Human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) have become major healthcare issues of our time. Millions have become infected with HIV and thousands have died from opportunistic infections associated with AIDS. Familiarity with the disease’s spectrum of expression in our patients is necessary; mastering the growing arsenal of information about HIV is a professional imperative.

Treating HIV Infection

HIV is a retrovirus, which means it contains enzymes (reverse transcriptase) that insert genetic material into host DNA, creating permanent infection. HIV also infects CD4+ receptors, particularly T4 lymphocytes. This disease has a long period of latency and a course of complications. Nevertheless, great strides have been made to slow the HIV-replication process with treatment and prevention.

Although patients with AIDS may require treatment for cancer, other infections, and conditions, the underlying HIV infection is the crucial infection to diagnose and treat. Medications include nucleoside analog reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs), which interfere with the mature budding of infectious virions that spread HIV intracellularly. Table 1 contains a listing of anti-HIV medications. The acronym HAART (highly active antiretroviral therapy) was coined in 1996 because of the response to the efficacy of using these therapies in combination. In fact, some patients have responded so well that their HIV infection has become undetectable using currently available methods for detecting serum viral load.

The incidence of many opportunistic infections (OIs) has declined dramatically in the HAART era.^1,2 Potent antiretroviral treatment infers a considerable delay in clinical progression to the development of OIs. Therefore, every effort should be made to treat the underlying HIV infection to avoid further OIs.

Sadly, some patients with HIV infection continue to be at-risk for progression to AIDS. OIs and progression to AIDS is still occurring among key members of our global society, including the —

• Undiagnosed
• Untreated
• Disenfranchised or marginalized (e.g., African-American community)
• Under-treated
• Unempowered (e.g., women)
• Impaired (e.g., psychiatric or addicted members of society)
• Nonadherent patients
• Patients in developing countries who do not have access to HAART
• Patients not under the care of an HIV-specialist or experienced HIV provider
• Patients who are just starting treatment
• Patients for whom antiretroviral therapy has failed

Clinicians assess treatment by monitoring CD4+ cell lymphocyte counts at least every six months. More frequent counts are indicated if the patient has a fever, thrush, a recent rapid decline, or a count below 250/µL. However, serum viral load measurements have replaced CD4+ lymphocyte counts as more relevant indicators in clinical practice for some treatment-related decisions such as initiation of antiviral treatment. CD4+ counts remain pivotal in decisions made about treating or preventing OIs. Table 2 lists the recommendations for preventative regimes against OI that expert clinicians employ.

Providers counsel patients to eliminate alcohol and tobacco, eat well-balanced meals supplemented with vitamins and minerals, take measures to reduce stress, and exercise. Every effort must be made to strengthen the psychological, social, and spiritual support systems of people with AIDS (PWAs) so they may live fulfilling lives in the face of this chronic illness and effectively participate in their healthcare. Additional preventative techniques for patients to prevent acquisition of an OI (e.g., not drinking lake water in order to prevent the acquisition of cryptosporidiosis) are located in Table 3.

General Management of Opportunistic Infections

OIs that can develop in PWAs share many characteristics.³ They are caused by a diverse spectrum of pathogens, many of which are ubiquitous in nature and yet rarely cause disease in immunosuppressed individuals. In many instances, the diseases are reactivations or a secondary reappearance of a pathogen acquired before debility or during childhood, such as herpes zoster (chicken pox), herpes simplex, or pneumocystis. Effective antiretroviral treatment can prevent most of these OIs. OIs almost solely develop in immunoincompetent AIDS patients — those with a low CD4+ cell count. In the event of their occurrence, treatment is directed at suppressing or controlling the infection — it can rarely be fully cured and remains active or latent until the immune system is improved by antiretroviral treatment. That said, more data is showing that patients can safely stop some preventative suppressive medications once their immune system is consistently restored over time (i.e., elevated CD4+ for at least 3 months) and their HIV infection is controlled by antiretroviral therapy.¹

Infections can have atypical sites of presentation, such as extrapulmonary tuberculosis, and atypical presentations, as with aggressive herpes simplex. Historically, OIs and other related diseases have accounted for much of the morbidity and mortality associated with HIV infection. This article, recognizing that undiagnosed, untreated, and newly treated patients, as well as patients who have failed treatment, continue to be at risk for OIs, reviews the diagnosis and treatment of these major infections and conditions. Also, HIV patients in countries where access to HAART is not available continue to manifest the full course of HIV disease, including OIs.

