How HIV Causes AIDS: Ultimate Guide To HIV & AIDS

How HIV Causes AIDS - The ultimate guide to HIV & AIDS, including facts and information about HIV & AIDS.

How HIV Causes AIDS - The Ultimate Guide To HIV & AIDS

How HIV Causes AIDS: Introduction

Not only do microorganisms tend to be selective about the hosts they infect, but most are selective about how they are spread. The first step in infection, introduction of HIV into a human host, is exposure to HIV. Every new HIV infection, like every new infection of any type, begins with the microorganism. HIV needs a route of transmission, or a way to get into an uninfected person. People who are not infected with HIV cannot spread HIV.

How HIV Causes AIDS: Routes Of Transmission

HIV is spread through several routes of transmission. HIV cannot survive drying or high temperatures. Thus, transmission requires transfer from the infected host to another host's tissue, where there will be cells with the binding sites that HIV needs to infect a cell, without drying or heating in between.

The most common routes of exposure to HIV are:

How HIV Causes AIDS: Direct Contact With Infected Blood

The most efficient way to spread HIV is by injecting it into the blood of an uninfected person. A transfusion from an infected donor with viral particles in his or her blood is very likely to transmit the infection to an uninfected recipient. A tiny amount of blood in a needle or syringe used by an infected injection drug user may contain many viral particles. If an uninfected person uses this needle or syringe to inject something into his or her vein or skin, these viral particles can easily enter the bloodstream.

Experiments with Rhesus monkeys, which develop a disease very much like human AIDS, have been done using a combination of the human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) called SHIV. These experiments have shown that few viral particles are needed to transmit the SHIV to uninfected monkeys if injected into the blood. However, if a monkey has the virus placed in its rectum, it takes a higher quantity of the viral particles to establish infection. If the virus is placed in the vagina, even more virus is needed to establish infection.

How HIV Causes AIDS: Sexual Contact With An Infected Partner

Sexual transmission is the way that HIV is most commonly spread worldwide. Unbroken skin is virtually impenetrable by HIV. Sex acts that involve only contact between normal, unbroken skin surfaces (e.g., hand to genital) do not transmit HIV. The tissues of the genitals, mouth, and eyes are much less resistant than the skin of the arms and hands. However, even these tissues, called mucous membranes, are formidable barriers to HIV. When they are intact, the cells are arranged so that they constitute a strong defense. The likelihood that HIV will be transmitted through sex depends on several factors.

How HIV Causes AIDS: Mothers Passing The Infection To Their Babies

Mothers can spread HIV to their babies during pregnancy, while giving birth, or by breastfeeding. Babies are generally very well protected from most organisms in the mother's blood, including HIV, by a normal, healthy placenta, particularly in the first months of pregnancy. Thus, most transmission occurs during the last months of pregnancy or delivery.

Most transmission from mother to infant occurs when the baby is exposed to the mother's blood during birth. During delivery through the vagina, the baby is covered with the mother's blood, and will have blood in the eyes, mouth, and other mucous membranes. The mother's blood also enters nicks and scratches that the baby may sustain during the birth process, particularly if the baby is premature, with skin that is not yet completely developed.

The likelihood of the mother transmitting HIV to her baby depends on several factors, including:

In general, the risk of a mother with HIV transmitting infection to her child is estimated to be somewhere between 20% and 40%. After birth, if the mother breastfeeds, her milk may carry HIV to the baby. Because the mucous membranes of the baby are still quite delicate for months after birth, the risk of HIV transmission is greatest if the mother has a high amount of HIV in her milk, if she has infection or inflammation in her breasts or nipples, with inflammatory cells that carry HIV, or if the baby has inflammation or infections in its mouth or gastrointestinal tract.

Most women with HIV who deliver babies in the United States take antiretroviral medicines. In many of those women, no virus can be found in the blood. Their babies have less than a 2% chance of being infected. If the baby is delivered by caesarean section , so that the baby is not exposed to the mother's blood or genital fluids, the risk can also be very low. If the baby is born uninfected and is fed with formula instead of breast milk, the mother's infection will not be transmitted to the baby.

How HIV Causes AIDS: Will Sexual Exposure To HIV Lead To Infection?

