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HIV/AIDS: an update.

Article Excerpt
After completing this article, readers should be able to:

* Discuss evidence that the human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS).

* Describe the life cycle of the virus.

* Summarize epidemiologic trends for HIV/AIDS, both in the United States and in other parts of the world.

* Name the 4 types of drugs used to treat HIV/AIDS and explain why and how patients' treatment regimens might be changed.

* List recommended strategies for AIDS prevention programs.

* Discuss the role of imaging in treating HIV/AIDS.

Acquired immunodeficiency syndrome (AIDS) was first reported in the United States in 1981 and has a worldwide pandemic since. Experts suspect that AIDS is caused by the human immunodeficiency virus (HIV). By contributing to the destruction or functional impairment of immune system cells, notably cluster of differentiation 4 (CD4) receptor T-lymphocytes (T-cells), HIV progressively destroys the body's ability to fight infections and certain cancers. An HIV-infected person is diagnosed with AIDS when his or her immune system is seriously compromised and manifestations of HIV infection are severe.

The U.S. Centers for Disease Control and Prevention (CDC) defines AIDS in an adult or adolescent aged 13 years or older as the presence of 1 of 26 conditions indicative of severe immunosuppression associated with HIV infection. An example of 1 such condition is Pneumocystis carinii pneumonia (PCP), a disease that is extraordinarily rare in people without HIV infection. Most other AIDS-defining conditions are also opportunistic infections that rarely harm healthy individuals. A diagnosis of AIDS is made when an HIV-infected individual's CD4 T-cell count falls below 200/[micro]L. Normally, adults have approximate CD4 T-cell counts between 600 and 1500/[micro]L. In HIV-infected children younger than 13 years old, the CDC definition of AIDS is similar to that of adolescents and adults, except for the addition of certain infections commonly seen in pediatric patients with HIV.

In many developing countries, where diagnostic facilities may be minimal, health care workers use the World Health Organization (WHO) AIDS case definition based on the presence of clinical signs associated with a deficient immune system and the exclusion of other known causes of immunosuppression, such as cancer or malnutrition. An expanded WHO AIDS case definition, with a broader spectrum of clinical manifestations of HIV infection, is used in settings where HIV antibody tests are available.

Much evidence suggests that HIV causes AIDS. The strongest proof is that HIV fulfills Koch's postulates as the cause of AIDS. Koch's postulates have been used since the late 19th century to prove links between presumed pathogenic (ie, disease-causing) agents and disease. Three postulates form the litmus test for determining the cause of any epidemic disease: 1) an epidemiological association in which the cause must be strongly associated with disease, 2) isolation and propagation of the suspected pathogen outside the host and 3) transfer of the suspected pathogen to an uninfected host, either man or animal, that produces the disease in the host.

As far as postulate #1 is concerned, numerous studies from around the world have shown that virtually all AIDS patients are HIV-seropostive (ie, they carry antibodies that indicate HIV infection). With regard to postulate #2, modern culture techniques have isolated HIV in virtually all patients with AIDS, as well as in almost all HIV-seropositive individuals with both early- and late-stage disease. In addition, polymerase chain reaction and other sophisticated molecular techniques have enabled researchers to document the presence of HIV genes in virtually all patients with AIDS, as well as in individuals in earlier stages of HIV disease. Postulate #3 was demonstrated by tragic incidents involving 3 laboratory workers with no other risk factors who developed AIDS or severe immunosuppression after accidental exposure to concentrated, cloned HIV in the laboratory. In all 3 cases, HIV was isolated from the infected individual, sequenced and shown to be the infecting strain of virus.

In addition, through December 1999 the CDC had received reports of 56 health care workers in the United States with documented, occupationally acquired HIV infection, of whom 25 have developed AIDS in the absence of other risk factors. The development of AIDS following known HIV seroconversion also has been observed many times in pediatric and adult blood transfusion patients, in mother-to-child transmission and in studies of hemophilia, injection drug use and sexual transmission in which seroconversion can be documented using serial blood samples. In a 10-year investigation in the Netherlands, researchers studied 11 children who were infected with HIV as neonates by small samples of plasma from a single HIV-infected donor. During the 10-year period, 8 of the children died of AIDS. The remaining 3 children all showed a progressive decline in cellular immunity and 2 of the 3 had symptoms probably related to HIV infection. These tragic accidents confirm the third part of Koch's postulates and strongly suggest that the HIV virus indeed does cause AIDS. (1)

Most scientists think that HIV causes AIDS by directly bringing about the death of CD4 T-cells or interfering with their normal function, and by triggering other events that weaken a person's immune function. For example, the network of signaling molecules that normally regulates a person's immune response is disrupted during HIV infection, impairing a person's ability to fight other infections. The HIV-mediated destruction of the lymph nodes and related immunologic organs plays a role in causing the immunosuppression seen in people with AIDS.

Although HIV was first identified in 1983, studies of previously stored blood samples indicate that the virus entered the U.S. population sometime in the late 1970s. The CDC reported a total of almost 1.2 million cases of AIDS in the United States through 2005 and 522 723 deaths among people with AIDS through the end of 2004, the most recent years for which data are available. (2) Approximately 40 000 new HIV infections occur each year in the United States; 70% of these are in men and 30% in women. (3)

Pathogenesis and the Life Cycle of HIV

HIV is a retrovirus in which the genetic material is encoded in 2 single ribonucleic acid (RNA) strands instead of the regular double-stranded deoxyribonucleic acid (DNA). HIV contains the enzyme reverse transcriptase, which transcribes RNA into DNA in a host cell. This is an opposite process from the normal way DNA transcribes RNA in plant and animal cells. The core of the HIV virus is composed of the 2 RNA strands, reverse transcriptase and 2 other enzymes, protease and integrase. It is surrounded by a lipid envelope composed of glycoproteins gp120 and gp41. HIV binds the gp120 molecule on its lipid envelope to the CD4 surface molecule on the T-cells, monocytes and macrophages. HIV then uses CD4 and a coreceptor to enter the cell. (4)

Once the HIV is attached to the T-cell, the viral protein core releases viral RNA and the enzymes into the host cell's cytoplasm. Reverse transcriptase transcribes the viral RNA into viral DNA. The viral DNA then is inserted into the host's DNA by the enzyme integrase. At this point, the virus might remain quiescent in an infected host or it might replicate actively. If assembly of the virus begins, the infected host's immune system is activated by antigens, mitogens or cytokines. Then viral DNA is transcribed into...

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