7.3 Introduction to HIV, AIDS, and Antiretrovirals

Pathophysiology

The human immunodeficiency virus (HIV) is responsible for causing deterioration in the infected individual’s immune system, leaving them vulnerable to a variety of opportunistic infections and cancers. This state of immunodeficiency is known as acquired immunodeficiency syndrome (AIDS). Since HIV was first identified in the 1980s, highly effective medications for antiretroviral therapy (ART) have been developed to suppress the virus and delay the development of AIDS-defining illnesses such as Pneumocystis jirovecii pneumonia (PJP; previously known as Pneumocystis carinii pneumonia or PCP), cytomegalovirus (CMV) infection, and the cancer known as Kaposi’s sarcoma. However, HIV infection is a lifelong condition with no known curative treatment.

After the individual’s initial exposure to HIV, the virus targets the CD4 T lymphocytes (helper T cells). It binds to and fuses with the CD4 cell and then enters it. From there, the enzyme reverse transcriptase takes the HIV RNA and forms a complementary strand of DNA. The enzyme integrase then incorporates the viral DNA into the individual’s DNA, which causes the host cell to begin producing viral proteins. The enzyme protease then cuts the viral proteins into their mature form, and the new copy of the virus is ready to bud off from the infected cell to go infect a new CD4 cell (Figure 7.4). As this process continues, there is continual degradation in the number of CD4 cells available to fight infection, and the person becomes immunocompromised and more at risk for various opportunistic infections and cancers. Once an individual develops one of these opportunistic illnesses or their CD4 cell count drops <200 cells/mL of blood, they are considered to have AIDS. People with AIDS have badly damaged immune systems. Understanding the life cycle of the virus is important because these steps present different drug targets that can be used to suppress viral replication. HIV treatment can slow or prevent progression of the disease. There are three stages of HIV. The first stage is acute HIV infection, in which clients have a large amount of HIV in their blood and are very contagious. Many have flu-like symptoms. Stage two is chronic HIV infection, also called asymptomatic HIV infection or clinical latency. HIV is still active, and the client can still transmit the infection to others as it continues to reproduce in the body. The third stage is when the client is diagnosed with AIDS. This is the most severe form of HIV. Clients have a high viral load and can easily transmit the virus.

Figure 7.4 HIV attaches to the CD4 receptor of an immune cell and fuses with the cell membrane. Viral contents are released into the cell, where viral enzymes convert the single-stranded RNA genome into DNA and incorporate it into the host genome. (credit: “HIV Replication Cycle” by National Institute of Allergy and Infectious Diseases (NIAID)/Flickr, CC BY 2.0)

Clinical Manifestations

Upon initial infection, many individuals may have few to no symptoms. Early symptoms may mimic the symptoms of mononucleosis, including fever, enlarged lymph nodes, and fatigue. After several weeks, the virus enters a latent period, and the person becomes asymptomatic. This provides a false sense of security because the virus is continually replicating, and immune cell destruction is occurring steadily. Once the client’s CD4 cell count falls to less than 200 cells/mL of blood, the client may present with an opportunistic infection such as PJP, which may be the first time the client is evaluated for HIV infection. Without HIV treatment, people with AIDS typically survive about 3 years due to complications caused by opportunistic infections and malignancies. People who are treated for HIV in stage one or two may never move into stage three. Without HIV treatment, stage two may last a decade or longer. At the end of this stage, the viral load of HIV in the blood increases and the person may move into stage three (AIDS).

HIV Transmission

HIV transmission can occur in different ways. Many bodily fluids from an infected individual, including blood, breast milk, semen, and vaginal fluids, contain the virus. These fluids can then be transmitted to an uninfected person via unprotected sexual intercourse, sharing of contaminated needles during injection drug use, or perinatal transmission from a pregnant client to their fetus. The type of sexual exposure can also affect the possibility of transmission of the virus to uninfected individuals. The risk of transmission is low during oral intercourse. Transmission rates are higher for penile–vaginal intercourse, and anal intercourse, especially receptive anal intercourse, carries the highest risk for transmission.

One factor that may influence the risk for viral transmission is the infected individual’s viral load, or the number of copies of the viral RNA that are measured in the blood. The higher the viral load in the blood, the more likely the infected individual’s fluids will contain copies of the virus capable of infecting another individual. This is why viral suppression with ART can help prevent the spread of HIV, along with other techniques such as using condoms and clean needles.

Laboratory Testing

Testing for and diagnosing HIV infection can be done with several types of tests, including antibody tests, antigen/antibody tests, and nucleic acid tests. The first two tests look for the presence of antibodies against the virus that the body has produced; therefore, the test may be negative if the client was recently infected and has not had time to develop antibodies. The nucleic acid test looks for copies of the viral RNA and can detect the presence of HIV sooner than antibody-based tests can. It is important for high-risk individuals (e.g., those who share needles, those who have unprotected sex with multiple partners) to be screened more often for HIV to ensure early diagnosis because treatment with ART can preserve immune function for as long as possible.

Two primary laboratory tests are used to track the efficacy of ART in HIV-infected individuals. The first is the viral load, which is a measure of how actively the virus is reproducing itself. The second is the CD4 cell count, which shows the degree of immune system degradation that has occurred and the degree of risk for developing opportunistic infections. Ideally, under ART treatment, the HIV viral load will be undetectable, and the CD4 cell count will be 500–1600 cells/mm³. The CD4 cell is a type of white blood cell that plays a key role in the immune system by alerting other immune cells to the presence of infections in the body.

Testing can also be performed to determine the sensitivity or resistance to a variety of ART drugs. This is helpful to make sure that any treatment the client is receiving will be able to sufficiently suppress viral replication. HIV is prone to making mistakes when it copies itself, which leads to frequent mutations that induce resistance to various ART drugs, so sensitivity testing is critical to choosing an effective regimen.

Antiretroviral Drugs

Treatment of HIV is an ever-evolving subject, with guidelines frequently recommending different preferred ART regimens based on up-to-date research. The best place to get accurate, timely recommendations for ART is through the National Institutes of Health’s HIV information website. For effective ART, multiple drugs utilizing different mechanisms of action are used together to synergize and suppress viral replication. The client’s adherence is critical to achieve viral suppression and preserve their immune function. Nonadherence will often lead to viral resistance against ART drugs. Choosing combination products that reduce the number of pills a client takes in a day can help decrease regimen complexity and increase adherence.