1-1 Epidemiology of HIV Infection in the Developing World

Authors: Suniti Solomon, MD, Sunil Solomon, MBBS, PhD, MPH

Date Released: October 01, 2009

Abstract: Despite increased access to antiretroviral treatment and scaled-up efforts to prevent the spread of HIV infection in many nations, HIV remains an enormous health challenge throughout the world. The profound impact of HIV/AIDS continues to present a particular challenge in resource-limited areas of the developing world where approximately 90% of all individuals living with HIV reside. Sub-Saharan Africa continues to shoulder the largest HIV burden as home to 67% of the world’s HIV-infected population. Recent studies have shown that the global prevalence of HIV appears to have stabilized since 2000 and the annual number of deaths attributable to AIDS has decreased; however, several nations, including Indonesia and the Russian Federation, are currently experiencing an alarming increase in the number of new infections. With the exception of nations located in sub-Saharan Africa, HIV infection is often concentrated among high-risk populations including men who have sex with men, sex workers, and injection drug users. Issues surrounding stigma and discrimination present considerable obstacles to addressing the needs of these populations in many resource-limited settings. In this CME-certified chapter, Suniti Solomon, MD, and Sunil Solomon, MBBS, PhD, MPH, describe the current status of the HIV epidemic in the developing world, focusing on the relative contribution of particular modes of transmission in different regions and ongoing efforts and challenges associated with the scaled-up efforts of prevention and treatment programs.

1-2 Epidemiology of HIV Infection in the Developed World

Authors: Mauro Schechter, MD, PhD, Suely Tuboi, MD, PhD

Date Released: October 01, 2009

Abstract: In the more than 25 years since the first cases of what is now called AIDS were reported among homosexual men in San Francisco, the world has witnessed a dramatic change in the epidemiologic profile of HIV infection. A driving force of this change was the advent of HAART, the most important factor shifting the natural history of AIDS. HAART has profoundly altered the profile of comorbidities and causes of death among patients with HIV and AIDS, posing new challenges to the understanding and management of HIV infection. Although men who have sex with men have been the HIV risk group affected most significantly in most developed countries, HIV infection and AIDS are now increasingly affecting racial minorities overall, as well as racial subgroups of men who have sex with men. The causes of racial disparities are not well understood but are widely recognized to be based on a complex interplay of historical, cultural, and structural variables, highlighting the importance of understanding contextual factors as determinants of disease in addition to individual risk factors. In this chapter, Mauro Schechter, MD, PhD, and Suely Tuboi, MD, PhD, summarize the epidemiology of HIV-1 infection in resource-rich settings by: 1) providing historical and geographic perspectives of the HIV epidemic; 2) reviewing the latest available data on the HIV epidemic among men who have sex with men, injection drug users, and other specific risk categories and discussing the implications of these data on clinical management; and 3) assessing the impact of HAART on the epidemiology of HIV-1 infection and the subsequent effects on clinical practice.

1-3 HIV Testing and Diagnosis

Author: Peter Leone, MD

Date Released: October 01, 2009

Abstract: The number of new HIV infections in the United States each year has remained at a consistent level since 2000, indicating that more effective prevention strategies are needed to reduce the continued spread of HIV. It is estimated that more than one half of all transmission events in the United States are attributable to transmission from HIV-infected individuals who remain undiagnosed and, therefore, are unaware of their HIV status. Normalization of HIV screening in medical settings and expansion of HIV testing to reach populations who do not access healthcare is critical for increasing individual awareness of HIV status and curtailing transmission. In 2006, the Centers for Disease Control and Prevention recommended routine opt-out HIV screening for all individuals 13-64 years of age in all healthcare settings in the hopes of identifying those unaware of their infection and bringing them into counseling and care earlier to reduce the risk for transmission. In this chapter, Peter Leone, MD, discusses key implications of this strategy, barriers to implementation, and important considerations for the appropriate timing of different types of HIV detection methods. The critical role of acute HIV infection in the spread of HIV and intervention approaches for linking HIV-infected individuals to treatment once they have been diagnosed are also reviewed.

1-4 Overview of HIV Prevention

Author: Sharon L. Hillier, PhD

Date Released: October 01, 2009

Abstract: Recent statistics on the global HIV epidemic from the Joint United Nations Program on AIDS and reports from the US Centers for Disease Control and Prevention illustrate that HIV incidence continues to increase. These updated estimates are stark reminders of the urgent need for new and more effective HIV prevention tools. Despite intense efforts by investigators, communities, and funders, HIV prevention research has yielded only a few successes, with a number of strategies showing disappointing results. HIV prevention trials have been conducted assessing a range of different approaches to decrease the risk of HIV infection, including behavioral interventions in men who have sex with men, vaccination, treatment of sexually transmitted infections, circumcision, cervical diaphragms, and several microbicides. In this CME-certified chapter, Sharon L. Hillier, PhD, reviews the recent research on various HIV prevention strategies and emphasizes emerging data that suggests that several prevention strategies will likely be needed for optimal efficacy, especially in high-risk communities.

1-5 Management of Occupational and Nonoccupational HIV Exposure

Authors: Raphael Landovitz, MD, Paymon Ebrahimzadeh, MPH

Date Released: October 01, 2009

Abstract: The enormous success of HAART in reducing morbidity and mortality from HIV disease contrasts sharply with the failures in HIV prevention. Each year, 2.5 million new cases of HIV infection occur worldwide, and 50,000 of such cases occur in the United States alone. Behavioral intervention programs have had limited success in reducing HIV incidence, and interest in the use of biomedical prevention technologies as adjuncts to behavioral risk-reduction programs is increasing. Biomedical prevention refers to the use of HIV antiretroviral agents as prevention tools, that is, administering to HIV-negative patients agents that are currently used to treat patients with chronic HIV infection—either before or after an exposure to HIV—in an attempt to prevent infection. Administration of antiretroviral agents after an exposure has already occurred has been termed postexposure prophylaxis, and administration of antiretrovirals before an exposure occurs has been termed pre-exposure prophylaxis. In this chapter, Raphael Landovitz, MD, and Paymon Ebrahimzadeh, MPH, discuss the current and future role of occupational and nonoccupational postexposure and pre-exposure prophylaxis, and review recommendations for their use.

