HIV Primary Care Guidelines ��� CID 2009:49 (1 September) ��� 651 I D S A G U I D E L I N E S Primary Care Guidelines for the Management of Persons Infected with Human Immunodeficiency Virus: 2009 Update by the HIV Medicine Association of the Infectious Diseases Society of America Judith A. Aberg,1 Jonathan E. Kaplan,2 Howard Libman,3 Patricia Emmanuel,5 Jean R. Anderson,6 Valerie E. Stone,4 James M. Oleske,7 Judith S. Currier,8 and Joel E. Gallant6 1New York University School of Medicine, Bellevue Hospital Center, New York 2Centers for Disease Control and Prevention, Atlanta, Georgia 3Beth Israel Deaconess Medical Center and 4Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 5University of South Florida, Tampa 6Johns Hopkins University School of Medicine, Baltimore, Maryland 7University of Medicine and Dentistry of New Jersey, Newark and 8University of California, Los Angeles Evidence-based guidelines for the management of persons infected with human immunodeficiency virus (HIV) were prepared by an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America. These updated guidelines replace those published in 2004. The guidelines are intended for use by health care providers who care for HIV-infected patients or patients who may be at risk for acquiring HIV infection. Since 2004, new antiretroviral drugs and classes have become available, and the prognosis of persons with HIV infection continues to improve. However, with fewer complications and increased survival, HIV- infected persons are increasingly developing common health problems that also affect the general population. Some of these conditions may be related to HIV infection itself and its treatment. HIV-infected persons should be managed and monitored for all relevant age- and gender-specific health problems. New information based on publications from the period 2003���2008 has been incorporated into this document. SUMMARY OF CHANGES These updated guidelines replace those published in 2004 [1]. The following general changes have been made to the document since the previous publication: ��� Formatting changes have been incorporated to help readers easily identify the recommendations. Each Received 25 May 2009 accepted 26 May 2009 electronically published 29 July 2009. This guideline might be updated periodically. To be sure you have the most recent version, check the Web site of the journal (http://www.journals.uchicago .edu/page/cid/IDSAguidelines.html). Reprints or correspondence: Dr. Judith A. Aberg, AIDS Clinical Trials Unit, Bellevue Hospital Center, New York University School of Medicine, 550 First Ave., BCD 5 (Rm. 558), New York, NY 10016 (judith.aberg@nyumc.org). Clinical Infectious Diseases 2009 49:651���81 2009 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2009/4905-0001$15.00 DOI: 10.1086/605292 section begins with a specific question and is followed by numbered recommendations and a brief evidence- based summary. ��� Tables on immunizations and routine health care maintenance issues have been added. ��� Many other human immunodeficiency virus (HIV)��� related guidelines have been updated, as have our recommendations that are based on other revised guidelines. Specific changes and/or additions are as follows: ��� There is an expanded list of diagnostic HIV tests. ��� All HIV-infected patients should have a genotypic It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. The Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient���s individual circumstances.

652 ��� CID 2009:49 (1 September) ��� Aberg et al resistance test performed at baseline regardless of whether antiretroviral therapy will be initiated (A-III). ��� Patients who are seronegative for varicella zoster virus (VZV) or who do not give a history of chickenpox or shingles should receive postexposure prophylaxis with VZV immune globulin (VariZIG) as soon as possible (within 96 h) after exposure to a person with chickenpox or shingles (A-III). ��� Varicella primary vaccination may be considered for HIV- infected VZV-seronegative persons aged 18 years with CD4 cell counts 1200 cells/mm3 (C-III) and in HIV-infected chil- dren aged 1���8 years with CD4 cell percentages 15% (B-II). ��� Among patients with syphilis, cerebrospinal (CSF) exami- nation should be performed for persons with neurologic or ocular signs or symptoms, active tertiary syphilis, and syphilis treatment failure. CSF examination is also recommended for HIV-infected persons with late-latent syphilis, including those with syphilis of unknown duration (A-II). ��� HLA-B*5701 testing should be performed prior to initiating abacavir therapy to reduce the risk of a hypersensitivity re- action (A-I). Patients who are positive for the HLA B*5701 haplotype should not be treated with abacavir (A-II). ��� Baseline urinalysis and calculated creatinine clearance should be considered, especially in black patients, because of an in- creased risk of