Search

This chapter describes the pathophysiology of cardiovascular disease and myocardial infarction in persons with HIV and the association between HIV infection and the increased risk of cardiovascular disease, myocardial infarction, stroke, peripheral artery disease, and sudden cardiac death. The learner will also understand the association between specific antiretroviral therapies and cardiovascular risk and myocardial infarction, and how to assess risk for cardiovascular disease using the American College of Cardiology/American Heart Association (ACC/AHA)10-year risk calculator for atherosclerotic cardiovascular disease. Lastly, the learner will become familiar with medical therapies such as statins and non-statins and lifestyle interventions such as diet, exercise, weight loss, and smoking cessation to lower the risk of cardiovascular disease and myocardial infarction in persons with HIV.

This chapter reviews the origin of HIV and its entry into humans as well as the different strains and subtypes of HIV. A section of the chapter is dedicated to examining the spread of HIV throughout Africa and the rest of the world. The diversity of HIV is discussed in detail along with treatments and vaccine developments. The chapter concludes with a brief discussion about the future of HIV regional and global genetic diversity.

Upon completion of this chapter, the reader should be able to • To gain a greater understanding of the pathophysiology of CVD and myocardial infarction in persons living with HIV infection. • To understand the link of chronic HIV infection as it relates to increased risk of CVD and myocardial infarction....

Preview Reiter's syndrome is an often overlooked and misdiagnosed complex of symptoms. Patients may not present with the classic triad of symptoms, or they may forget to mention other pertinent manifestations. How can you make an accurate diagnosis? And what is an effective approach to management? Dr Kirchner reviews studies on the epidemiology, causes, and pathogenesis of the syndrome and discusses key factors in clinical evaluation and treatment.

Preview The increasing number of patients surviving with advanced HIV infection presents new challenges to physicians who care for them. As a patient's CD4+ T-lymphocyte count declines, susceptibility to opportunistic fungal infections increases. In this article, Dr Kirchner discusses two commonly encountered pathogens, Cryptococcus neoformans and Histoplasma capsulatum.

Or has he been made to think so by direct-to-consumer advertising? Here's how to properly screen patients and when to recommend treatment.

There is a growing body of evidence that HIV-infected persons are at increased risk for cardiovascular disease (CVD) and associated complications, including myocardial infarction and stroke. Autopsy studies have noted premature atherosclerosis in HIV-infected adults, and epidemiological studies demonstrate higher rates of CVD among HIV-infected compared to HIV-uninfected patients. These findings are in part due to chronic inflammation and immune activation associated with HIV infection. Traditional CVD risk factors, including hypertension, hyperlipidemia, and cigarette smoking, also play keys roles. There is additional evidence from observational cohort studies that some antiretroviral drugs, including protease inhibitors and nucleoside reverse transcriptase inhibitors, may increase the risk of myocardial infarction. Treatment interventions to reduce the risk of CVD include diet, exercise, smoking cessation, lipid-lowering agents, and antihypertensive medications. For select patients, changing antiretroviral therapy to improve lipid profiles may be appropriate but should not compromise virologic or immunologic control.

HIV-1 originated in the early 1920s in southern Cameroon and the Democratic Republic of Congo. From Africa, HIV rapidly spread in the late 1960s to the Caribbean and then the United States, Europe, and other areas of the world, leading to the global AIDS pandemic. Both HIV-1 and HIV-2 descended genetically from Simian immunodeficiency virus via cross-species transmission. HIV-1 group M was the first lineage discovered and represents the pandemic form of the virus. Group M consists of nine viral subtypes (A–K), has a widespread distribution, and accounts for approximately 95% of all HIV-1 infections. HIV-2 was not discovered until 1986 and makes up approximately 3% of cases worldwide. It is found mainly in West Africa. The genetic diversity of HIV does not appear to significantly affect viral response to antiretroviral therapy. However, viral diversity continues to present challenges for the development of an effective HIV vaccine.

With the approval of single-tablet regimens that contain 3 or 4 drugs, many patients take just one pill a day. So what are the options and what's on the horizon?

Having a high index of suspicion is key to recognizing the signs of HIV infection in patients without classic risk factors. How quickly would you have spotted these 3 cases?