On a very positive note, among patients with good immunologic and virologic responses to HAART, it has proved possible to stop primary prophylaxis and maintenance therapy in patients with previously active infections. The guidelines issued by the US Public Health Service and the Infectious Diseases Society of America currently recommend that following a rise in CD4+ cell count and control of viral replication, a patient can stop primary and secondary prophylaxis for virtually all OIs.¹

Bacterial Diseases

An estimated 10 to15 million Americans are infected with mycobacterium tuberculosis bacteria, with the potential to develop active TB disease in the future. About 10% of these infected people will develop TB at some point in their lives. Because HIV/AIDS weakens the immune system, people dually infected with TB and HIV have a 100 times greater risk of developing active TB and become infectious. The overall case rates for TB is declining and it is estimated that about 10% of all TB cases in the US were in HIV-infected patients. Studies have shown that non-Hispanic blacks in southern states have TB at rates eight times greater than non-Hispanic whites. These racial disparities have been linked to socioeconomic status, poverty, and differential access to health care. Regarding treatment, blacks were found to have equal access to directly-observed therapy (DOT) consistent with low rates of infection with multidrug resistant TB. Approximately 2 billion people (one-third of the world’s population) are infected with Mycobacterium tuberculosis. The World Health Organization estimates that TB is the cause of death for 11% of all AIDS patients.^2,4,5

TB occurs regardless of the CD4+ cell count, but the manifestations may be altered by the degree of immunosupression. Those with more advanced immunocompromise are more likely to have extrapulmonary or disseminated disease. Treatment of HIV-1-related TB disease should follow the general principles developed for TB treatment and DOT is strongly recommended so that effective therapy to prevent acquired drug-resistance is achieved and to allow a cure to be attained in a relatively short time period of six to nine months. Treatment should include a six-month regimen of INH, RIF or rifabutin, PZA, and EMB given for two months followed by Isoniazid (INH) and RIF (or rifampin) for four months. When the disease is susceptible to INH, RIF, and PZA, EMB should be discontinued. A detailed clinical assessment should be performed at least monthly to assess adherence and identify possible medication intolerance. Patients can experience overlapping toxicities, drug-drug interactions, and paradoxical increase in symptoms as their immune system is reconstituting.^2,4,5

Most cases of disseminated mycobacterium avium complex (DMAC) infection occur in patients with a CD4+ cell count <50/uL. MAC disease among patients with AIDS, in the absence of antiretroviral therapy, is generally a disseminated multiorgan infection. Early symptoms might be minimal and might  precede detectable intermittent or continuous mycobacteremia by several weeks. Symptoms include diarrhea, abdominal pain, fever, night sweats, malaise, and weight loss. Immune reconstitution inflammatory syndrome, which is characterized by focal lymphadenitis with fever, has been described among patients with subclinical or established MAC disease and advanced immunosupression who begin antiretroviral treatment and have a rapid and marked rise in CD4+ cell count. This syndrome can be either mild or severe. Initial treatment of DMAC includes two antimycobacterial drugs to delay or prevent the emergence of drug resistance. It is usually treated with clarithromycin (Biaxin) or azithromycin (Zithromax), possibly in combination with ethambutol (Myambutol).^2,4,5

Recurrent bacterial pneumonia, also called bacterial respiratory disease, is common in HIV-1-infected patients (i.e., almost eight times more likely to develop than in HIV-negative people). Patients can develop severe pneumococcal infections with relatively preserved CD4+ cell counts. The most common pneumonias are Streptococcus pneumoniae (i.e., 150 times higher rate than HIV-negative controls), Haemophillus influenza, Pseudomonas aeruginosa, and staphylococcus aureus. Symptoms in HIV-infected patients are similar to those without HIV infection — an acute illness characterized by chills, rigors, pleuritic chest pain, and purulent sputum. Physical exam findings include fever, tachypnea, tachycardia, rales or rhonchi, and other signs of consolidations. Patients should respond to treatment in 48 to 72 hours. Pneumococcal vaccination is given to patients whose T-cell count <200 cell/uL.^2,4,5

Fungal Infections

The most common manifestation of Candida albicans is pseudomembranous candidiasis (thrush), which manifests as yellowish, curd-like patches with an erythematous base on the buccal mucosa and tongue surfaces, and esophageal candidiasis. Esophageal infection is occasionally asymptomatic, but often presents with fever, retrosternal burning pain and odynaphagia (discomfort in swallowing). Vulvovaginal candidiasis causes pruritis of the vulva with a curd-like vaginal discharge and inflammation of the labia, vulva, and perineum. It can be more severe with longer duration or even refractory to treatment in patients with advanced immunosuppression. Although fungal infections respond to treatment with nystatin (Mycostatin), clotrimazole (Lotrimin), ketoconazole (Nizoral), fluconazole (Diflucan), and amphotericin B (Fungizone), depending on the site of infection, recurrence is common and drug resistance can develop. Patients must be taught the correct use of medications to minimize drug-resistant strains in addition to daily oral hygiene and skin care.^2,6