1-6 The Role of HIV Providers in Secondary HIV Prevention

Author: W. David Hardy, MD

Date Released: October 01, 2009

Abstract: In 2003, the Centers for Disease Control and Prevention (CDC) launched a new initiative designed to reinvigorate responses to a burgeoning domestic HIV/AIDS epidemic. The new strategy, “Advancing HIV Prevention,” was designed to address a changing environment, in which reductions in HIV-related morbidity and mortality because of HAART had resulted in an increasing population of people living with HIV infection. In addition, evidence of rising rates of new HIV infections, together with outbreaks of syphilis, was emerging, particularly among high-risk communities, such as men who have sex with men. The new strategy emphasized 4 major objectives: 1) to routinize HIV testing, 2) to encourage HIV testing outside medical settings, 3) to further reduce perinatal HIV infections, and 4) to prevent new infections by providing counseling to people diagnosed with HIV and their partners. This last objective—to target people with HIV specifically—signaled a major shift in HIV prevention strategy, requiring greater involvement of HIV care providers. In recognition of this shift in emphasis, a joint publication from the CDC, the National Institutes for Health, and the HIV Medicine Association of the Infectious Diseases Society of America issued new recommendations on secondary HIV prevention. This document provides an evidence-based framework for structured intervention by HIV care providers, highlighting the health benefits that HIV-positive persons may derive from behavior change while acknowledging what should be self-evident—that every new infection is transmitted by a person with HIV, making HIV-infected individuals a vitally important target of HIV prevention activities. This chapter reviews recommendations regarding secondary HIV prevention contained in the 2003 CDC guidelines, along with other new models for approaching HIV prevention in HIV medical care settings.

2-1 Clinical Implications of HIV Pathogenesis

Author: David M. Margolis, MD

Date Released: October 01, 2009

Abstract: HIV infection results in a wide range of clinical consequences, from an asymptomatic state to fatal opportunistic disease. In persons infected with this virus, ongoing viral replication produces a sequential decline in and ablation of cell-mediated immunity, giving rise to diverse manifestations of opportunistic disease. AIDS is the most advanced stage of this illness, in which the infected host can no longer control opportunistic organisms or malignancies that rarely cause illness in immunocompetent individuals. The clinical features of HIV infection may vary according to the individual’s age, sex, race, geographic location, treatment status, and behavioral history. In this chapter, David M. Margolis, MD, reviews the current understanding of the nature of HIV pathogenesis both in acute infection and during treatment with HAART.

2-2 Primary Care of the Newly Diagnosed HIV-Infected Patient in Developed Countries

Author: Joel E. Gallant, MD, MPH

Date Released: October 01, 2009

Date Updated: November 10, 2009

Abstract: Medical care of HIV-infected patients should be managed under the direction of an expert HIV physician. Treatment of HIV infection is complex, and expert care has been associated with reductions in morbidity, mortality, and the cost of care. However, the management model popular in the early years of the AIDS epidemic, in which HIV experts provided comprehensive care to HIV-infected patients, may no longer be a viable option in many settings. Nonetheless, as the care of more HIV-infected patients is “mainstreamed” into general medical practices, oversight or comanagement by HIV experts remains critical. In this chapter, Joel E. Gallant, MD, MPH, provides a comprehensive outline of primary care of the HIV-infected patient.

2-3 Primary Care for HIV-Infected Patients in Resource-Limited Settings

Authors: Charles van der Horst, MD, Arthur Jackson, MB BCh, MRCPI

Date Released: October 01, 2009

Date Updated: December 18, 2009

Abstract: The treatment of HIV infection in developing regions of the world is hampered by many factors including a shortage of skilled and experienced personnel, lack of sustainable funding, weak services in rural areas, poor health infrastructure for managing chronic illness, and lack of basic services for those living with HIV/AIDS. In addition, the majority of people living with HIV in the developing world are unaware of their status and thus do not seek care until features of advanced disease have emerged. Serious comorbidities that are not directly related to HIV are also prevalent, further complicating disease management. Primary care in resource-limited settings is often the only HIV care available to an HIV-infected patient. Therefore, it is critical that primary care in these regions encompass a full range of HIV-related services including prevention education and counseling, diagnosis and testing, management of antiretroviral therapy, and subspecialty expertise to address the needs of special populations. In this chapter, Charles van der Horst, MD, and Arthur Jackson, MB BCh, MRCPI, provide a detailed analysis of key issues associated with the primary care of patients infected with HIV in developing nations including prevention, diagnosis, treatment, palliative care, and effective service provision. Guideline recommendations on the optimal timing of treatment initiation, preferred first-line regimens, on-treatment monitoring, and switch strategies for patients in developing regions of the world are also discussed.