Background: 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy), a compound chemically related to stimulant and hallucinogenic drugs, has been found to induce a state of euphoria and increased self-awareness. MDMA has been increasingly used for recreational purposes, especially among college students and other young adults, and has been associated with multiple toxic effects. Methods: Using MEDLINE, the medical literature was searched from 1986 using the key words “ecstasy,” “MDMA,” and “designer drugs.” Articles dating before 1986 were accessed from cross-reference of the more recent articles. A case report is described. Results: MDMA was developed in 1912 as an appetite suppressant but never became commercially successful. It resurfaced in the 1950s as a psychotherapeutic agent. In 1985 MDMA was classified as a schedule 1 drug by the Food and Drug Administration after reports of neurotoxicity in laboratory animals. It again resurfaced in the mid 1980s as a recreational drug used primarily among college students and other young adults. There are a number of case reports describing toxic effects from MDMA, including hyperthermia, rhabdomyolysis, coagulopathy, and acute renal failure. Little information is available regarding acute management or treatment of toxic ingestions. Conclusions: MDMA ingestion has been associated with severe toxic effects. Although the literature describes numerous cases of toxic ingestion, there are no published recommendations or suggestions to guide physicians in the evaluation and treatment of such cases. By reviewing the history, neurochemistry, and toxicology of MDMA, as well as providing some guidance regarding management of toxic ingestion, we can arm the provider with valuable information for use in the acute setting. In addition, this information will assist providers in counseling young adults regarding the possible consequences of using this substance.

Preview The increasing number of patients surviving with advanced HIV infection presents new challenges to physicians who care for them. As a patient's CD4+ T-lymphocyte count declines, susceptibility to opportunistic fungal infections increases. In this article, Dr Kirchner discusses two commonly encountered pathogens, Cryptococcus neoformans and Histoplasma capsulatum.

Preview Reiter's syndrome is an often overlooked and misdiagnosed complex of symptoms. Patients may not present with the classic triad of symptoms, or they may forget to mention other pertinent manifestations. How can you make an accurate diagnosis? And what is an effective approach to management? Dr Kirchner reviews studies on the epidemiology, causes, and pathogenesis of the syndrome and discusses key factors in clinical evaluation and treatment.

Dyslipidemia is common in patients with human immunodeficiency virus (HIV) and may result in significant morbidity, including coronary heart disease (CHD). Treatment of dyslipidemia in these patients is generally based on the National Cholesterol Education Program Adult Treatment Panel III goals for individuals without HIV. For individuals with ≥ 2 cardiovascular risk factors, the risk of CHD should be evaluated using the Framingham risk calculator and managed accordingly. Switching to an antiretroviral regimen with a favorable lipid profile should be considered before pharmacologic management if virologic suppression can be maintained. Statins are the first-choice therapy for elevated low-density lipoprotein cholesterol, but in HIV-infected individuals, special consideration must be given to drug-drug interactions, specifically those between protease inhibitors and statins. Management of dyslipidemia in HIV-infected individuals is a challenging but important aspect of chronic disease management. Additional research, specifically related to the role of chronic inflammation, is needed to better define the relationship between HIV infection and cardiovascular disease.

Background: Current antiretroviral (ARV) therapies have greatly extended the life expectancy for many living with HIV infection. Given that ARV therapies must be taken chronically, long-term tolerability associated with these agents is of great importance. Clinical trials and experience have helped clarify short and long-term adverse event data. Among non-nucleoside reverse transcriptase inhibitors (NNRTIs), common laboratory markers of toxicity and tolerability include transaminase elevations and lipid alterations. Some of these issues appear to be a class-specific effect, whereas others appear to be more agent-specific. Selection of the appropriate NNRTI to use while limiting drug-related side effects is an important clinical objective. Objective: To review clinically relevant data regarding long-term tolerability of NNRTIs. Methods: A PubMed search was performed using the following keywords: NNRTI, non-nucleoside reverse transcriptase inhibitor, efavirenz, nevirapine, etravirine, rilpivirine and safety, tolerability or clinical. Papers published before 2007 were excluded; papers were included if they reported clinically relevant tolerability outcomes, enrolled more than 50 patients and were conducted for ≥ 48 weeks in HIV-infected patients. Results: Newer agents and formulations have significantly improved the tolerability issues associated with older ARVs and earlier treatment approaches. Conclusions: Tolerability profile remains to be a distinguishing feature among the agents in this class, and is a key consideration when considering a first-line NNRTI-containing regimen that is individualized to the patient and can achieve long-term virologic suppression. This information may help guide treatment choices in clinical practice.

Despite the availability of a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine in the United States since 2005, the vaccine remains underutilized and perhaps misunderstood by many physicians. Pertussis continues to be a major public health problem, with adults being the primary source of infectious transmission to unprotected infants. Consequently, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices has expanded the indications for the Tdap vaccine. In addition, the vaccine can be safely administered regardless of the time since the patient's last tetanus-diphtheria booster. Widespread use of the Tdap vaccine-especially in health-care workers, adolescents, and adults aged 19 to 64 years-should greatly reduce the incidence of Bordetella pertussis infection in the United States. The recent Food and Drug Administration approval of the Tdap vaccine for individuals aged 65 years or older should increase the use of this vaccine.