Inhaled Histoplasma capsulatum spores (from soil contaminated with bird and bat excrement) settle in the small bronchioles and alveoli and can cause histoplasmosis later in life when one is immunocompromised. Major endemic areas in the US are the Midwest and Puerto Rico. Histoplasmosis in HIV-infected patients may be due to reactivation of a previously acquired infection or to reinfection from constant exposure. Disseminated histoplasmosis generally occurs in patients whose CD4+ cell count is <150 cell/uL. The most common clinical presentation is disseminated multiorgan disease with patients manifesting fever, fatigue, and weight loss in addition to respiratory tract symptoms of cough, chest pain, and dyspnea. Initial treatment includes amphotericin B followed by itraconazole (Sporanox) suppressive and maintenance therapy.^2,6

Cryptococcosis usually occurs in advanced HIV disease (i.e., <50 CD4+ cell count) as a reactivation of a latent infection. The incidence has declined significantly in those patients on effective antiretroviral treatment. The patient presents with mild headache, fever, and progressive malaise. The most common manifestation is meningitis but classic meningitis symptoms (i.e., stiff neck or photophobia) occur in only one-third to one-fourth of patients and one-half of patients with disseminated disease present with pulmonary involvement. Initial treatment includes amphotericin B and flucytosine (Ancobon), followed by fluconazole (Diflucan).^2,6

Protozoal Infections

Pneumocystis jiroveci pneumonia (previously called P. carinii) [PCP]) historically was the most common parasitic infection in HIV-infected patients. There have been dramatic declines in its incidence in the US; however, it remains the most common AIDS-defining OI and a significant health problem in the developing world. Fever, a dry and nonproductive cough, weight loss, difficulty breathing, night sweats, and fatigue are all symptoms. Diagnosis is confirmed with chest x-ray, sputum studies, and bronchoscopy. Treatment for PCP includes TMP/SMX (Bactrim, Septra), with the addition of corticosteroids for moderate to severe cases. If the patient has an allergy to TMP/SMX, pentamidine (Pentam) is often used.^2,7

Cryptosporidiosis is caused by Cryptosporidium species, a group of protozoan parasites that infect the small bowel mucosa, and in immunocompromised persons, the large bowel and extraintestinal sites. Those at greatest risk for disease are the patients with advanced immunosuppression (i.e., CD4+ cell count <100 u/L). It causes severe debilitating diarrhea. Stool tests, bowel biopsy, and endoscopy confirm the presence of the organism. In the absence of curative therapy for cryptosporidiosis, effective antiretroviral treatment with immune restoration of an increase in CD4+ cell count >100 cells u/L is paramount. Medications to slow GI motility and diarrhea, diet modification, and parenteral fluids and electrolytes help to control symptoms. The most effective way to prevent cryptosporidiosis is to perform scrupulous handwashing and use barriers during anal sex.^2,7

Toxoplasmosis is commonly manifested by encephalitis. Disease occurs almost exclusively by reactivation of a latent infection. Fever, severe headaches, altered levels of consciousness or mood, and stroke-like symptoms are signs of the infection. Diagnosis is based on symptomatology, positive antibody tests, and computerized tomography, which reveals brain lesions. Treatment involves pyrimethamine (Daraprim) plus sulfadiazine and leucovorin.^2,7

Microsporidiosis has declined dramatically in incidence with the development of effective antiviral treatment. The most common clinical manifestations are GI track infection with diarrhea; however encephalitis, ocular infection, sinusitis, myositis, and disseminated infection can occur. The primary treatment is effective antiretroviral therapy. Albendazole (Albenza) may be used.^2,7

Viral Infections

Before potent antiretroviral therapy, Cytomegalovirus (CMV) retinitis occurred in about 30% of patients with advanced immunocompromise. Its incidence has declined substantially. CMV is generally caused by reactivation of a latent infection. Retinitis is the most common type of CMV disease in people with advanced HIV (i.e., CD4+ cell count <50 cells/uL). CMV can cause damage to the retina, which leads to blurred vision and even blindness. While usually not life-threatening, visual disturbances and blindness are usually permanent, even if treatment has been successful. Other manifestations of CMV include encephalitis, colitis, gastritis, and esophagitis. CMV is treated depending on the location and severity with foscarnet (Foscavir), ganciclovir (Cytovene), or valganciclovir (Valcyte).²