3-1 Overview of Antiretroviral Agents

Authors: Philip Grant, MD, Andrew R. Zolopa, MD

Date Released: October 01, 2009

Date Updated: December 17, 2009

Abstract: Potent combination antiretroviral therapy has dramatically changed the prognosis for patients with HIV infection, allowing the infection to be effectively managed with medication. Understanding of HIV viral life cycle has allowed the development of drugs that interrupt different steps of the cycle. Combinations of these agents have allowed for suppression of viral replication and interruption of disease progression. Philip Grant, MD, and Andrew R. Zolopa, MD, review the currently available antiretroviral agents, the use of antiretroviral agents in combination therapy, and medications currently being investigated in phase III trials. They discuss current strategies for therapy for both antiretroviral-naive and treatment-experienced patients.

3-2 Timing of Initiation of First-line Antiretroviral Therapy

Authors: Timothy Wilkin, MD, MPH, Marshall J. Glesby, MD, PhD

Date Released: October 01, 2009

Date Updated: December 16, 2009

Abstract: Optimal initiation of antiretroviral therapy for treatment of HIV infection in treatment-naive patients cannot yet be based upon exact knowledge or experience. Development of effective antiretroviral therapy combinations in the mid-1990s led to recommendations for treatment initiation in nearly all HIV-infected individuals. Confidence in these recommendations, however, was tempered by the realization that eradication of HIV was not possible with antiretroviral therapy, by occurrence and frequency of drug-related toxicity, and by the difficulty patients were experiencing in sustaining adherence to complex antiretroviral therapy regimens. Early regimens lacked sufficient potency, and drug resistance developed commonly. Over the last several years, initial antiretroviral therapy regimens have become much simpler, more effective, and less toxic. There has also developed a growing appreciation of the “toxicity” of uncontrolled HIV infection itself and its relationship to important non–AIDS-defining conditions such as coronary artery disease, liver and kidney disease, and non–AIDS-defining malignancy. These observations and key epidemiologic studies prompted treatment guidelines to indicate that antiretroviral therapy be initiated for all patients with a CD4+ cell count < 350 cells/mm³; indeed, the December 2009 version of the Department of Health and Human Services treatment guidelines recommend treatment for patients with CD4+ cell counts between 350-500 cells/mm³.One half of the guideline panel also recommended therapy for patients with CD4+ cell counts > 500 cells/mm³ whereas the other panelists viewed treatment in this setting as optional. In this chapter, Marshall J. Glesby, MD, PhD, and Timothy J. Wilkin, MD, MPH, address the question of the optimal time of initiation of antiretroviral therapy by reviewing cohort and randomized clinical trial data.

3-3 Key Principles and Recommended Regimens for First-Line Antiretroviral Therapy

Author: Paul E. Sax, MD

Date Released: October 01, 2009

Date Updated: December 16, 2009

Abstract: There are currently more than 20 antiretroviral agents approved by the FDA for the treatment of HIV and 5 coformulated combination products. Among the numerous options available today, how can clinicians select the optimal treatment for an individual patient? Paul E. Sax, MD, covers the basic principles behind regimen selection. He then explores some commonly encountered patient scenarios that make particular treatments favored in certain settings.

3-4 Optimizing Adherence to Antiretroviral Therapy

Author: Nancy Reynolds, PhD, RN, C-NP, FAAN

Date Released: October 01, 2009

Abstract: Potent combinations of antiretroviral medications have dramatically improved HIV treatment outcomes. Yet the full benefits of these combinations cannot be realized without consistent adherence to dosing schedule to maintain drug exposure at levels necessary to achieve durable virologic suppression and immune reconstitution. It is critically important that strategic actions to support and sustain patient adherence to antiretroviral therapy be implemented as a standard component of HIV clinical care. In this chapter, Nancy R. Reynolds, PhD, RN, C-NP, FAAN, offers an overview of the current understanding of factors that influence adherence behavior and strategies that can be employed in clinical settings to optimize adherence to antiretroviral medications to improve long-term success.

3-5 Laboratory Assays in the Clinical Management of Antiretroviral Therapy

Author: Mark Holodniy, MD

Date Released: October 01, 2009

Date Updated: December 16, 2009

Abstract: The development of tests to monitor HIV-1 infection parallels discoveries of the structure and function of the virus. Physicians face the challenge of keeping abreast of scientific advances so that they can apply new knowledge in the care of their patients. In this chapter, Mark Holodniy, MD, surveys the evolution of HIV-1 laboratory tests, the significance of surrogate markers in assessing HIV-1 infection, and guidelines and recommendations for the most appropriate use of individual tests.

3-6 Management of Treatment-Experienced HIV-Infected Patients

Author: Eric S. Daar, MD

Date Released: October 01, 2009

Date Updated: March 16, 2010

Abstract: Major advances have been made in the management of antiretroviral-experienced patients. In this chapter, Eric S. Daar, MD, summarizes the types of treatment-experienced patients currently being followed in the clinic and some of the unique scenarios that clinicians are confronting on a daily basis. Key principles for treating these patients will be outlined and strategies summarized for managing those who have minimal, moderate, or extensive drug-resistant virus.

3-7 Modifying Antiretroviral Therapy in Virologically Suppressed HIV-Infected Patients

Author: José R. Arribas, MD

Date Released: October 01, 2009

Date Updated: March 19, 2010

Abstract: José R. Arribas, MD, reviews available evidence supporting clinical decisions regarding modification of antiretroviral regimens in virologically suppressed patients for reasons such as drug intolerance or the need to simplify the regimen. Focus is given to antiretroviral drugs currently considered the preferred options by international treatment guidelines and to strategies for which there are data from randomized clinical trials.

