HIV

Shortly after the first cases of acquired immunodeficiency syndrome (AIDS) were recognized among civilians in 1981, early forms of the disease (AIDS-related complex and lymphadenopathy syndrome) were detected among active duty personnel. The causative virus (now called the human immunodeficiency virus, HIV) was first isolated from ill soldiers and their asymptomatic but nonetheless infected wives in 1984. These military studies provided the first proof that HIV could be transmitted through heterosexual intercourse. Nationwide blood bank testing for HIV began in June 1985. Shortly thereafter, in October 1985, the Department of Defense (DoD) began screening all civilian applicants for military service; those who tested positive for the virus were medically disqualified from service. Overall, 1 in 650 applicants was found to be infected, but prevalence rates in various geographic and demographic subpopulations varied from as low as 1 in 20,000 in the upper Midwest to 1 in 50 in northeastern urban centers. The HIV screening program was the first population-based screening program in the United States, and provided the first hard data that the epidemic had already spread silently throughout the country by the mid-1980s.
HIV screening of active duty military personnel began in 1986. Based largely on the recommendations of the Armed Forces Epidemiological Board, policies for HIV infection were established to be comparable to those for any other chronic medical condition. Infected military personnel were to remain on active duty, to lodge in military quarters, and to continue work in their duty assignment. Implemented at a time when fear of HIV contagion was widespread in the United States, these policies were farsighted and courageous. All DoD HIV-positive personnel were to be medically evaluated periodically, and those with advanced disease were honorably discharged with medical disability and benefits. HIV-infected personnel were restricted from overseas deployment, from health care jobs where potentially risky procedures were performed, and from sensitive Personal Reliability Program (e.g., nuclear missile) positions. In an effort to decrease HIV transmission, HIV-infected active duty personnel were counseled by their commanders that if they knowingly put others at risk of infection through sexual intercourse, they could be prosecuted through the military justice system. Overall, DoD policies were designed to reflect fair and rational public health principles.
Screening was originally undertaken annually for all active duty personnel, but this interval has gradually lengthened with a number of new service-specific regulations. For example, testing takes place every five years for all air force personnel, or for the following clinically indicated reasons: during pregnancy; on entry into a drug/alcohol rehabilitation program; on presenting at a STD (sexually-transmitted disease) clinic; on deployment overseas; on PCS (Permanent Change of Station) overseas. However, all personnel must be proven negative within six months of any overseas deployment.
The U.S. military HIV research program began in 1986, when Congress provided $40 million for this purpose. The U.S. Army Medical Research and Development Command, as the lead agency for infectious disease research, managed the tri-service program. Major accomplishments include the following firsts: definition of antibody test criteria for a diagnosis of HIV (criteria used worldwide today); evidence that HIV was becoming a serious problem among minorities; detection of transmission of drug-resistant HIV strains; tracking the global spread of genetic variants; vaccine therapy trials; and international preventive vaccine trials.
At the heart of the controversy over HIV/AIDS research is the question of its relevance to the military. HIV/AIDS has little or no direct impact on readiness or combat operations for U.S. forces. However, recent studies have shown very high HIV prevalences among some African (one in four) and Asian (one in ten) military populations. From a broader national security point of view, the global pandemic is a threat requiring maximal efforts by all capable U.S. agencies.
Rates for new infections have decreased; in 1995, the DoD's total of infections among active duty personnel was approximately 300. In 1996, an amendment to the department's authorization bill ruled that all HIV-infected personnel on active duty must be involuntarily separated, regardless of their fitness for duty or years of service; however, as of 1999, the policy was not to separate HIV-infected personnel who were physically fit. The impact of this legislation on the effectiveness of public health control of HIV within the military remains to be determined.


HIV

HIV, the human immunodeficiency virus, is the virus that causes AIDS, a debilitating and deadly disease of the human immune system. HIV is one of the world's most serious health problems: at the end of 2001, more than 40 million people worldwide were infected with HIV and living with the virus or AIDS. The World Health Organization estimates that about 20 million people have died from AIDS since the infection was first described in 1981. Nearly 500,000 of those deaths have occurred in the United States. Although there is no cure for the disease, therapies exist that reduce the symptoms of AIDS and can extend the life spans of HIV-infected individuals. Researchers are also pursuing protective vaccines, but a reliable vaccine might still require years to develop.

Hiv and Aids

HIV infects certain cells and tissues of the human immune system and takes them out of commission, rendering a person susceptible to a variety of infections and cancers. These infections are caused by so-called opportunistic agents, pathogens that take advantage of the compromised immune system but that would be unable to cause infection in people with a healthy immune system. Rare cancers such as Kaposi's sarcoma also take hold in HIV-infected individuals. The collection of diseases that arise because of HIV infection is called acquired immune deficiency syndrome, or AIDS. HIV is classified as a lentivirus ("lenti" means "slow") because the virus takes a long time to produce symptoms in an infected individual.