PreviewFor reasons that are not fully understood, there is an association between Clostridium septicum infection and carcinoma. In this article, Dr Kirchner describes the examination and treatment of a patient with C septicum infection in whom metastatic cancer was found on laparotomy.

PREVIEWExercise-induced bronchospasm (EIB) is an often-undiagnosed but common problem affecting both recreational and elite athletes. Although exercise can trigger exacerbation of chronic asthma, EIB should not be confused with the chronic inflammatory disease. In this article, Drs Hermansen and Kirchner review the incidence, diagnosis, and treatment of EIB and explain how to distinguish EIB from chronic asthma.

Hepatitis B causes significant morbidity and mortality worldwide. More than 400 million persons, including 1.25 million Americans, have chronic hepatitis B. In the United States, chronic hepatitis B virus infection is responsible for about 5,000 annual deaths from cirrhosis and hepatocellular carcinoma. Hepatitis B virus is found in body fluids and secretions; in developed countries, the virus is most commonly transmitted sexually or via intravenous drug use. Occupational exposure and perinatal transmission do occur but are rare in the United States. Effective vaccines for hepatitis B virus have been available since 1982; infant and childhood vaccination programs introduced in the 1990s have resulted in a marked decrease in new infections. Risk factors for progression to chronic infection include age at the time of infection and impaired immunity. From 15 to 30 percent of patients with acute hepatitis B infection progress to chronic infection. Medical therapies for chronic hepatitis B include interferon alfa-2b, lamivudine, and the nucleotide analog adefovir dipivoxil.

Renal failure is a known complication of HIV infection. The most common form is HIV-associated nephropathy, or HIVAN. It is characterized by high-grade proteinuria with rapid progression to end-stage renal disease. The kidneys of affected patients appear enlarged on ultrasonography. Histopathologically, there is focal segmental glomerulosclerosis with glomerular collapse. Before the era of HAART, patients with HIVAN had limited survival, although in some cases this was prolonged if dialysis was instituted. Over the past few years, isolated case reports have shown that patients with HIVAN will recover renal function following initiation of HAART. We report 3 patients believed to have HIVAN who exhibited marked improvement in renal function after treatment with a regimen comprising 2 nucleoside reverse transcriptase inhibitors and a protease inhibitor.

This article reports the proceedings of an expert panel discussion on current clinical management practices for the treatment of recurrent genital herpes. The panel reviewed the effectiveness of primary and specialist care settings in the UK and USA and identified the principal clinical needs of patients with recurrent genital herpes. The ideal alternative to daily suppressive nucleoside analogue therapy is a treatment with long-term impact on the natural history and prognosis of recurrent genital herpes. The potential of resiquimod, an immune response modifier, to resolve this unmet need was examined. Resiquimod is reported to delay the onset of recurrent genital herpes symptoms in patients in a Phase II clinical trial. While awaiting clinical confirmation of this new development in immunotherapy, the panel concluded with two recommendations: a reassessment of recurrent genital herpes management in terms of physician education of patients, and the promotion of a positive patient-physician relationship in the approach to treatment.

PREVIEWThe transition out of the reproductive years can often be accompanied by uncomfortable and disruptive symptoms, one of the most common of which is hot flashes. Drs Morrissey and Kirchner describe this and other typical menopausal symptoms, as well as pharmacologic, hormonal, and lifestyle options that can bring relief and enable a smooth midlife passage

(1999). Progressive Vision Loss After Pneumonia. Hospital Practice: Vol. 34, No. 11, pp. 150-158.

Infectious mononucleosis is common in adolescents and young adults. Although the syndrome is most often associated with Epstein-Barr virus, several other organisms can also cause infectious mononucleosis. Diagnosis is based on clinical findings and the presence of heterophil antibodies and atypical lymphocytes. Diagnosis may be more difficult in older adults because the presenting symptoms often differ from those seen in children. Symptoms usually resolve in 2 to 3 weeks. Treatment of uncomplicated infectious mononucleosis is supportive, but corticosteroids may be beneficial for the treatment of several complications associated with Epstein-Barr virus. Physically active patients should be counseled about the risks of splenic injury.