3-8 Metabolic Complications of HIV and Antiretroviral Therapy: Dyslipidemia, Insulin Resistance, and Cardiovascular Disease

Authors: Judith S. Currier, MD, MSc, Risa Hoffman, MD

Date Released: October 01, 2009

Abstract: The unequivocal success of antiretroviral therapy in controlling HIV replication and restoring immune function has been tempered by the recognition of important metabolic complications resulting from the interplay between traditional risk factors for cardiovascular disease, HIV infection, and antiretroviral medications. Increased rates of dyslipidemia, abnormal glucose metabolism, and cardiovascular disease have been demonstrated in a multitude of studies involving HIV-infected persons, in a variety of settings. In this chapter, Judith S. Currier, MD, MSc, and Risa Hoffman, MD, focus on these 3 important complications, discussing risk factors, mechanisms, diagnosis, treatment, and prevention. Where appropriate, special considerations for resource-limited settings are addressed.

3-9 Management of Lipoatrophy, Lipohypertrophy, Mitochondrial Disorders, and Bone Disease

Author: Donald P. Kotler, MD

Date Released: October 01, 2009

Abstract: HAART has been associated with markedly diminished morbidity and mortality, a development that has led to increased appreciation of other possible disease sequelae, including changes in body composition as well as bone-disease complications. To the extent that these complications are related to antiretroviral agents, their development diminishes the benefits associated with antiviral therapy. Numerous epidemiologic studies have established multiple associations, with overlapping features. In addition to antiretroviral agents (both specific agents and classes of agents as well as duration of therapy), host factors such as age, sex, race, family history, body mass index, diet, exercise, tobacco use, and disease factors such as duration, severity of immune depletion, and the magnitude of immune reconstitution are also important epidemiologic factors. Other confounding factors common to these toxicities include difficulty in obtaining measurements (eg, studies of fat distribution or bone density), as well as difficulties in distinguishing HIV effects from those of normal aging. In this chapter, Donald P. Kotler, MD, discusses the changes in body composition, both fat loss (lipoatrophy) and fat gain (lipohypertrophy), as well as bone disease, and includes epidemiology, pathogenesis, and management strategies.

3-10 Key Pharmacologic Principles and Drug-Drug Interactions in HIV Patient Care

Authors: Amanda H. Corbett, PharmD, BCPS, AAHIVE, Julie B. Dumond, PharmD, BCPS, AAHIVE

Date Released: October 01, 2009

Abstract: There are more than 25 antiretroviral medications, in 6 distinct classes, currently approved for the treatment of HIV-1 infection by the US Food and Drug Administration. Each of these classes has unique properties and varying potential for drug-drug interactions. Since many HIV-infected patients take multiple medications in addition to their antiretrovirals, Amanda H. Corbett, PharmD, BCPS, and Julie B. Dumond, PharmD, BCPS, AAHIVE, provide a comprehensive overview of common interactions between antiretrovirals and other medications that are potentially critical to the management of HIV-infected patients.

4-1 Management of HIV-Exposed and HIV-Infected Children

Author: James B. McAuley, MD, MPH

Date Released: October 01, 2009

Date Updated: March 17, 2010

Abstract: An estimated 2.1 million children younger than 15 years of age are living with HIV infection worldwide, the vast majority of whom acquired the infection from their mother. In resource-rich countries, mother-to-child transmission has become increasingly rare, whereas in resource-poor countries, it continues at an alarming rate. Therefore, there are currently 2 very different epidemics of HIV infection in children. One epidemic is specific to resource-rich countries and mainly involves older children who have experienced antiretroviral therapy for many years, often as sequential monotherapy, and who consequently now have highly resistant virus. The second epidemic applies to resource-poor countries and is characterized by large numbers of young children with HIV infection who require treatment. In addition to these 2 unique epidemics of HIV infection, a third group—uninfected children exposed to HIV and antiretroviral therapy while in utero—also requires the attention of clinicians. Although the pathogenesis of HIV infection and the general virologic and immunologic principles underlying the use of antiretroviral therapy are similar for HIV-infected persons of all ages, there are unique considerations that apply to HIV-infected infants and children. Therefore, this chapter addresses each of the following issues: 1) differences in the clinical and virologic manifestations of perinatal HIV infection secondary to the occurrence of the primary infection in growing, immunologically immature persons; 2) in utero, intrapartum, and/or postpartum neonatal exposure to zidovudine and other antiretroviral medications; 3) the requirement for the use of HIV virologic tests instead of antibody tests to diagnose perinatal HIV infection in infants younger than 18 months of age; 4) age-specific differences in CD4+ cell counts; 5) age-specific changes in pharmacokinetic parameters caused by the continuing development and maturation of organ systems involved in drug metabolism and clearance; and 6) issues associated with antiretroviral treatment adherence in infants and young children. In addition, a discussion of the management of HIV-exposed infants will be included; this population represents the largest number of patients seen by HIV care providers in the United States each year, as the majority of children born to HIV-infected mothers will not be infected.

4-2 Special Considerations in the Management of HIV-Infected Women, Including Management of Conception and Pregnancy

Author: Kristine Patterson, MD

Date Released: October 01, 2009

Date Updated: March 16, 2010

Abstract: Just more than 50% of HIV-infected adults worldwide are women. The predominant mode of HIV transmission among women continues to be through heterosexual intercourse. With the widespread use of potent antiretroviral therapy, women are now living longer with HIV. As a result, many HIV-infected women will undergo normal life events, including pregnancy and menopause. Although women of childbearing potential continue to encompass the majority of women living with HIV, the number of older HIV-infected women increases each year. In this review, Kristine Patterson, MD, focuses on specific topics to consider in the clinical care of HIV-infected women in different life stages. In addition, a global overview of treatment-related issues and complications specific to HIV-infected women are provided.

