HIV

Background and Importance

Acquired immunodeficiency syndrome (AIDS) is a pandemic caused by the human immunodeficiency virus (HIV). HIV has caused tremendous human suffering and has had an immeasurable impact on demographics, cultures, economics, and politics in most societies around the globe. There are an estimated 37.9 million people living with HIV infection worldwide, and approximately 770,000 deaths annually. Significant strides have been made in areas of prevention and treatment. Since 2010 the number of new HIV infections has decreased by 16%, and the number of AIDS-related deaths by 33%. ^, Decline in the incidence of new cases of HIV infection and AIDS-related deaths is mostly due to the widespread use of highly active antiretroviral therapy (ART) and the treatment as prevention paradigm, resulting in a decline in the overall HIV incidence worldwide. Recent advances in HIV management have focused on the scale-up of preventative strategies such as preexposure prophylaxis (PreP), universal ART, and even same-day initiation (SDI). However, there is no cure for HIV and significant treatment gaps in at-risk populations have resulted in an increase in global HIV prevalence. Therefore, a significant number of patients in the ED may present with HIV coinfection, as well as ART-related or AIDS-related complications ( Figs. 121.1 and 121.2 ).

Pathophysiology

HIV, a retrovirus from the lentivirus subfamily, is the cause of AIDS. There are two main subtypes of HIV, HIV-1 and HIV-2. Worldwide, the predominant virus is HIV-1. HIV-1 accounts for around 95% of all infections worldwide. HIV-2 is estimated to be more than 55% genetically distinct from HIV-1. The relatively uncommon HIV-2 virus is concentrated in West Africa but has been seen in other countries with links to West Africa. It is less infectious and progresses more slowly than HIV-1, resulting in fewer deaths. HIV-1 can be further divided into four groups; group M is the strain responsible for the global HIV epidemic and can be further divided into nine genetically distinct subtypes. The individual characteristics of each of the subtypes are beyond the scope of emergency medicine, but clinicians should be aware that most ART is largely tested on populations with subtype B, and tests used to diagnose HIV may not be sensitive to all subtypes. This is a concern in places where diverse subtypes are prevalent.

The mature HIV virion is a spherical structure with an outer envelope and inner core ( Fig. 121.3 ). The core contains two copies of the RNA genome, enzymes (reverse transcriptase and integrase), and regulatory proteins. Surrounding the core is the viral membrane, containing the glycoproteins responsible for the attachment and entry of the virus into a CD4 ⁺ cell. In a multistep process, the HIV virion invades the host cell and integrates its genetic material into the host’s chromosome ( Fig. 121.4 ). The infection begins with the binding of the virus to the CD4 ⁺ host cell. The virus enters the cell by fusing its envelope with the target cell membrane. After internalization, reverse transcriptase forms viral DNA from the original RNA. The viral enzyme integrase then transports the newly formed viral DNA into the nucleus, where it integrates with human chromosomal DNA. Viral polyproteins and RNA are formed, and new infectious viral particles are created. This cycle continues with HIV infecting more CD4 ⁺ cells. Major targets of ART include reverse transcriptase, protease, integrase, and the CCR5 coreceptor.

The hallmark of HIV infection is CD4 ⁺ T cell destruction, leading to a deficient cell-mediated arm of the immune system. Humoral immunity is also impaired through B cell proliferation and the production of abnormal antibodies, making HIV-infected individuals more vulnerable to infections by encapsulated bacteria. HIV infection also leads to chronic immune activation. Ongoing viremia, along with pro-inflammatory cytokines, B cell proliferation, and hypergammaglobulinemia leads to a chronic inflammatory state that contributes to cardiovascular disease, cancer, and other chronic diseases in HIV-infected individuals. Increased immune activation persists, even in patients with immune reconstitution on antiretroviral therapy.

HIV has been isolated from a wide range of body fluids, including semen, vaginal secretions, lymphocytes, cell-free plasma, cerebrospinal fluid (CSF), tears, saliva, urine, and breast milk. However, only semen, blood, vaginal secretions, and breast milk are significantly infectious. For transmission to occur, these fluids must come into contact with damaged tissue or with a mucous membrane or be directly injected into the bloodstream. After transmission, the virus replicates in the mucosal surface or lymphoid tissue at the site of entry in lymphocytes and macrophages. If enough cells are infected, the virus spreads to draining lymph nodes and infection is established, usually within 48 to 72 hours.