Herpes simplex virus (HSV) is found in HIV-infected people in two forms: HSV-1 (oral) and HSV-2 (genital). HSV usually represents a reactivation of a previously acquired infection. Effective antiretroviral treatment has not had an impact on the incidence of this disease — approximately 95% of HIV-1-infected persons are seropositive for either HSV-1 or HSV-2. In recurrent orolabial herpes, the patient may describe one- to two-day prodromal sensations of paresthesias, itching, and tingling at the site of the pending eruption, followed by a painful vesicular lesion that becomes an ulcer.⁸ Fever, pharyngitis, and cervical lymphadenopathy must also be present. The course of illness in untreated subjects is seven to 10 days and lesions recur one to 12 times per year and are often triggered by stress or sunlight. HSV genitalis is the more common manifestation of HSV-2 infection. In recurrent genital herpes, the patient may describe one- to two-day prodromal sensations at the site of the pending eruptions. The infection first manifests as papules, then vesicles, which open and form shallow ulcerations. Local irritation and tenderness are often present.⁸ Treatment includes acyclovir (Zovirax), famciclovir, or valacyclovir; local care of mucocutaneous lesions; prevention of superimposed bacterial or fungal infections on ulcerated HSV lesions; and avoidance of skin-to-lesion contact to avoid spread.

Varicella zoster virus (VZV) infection (also called shingles or herpes zoster) is usually a reactivation of previously acquired chicken pox. Patients who have not had chickenpox as a child, especially the elderly, debilitated, or pregnant, should avoid others with chickenpox or herpes zoster. Up to 95% of the adult population is seropositive for VZV. The incidence of recurrent disease in the form of herpes zoster is 15 to 25 times greater in HIV-1-infected persons than in the general population and three to seven times greater than among the elderly. Zoster can occur at any level of CD4+ cell count, but can have different disease manifestations in patients with advanced immunosupression. VZV is transmitted by cutaneous exposure to serum from infectious vesicles and via aerosolized droplets. Patients often experience a prodrome of pain that resembles a burn or muscle injury in the affected dermatome. Zoster cutaneous eruptions can become secondarily infected with bacteria or fungi.⁹ Treatment includes famciclovir or valacylovir.²

Human Herpesvirus-8 is associated with all forms of Kaposi sarcoma and certain rare neoplastic conditions, such as primary effusion lymphoma. The overall incidence of Kaposi sarcoma was high early in the epidemic, but abated probably as a result of the use of antiviral agents to control and suppress the widespread incidence of CMV retinitis in the same HIV-infected population.²

Progressive multifocal leukoencephalopathy (PML) is a neurological condition caused by the JC virus. The majority of humans are infected early in life. PML is the only known illness caused by the JC virus. It is a disease with an insidious onset that produces a neurological deficit that worsens over weeks and months to include cognitive dysfunction, dementia, seizures, ataxia, aphasia, hemiparesis, and eventually coma. No effective treatment for JC virus exists, although certain patients have improved or stabilized on effective antiretroviral treatment. However, some patients have worsened.²

Hepatitis C is common in people living with HIV. Between 25% and 33% of all HIV-positive people in the US are infected with the hepatitis C virus (HCV). HCV is one of the most common causes of chronic liver disease in the US and HCV infection progresses more rapidly to liver damage in HIV-infected people.¹⁰ HCV is transmitted primarily by large and repeated direct percutaneous exposure to contaminated blood, therefore coinfection with HIV and HCV is common in injection drug users and hemophiliacs who received clotting factor concentrates before 1987. HCV-related liver disease has become a major cause of hospital admissions and deaths among HIV-infected patients. At-risk patients should receive hepatitis A and hepatitis B vaccination. Treatment for chronic hepatitis C includes alpha interferon and combination therapy of alpha interferon with ribavirin. Alcohol abstinence adds an additional protective effect against the risk of ongoing liver injury.¹⁰

Ethical and Legal Considerations in Clinical Practice

Clinical practice with HIV/AIDS patients involves many of the important ethical challenges of our age — discrimination, prenatal testing, birth control, freedom of the individual versus public compulsion, justice in healthcare, suicide and assisted suicide, informed consent, privacy, and confidentiality. Patients with HIV are also confronted with multiple legal decisions. Patients must be guided by applicable federal and state laws concerning wills and power of attorney, advanced directives (e.g., living will, power of attorney, and healthcare proxy), debtor or creditor issues, guardianship, discrimination in the workplace, and confidentiality/privacy, some of which can affect the patient-nurse relationship and nursing care activities. Many HIV/AIDS community-based organizations provide legal assistance as well as case management services, social support networks, access to benefits, and financial assistance programs.

Patients with HIV can develop a wide assortment of clinical manifestations. Every effort should be made with respect to case-finding and diagnosing people with HIV infection, so they can benefit from the dramatic clinical improvement offered from effective antiretroviral therapy. Nursing care of patients experiencing opportunistic infections is intensive yet stimulating and multifaceted. Well-prepared nurses with mature skills in clinical management, patient education, and communication can be of great benefit to these patients.