4-3 Special Considerations in the Management of HIV-Infected Patients From Minority Communities

Authors: Bisola Ojikutu, MD, MPH, Valerie E. Stone, MD, MPH

Date Released: October 01, 2009

Abstract: Despite advances in HIV treatment and increased awareness of effective preventive interventions, minority populations in the United States, particularly blacks and Latinos, continue to suffer disproportionately higher rates of HIV infection than their white counterparts. Once infected with HIV, both blacks and Latinos are significantly more likely to die than patients of other races living with HIV/AIDS in the United States. A complex interplay of cultural, social, behavioral, and economic factors appear to determine much of the difference in incidence and outcome observed. In addition, studies have begun to explore the possibility of genetic determinants of disease manifestation, progression, and drug metabolism. Much work remains to be done to both elucidate root causes and develop effective interventions to overcome the modifiable variables that drive these disparities. It is imperative that providers caring for minority patients with HIV/AIDS remain current with new research findings and be aware of the factors that may impact the treatment of their patients. In this chapter, Bisola Ojikutu, MD, MPH, and Valerie E. Stone, MD, MPH, provide a brief overview of these disparities and comprehensively review the unique care and treatment challenges affecting minorities, particularly blacks and Latinos, living with HIV/AIDS. Strategies to overcome these challenges and areas of ongoing research are highlighted.

4-4 Special Considerations and Clinical Management of HIV-Infected Drug Users

Author: Frederick Altice, MD

Date Released: October 01, 2009

Abstract: Illicit drug use and HIV/AIDS adversely impact tens of millions of people, with explosive epidemics of both described worldwide. Injection drug use (IDU), largely of opiates, has been reported in 148 countries, and 120 of these countries have reported HIV among IDUs. The link between drug use, particularly IDU, and HIV has been described since the beginning of the HIV pandemic. The world’s most volatile and emerging epidemics are in areas that are fueled by illicit drug use. In light of the increasingly central role of injection drug use in the global HIV/AIDS epidemic, issues of HIV clinical care and therapeutics in this population are of great importance. In addition, noninjection drug use may also contribute to adverse outcomes in HIV-infected patients through increased HIV risk behaviors, suboptimal adherence to HIV treatment, and more frequent or severe adverse events during antiretroviral therapy. In this chapter, Frederick Altice, MD, reviews the special clinical features of HIV disease in drug-dependent patients, the treatment of HIV disease itself in this population, the special difficulties in providing care to drug users, and the treatment of drug dependence.

4-5 Special Considerations in the Management of HIV-Infected Adolescents

Authors: Krystn Wagner, MD, PhD, Jack Rusley

Date Released: October 01, 2009

Abstract: HIV infection among adolescents and young adults represents a considerable health challenge across the globe, including in the United States. In 2006, individuals aged 13-29 years accounted for 34% of new HIV infections reported in the United States. Adolescents and young adults infected with HIV are a heterogeneous group who often present with complex issues relating to the radical psychosocial changes and challenges that accompany these developmental stages. In addition to coping with changes in schooling, social and family relationships, and sexual development, adolescents approaching adulthood also face the sometimes daunting prospect of healthcare transition. The advent of HAART and resulting transformation of HIV/AIDS into a chronic illness has vastly improved rates of survival into adulthood among HIV-infected youth and created a need to establish effective systems for transitioning young patients from child-centered to adult-oriented healthcare systems. This process is critical because it reflects the realities of the medical and psychosocial lives of youth, facilitates healthy development, and provides opportunities for more effective treatment options. However, because healthcare transition is a relatively recent phenomenon in pediatric HIV/AIDS and is generally fraught with complexity, it is not always accepted or practiced by families or providers. In this chapter, Krystn Wagner, MD, PhD, and Jack Rusley review key challenges associated with the management of HIV infection among adolescents and young adults with a particular focus on the status and challenges of healthcare transition.

4-6 Special Considerations Related to Aging in HIV-Infected Patients

Author: Matthew B. Goetz, MD

Date Released: October 01, 2009

Date Updated: March 18, 2010

Abstract: The number of older (ie, aged 50 years or older) HIV-infected patients has greatly increased since the advent of effective combination antiretroviral therapy. Not only are many patients who were infected in youth now living into their 50s, 60s, and longer, but the average age at the time of infection has increased. A report from the Centers for Disease Control and Prevention demonstrated that from 2000-2004, the number of patients aged 50 years or older living with AIDS rose from 19% to 27%. As a result of these trends, it is expected that more than 50% of HIV-infected persons in the United States are likely to be older than 50 years of age by the Year 2015. In this review, Matthew B. Goetz, MD, discusses the natural history of untreated HIV infection in older vs younger patients; the relationship among HIV infection, antiretroviral therapy, aging, and medical comorbidities; and antiretroviral efficacy in older patients.

5-1 The Approach to the HIV-Infected Patient With Specific Symptom Complexes/Common Presentations

Author: Steven C. Johnson, MD

Date Released: October 01, 2009

Abstract: The clinical manifestations of HIV infection and its complicating diseases can lead to signs and symptoms involving every organ system. Before the development of potent antiretroviral therapy and opportunistic infection prophylaxis, most signs and symptoms in HIV-infected persons were attributable either to the direct effects of the virus itself or to the occurrence of opportunistic infections and malignancies. During the last 15 years, in areas of the world where antiretroviral therapy is fully accessible, the incidence of opportunistic diseases has declined dramatically as antiretroviral therapy has either prevented the development of immunodeficiency in the first place or allowed immune reconstitution in those who have progressed to AIDS. In the current era, disease manifestations in HIV-positive persons may frequently be due to comorbid diseases or diseases common to the general population. An understanding of the types of illnesses that can occur in persons living with HIV infection is important to generate an accurate differential diagnosis and to choose the appropriate diagnostic testing in the symptomatic patient. In this chapter, Steven C. Johnson, MD, focuses on the etiologic considerations and diagnostic approach to common symptom complexes and presentations occurring in persons living with HIV infection.

