BIOLOGY Volume 2 - A Guide to General Biology - 2004

15. HEALTH AND DISEASE

15.3. Infectious Diseases

15.3.4. Acquired Immunodeficiency Syndrome (AIDS)

It is believed that the HUMAN IMMUNODEFICIENCY VIRUS (HIV), which causes AIDS, was introduced to America and Europe from Central Africa. It was first identified in the United States, and subsequently, the virus was detected in 71 other countries. By the end of 1993, the number of infected individuals reached 14 million, with 3 million actually suffering from AIDS. By 1995, the number of HIV-infected individuals had already risen to 23 million (Fig. 15.10), with 3.1 million newly infected that year and 1.5 million deaths from AIDS. Typically, HIV is diagnosed in people under 25 years of age, with half of those infected being women. Figure 15.10 shows that the AIDS problem is most acute in sub-Saharan Africa, which accounts for the highest number of new cases. The disease is spreading rapidly in Asia (primarily in India, China, Vietnam, and Cambodia), as well as in Central and Eastern Europe.

HIV is an RNA-containing virus, The Structure of which is shown in Fig. 2.21 (see also Figs. 2.23 and 2.24). As its full name implies, it attacks the human immune system, or more specifically, replicates within T4 lymphocytes, also known as T-helper Cells (see Section 14.9.2). As a result, they lose their ability to "help" other lymphocytes—in particular, they cease to stimulate the proliferation of T-killer cells, which are responsible for destroying pathogens that have entered the body. The human immune system breaks down, leaving the individual vulnerable to infectious diseases (see below). It is important to understand, however, that HIV infection is not synonymous with AIDS. Some HIV-infected individuals remain asymptomatic carriers of the pathogen for many years.

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Fig. 15.10. Estimated numbers of HIV-infected adults in various Regions of the world in 1996. (From UNAIDS Geneva.)

Transmission Routes and Symptoms

HIV survives only in certain Body Fluids and is usually transmitted via Blood or semen. In 90% of cases, transmission occurs through sexual contact. Individuals become infected through the following routes.

1. Sexual contact. Initially, AIDS was considered a disease of homosexuals because it was particularly prevalent in large American cities such as San Francisco, Los Angeles, and Miami, which have large populations of non-heterosexual individuals. Later, it became clear that transmission also occurs through heterosexual contact. HIV is transmitted via vaginal, anal, and oral intercourse, with the risk of infection increasing in proportion to the number of sexual partners. In America and Europe, homosexuals and bisexuals still predominate among those infected with HIV, but in Africa, many of those affected are heterosexual. In Western countries, sex workers should probably be considered the highest-risk group. It is estimated that by October 1988, 50,000 HIV cases were registered in Great Britain, 85% of which were among homosexuals. It was projected that over the following 10–15 years, the majority of them would die of AIDS.

2. Introduction of infected blood into the body. HIV spreads rapidly among drug users who share non-sterile needles and syringes. Officially, it is estimated that in New York City, 60% of the 250,000 intravenous heroin users are already HIV-infected. From drug users, the virus can be transmitted to their sexual partners. Transmission also occurs through transfusions of blood and blood products (such as Factor VIII, required by hemophiliacs) containing the virus. As a result of implementing universal screening (testing for the presence of HIV) of donor blood in countries with well-established healthcare systems, this route of transmission has now been virtually eliminated.

The virus can also be transmitted through contact with a patient's blood, for example, when treating their wounds or during surgical Procedures, which requires special caution from healthcare workers.

3. Mother-to-child transmission. From an HIV-infected woman, the virus can cross the Placenta into the fetus's bloodstream during prenatal development and during childbirth, and can also be transmitted to the newborn via breast milk. The probability of infection through these routes is estimated at 25–50%.

The virus binds to receptors On the surface of T4 lymphocytes and then "injects" its RNA into The Cell (Fig. 2.23). Using the viral RNA as a template, a complementary DNA strand is synthesized with the aid of an enzyme called Reverse Transcriptase (Sections 2.4.5 and Fig. 2.23). This DNA copy (provirus) enters the lymphocyte's Nucleus and integrates into its genome, thereby becoming a permanent component of the infected cell. When lymphocytes divide, the provirus replicates along with their DNA, resulting in a rapid increase in the population of infected T4 cells within the body.