A person's chance of becoming infected with HIV increases with the number of times he or she is exposed to the virus. The higher the number of exposures, the more likely it is that infection will occur. However, even one exposure can result in infection. Many variables influence how vulnerable a person is to developing an HIV infection after one exposure, including:

How HIV Causes AIDS: Which Partner In A Sexual Encounter Is Infected

Certain factors affect whether an uninfected person will become infected with HIV through having sex with an infected partner. If the infected partner is the one who inserts his penis into the uninfected partner's vagina, mouth, or rectum, it is more likely that HIV will spread to the uninfected partner than if it is the uninfected partner who inserts his penis into the infected partner's vagina or rectum. If either partner has a cut, nick, sore, or irritation on his or her genitals, even if these are not visible to the naked eye, the chance of spreading the infection increases greatly.

How HIV Causes AIDS: Levels Of HIV In The Infected Partner's Blood

In addition, the higher the concentration of virus in the infected partner's blood or genital fluids, the more likely that the exposure will lead to HIV spread. Although there is antibody in many body fluids, antibody is made by the host's B cells in response to HIV and cannot spread the disease. Only the virus itself can establish infection. The amount of virus found in saliva, urine, or mucus without blood is not enough to be able to spread infection.

The concentration of HIV in an infected person's blood changes during the course of the infection. During some stages of the disease, the HIV level is very high. At other times, it is very low. During those periods when it is low, however, HIV still resides in the body's cells, slowly reproducing. When people have very high levels of virus in their blood, the virus is also often found at high levels in other body fluids, such as genital fluids, but minimal, if any, virus is found in the sweat, urine, or tears. Sexual partners of people with high levels of HIV in their bloodstreams are very often infected, unless they have consistently taken measures to reduce their risk.

How HIV Causes AIDS: Other Infections Can Make The Immune System More Vulnerable

Other infections may also increase the chance of transmitting or being infected with HIV because the person's immune system is already being challenged. In the partner with HIV infection, other infections cause helper T cells to become activated to fight those infections. While reproducing, they make billions of new HIV particles, as do their daughter T cells. In the uninfected partner, other infections increase the number of helper T cells, and the numbers of "handles" per T cell, making these cells that are the main target of HIV readily available. Of course, infections that cause ulcers or sores on the genitals or rectum, or that bring vulnerable white blood cells to the area where genital fluids with HIV will be found, dramatically increase the risk of spread.

How HIV Causes AIDS: Some People Can Resist HIV Infection

Some individuals appear to be resistant to HIV infection even after having unprotected sex with an infected partner many times. Some of these highly exposed, persistently seronegative (HEPS) (uninfected) individuals do not have the genes that code for CCR-5 or other binding sites that HIV needs to infect cells. Despite many exposures to HIV, they will not become infected.

Other research suggests that HEPS individuals may be more likely to be infected with "hepatitis" G virus than people who do get infected when they are exposed to HIV. The "hepatitis" G virus does not cause hepatitis or any other disease, but it may provide protection against infection by other microorganisms.

People who repeatedly have protected sex with those who have HIV infection, such as the wives of men infected with HIV who consistently and correctly use latex condoms, are also very unlikely to become infected.

How HIV Causes AIDS: First Symptoms Of HIV Infection

Nobody can tell immediately whether he or she has been infected with HIV after an exposure. About one in three people who are infected with HIV experience some symptoms, such as a rash, fever, or swollen lymph nodes, a few weeks after becoming infected. During those days, the person's blood will contain virus particles and the number of CD4+ T-cells dips. These symptoms are called retroviral or seroconversion syndrome . This name is given because at the time when symptoms are present, the antibody against HIV can start to be detected in the patient's serum , so his or her serum will be converted from negative to positive.

As the antibody becomes detectable, the number of CD4+ T cells increases again and the amount of virus in the blood decreases. For years, the antibody appears to control the HIV, and the number of CD4+ T cells remains high enough to fight off opportunistic infections.