5-2 Sexually Transmitted Diseases in HIV-Infected Patients

Author: Jeanne Marrazzo, MD, MPH

Date Released: October 01, 2009

Abstract: Sexually transmitted diseases (STDs) occur frequently in HIV-infected persons. Although these pathogens cause well-recognized clinical syndromes, most are asymptomatic. Thus, screening for asymptomatic infections is essential to interrupt the chain of transmission and adverse sequelae. Key current trends of STDs in HIV care settings include the following: a syphilis epidemic among men who have sex with men that shows no sign of abating; progressive increases in antibiotic-resistant gonorrhea; and the role of inflammatory STDs in increasing the amount and frequency of genital HIV shedding, which can be reversed with successful treatment. In this chapter, Jeanne Marrazzo, MD, MPH, highlights several recommendations relevant to the care of HIV-infected patients with comorbid sexually transmitted diseases.

5-3 Tuberculosis and Other Mycobacterial Infections in HIV-Infected Patients

Authors: Celine Gounder, MD, ScM, Richard E. Chaisson, MD

Date Released: October 01, 2009

Abstract: Tuberculosis (TB) represents one of the 3 largest infectious causes of morbidity and mortality worldwide, along with HIV/AIDS and malaria. An estimated 15% of incident TB cases and and 25% of TB deaths cases exhibit HIV coinfection. Among persons with HIV infection, TB is the most common opportunistic infections and is the most common cause of death globally. Because of the intertwined nature of the TB and HIV epidemics, the World Health Organization recommends a strategy of integrated service delivery, including HIV interventions among TB patients and TB interventions among HIV patients. Mycobacterium avium complex (MAC) is the most common of the nontuberculous mycobacteria to cause disease in humans. It rarely causes disease in individuals with CD4+ cell counts > 100 cells/mm³ but is common in individuals with AIDS, particularly those with CD4+ cell counts < 50 cells/mm³. Both TB and MAC are complicated by the immune reconstitution inflammatory syndrome in patients with HIV receiving potent antiretroviral therapy. In this chapter, Celine Gounder, MD, ScM, and Richard E. Chaisson, MD, focus on the global burden of TB and MAC in HIV, strategies for identification and management, and the current challenges, including multidrug-resistant TB.

5-4 Viral Infections in HIV-Infected Patients

Authors: Bruce Polsky, MD, Jin S. Suh, MD, FACP

Date Released: October 01, 2009

Abstract: The incidence of nearly all AIDS-defining opportunistic infections, including viral infections, has decreased significantly since the introduction of HAART. With the recovery of immune function associated with effective antiretroviral therapy, chronic and refractory infections have become more amenable to treatment, and, for many infections, primary and/or secondary prophylaxis are no longer necessary. But, despite advances in investigators’ understanding of their pathogenesis and the development of more sensitive diagnostic laboratory techniques, viral infections remain an important cause of morbidity and mortality in HIV-infected patients. Such infections occur most notably in individuals who are unaware that they are HIV infected, who cannot tolerate HAART or adhere to it poorly, or who have poor access to adequate healthcare. In this chapter, Jin S. Suh, MD, FACP, and Bruce Polsky, MD, examine the main clinical viral syndromes in HIV disease.

5-5 Bacterial Infections in HIV-Infected Patients

Author: John G. Bartlett, MD

Date Released: October 01, 2009

Abstract: Despite major advances in HIV therapy that have vastly improved prognosis for individuals infected with HIV over the last 15 years, opportunistic infections still remain a challenging complication, particularly among highly immunosuppressed individuals who present at later disease stages. Opportunistic infections associated with HIV/AIDS represent a broad category of diseases that encompass bacterial, viral, fungal, parasitic, and mycobacterial infections. Recommended prophylaxis and treatment regimens vary substantially between these conditions. For example, nearly all opportunistic bacterial infections are susceptible to antibiotic therapy; however, the necessary antimicrobial agents are often pathogen specific. This chapter specifically reviews the etiology, clinical presentation, diagnosis, and clinical management of bacterial infections that are most frequently acquired by and have the greatest impact on patients with HIV infection. It should be emphasized that many of these infections also commonly occur in healthy hosts, but have increased frequency or unusual clinical features in patients with advanced HIV infection.

5-6 Fungal Infections in HIV-Infected Patients

Author: William G. Powderly, MD

Date Released: October 01, 2009

Abstract: Like other opportunistic infections, HIV-associated fungal infections have decreased significantly in incidence with the advent of effective antiretroviral therapy. However, certain fungal infections such as oropharyngeal candidiasis remain sentinel signs of HIV infection, and the appearance of oropharyngeal candidiasis in a person at risk of HIV infection should prompt HIV testing. In an HIV-infected person, the development of a fungal infection suggests disease progression and immune dysfunction and should prompt consideration of new or altered antiretroviral therapy.

5-7 Parasitic Infections in HIV-Infected Patients

Authors: José M. Miró, MD, PhD, Miriam J. Álvarez-Martinez, MD, PhD

Date Released: October 01, 2009

Abstract: The introduction of HAART has dramatically reduced morbidity and mortality resulting from opportunistic infections (OIs) in well-resourced settings. In under-resourced settings where antiretroviral therapy is not widely available, OIs remain common and continue to occur even in developed countries, largely because of late presentation of patients who are unaware of their HIV status. HIV infection may go untreated for either psychosocial or economic reasons and in patients who are taking antiretroviral therapy, treatment may fail for multiple reasons, including nonadherence, drug resistance, toxicity, pharmacokinetics, or unexplained factors. In this chapter José M. Miró, MD, PhD, and Míriam J. Álvarez-Martínez, MD, PhD, review major parasitic OIs affecting HIV-infected persons, including infections seen in tropical settings and in travelers to these regions. For each infection reviewed, epidemiology, clinical manifestations, diagnosis, prevention of exposure to the pathogen, primary prophylaxis, treatment, secondary prophylaxis (or maintenance therapy), and withdrawal criteria for prophylaxis are discussed.