Gonorrhea has been declining since its 1975 peak. Risk factors include age 15 to 19 years, multiple or casual sexual contacts, sexual activity related to drug use, and low socioeconomic status. Infection is usually mild but may be asymptomatic. While no physical signs are specific to the gonococcus, pelvic inflammatory disease is a common complication and cause of infertility and should be treated if it is suspected. Diagnosis of gonorrhea is typically by culture. Newer, more accurate tests are available but are more expensive. For treatment, the CDC recommends only highly effective regimens. Patients need to refer recent sexual partners for treatment and abstain from sexual intercourse until completion of therapy and resolution of symptoms. The incidence of syphilis appears to be declining in the United States, but it should be considered if an ulcer is found in the genital region. If untreated, the disease progresses through primary, secondary, latent, and tertiary phases, and systemic symptoms can mimic other conditions. Positive standard screening tests should be confirmed by fluorescent treponemal antibody absorption testing. Darkfield microscopy is appropriate for diagnosis of an ulcer. The treatment of choice for all phases of syphilis is a single dose of intramuscular benzathine penicillin. Other components of therapy include partner notification and patient follow-up. The spread of HIV is closely linked to STD transmission. Therefore, testing for HIV is strongly encouraged when another STD has been diagnosed.

C trachomatis infection is the most commonly reported STD in the United States, and the majority of women infected are asymptomatic. Screening is recommended for those at high risk, including women who are between 15 and 21 years of age, live in urban areas, are single, or have new or multiple sexual partners. The "gold standard" for diagnosis is chlamydial culture; however, techniques that use DNA and RNA amplification are nearly 100% sensitive and specific and may prove cost-effective. Doxycycline is a recommended first-line therapy, but certain other antibiotics may also be effective. Herpes simplex virus affects more than one third of the world's population. It is diagnosed by observation of shallow, tender ulcerations around the genitalia and by viral isolation using tissue culture. Initial treatment is with antiviral drugs, which may also be necessary episodically or as a suppressive regimen for recurrences. Patient education about prevention of these and other STDs, as well as the impact of such disease on sexual partners, is critical. Physicians should therefore become comfortable questioning and counseling patients about sexual issues and risks for STDs.

Parkinson's disease is a progressive neurologic disorder without cure. About 1% of the US population over 50 years of age is afflicted. Loss of dopaminergic neurons originating in the substantia nigra is the typical pathologic feature. It is theorized that both genetic and environmental factors have a role in the etiology of the disease. The classic tetrad of parkinsonian signs includes tremor, rigidity, bradykinesia, and disturbances in posture and gait. Initial signs and symptoms can be subtle and nonspecific. As the disease progresses, vocal, neurologic, autonomic, and psychiatric complications may develop. Mortality rates have not changed in 30 years despite new therapy. Differentiating true Parkinson's disease from other causes of parkinsonism can be challenging but is crucial to outcome.

Immune thrombocytopenic purpura is a relatively common disease that occurs in both pediatric and adult populations. The acute form predominates in children and the chronic form is seen much more often in adults. The diagnosis is one of exclusion but often can be made on the basis of thorough history taking and physical examination and a limited number of laboratory studies. More intensive diagnostic studies, including bone marrow examination, may be needed to rule out other causes of thrombocytopenia. For patients in whom spontaneous remission does not occur, effective treatments are available, and morbidity and mortality rates are quite low.

Many of the goals in caring for patients with non-life-threatening rheumatic conditions can be safely met with nonsteroidal anti-inflammatory drug (NSAID) therapy. These drugs relieve pain and stiffness and help to maintain joint mobility. However, no course of treatment can be successful without patient compliance. The difficulties of following dosage requirements and scheduling, together with the increased risk of adverse side effects, are particular problems for the elderly-the very patients who are the major consumers of NSAIDs. The key to successful NSAID therapy is maintaining patient comfort and function while using the simplest and safest medical regimen available. The author discusses ways in which these goals can be achieved.

To the Editor. — I found Peters' 1 suggestion of financial reimbursement for organ donation to be novel yet naive. As for denying the alcoholic a liver transplant, the arguments for and against treatment could be applied to any of our patients whose diseases are a result of self-destructive behavior. The underlying component in the issue of organ transplantation remains that of cost, not how we can obtain more hearts, kidneys, and livers. Peters states that 20 177 patients were waiting for organs as of March 1990. 1 The average cost of a kidney transplant is $30 000, and the average cost for a heart or liver transplant ranges from $100 000 to $200 000. 2 This does not include the cost of follow-up care, chronic immunosuppressive therapy, and complications. If only 50% of the patients currently waiting could have these procedures, the costs would approach or exceed $1 billion.