Human Immunodeficiency Virus Infection

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175 Human Immunodeficiency Virus Infection

Ellen M. Slaven

• In the United States, more than 1.1 million people are estimated to be living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), and approximately 50,000 new infections occur each year.

• When the CD4 cell count falls to less than 200 /µL (from a normal level of approximately 1000 cells/µL), opportunistic infections are more likely to develop.

• The Centers for Disease Control and Prevention continue to emphasize “opt out” routine HIV screening during any health care encounter, including in the emergency department, for patients between the ages of 13 and 64 years, to allow for earlier detection and treatment and to prevent transmission.

• Current treatment recommendations include early initiation of antiretroviral therapy in asymptomatic patients with CD4 cell counts of up to 500/µL.

In 1981, the first report of Pneumocystis (carinii) jiroveci pneumonia (PCP), in 5 healthy young men, heralded the arrival of a previously unknown pathogen and the disease it caused, later identified as human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). Since then, the infection has spread globally and has led to the untimely deaths of more than 25 million people. In the United States alone, more than 1.1 million people are estimated to be currently living with HIV/AIDS, and more than 50,000 new infections occur each year. Many of those infected, estimated to be more than 20%, may be unaware of their own HIV infection.

Despite some early advances in decreasing the yearly incidence of new infections, progress appears to have stalled. In certain subpopulations, the prevalence of HIV infection rivals that of some sub-Saharan African countries, such as men who have sex with men in New York City and black men in Washington, D.C. Injection drug users remain a high-risk group.

The mainstay of transmission of HIV infection is sexual exposure. The sharing of needles for illicit drug use also leads to transmission of HIV. An HIV-infected mother has approximately a 30% chance of passing the virus to her newborn, but with treatment, the risk plummets to less than 1%. Health care workers have a less than 0.3% chance of becoming infected with HIV following an accidental stick with a contaminated needle. Only in rare cases is HIV now transmitted through infected blood products (estimated to be less than 1 transmission per 500,000 blood transfusions) (Table 175.1).

Table 175.1 Risk of Human Immunodeficiency Virus Infection

ROUTE OF TRANSMISSION	PER 10,000 EXPOSURES	PERCENTAGE OR INCIDENCE
Transfusion of contaminated blood	9000	Almost 100%
Transfusion of blood after screening	—	1/500,000
Mother-to-child without treatment	3000	30%
Mother-to-child with treatment	—	<0.01%
Needle stick in health care worker	30	0.3%
Unprotected receptive penile-vaginal intercourse	10	—
Unprotected insertive anal intercourse	6	0.01-1.0%
Unprotected insertive vaginal intercourse	5	0.01-1.0%
Unprotected receptive penile-vaginal intercourse with genital ulcers	100	0.1-10%
Unprotected receptive oral intercourse	1	—
Unprotected insertive oral intercourse	0.5	—

The HIV virions enter the host and primarily target the lymphocytes, particularly a subset of T lymphocytes known as CD4 cells. The virus establishes itself within the cells, where it prepares strands of DNA from its own viral RNA and the cells’ own enzyme reverse transcriptase. The new viral DNA becomes integrated within the lymphocytes’ DNA, and new virions are produced. The new virions are released from the host cell by budding and are free to invade other uninfected cells.

Initially, viral replication goes unchecked, and the high level of viremia may lead to symptoms such as fever, rash, pharyngitis, and enlarged lymph nodes. This stage is a transient illness, lasting days to several weeks, and has been termed acute HIV infection, or acute retroviral syndrome.

The immune system eventually responds to the viremia and suppresses viral replication. The viral load diminishes, and the symptoms of the acute infection resolve. Low-grade viral production continues at a steady state, and the host and virus reach a balance of viral suppression and continued viral production. This chronic steady state may be maintained for years until the immune system eventually is overwhelmed.

Infection with HIV is a progressive disease. Following years of viral replication, and eventual destruction of CD4 cells, the immune system begins to fail. During the chronic phase of infection, patients have a predictable decline of approximately 70 CD4 cells/µL/year. When the CD4 count approaches 200 cells/µL (from a normal level of approximately 1000 cells/µL), opportunistic infections (e.g., PCP, Kaposi sarcoma, pulmonary tuberculosis) begin to appear. When the CD4 cell count falls to less than 50 cells/µL, immunosuppression is profound.

Testing

The detection of HIV-specific antibodies in serum or plasma establishes the diagnosis of HIV infection. Tests of HIV antibodies are highly sensitive and specific. The enzyme-linked immunosorbent assay (ELISA) is the most commonly used screening test for HIV because of its high sensitivity and rapid results. All positive test results should be confirmed by Western blot. The Western blot test uses electrophoresis to separate HIV proteins, which produce a colored band after reacting with specific antibodies found in a sample of blood. It is the most commonly used confirmatory test and is considered the “gold standard.”

Following the initial HIV infection, antibody production occurs at such low levels that antibodies are undetected by most assays. This window period, in which HIV antibody testing leads to false-negative results, lasts approximately 4 weeks. In this setting, testing directly for the viral antigen p24 or polymerase chain reaction (PCR) testing for viral RNA may be performed. The U.S. Food and Drug Administration (FDA) has approved a newer test that detects both p24 antigen and antibodies to HIV. This highly sensitive assay, the ARCHITECHT HIV Antigen/Antibody (Ag/Ab) Combo, will be instrumental in detecting early stages of infection.