5-8 AIDS-Defining Cancers

Authors: Liron Pantanowitz, MD, Bruce J. Dezube, MD

Date Released: October 01, 2009

Abstract: HIV-infected individuals are at an increased risk of developing several cancers, 3 of which are classified as AIDS-defining malignancies: Kaposi’s sarcoma; high-grade B-cell non-Hodgkin’s lymphoma, including primary central nervous system lymphoma; and invasive cervical cancer. The management of HIV-infected patients with these cancers is frequently complicated by treatment-induced immunosuppression, comorbid disease, drug interactions, and social issues. Moreover, there is often limited expertise in the area of AIDS oncology. Multidisciplinary cooperation between oncologists and HIV physicians is often needed to ensure that patients with AIDS-defining malignancies are suitably managed. Early referral of HIV-infected patients with malignancy to centers with expertise in the management of these diseases appears to be associated with more favorable outcomes. In this chapter, Liron Pantanowitz, MD, and Bruce J. Dezube, MD, review the current management of these 3 AIDS-defining cancers.

5-9 Non–AIDS-Defining Cancers

Authors: Liron Pantanowitz, MD, Bruce J. Dezube, MD

Date Released: October 01, 2009

Abstract: The term “non–AIDS-defining cancers” refers to neoplasms other than AIDS-defining malignancies (ie, Kaposi’s sarcoma, high-grade B-cell non-Hodgkin’s lymphoma, and cancer of the cervix) that occur in individuals with HIV infection. Recently, both the spectrum and incidence of various neoplasms being reported among persons infected with HIV have increased. This emerging and crucial problem has contributed to the mortality of HIV-positive persons in the pre-HAART era. Even in resource-poor settings where antiretroviral therapy is limited in its availability, non–AIDS-defining cancers have increased along with AIDS-defining cancers in the growing HIV-infected population. In this chapter, Bruce J. Dezube, MD, and Liron Pantanowitz, MD, focus on several of the non–AIDS-defining cancers likely to be encountered in clinical practice.

5-10 Hematologic Disorders in HIV-Infected Patients

Author: Richard D. Moore, MD, MHS

Date Released: October 01, 2009

Abstract: Hematologic abnormalities were identified early in the HIV epidemic. The most commonly observed hematologic complications associated with HIV infection are cytopenias, including anemia, neutropenia, and thrombocytopenia. The prevalence of each of these cytopenias tends to increase as HIV infection progresses from asymptomatic infection to advanced disease and AIDS. HIV infection of lymphocytes, monocytes, and macrophages is thought to induce abnormalities in cytokine production that, in turn, affects hematopoiesis. In addition, myelosuppression from drugs, infections, and malignancies contributes to the development of cytopenias in patients with HIV. Cytopenias play a considerable role in the morbidity associated with HIV and AIDS because they hinder therapy directed at HIV and the opportunistic infections and neoplasms of AIDS, and they may increase the risk of bacterial infection. In this chapter, Richard D. Moore, MD, MHS, reviews the epidemiology and etiology of hematologic disorders commonly associated with HIV infection and describes the latest data and guideline recommendations on the optimal diagnostic and treatment strategies for managing HIV-infected patients presenting with hematologic complications.

5-11 Hepatic Disease in HIV-Infected Patients

Author: Mark S. Sulkowski, MD

Date Released: October 01, 2009

Abstract: Liver disease ranks as the second most common cause of morbidity and mortality in HIV-infected persons receiving antiretroviral therapy. Liver disease-related deaths in this population most commonly result from chronic infection with hepatitis B and/or hepatitis C virus and management of these conditions in HIV-infected persons requires careful consideration, balancing the potential benefits of therapy with the potential for significant treatment-related adverse effects, viral resistance, and/or hepatitis flares. Other etiologies of liver injury include nonalcoholic fatty liver disease, alcoholic liver disease, and drug-induced liver injury. In this chapter, Mark S. Sulkowski, MD, discusses screening, medical evaluation (serologic testing, liver imaging, histologic evaluation), and differential diagnosis and treatment of HIV-infected patients with chronic liver injury.

5-12 Endocrine Disorders in HIV-Infected Patients

Author: Todd T. Brown, MD, PhD

Date Released: October 01, 2009

Abstract: Since early in the AIDS epidemic, endocrine abnormalities have been commonly observed among HIV-infected patients. In the mid-1980s, adrenal insufficiency and hypogonadism were described in patients with advanced AIDS. With the introduction of potent combination antiretroviral therapy, endocrine abnormalities that were associated with advanced illness, such as hypogonadism, initially decreased in frequency. However, with the aging of the HIV population, many age-related endocrine problems are again becoming important. In this chapter, Todd T. Brown, MD, PhD, describes the diagnosis and management of 4 commonly encountered endocrine abnormalities: adrenal insufficiency, hypogonadism, thyroid dysfunction, and diabetes mellitus. Special attention is given to differences in the presentation and management of endocrine abnormalities in the HIV-infected population that arise from chronic HIV infection, antiretroviral therapy, or HIV-related comorbidities.