HIV-associated nephropathy (B-II). ��� Urinalysis and calculated creatinine clearance should also be performed prior to initiating treatment with drugs such as tenofovir or indinavir, which have the potential for neph- rotoxicity (B-II). ��� Tropism testing should be performed before initiation of treatment with a CCR5-antagonist antiretroviral drug (A-II). ��� For women aged 40���49 years, providers should periodically perform individualized assessment of risk for breast cancer and inform the patient of the potential benefits and risks of screening mammography (B-II). ��� The routine use of hormone replacement therapy has been associated with a slightly increased risk of breast cancer, car- diovascular disease, and thromboembolic disease and is not currently recommended (A-I). However, hormone replace- ment therapy may be considered in women who experience severe menopausal symptoms (eg, vasomotor symptoms or vaginal dryness) but should generally be used only for a limited period of time and at the lowest effective doses (B-II). ��� Emphasis should be placed on the importance of adherence to care rather than focusing solely on adherence to medi- cations (B-II). INTRODUCTION It has been 125 years since the first case of AIDS was identified. There have been dramatic changes in the management of HIV infection since the introduction of potent antiretroviral therapy in 1996. There has also been a significant decrease in morbidity and mortality among persons living with HIV infection, re- sulting from improved access to care, prophylaxis against op- portunistic infections, and antiretroviral therapy. A working group of clinical scientists was chosen by the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA) to develop guidelines addressing the primary care of HIV-infected persons. The purpose of these guidelines is to assist health care providers in their management of HIV- infected persons. Because of the improved survival among peo- ple living with HIV infection, it is imperative that, in addition to screening for conditions related to HIV infection and its management, all such persons should receive other recom- mended preventive health interventions as determined on the basis of their age and gender. These guidelines discuss the following topics: (1) transmis- sion of HIV infection (2) HIV diagnosis (3) risk screening (4) management, with special sections concerning women and children and (5) adherence to care. It is not our intent to du- plicate the extensive guidelines endorsed by the United States (US) Public Health Service, the Department of Health and Human Services, the Centers for Disease Control and Preven- tion (CDC), IDSA, or other accredited organizations. We have referred to these guidelines where applicable, so that this doc- ument may also serve as a ���guide to the guidelines��� (table 1). The following clinical questions are addressed: I. What is the optimal way to diagnose HIV infection? II. What risk-screening measures and interventions are ap- propriate for HIV-infected patients? III. What initial evaluation and laboratory testing should be performed for HIV-infected patients? IV. How is HIV disease staged? V. What is the schedule-of-care evaluation for HIV-infected patients? VI. What are the special considerations for women? VII. What are the special considerations for mother-to-child transmission and children? VIII. What are the long-term metabolic complications as- sociated with antiretroviral therapy? IX. How can patient adherence to HIV care be optimized? Modes of HIV Transmission The modes of transmission of HIV���sexual contact, exposure to infected blood through sharing of injection drug use para- phernalia or receipt of contaminated blood products, and per- inatal transmission���were clarified early in the AIDS epidemic. In the United States, their relative importance is reflected by the frequency of risk behaviors among reported persons with HIV/AIDS. These data, which include information on HIV- infected persons with and without AIDS, were available from

HIV Primary Care Guidelines ��� CID 2009:49 (1 September) ��� 653 33 US states for persons who received a diagnosis of HIV/AIDS in 2006. In 2006, male-to-male sexual contact was the most frequently reported risk factor for HIV exposure among adult and ado- lescent males, accounting for 67% of reported HIV/AIDS cases in men. The second most frequently reported risk factor among men was high-risk heterosexual contact, accounting for 16% of cases, followed by injection drug use (12% of cases). An additional 5% of cases were diagnosed among men who re- ported both male-to-male sexual contact and injection drug use [24]. Twenty-six percent of cases of HIV/AIDS reported among adults and adolescents in 2006 occurred in women. High-risk heterosexual contact accounted for 80% of cases in women, and injection drug use accounted for 19% of cases [24]. The epidemic continues to