Hiv Life Cycle: Entering Cells

Like a typical virus, HIV infects a cell and appropriates the host's cellular components and machinery to make many copies of itself. The new viruses then break out of the cell and infect other cells. HIV stores its genetic information on an RNA molecule rather than a DNA chromosome. This is a distinguishing characteristic of retroviruses, which are viruses that must first convert their RNA genomes into DNA before they can reproduce.

Each HIV virion (viral particle) is a small sphere composed of several layers. The external layer is a membrane coat, or envelope, obtained from the host cell in which the particle was made. Underneath this membrane lies a shell made from proteins, called a nucleocapsid. Inside the protein shell are two copies of the virion's RNA genome and three kinds of proteins, which are used by the virion to establish itself once inside the cell that it infects.

Two proteins, called gp120 and gp41, enable the virion to recognize the type of cell to enter. These proteins project from the HIV membrane coat. Gp120 binds to two specific proteins found on the target cell's surface (these target-cell proteins are called receptors). The first receptor, CD4, is found on immune system cells known as CD4 T cells, and also sometimes on two cell types known as macrophages and dendritic cells. The immune system uses CD4 T cells in the initial step in making antibodies against infectious agents. After binding to CD4, the HIV protein called gp120 binds with a second cell membrane protein, commonly referred to as the co-receptor. The co-receptor can be one of many different proteins, depending on the cell type. The two most common are CXCR4, which is normally found on CD4 T cells, and CCR5, a receptor found on CD4 T cells as well as on certain macrophages and dendritic cells. In the absence of HIV, CXCR4 and CCR5 allow these immune system cells to respond to chemical signals, but when HIV infects the cells, the HIV commandeers their usage. In some cases, individuals have a mutation in their co-receptor that prevents HIV from entering their cells.

Once gp120 has bound to both the CD4 receptor and co-receptor, the gp41 protein fuses HIV's membrane envelope with the cellular membrane, injecting the virus into the target cell. Once in the cytoplasm, the viral protein shell opens up and releases the viral proteins—a reverse transcriptase, a viral integrase, and a protease—along with the viral RNA strands. The reverse transcriptase copies the RNA strands into DNA. The viral integrase then helps insert the DNA copies into the cell's chromosome. At this point, the virus is called a provirus, and the life cycle halts. The provirus may remain dormant in the cell's chromosome for months or years, waiting for the T cell to become activated by the immune system.

Hiv Life Cycle: Reproduction

When the immune system recruits T cells to fight an infection, the T cells start producing many proteins. Along with the normal cellular protein products, a T cell carrying an HIV provirus also produces HIV proteins. The first HIV proteins made are called Tat and Rev. Tat encourages the cellular machinery to copy HIV's proviral DNA into RNA molecules. These RNA molecules are then processed in the nucleus to become templates for several of the HIV proteins, some of whose functions are not well understood.

Rev, on the other hand, ushers the HIV's RNA molecules from the nucleus, where they are being reproduced, into the host cell's cytoplasm. Early in HIV reproduction, with only a few RNA molecules from which to make protein, a small quantity of Rev is made. Therefore, most of the RNA molecules remain in the nucleus long enough to get processed. As time passes, however, and Tat continues to instigate RNA production, more Rev is made. A higher amount of Rev protein increases the speed with which RNA molecules are ejected from the nucleus. These RNA molecules, which have undergone little or no processing, become templates to make different HIV proteins. The newer proteins are made in long chains that require trimming before they become functional. One of the proteins in the chain is the protease, the protein that trims. Other proteins include those that make up the protein shell, the reverse transcriptase, and integrase.

After the newly created proteins are processed to the right size, they form new virions by first assembling into a shell, then drawing in two unprocessed RNA molecules and filling up the remaining space with integrase, protease, and replicase. The new virions bud from the host-cell membrane, appropriating some of that membrane to form an outer coat in the process. The mature virus particles are now ready to infect other cells.

Hiv's Immune-System Impairment Mechanism

One of the most disastrous effects of HIV infection is the loss of the immune system's CD4 T cells. These cells are responsible for recognizing foreign invaders to a person's body and initiating antibody production to ward off the infection. Without them, people are susceptible to a variety of diseases. HIV destroys the T cells slowly, sometimes taking a decade to destroy a person's immunity. However, in all the time before an HIV-infected individual shows any symptoms, the virus has been reproducing rapidly. The lymph tissue, the resting place for CD4 T cells, macrophages, and dendritic cells, becomes increasingly full of HIV, and viral particles are also released into the bloodstream.

HIV's main target is the population of CD4 T cells within a host's body. HIV kills them in one of three ways. It kills them directly by reproducing within them, then breaking them upon exit; it kills them indirectly by causing the cells to "commit suicide" by inducing apoptosis; or it kills them indirectly by triggering other immune cells to recognize the infected T cell and kill it as part of the immune system's normal function.