How HIV Causes AIDS: The Progression Of HIV Infection

The length of time between getting the infection and developing symptoms of the disease depends on a number of factors. For most adults in the United States and other industrialized countries, the time between HIV infection and death is more than 5 years, generally about 10 years. However, babies infected before or during birth usually have signs of serious immunodeficiency within months of birth. The amount of virus that infects the person appears to be important. Some HIV strains may also be far more aggressive than others. Babies, especially premature babies, are exposed to a large quantity of virus relative to their size. Similarly, people who are infected via blood transfusions or are accidentally stuck with a syringe that has a lot of blood (a quarter teaspoon or more) probably get many millions of virions; the amount of time from their infection to the time of onset of disease may be small. In contrast, the amount of HIV that is transmitted to adults having consensual sex may be small, so it often takes longer to become ill.

Sometimes, having other infections can upregulate HIV. Dutch researchers have found that bacterial infections can encourage HIV replication through upregulation of chemokine receptors on T cells. Upregulation means that a bacterial infection will increase the number of co-receptors that HIV can use to fuse to the T cell. Upregulation also increases the number of infected T cells that are reactivated. Because only activated T cells produce virions, activating T cells that have provirus in their DNA increases the amount of virus in the blood.

HIV does not actually kill T cells as it leaves them. Often, T cells that are infected by HIV and are reactivated become HIV factories, meaning that they produce huge quantities of HIV particles, without appearing to be damaged. However, this does not fully explain why, at a certain point in the course of infection, the ability of the immune system to protect itself is overwhelmed. It is unclear why this happens. In order for HIV to survive, the immune system must not break down too soon after infection; if the system remains viable for several years (even more than a decade in some people), the HIV has more opportunity to replicate itself into billions of HIV virions. These virions can then spread the HIV infection to many more hosts.

At some point, the amount of HIV DNA in the host's blood increases, and the number of CD4+ T cells declines. The number of CD4+ T cells remains the most important indicator of immune response. Once that number declines, many organisms that normally could do no harm or only limited harm attack. This results in opportunistic infections.

How HIV Causes AIDS: Opportunistic Infections

The cell-mediated immunity in the body protects against many infections, especially those caused by viruses, yeasts, and bacteria of the genus Mycobacterium, which includes Mycobacterium tuberculosis and other species. HIV-infected individuals' cell-mediated immunity becomes weakened. Therefore, they are vulnerable to becoming infected by many other microorganisms and developing serious or fatal diseases. All opportunistic infections that are seen in people whose immune systems are weakened by HIV can also be seen in people whose immune systems are severely weakened by other causes, including genetic diseases or medicines used to suppress the immune system, such as those to prevent rejection of transplants. Common opportunistic infections include esophagus (food tube) infections due to Candida yeast species; blindness, meningitis, and other severe diseases from cytomegalovirus or usually harmless amoebas; and Pneumocystis carinii pneumonia. Many of these illnesses are never seen in people with normal immune systems. Others, such as mucous membrane Candida infections (thrush), are seen in people with normal immune systems, but they are more likely to be severe or fatal in immunodeficient people.

How HIV Causes AIDS: Tuberculosis Is The Most Common Opportunistic Infection

Worldwide, tuberculosis is the most common opportunistic infection related to HIV. Tuberculosis is caused by the bacterium Mycobacterium tuberculosis. If a person with HIV has untreated M. tuberculosis infection, his or her first opportunistic infection will generally be tuberculosis.

Almost a third of people on Earth have M. tuberculosis infection, but only about 10% of them actually develop active tuberculosis if they have a normally functioning immune system. Their T cells keep M. tuberculosis confined in lymph nodes, where they can do no harm. However, virtually all people with M. tuberculosis infection whose cell-mediated immunity is weakened will progress to active tuberculosis, many will have unusually severe disease, and all will die of tuberculosis if not treated.

Medicines have been available for years to prevent M. tuberculosis infection from progressing to tuberculosis and to treat active tuberculosis. Nevertheless, in many developing countries, including some in sub-Saharan Africa and in some populations in the United States, many HIV-related deaths are due to tuberculosis. When individuals with HIV develop active tuberculosis, they are no longer said to have just HIV infection; they are then classified as having AIDS. Of course, many people who progress to tuberculosis do not have HIV. Their immune system will just be weakened because they are babies, very old, or have other chronic diseases, such as diabetes, or stressors, such as malnutrition, homelessness, or other factors.