The viral DNA may remain dormant for up to six years—this is known as the latent period of the disease. However, at some point, for reasons that remain unclear, the lymphocyte begins synthesizing RNA copies of the HIV genes. This mRNA migrates from The Nucleus to the Cytoplasm and "forces" the cell to work for it: synthesizing viral Proteins and RNA. New Viral Particles assemble from these components and leave the cell by budding off its surface (Fig. 2.24). They infect still-healthy T4 lymphocytes, as well as Cells of the Brain and certain other Organs. Ultimately, all cells in which the virus replicates will die.

According to current data, AIDS develops annually in 1–2% of HIV-infected individuals, while AIDS-related symptoms appear in 5–10%.

There are four distinct Phases of the disease.

1. Primary HIV infection is accompanied by The production of Antibodies against the virus and, in some cases, a brief flu-like malaise. A rash may appear, and Lymph Nodes may swell. These symptoms resolve easily without hospitalization.

2. The second phase is the HIV-positive asymptomatic stage. It is characterized by the persistent presence of HIV antibodies in the blood; anywhere from several weeks to well over 13 years may pass between infection and the appearance of clinical signs of the disease.

3. The third phase is characterized by The Development of AIDS-associated, so-called opportunistic infections, although at this stage they are not yet life-threatening. These involve common bacterial, viral, and fungal diseases that show increased resistance to Treatment. Typical Examples include oral or genital herpes and tinea pedis (athlete's FOOT). Wasting, with a loss of up to 10% of body weight, may occur. The count of T-helper cells drops significantly.

It is precisely at this stage that proper medical and psychological support becomes necessary, as the patient not only suffers from symptoms during this period but also begins to face a genuine threat to their life.

4. The fourth phase—AIDS proper—is characterized by severe opportunistic infections affecting multiple organs and the development of secondary malignancies. The patient experiences severe weight loss and complains of extreme fatigue. This wasting may be caused by Intestinal Cancer leading to nutrient malabsorption, or by catabolic processes prevailing over anabolic ones, causing the body to essentially "burn out" without managing to recover the losses associated with Respiration. Opportunistic infections can be bacterial, viral, or fungal; protozoan infections are also present in many cases (Table 15.8).

Fig. 15.11. Progression of HIV infection. Many people die upon contracting their first serious opportunistic infection. Determining the exact onset of the terminal stage of the disease is very difficult. Anywhere from several months to, at times, years of a latent period may pass between HIV infection and the Clinical presentation of AIDS.

Table 15.8. Diseases correlating with HIV infection

Diagnostic testing

To determine whether an individual is infected with HIV, a blood test is required. The immune system is known to respond to the invasion of pathogens by producing antibodies. A sample of the blood being tested is mixed with commercially produced HIV proteins. If antibodies against the virus are present in the blood, the reaction is positive, and the tested patient is referred to as HIV-positive. However, a negative result does not completely rule out infection, as a sufficient concentration of antibodies for detection by standard Methods sometimes takes up to three months or even longer to accumulate in the blood following exposure.

Treatment and Prevention

Since AIDS is caused by a virus, Antibiotics that kill Bacteria are ineffective against the disease. As with other viral infections, treatment in this case is primarily symptomatic and supportive.

Currently, three main approaches are being pursued in the search for treatments and prevention strategies for AIDS:

1) restoring the patient's immune system;

2) developing drugs that suppress viral Replication, as well as opportunistic infections and symptoms developing in HIV-positive patients;

3) developing an HIV vaccine.

These three approaches are discussed below.

RESTORING THE IMMUNE SYSTEM. The most logical way to help the body fight the virus is to strengthen its immune system. For instance, in vitro studies have shown that T-suppressor cells inhibit HIV replication. There are also documented cases of HIV-infected individuals in whom viral particles are undetectable in the blood. In 1987, it was discovered that if T-suppressor cells are removed from the blood samples of such patients (who have HIV antibodies but no detectable virus by standard methods), the virus begins to replicate. Reintroducing these cells back into the blood halts HIV replication once again. Consequently, introducing the virus into the body does not necessarily lead to disease; in other words, AIDS can to some extent be viewed as an infection dangerous only to individuals with an already compromised immune system (immunodeficiency).

In the treatment of leukemia, healthy bone marrow transplantation has proven highly effective. The success of the Procedure depends on the genetic compatibility of the donor and recipient, who ideally should be identical twins. Theoretically, a similar approach is applicable to AIDS: introducing a source of immune cells into the patient. Unfortunately, at present, noticeable success has only been achieved by combining bone marrow transplantation (from an identical twin) with antiviral medications and lymphocyte transfusions.