Rapid Assays

Rapid assays for detecting HIV-specific antibodies in serum can yield results in less than 30 minutes. These tests have high sensitivity and specificity and have proven effective for screening. HIV-specific antibodies may be detected in oral fluids, whole blood, serum, and plasma. Many people find oral fluid testing more acceptable than blood testing. Unfortunately, the rapid tests suffer from the same limitation as ELISA. They produce false-negative results during the window period. Positive results on rapid assays require confirmation with the Western blot.¹

Opt-Out Testing

In 2006, the U.S. Centers for Disease Control and Prevention (CDC) revised the recommendations for HIV screening to include routine (i.e., nontargeted) testing in all health care settings, including emergency departments (EDs). Understanding that an estimated 20% of patients infected with HIV are unaware of their status and that ongoing HIV transmission continues at a steady rate, the new recommendations highlight the need to expand screening. Additionally, the number of persons who are newly diagnosed with HIV and who already have advanced disease is unacceptably high. Routine testing will also decrease the number of “late testers” and provide earlier entry to care. Testing now should be done on all patients 13 to 64 years old, regardless of risk factors, at all health care facilities where the prevalence of undiagnosed HIV infection is greater than 0.1%. Patients are to be informed of the testing and have the opportunity to decline or opt out of it. General consent for medical care is sufficient for testing, and special written consent for HIV testing is not required, except in the few states that continue to require written consent. Pretest and post-test counseling is no longer required.²

Monitoring Infection and Treatment

Monitoring the progression of infection with HIV has been likened to a runaway train on railroad tracks that lead to the edge of a cliff. The CD4 cell count is analogous to the distance between the train and the cliff, and the viral load is analogous to the speed of the train.

Close monitoring of the level of viremia and of the CD4 cell counts is crucial in the management of the HIV-infected patient. PCR testing quantitatively measures the viral RNA in copies per milliliter of plasma, the viral load. Untreated patients typically have viral loads of up to 1,000,000 copies/mL of HIV RNA. One goal of antiretroviral therapy is to decrease the viral load sufficiently to be undetectable, as occurs when fewer than 5 to 50 copies/mL of HIV RNA are present. The CD4 cell counts provide prognostic information. Patients with CD4 cell counts higher than 200 cells/µL rarely develop opportunistic infections, and those with counts higher than 50 cells/µL rarely die of HIV/AIDS.

Viral resistance to antiretroviral medications is an emerging phenomenon that may require alteration of a particular antiretroviral regimen. Two types of tests measure HIV resistance. The first is genotype testing, in which the sequences of the relevant viral genes are determined. The sequences reveal the presence or absence of mutations associated with antiretroviral resistance. Second, phenotypic tests excise relevant viral genes and insert them into a standard test virus. The test virus is then exposed to various antiretroviral medications to determine resistance.

Acute Infection

Acute HIV infection, also termed acute retroviral syndrome or primary HIV infection, is a self-limited stage that develops in the first few weeks following initial infection. During this period, viral replication is rapid and ongoing, leading to high viral loads. The CD4 cell count may decrease transiently during the acute phase. The signs and symptoms are nonspecific and most commonly include fever and rash (Box 175.1). Approximately one third of patients are asymptomatic. The average duration of illness is 14 days, but this stage may last from a few days to more than 10 weeks.³

Box 175.1 Signs and Symptoms of Acute Human Immunodeficiency Virus Infection

Lymphadenopathy

In time, the immune system recovers. CD8 cells proliferate, and the humoral immune system produces antibodies that lead to diminishing viremia. With the falling viral load, symptoms also subside. Testing for HIV-specific antibodies (e.g., ELISA) during the early phase often produces false-negative results because of the low levels of antibodies. Testing for viral p24 antigen and PCR testing of HIV RNA are other options.

As many as one half of all new HIV transmissions are estimated to occur from persons newly infected with HIV themselves. These people are likely to have extremely high viral loads, and many are unaware of their own HIV infection and therefore continue risky behaviors. The importance of establishing the diagnosis of acute HIV infection lies in early therapy for the individual and the decrease in transmission to others.

Current guidelines recommend antiretroviral therapy (ART) for symptomatic acute HIV infection. Early treatment decreases the viral load set-point, preserves immune function, suppresses the development of viral mutations, reduces transmission, and may slow the progression to AIDS.

Acute HIV infection is often not recognized in the primary care setting because the nonspecific symptoms resemble an influenza-like illness. When patients with febrile influenza-like illnesses are evaluated, clinicians need to consider inquiring about recent (past 2 to 6 weeks) high-risk behaviors. If suspicion of acute HIV infection arises, testing should include a plasma HIV RNA assay (viral load), or p24 antigen, in addition to HIV-specific antibody testing (ELISA). Consultation with an infectious disease specialist is warranted to arrange for further testing, to assist with initial ART, and to arrange a link to future care of the patient.

Opportunistic Infections

Opportunistic infections continue to be responsible for considerable morbidity and mortality in people infected with HIV. The introduction of ART has been profoundly beneficial in decreasing the number and severity of opportunistic infections. Unfortunately, not all HIV-infected people worldwide have access to ART, and resistance to ART continues to advance. The following sections discuss examples of opportunistic infections likely encountered in the ED.

Central Nervous System Infections

Toxoplasmosis

The protozoan Toxoplasmosis gondii is capable of causing focal encephalitis in HIV-infected patients with severe immune suppression. This condition is rarely identified in patients with CD4 cell counts higher than 200 cells/µL, and it is most commonly found in those with CD4 cell counts lower than 50 cells/µL. Symptoms include headache, fever, and confusion. More advanced encephalitis may cause seizures and coma. Physical examination findings may include focal weakness or stupor.

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