As infected T cells die, the immune system generates more to take their place. As new T cells become infected, they are either actively killed or induced to commit suicide. Meanwhile, the HIV virus is not completely hidden from the immune system. As with any infectious agent, HIV presents its proteins to the immune system, which develops antibodies against it. This antibody production, however, is hampered by the fact that HIV mutates rapidly, changing the proteins it displays to the immune system. With each new protein, the immune system must generate new antibodies to fight the infection. Thus, an HIV infection is a dramatic balance between a replicating, ever changing virus and the replenishing stores of T cells that are fighting it. Unfortunately, the immune system, without therapeutic intervention, eventually loses the battle.

Once the CD4 T cells are depleted, the immune system can no longer ward off the daily bombardment of pathogens that all human organisms experience. Common infectious agents thus overwhelm the system, and HIV patients become susceptible to a variety of "opportunistic" diseases that take advantage of the body's reduced ability to fight them off. AIDS doctors report at least twenty-six different opportunistic diseases specific to HIV infection. These include unusual fungal infections such as thrush. The chickenpox virus may come out of dormancy, manifesting itself as the painful disease known as shingles. An obscure form of pneumonia, called pneumocystis pneumonia, is also common in AIDS patients. In addition, patients can acquire cancers such as B-cell lymphoma, which is a cancer of the immune system. Doctors generally consider patients with fewer than 200 CD4 T cells per cubic milliliter of blood as having AIDS. (In contrast, a healthy person counts more than 1,000.)

Anti-Hiv Drug Therapy

Drugs that interfere with viral replication can slow down HIV disease. Early trials relied on the administration of one drug at a time. While patients' health improved and their T cell count rose, in time HIV mutated enough to render the drugs ineffective. Since 1995, however, doctors have found that rotating patients through three different drugs in very high doses significantly improves the health of AIDS patients. Known as "highly active antiretroviral therapy" (HAART), this therapeutic approach also reduces the amount of HIV circulating in the bloodstream to nearly undetectable levels. People infected with HIV who are treated by HAART are now living longer, healthier lives than ever before.

Targeting Life-Cycle Points

Drugs meant to knock out HIV target the activities of two HIV proteins, the reverse transcriptase and the protease. HAART requires drugs of both types. Drugs called protease inhibitors prevent the viral protease from trimming down the large proteins made late during infection. Without those proteins, the viral shell cannot be assembled. In addition, the proteins that reproduce HIV's genetic information, the reverse transcriptase and the integrase, are not functional.

Drugs that inhibit the reverse transcriptase prevent it from copying the RNA into DNA. These drugs work early in the life cycle of HIV. Reverse transcriptase inhibitors include azidothymidine (AZT), whose structure resembles the DNA nucleotide thymine. When reverse transcriptase builds DNA with AZT instead of thymine, the AZT caps the growing DNA molecule and halts DNA production, due to AZT's slight difference in structure from the thymine that DNA production requires.



HIV
Retrovirus associated with AIDS. HIV attacks and gradually destroys the immune system, leaving the host unprotected against infection. It cannot be spread through casual contact but instead is contracted mainly through exposure to blood and blood products (e.g., by sharing hypodermic needles or by accidental needle sticks), semen and female genital secretions, or breast milk. A pregnant woman can pass the virus to her fetus across the placenta. The virus first multiplies in lymph nodes near the site of infection. Once it spreads through the body, usually about 10 years later, symptoms appear, marking the onset of AIDS. Multidrug "cocktails" can delay onset, but missing doses can lead to drug resistance. Like other viruses, HIV needs a host cell to multiply. It attacks helper T cells and can infect other cells. A rapid mutation rate helps it foil both the immune system and treatment attempts. No vaccine or cure exists. Abstinence from sex, use of condoms or other means to prevent sexual transmission of the disease, and avoidance of needle sharing have reduced infection rates in some areas.


HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. HIV-2, seen more often in western Africa, has a slower course than HIV-1. There are many strains of both types and the virus mutates rapidly, a trait that has made it especially difficult for researchers to find an effective treatment or vaccine. In many cases, a person's immune system will fight off the invasion of HIV for many years, producing billions of CD4 cells daily, always trying to keep up with the HIV's mutations, before it succumbs and permits the well-known signs of AIDS to develop.

HIV is especially lethal because it attacks the very immune system cells (variously called T4, CD4, or T-helper lymphocytes) that would ordinarily fight off such a viral infection. Receptors on these cells appear to enable the viral RNA to enter the cell. As with all retroviruses, once the RNA is inside the cell, an enzyme called reverse transcriptase allows it to act as the template for its own RNA to DNA transcription. The resultant viral DNA inserts itself into a cell's DNA and is reproduced along with the cell and its daughters.

The exact origin of the virus in humans is unclear. Scientists surmise that it jumped from an animal population, probably African monkeys or chimpanzees, to humans via a bite or meat. The first case documented in humans dates from 1959. The virus was isolated by Luc Montagnier of France's Pasteur Institute in 1983. It went through several name changes before the official name, human immunodeficiency virus, was agreed upon.