affect racial and ethnic minorities disproportionately. In the United States in 2006, 49% of HIV/ AIDS cases occurred in black persons, and 18% occurred in Hispanic persons. Among men, these percentages were 43% and 20%, respectively, and among women, they were 65% and 15%, respectively [24]. Studies have yielded estimates of the probability of HIV transmission by various routes in adults and adolescents. Per- act probabilities of transmission would be expected to vary considerably, depending on factors such as plasma HIV RNA level in the index case, presence of sexually transmitted diseases (STDs) (defined as chlamydia, gonorrhea, herpes simplex virus infection, human papillomavirus infection, and/or syphilis) in the index case or the partner, and the quantity of blood trans- ferred via needlestick. Nevertheless, the overall probability of becoming infected by transfusion with contaminated blood or blood products has been estimated to be 95 in 100, by perinatal transmission from mother to child in the absence of antiret- roviral therapy has been estimated to be 1 in 4, by needle sharing has been estimated to be 1 in 150, and by occupational needlestick exposure has been estimated to be 1 in 300. The risk of infection by male-to-male receptive anal intercourse has been estimated to be between 1 in 10 and 1 in 1600, by male- to-female vaginal intercourse has been estimated to be 1 in 200 to 1 in 2000, and by female-to-male vaginal intercourse has been estimated to be between 1 in 700 and 1 in 3000 [25]. The prevention of mother-to-child transmission of HIV has been highly successful over the past decade. The ACTG 076 study, published in 1994 [26], rapidly changed practice in well- resourced settings. In the decade after 1994, as the availability of antiretroviral drugs and access to effective treatment for pregnant women increased, the percentage of infants born to HIV-infected mothers who were perinatally infected with HIV decreased substantially in the United States and Europe, from 25% to !2%. In addition to specific perinatal prophylaxis, the availability of safe infant formula feeding to replace breast- feeding and of selective utilization of cesarean delivery has made perinatal transmission a rare event in developed countries [27, 28]. Given that the CDC estimates that 7000 HIV-positive women give birth every year in the United States, clinicians must remain vigilant in the diagnosis and treatment of HIV- infected pregnant women for this success to continue. PRACTICE GUIDELINES ���Practice guidelines are systematically developed statements to assist practitioners and patients in making decisions about appropriate health care for specific clinical circumstances. At- tributes of good guidelines include validity, reliability, repro- ducibility, clinical applicability, clinical flexibility, clarity, multi- disciplinary process, review of evidence, and documentation��� [29, p. 8]. METHODS Panel Composition A panel of experts composed of specialists in internal medicine, pediatrics, infectious diseases, obstetrics, and gynecology pre- pared these guidelines. Literature Review and Analysis For the 2009 update, the Expert Panel completed a review and analysis of literature on the management of persons with HIV published since 2000 and reviewed the older literature as well. Computerized literature searches of PubMed (for articles from January 2000 to December 2008) were performed. Data pub- lished after December 2008 were also considered in the final preparation of the manuscript. Only English language literature was reviewed. Process Overview In evaluating the evidence regarding the management of per- sons with HIV infection, the Panel followed a process used in the development of other IDSA guidelines. The process in- cluded a systematic weighting of the quality of the evidence and the grade of recommendation [30] (table 2). Consensus Development on the Basis of Evidence The Panel met on several occasions via teleconference and worked via e-mail communications to complete the work of these guidelines. The purpose of the teleconferences was to discuss the questions to be addressed, make writing assign- ments, and discuss recommendations. All members of the panel participated in the preparation and review of the draft guide- lines. Feedback from external peer reviewers was obtained. These guidelines were reviewed and cleared by the CDC and the IDSA Standards and Practice Guidelines Committee

