulties in obtaining insurance coverage for PrEP, but this may change as further research is done and health care coverage broadens.

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