5-13 Neurologic Diseases in HIV-Infected Patients

Authors: Jessica Robinson-Papp, MD, David M. Simpson, MD

Date Released: October 01, 2009

Abstract: During the past decade, HAART has led to dramatic improvements in the health of people living with HIV/AIDS. Despite this progress, neurologic complications of HIV are still common. To diagnose these complications, the clinician must be alert to potential neurologic symptoms, such as memory loss, headache, dizziness, weakness, numbness, pain, visual changes, or gait abnormalities, and must localize the source of these symptoms within the nervous system. The differential diagnosis of HIV-related neurologic disease is narrowed by an understanding of the role of HIV in different neurologic disorders. Some disorders occur almost exclusively in the setting of marked immunosuppression, such as opportunistic infections and primary central nervous system lymphoma. Others, such as HIV-associated distal symmetric polyneuropathy and HIV-associated dementia, are prevalent at all CD4+ cell counts. In many HIV-infected patients, neurologic problems may be unrelated to HIV, such as migraine or discogenic radiculopathy. In this chapter, Jessica Robinson-Papp, MD, and David M. Simpson, MD, provide a clinically oriented summary of the neurologic disorders associated with HIV. The focus is on recognition of signs and symptoms, appropriate consideration of the patient’s immune status, and efficient diagnostic evaluation and management.

5-14 Ocular Complications in HIV–Infected Patients

Authors: Patricia Pahk, MD, Douglas A. Jabs, MD, MBA

Date Released: October 01, 2009

Abstract: Ocular manifestations of HIV can involve any portion of the eye and can be divided by anterior or posterior segment involvement and by infectious or noninfectious etiology. Typically, posterior-segment infectious diseases are the result of an immunocompromised state and are considered ocular opportunistic infections. The incidence of ocular opportunistic infections decreased by 75% to 80% after the introduction of HAART in the mid-1990s. The Longitudinal Study of Ocular Complications of AIDS has shown that since the introduction of HAART, the incidence of HIV-related ocular complications—with the exception of cytomegalovirus retinitis—occurs in < 1% of patients. In this CME-certified chapter, Patricia Pahk, MD, and Douglas A. Jabs, MD, MBA, review the various ocular complications associated with HIV infection, compare disease severity and disease progression rates in the pre-HAART era with the post-HAART era, and discuss recommendations for preventing and treating such complications.

5-15 Management of Psychiatric Disorders in HIV-Infected Patients

Authors: Andrew Angelino, MD, DFAPA, Glenn J. Treisman, MD, PhD

Date Released: October 01, 2009

Abstract: The high prevalence of psychiatric disorders seen in patients treated in HIV clinics suggests that access to psychiatric services is necessary for optimal treatment of HIV. Psychiatric treatment has been shown to improve both adherence to antiretroviral medication and HIV outcomes. The gold standard for integrated treatment is to provide an on-site psychiatric service, including psychiatrists, psychologists, counselors, and nurses, as well as a range of associated services such as substance use disorder treatment and inpatient psychiatric services. However, this standard is likely to be unattainable in many HIV settings. It is, therefore, imperative for HIV clinics to identify the core functions that psychiatric treatment programs provide and develop appropriate referral pathways to external services. In this comprehensive module, Andrew Angelino, MD, DFAPA, describes psychiatric disorders common in HIV-infected patients and outlines their clinical management.

5-16 Renal Disease in HIV-Infected Patients

Author: Lynda Szczech, MD, MSCE, FASN

Date Released: October 01, 2009

Abstract: Kidney disease is a growing contributor to the overall disease burden among people with HIV infection. Kidney disease may be due primarily to the viral infection (ie, HIV-associated nephropathy) or secondary to a preexisting comorbidity or complication of HIV infection such as diabetes or hypertension. The kidney can provide a barometer of the vascular health of a patient and, regardless of its etiology, kidney disease and its management will continue to become an increasingly important determinant of patient outcomes. Regardless of the kidney-specific therapy employed, kidney disease should prompt an assessment of the cardiovascular risk profile and an assessment of the ongoing treatment of the individual. In this review, Lynda Szczech, MD, MSCE, FASN, discusses tools for the differential diagnosis and management of kidney injury in HIV-infected patients.

5-17 IRIS in HIV-Infected Patients

Authors: Philip Grant, MD, Andrew R. Zolopa, MD

Date Released: October 01, 2009

Abstract: Combination antiretroviral therapy has dramatically reduced morbidity and mortality associated with HIV, but its use can be complicated by immune reconstitution inflammatory syndrome (IRIS). During the era of zidovudine monotherapy, atypical presentations of Mycobacterium avium complex were reported. However, IRIS as a distinct clinical entity was not fully appreciated until the introduction of HAART. The current prevailing view on the pathophysiology of IRIS is that it represents an overexuberant restoration of pathogen-specific immune response that occurs during antiretroviral therapy. Although no uniform definition exists, the diagnosis of IRIS requires the worsening of a recognized (paradoxical IRIS) or unrecognized (unmasking IRIS) preexisting infection in the setting of improved immunologic function. Furthermore, alternate diagnoses such as a new opportunistic infection, drug toxicity, or progression of the primary disease due to drug resistance or nonadherence must be excluded when evaluating patients for a potential IRIS diagnosis. Although there are few prospective data comparing outcomes of different treatment strategies for IRIS, progress has been made in defining the clinical presentation and risk factors associated with IRIS. In addition, several recent studies have begun to identify management strategies that may prevent the development of IRIS in high-risk groups and expedite the resolution of IRIS symptoms once they occur. In this chapter, Philip Grant, MD, and Andrew R. Zolopa, MD, describe the pathophysiology and clinical presentation of IRIS, discuss epidemiology and risk factors associated with its development, and review the latest data on optimal strategies for preventing and managing IRIS in HIV-infected patients receiving HAART.