Table 1. Guidelines from Various Sources Regarding Aspects of Care of Human Immunodeficiency Virus (HIV)��� Infected Persons Topic Title URL Issuing agency Reference Antiretroviral therapy for adults and adolescents Guidelines for the Use of Antiretroviral Agents in HIV-In- fected Adults and Adolescents http://aidsinfo.nih.gov/ guidelines US Department of Health and Human Services [2] Antiretroviral therapy for pediatric patients Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection http://aidsinfo.nih.gov/ guidelines NIH [3] Antiretroviral therapy for pregnant women Recommendations for the Use of Antiretro- viral Drugs in Preg- nant HIV-1 Infected women for Maternal Health and Interven- tions to Reduce Peri- natal HIV-1 Transmis- sion in the United States http://aidsinfo.nih.gov/ guidelines US Public Health Ser- vice Task Force [4] Chronic Kidney Disease Guidelines for the Management of Chronic Kidney Dis- ease in HIV-Infected Patients http://www.journals .uchicago.edu/doi/ abs/10.1086/430257 HIVMA of IDSA [5] Diabetes Clinical Practice Recommendations http://care .diabetesjournals.org/ content/vol31/ Supplement_1/index .shtml American Diabetes Association [6] Hepatitis Management of Chronic Hepatitis B http://www.easl.ch/ PDF/cpg/EASL_HBV _CPGs.pdf European Association For The Study Of The Liver [7] Hepatitis Care of HIV Patients with Chronic Hepati- tis B ��� HIV-Hepatitis B Virus International Panel [8] Hepatitis Care of HIV Patients with Chronic Hepati- tis C ��� Hepatitis C virus-HIV International Panel [9] Hepatitis Guidelines for the Clini- cal Management and Treatment of Chronic Hepatitis B and C Coinfection In HIV-In- fected Adults http://www.european aidsclinicalsociety.org/ guidelinespdf/3 _Treatment_chronic _hepatitis_coinfection .pdf European AIDS Clinical Society [10] HIV testing and counseling Revised Guidelines for HIV Testing http://www.cdc.gov/ mmwr/preview/ mmwrhtml/rr5514a1 .htm CDC [11] Hyperlipidemia in HIV Guidelines for the Eval- uation and Manage- ment of Dyslipide- mia in HIV���Infected Adults Receiving An- tiretroviral Therapy http://www.journals .uchicago.edu/doi/ abs/10.1086/378131 HIVMA/IDSA Adult AIDS Clinical Trials Group [12] Immunization Schedules Child and Adolescent Immunization Schedule http://www.cdc.gov/ vaccines/recs/ schedules/ CDC

HIV Primary Care Guidelines ��� CID 2009:49 (1 September) ��� 655 Table 1. (Continued.) Topic Title URL Issuing agency Reference Immunizations Practice Guidelines for Quality Standards for Immunization http://www.cdc.gov/ vaccines/pubs/ACIP -list.htm#comp Advisory Committee on Immunization Practices [13, 14] Mental health Mental Health Care for People with HIV In- fection: Clinical Guidelines for the Primary Care Practitioner http://www .hivguidelines.org/ Content.aspx ?PageIDp261 New York State De- partment of Health AIDS Institute [15] Metabolic complica- tions in HIV Management of Meta- bolic Complications Associated with An- tiretroviral Therapy for HIV-1 Infection http://www.iasusa.org/ pub/Schambelan %20et%20al -JAIDS-11.1.02.pdf International AIDS So- ciety USA Panel [16] Occupational exposures Guidelines for the Management of Oc- cupational Exposures to HBV, HCV, and HIV and Recommen- dations for Postex- posure Prophylaxis http://www.cdc.gov/ mmwr/preview/ mmwrhtml/rr5011a1 .htm US Public Health Service [17] Opportunistic infections Guidelines for Treating Opportunistic Infec- tions among HIV-In- fected Adults and Adolescents http://aidsinfo.nih.gov/ guidelines U.S. Public Health Ser- vice HIVMA/ IDSA CDC [18] Opportunistic infec- tions in children Guidelines for Preven- tion and Treatment of Opportunistic In- fections among HIV- Exposed and HIV-In- fected Children http://aidsinfo.nih.gov/ guidelines US Public Health Ser- vice HIVMA/IDSA, CDC, Pediatric Infec- tions Diseases Society [19] Pediatric HIV Red Book: 2009 Re- port of the Commit- tee of Infectious Diseases http://aapredbook .aappublications.org/ American Academy of Pediatrics [20] Resistance testing Antiretroviral Drug Re- sistance Testing in Adults Infected with Human Immunodefi- ciency Virus Type 1 http://www.iasusa.org/ pub/ International AIDS So- ciety USA Panel [21] Risk assessment Incorporating HIV Pre- vention into the Medical Care of Per- sons Living with HIV http://www.cdc.gov/ mmwr/preview/ mmwrhtml/rr5212a1 .htm CDC, Health Re- sources and Ser- vices Administration, NIH, HIVMA/IDSA [22] Sexually transmitted diseases Sexually Transmitted Diseases Treatment Guidelines 2006 http://www.cdc.gov/ std/treatment/2006/ rr5511.pdf CDC [23] NOTE. CDC, Centers for Disease Control and Prevention HBV, hepatitis B virus HCV, hepatitis C virus HIV-1, HIV type 1 HIVMA, HIV Medicine Association IDSA, Infectious Diseases Society of America NIH, National Institutes of Health. (SPGC) and the boards of the HIVMA and the IDSA prior to dissemination. Guidelines and Conflict of Interest All members of the Expert Panel complied with the IDSA policy on conflicts of interest, which requires disclosure of any finan- cial or other interest that might be construed as constituting an actual, potential, or apparent conflict. Members of the Expert Panel were provided with the IDSA���s conflict of interest disclosure statement and asked to identify ties to companies developing products that might be affected by promulgation of the guidelines. Information was requested regarding em-