Another promising approach relies on proteins called lymphokines (derived from "lymphocyte" and the Greek kinein, meaning to move). These proteins are produced in small quantities by lymphocytes and, by diffusing among various Components of the immune system, coordinate their activity. Enhancing this coordination through lymphokines helps the body combat Viruses and cancer cells. Among lymphokines, the best known are interferons. They are widely used in cancer treatment. For example, alpha-interferon has achieved some success in treating Kaposi's sarcoma (a common skin cancer in AIDS). A similar clinical effect is produced by another immune system activator from the lymphokine group, interleukin.

Drug development

1. Azidothymidine (AZT), also known as zidovudine, is the best-known AIDS medication. Used since 1986, it has undoubtedly prolonged the lives of many patients. Side effects include anemia, which requires frequent blood transfusions. Additionally, the drug is expensive, and demand far exceeds supply.

2. Zalcitabine is structurally similar to azidothymidine and, like it, inhibits HIV replication in cell culture. Unfortunately, this drug is too toxic for humans, and its Prospects for treating AIDS remain unclear.

3. Glycyrrhizin is a substance found in licorice ROOT, used to treat hepatitis and certain types of allergies. Japanese researchers have demonstrated its ability to suppress HIV replication. Clinical trials have not yet been conducted.

4. Ribavirin is used in many countries to treat Influenza and other viral infections. In laboratory settings, it effectively inhibits HIV replication and increases the count of T4-lymphocytes without damaging infected cells.

Other AIDS medications are currently under development and testing. However, testing new drugs presents serious challenges in this context. First, the question arises whether it is ethical to administer a new drug to an experimental group of patients while giving a placebo—a deliberately ineffective substance—to a control group for comparison. Second, how can one weigh the side-effect risks of an insufficiently tested agent against the risk of dying from AIDS? Patients with nothing to lose are willing to take any medication if there is even the slightest hope of recovery. Nevertheless, official clinical approval for new drugs can only be granted after standard trials—comparing their effects with a placebo, studying toxicity, and so forth. Another crucial factor is the cost of the medications. Is it justifiable to invest massive resources into large-scale drug production if the drugs are insufficiently tested and their efficacy remains unproven?

VACCINE. The ideal protective measure against HIV infection would be a vaccine. The main difficulty in developing one is the immunodeficiency virus's ability to alter its genetic structure and, consequently, its surface proteins, which must be recognized by antibodies. Another challenge relates to the safety of an AIDS vaccine. It must contain an attenuated (weakened) virus capable of triggering an Immune Response without causing the disease itself. This is how Vaccines against measles, polio, rubella, and other viral infections work. However, even weakened viruses cause disease in certain individuals, and if that disease is AIDS, finding volunteers willing to receive experimental and preventive inoculations would be difficult.

Despite intensive research conducted worldwide, an HIV vaccine suitable even for human trials has not yet been developed. The most encouraging result in this field is the isolation of certain HIV protein Antigens, which are currently being tested on laboratory animals.

Even if a vaccine is successfully developed, aside from the formidable challenges of verifying its efficacy and safety in humans, numerous questions will arise that are currently scarcely discussed. Who should be vaccinated, and at what age? Should AIDS vaccination be a mandatory requirement for employment, marriage, obtaining an entry visa, or securing medical insurance? Will it be voluntary, mandatory, or mandatory for high-risk groups while voluntary for others? Can minors be vaccinated without parental consent? If so, should vaccination records be protected by medical confidentiality?

In the meantime, to protect against AIDS, adhering to the following straightforward precautions is recommended.

1. During sexual contact, one should isolate oneself from a partner's blood and semen using a condom. Due to the risk of AIDS, this traditional contraceptive method is experiencing a surge in demand globally.

2. Casual sexual encounters should be avoided; ideally, one should have a single, trusted partner.

3. Intravenous drug users must use sterile (ideally disposable) syringes and needles. In some European countries, such as the Netherlands, these are distributed free of charge to this vulnerable group.

4. All donated blood must be screened for HIV antibodies. In the UK, this rule has been strictly enforced since 1985.

5. Medical professionals have a duty to educate the public on the routes of transmission of the virus. People need to know that HIV is not spread via airborne droplets or through brief casual contact such as a handshake. Doctors and nurses caring for AIDS patients have never contracted the virus through such means.