People with HIV infection generally do not develop other serious opportunistic infections, such as Pneumocystis carinii pneumonia, until the number of CD4+ T cells they have is very low. However, progression to tuberculosis is common even in untreated people with HIV who have high numbers of CD-4+ T cells.

Most people with HIV infection who develop tuberculosis are infected with M. tuberculosis in late childhood or adolescence before they are infected with HIV. After a mild illness (primary tuberculosis), which most do not even notice, they recover. The infection still exists in the body, but it is kept in check by cell-mediated immunity. In this state, the infection is called latent because it appears to become inactive. However, once HIV causes immunosuppression, the infection becomes reactivated, and infected people go on to develop active tuberculosis. In people with HIV infection, tuberculosis is far more likely to spread beyond the lungs, causing disease in many other organs, including the kidneys, bones, heart, and intestines.

Because HIV is very likely to cause reactivation, it is recommended that all people with unknown HIV infection status who develop tuberculosis be offered HIV testing. Almost one-third of people in the United States and more than half of people in some developing countries who develop active tuberculosis have HIV infection. Conversely, many people with HIV infection have latent M. tuberculosis infection that, if untreated, will develop into tuberculosis.

In the 1990s, epidemics of tuberculosis in people with advanced cell-mediated immunosuppression due to HIV showed how fast people progress from infection with M. tuberculosis to active tuberculosis. These people were infected by a person with unrecognized active tuberculosis while in specialized wards for people with HIV infection. In crowded prisons or homeless shelters, people with active tuberculosis spread infection to people with HIV. The patients whose immune systems were weakened by HIV developed symptoms of tuberculosis about four months after their exposure and presumed infection with M. tuberculosis, without any latency period. Their tuberculosis was caused by a strain that was very resistant to antituberculosis drugs, so treatment was ineffective. They died of HIV-related tuberculosis (AIDS) within five months.

How HIV Causes AIDS: Other Infections Resulting From Cell-Mediated Immune Deficiency

However, if HIV-infected adults do not have M. tuberculosis infection, they are not likely to develop severe opportunistic infections until their CD4+ T cell count decreases. As this number declines, the person becomes susceptible to infection by many more organisms. When the T cell count is very low, many microorganisms that are usually harmless can kill the patient.

There are no early warning signs of severe cell-mediated immunity deficiency. The signs and symptoms that signify AIDS are many and varied, reflecting the variety of micro-organisms to which patients are exposed; most people with AIDS develop only a few of the myriad opportunistic infections that fit the case-definition of AIDS.

How HIV Causes AIDS: Pneumocystis Carinii Pneumonia

The most frequent opportunistic infection in people with HIV infection in the United States is Pneumocystis carinii pneumonia. People with normal immune systems who are infected with P. carinii, the organism that causes this type of pneumonia, can easily fight the organism and do not become ill at all. Many, if not most, adults are infected with P. carinii. It is not sexually transmitted, and is commonly found in soil and other harmless substances. Most people who have infection with P. carinii do not even know they have it. However, people with HIV who are infected with P. carinii and are not treated to prevent the pneumonia when they become immunosuppressed quickly progress to cough, chest pain, low oxygen in the blood, and severe disease. Without treatment, they often die.

How HIV Causes AIDS: Kaposi's Sarcoma

Certain cancers caused by viruses, such as Kaposi's sarcoma and cervical cancer (cancer of the cervix, the opening of the uterus), are also opportunistic infections that can arise after the number of T cells decreases. Kaposi's sarcoma is caused by one of the herpes viruses (human herpes virus 8), which can be spread sexually. This type of cancer develops when thousands of new, tiny blood vessels start growing unchecked, generally in the skin and mucous membranes of the mouth, nose, or eye. In people with normal immune systems, this process is slow and rarely life-threatening. In people with HIV/AIDS, the lungs, liver, stomach, intestines, and lymph nodes also may be involved, often causing severe disease or death.

How HIV Causes AIDS: Cervical Cancer

Cervical cancer is caused by certain types of human papilloma-virus ; other types of this virus can also cause common skin warts or genital warts, which are sexually transmitted. About 14% of women in the United States are infected with the papillomavirus that causes most cases of cervical cancer. Even in women with normal immune systems, these infections may progress to cervical cancer (although they generally do not). But women with HIV infection who are also infected with these viruses are very likely to quickly develop cervical cancer.