Means of transmission of HIV and the demographic distribution of the virus vary from country to country. Unprotected heterosexual intercourse with subsequent transmission of HIV to newborns and breast-fed babies (mother-to-child transmission) is the dominant mode of transmission worldwide, accounting for about 85% of all HIV infections. The main pattern of transmission in the higher-income countries of North America and western and central Europe is in men who have sex with men (MSM) and direct injection into the bloodstream in patients with intravenous drug use (IVDU).

The risk of transmission varies by modality. The average risk of HIV infection after a needlestick or cut exposure to HIV-infected blood is 0.3% while the risk after exposure of the eye, nose, or mouth to HIV-infected blood is estimated to be, on average, 0.1%. For people who inject drugs, the risk of transmission per injection from a contaminated needle has been estimated to be between 0.7% and 0.8%. The risk estimates for the sexual transmission of HIV, per act, vary from 0.5% to 3.38% for receptive anal intercourse; 0.06% to 0.16% for insertive anal intercourse; 0.08% to 0.19% for male-to-female vaginal intercourse; and approximately 0.05% to 0.1% for female-to-male vaginal intercourse. Notably, the risk of HIV transmission is reduced by 99.2% with the combined use of condoms and antiretroviral treatment of the HIV-infected partner.

Acute HIV Infection

Acute HIV infection, also referred to as primary HIV infection, describes the earliest stage of infection with the HIV virus. Patients present with symptoms consistent with an acute, self-limited viral infection, including fever, fatigue, sore throat, pharyngitis, lymphadenopathy, muscle aches, diarrhea, and a rash. They can occur within a few days of exposure or up to 6 weeks after, and usually last about 14 days. Acute HIV infection can be complicated by encephalitis, Guillain-Barré syndrome, and mononeuritis. CD4 ⁺ counts also transiently drop, occasionally to the level at which opportunistic infections can occur. Among others, Pneumocystis jiroveci pneumonia (PCP), toxoplasmosis, cytomegalovirus (CMV) infection, and thrush may occur in this stage.

During this time, the virus is actively replicating and antibodies to HIV have not been produced. The virus has many potential targets and viral loads are often enormous. The diagnosis of acute HIV infection has significant public health benefits. Patients with acute HIV infection transmit the infection disproportionately; these patients often do not know that they are infected, and their viral load may be in the range of millions of RNA copies per milliliter.

Diagnosis of acute HIV infection requires remembering the constellation of symptoms and understanding the pitfalls of laboratory testing for early infection. The results of routine HIV antibody testing may be negative for several weeks or even months after exposure. The diagnosis of acute HIV infection is confirmed with the presence of high titers of viral RNA and a negative antibody screen. Assay reactivity is dynamic; a plasma RNA test will detect HIV infection approximately one week before the ability to detect the p24 antigen and 12 days before antibodies to HIV develop ( Table 121.1 ). A viral load test in the absence of symptoms of acute HIV infection is not recommended because false-positive results occur, and the test is costly.

Chronic HIV Infection

The second stage of HIV infection is chronic HIV infection (also known as asymptomatic HIV infection or clinical latency). Many patients have few or no clinical manifestations of HIV infection. There are several host and viral factors that are involved and affect the rate of progression. As a result, the asymptomatic period is variable; the average onset to AIDS from seroconversion is approximately 8 to 10 years. People who are taking ARTs may be in this stage for decades. Approximately 5% of patients are long-term nonprogressors (LTNP), sometimes also called elite noncontrollers; they are individuals who do not take ARTs and still maintain CD4 counts in the normal range indefinitely.

AIDS

AIDS is the final and most severe stage of HIV infection. Due to a severely immunocompromised state (CD4 ⁺ count <200 cells/μL), the body is unable to fight off opportunistic infections, which for diagnostic purposes are reported as AIDS-defining conditions ( Box 121.1 ). The types and frequency of opportunistic infections are more severe as the CD4 ⁺ count continues to deteriorate. Some infections are so common in patients with AIDS that primary prophylaxis is indicated and is cost-effective. Prophylaxis is started for PCP when CD4 ⁺ counts are less than 200 cells/μL, for toxoplasmosis when CD4 ⁺ counts are less than 100 cells/μL and, for Mycobacterium avium complex (MAC) infection when CD4 ⁺ counts are less than 50 cells/μL ( Table 121.2 ). Furthermore, isoniazid preventative therapy is given to all patients with a positive tuberculin skin test (TST) to prevent latent TB.

Clinical Manifestations by Organ System

Manifestations of HIV infection vary greatly, depending on the patient’s immune status and whether the patient is receiving ART. Some of the clinical manifestations are secondary to severe immunocompromise state and secondary opportunistic infections, and others are due to the proinflammatory pathology of the disease process.