How HIV Causes AIDS: Other Cancers

Other cancers that threaten people with HIV are probably not caused by viruses; these cancers may be related to loss of the T cell functions related to monitoring and destroying cells whose growth appears to be abnormal.

How HIV Causes AIDS: Diseases At The End Stage Of AIDS

During the most severe stage ("end stage") of AIDS, and probably throughout the course of infection, the virus directly damages some organs, particularly in infants. HIV damages the brain and can result in mental retardation in children and AIDS dementia in adults. Most people with severe AIDS get diarrhea, which is sometimes caused by opportunistic infections or HIV damage to the intestine. Many people with AIDS experience loss of appetite, nausea, and sometimes vomiting, along with diarrhea. Dehydration and weight loss often occur in AIDS patients. People who lose a significant amount of weight are said to have "wasting" or "slim" disease.

How HIV Causes AIDS: Epidemiologic Synergy: When One Disease Is Made Worse By Another Disease

The term synergy means that when two or more things are combined, their effect is greater than would be expected by just adding the effects of each. For example, when two drugs work synergistically, the results are stronger than just the effects of one drug plus the effects of the other drug. Similarly, some infectious diseases enhance each other's disease-causing effects. For example, the progress of HIV infection is greatly accelerated by infection with M. tuberculosis and herpes simplex virus. Herpes simplex 1 and 2 are DNA viruses of a large class that cause chronic infections. After an initial infection, usually in the mucous membranes of the mouth or anal and genital areas, these viruses remain latent in nerve cells. Infections with these organisms tend to activate cells that have HIV proviruses in their DNA. This activation makes these cells produce more HIV. Infections with herpes simplex virus and M. tuberculosis make cells produce more co-receptors (upregulation), making many more cells much more likely to be invaded by HIV. When people with HIV infection have these other infections, HIV disease advances more quickly. They have higher levels of HIV in their blood and transmit HIV much more readily.

On the other hand, HIV-related immunosuppression allows other infections to progress to very severe disease. In most people without HIV infection, warts caused by human papilloma-viruses, and genital herpes, fever blisters in the mouth, or shingles caused by herpes viruses occasionally reoccur. People with HIV who are infected with these viruses, however, are plagued with severe, frequent recurrences. These become harder to control as immunosuppression worsens. Often, children and adults with HIV become covered with skin warts for years and may have scarring, painful shingles on their torsos or limbs, or suffer from severe, chronic oral or genital blisters and sores.

Vaginal and oral candidiasis (referred to as "yeast infections" and "thrush") are usually mild infections that annoy but do not endanger women and infants with normal immune systems. In people with HIV, these infections cause stubborn, peeling skin lesions; burning, painful vaginal lesions; and oral lesions that spread into the esophagus, making eating difficult.

Gonorrhea and Chlamydia trachomatis are sexually transmitted infections that often cause no symptoms in women, although if untreated, they can cause irreversible damage. In women with HIV, however, these infections quickly rise from the cervix to the womb, the ovaries, and fallopian tubes, causing painful, pus-filled lesions called tubo-ovarian abscesses.

A person who does not have HIV but has been infected by these other organisms is more likely to become infected with HIV if exposed to it. Weaknesses in the body's first line of defense against HIV infection (the mucous membranes or skin of the genitals), caused by genital ulcers due to syphilis, genital herpes, or chancroid (a sexually transmitted ulcer), greatly increase the risk that an exposure to HIV will result in HIV transmission. Infections with Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and genital infections that are not sexually transmitted, such as bacterial vaginosis and yeast infections, also increase the likelihood that a sexual exposure will result in HIV transmission.

Through different mechanisms, these infections make the uninfected partner more susceptible to infection. Ulcers and infections that cause itching and scratching do this by stripping away protective layers of cells. These and other infections may also cause inflammation, which brings CD4+ T cells to the area that can readily be infected by HIV. Bacterial vaginosis causes the beneficial bacteria that make acid products that protect against HIV to be replaced by other bacteria, which promotes HIV invasion.

How HIV Causes AIDS: References