Symptoms of Lymphadenopathy Syndrome (LAS)

• Unexplained fever
• Difficulty in swallowing
• Swollen glands
• Fatigue/Lethargy
• Night sweats and chills
• Apathy
• Gradual loss of weight
• Diarrhea
• Sore throat
• Impotence

Lymphadenopathy Syndrome (LAS)

Lymphadenopathy Syndrome (LAS) is a mild form of HIV infection, generally characterized by some of the symptoms in Figure 4.

Lymphadenopathy means "disease of the lymphatic system." The lymphatic system is the human body's second fluid system which contains a clear fluid called lymph (see Figure 3). The lymphatic system aids the blood system by draining fluid out of the body' s tissues. The lymphatic system is not a closed loop like the bloodstream, meaning it does not flow in a circle, and it has no pump like the heart. Nevertheless, lymph flows from smaller vessels into larger lymph ducts in the upper chest. In doing so, lymphatic fluid passes through a series of filtering stations called lymph nodes, or lymph glands. Lymph nodes filter bacteria (one-celled organisms), foreign substances, and dead white blood cells out of the fluid.

The lymphatic system is a vital part of the body's immune system. Lymph nodes store and mature lymphocytes and other white blood cells and also manufacture antibodies. T-cells and macrophages can migrate back and forth between the blood system and the lymphatic system, perhaps exposing newly generating cells to HIV during their formative stages.

Figure 3: The Lymphatic System

Healthy Carrier State

A carrier is someone who is infected with a disease and shows no clinical symptoms, but who is capable of infecting other people with the disease. ("Clinical" means "seen in the doctors office.")

HIV has been isolated (removed) and cultured ("grown" in a laboratory dish) from healthy people who show no clinical signs of HIV infection.

It is not yet clear when an HIV-infected person becomes infectious. At this time, the only safe practice is to assume that anyone carrying the virus is capable of transmitting it to others.

Types of HIV Infections (AIDS)

For the first few years of the AIDS epidemic, it appeared that some HIV-infected people sickened and died quickly while the others stayed healthy indefinitely or slowly progressed into sickness. Now it appears the greater majority of HIV-infected will gradually become very sick and eventually die. There are reports of long-term survivors of HIV infection; but, they seem to be the exception rather than the rule.

The average (the mean) incubation time for HIV infection is 10 years. Incubation time means the time from initial infection until the development of "full-blown AIDS," discussed below. The average is a bell curve, with 10 years at the center. Some individuals develop illness sooner than 10 years and some later than 10 years.

Most symptoms and diseases common to HIV infection are listed in Figures 4, 5 and 6. The presence of these symptoms and diseases varies from one patient to another. These diseases may occur in sequence or simultaneously.

Obviously, many of these symptoms can be caused by a number of common illnesses. These diseases are listed here for the sake of education, not for the purpose of self-diagnosis. In case of any persistent illness, consult your health care provider.

The popular classification system of HIV infections, used here, is a collection of haphazard definitions that evolved as the AIDS epidemic unfolded. These labels are ones of convenience, not ones of scientific or medical accuracy. Medical authorities use different, more complex, classification systems.

Basically, four loosely defined different stages of HIV infection exist: I ) the healthy carrier state, 2) the lymphadenopathy syndrome (LAS), 3) AIDS-related complex (ARC), and 4) AIDS or "frank AIDS," or "full-blown AIDS." These forms or the symptoms of each may overlap the other

Down the Road: New Drugs in the Pipeline

The Pharmaceutical Research and Manufacturers Association of America maintains a database of new drugs in development to treat HIV infection. They include new protease inhibitors and more potent, less toxic RT inhibitors, as well as other drugs that interfere with entirely different steps in the virus' lifecycle. These new categories of drugs include

• Entry inhibitors that interfere with HIV's ability to enter cells
• Integrase inhibitors that interfere with HIV's ability to insert its genes into a cell's normal DNA
• Assembly and budding inhibitors that interfere with the final stage of the HIV life cycle, when new virus particles are released into the bloodstream
• Cellular metabolism modulators that interfere with the cellular processes needed for HIV replication
• Gene therapy that uses modified genes inserted directly into cells to suppress HIV replication. These cells are designed to produce T cells that are genetically resistant to HIV infection.

In addition, scientists are exploring whether immune modulators help boost the immune response to the virus and may make existing anti-HIV drugs more effective. Therapeutic vaccines also are being evaluated for this purpose and could help reduce the number of anti-HIV drugs needed or the duration of treatment.

NIAID Research on the Complications of Antiretroviral Drugs

NIAID supports studies aimed at understanding the side effects of antiretroviral drugs as well as strategies to reduce exposure to potentially toxic drug regimens, such as

• Structured treatment interruption (STI) protocols
• Use of immune-based therapies with HAART
• Studies to compare different drug dosing schedules or combinations
• Studies to compare early versus delayed treatment

NIAID also supports projects evaluating regimens containing agents associated with toxicities. For example, NIAID-funded researchers are conducting studies to evaluate treatments for several drug-associated metabolic complications, including fat redistribution, lipid and glucose abnormalities, and bone loss. In addition, researchers are studying the long-term metabolic effects of various antiretroviral regimens in pregnant women and their infants and in HIV-infected children and adolescents.

Development of New Safe and Effective Antiretroviral Drugs

NIAID supports the development and testing of new therapeutic agents, classes, and combinations of antiretroviral drugs that can continuously suppress the virus with few side effects. Through human clinical trials, NIAID-supported studies provide accurate and extensive information about the safety and efficacy of drug candidates and combinations, and identify potential uncommon but important toxicities of newly approved agents. Studies are also under way to assess rare toxicities of older approved agents, especially as a result of long-term use.

Through the Multicenter AIDS Cohort Study and Women's Interagency HIV Study, NIAID supports long-term studies of HIV infection and its treatment in both men and women. Since their inception, these cohort studies have enrolled and collected data from more than 10,000 people. In addition, NIAID supports treatment studies conducted through three HIV/AIDS clinical trials networks: the AIDS Clinical Trials Group, the International Maternal Pediatric Adolescent AIDS Clinical Trials Group, and the International Network for Strategic Initiatives in Global HIV Trials.

Side Effects of Antiretroviral Drugs

People taking antiretroviral drugs may have low adherence to complicated drug regimens. Current recommended regimens involve taking several antiretroviral drugs each day from at least two different classes, some of which may cause unpleasant side effects such as nausea and vomiting. In addition, antiretroviral drugs may cause more serious medical problems, including metabolic changes such as abnormal fat distribution, abnormal lipid and glucose metabolism, and bone loss. Therefore, NIAID is investigating simpler, less toxic, and more effective drug regimens.

Antiretroviral Drug Effects on Opportunistic Infections and AIDS-associated Co-infections

People infected with HIV have impaired immune systems that can leave them susceptible to opportunistic infections (OIs) and AIDS-associated co-infections, caused by a wide range of microorganisms such as protozoa, viruses, fungi, and bacteria. One example of an associated co-infection is hepatitis C virus infection, which can lead to liver cancer.

Potent HIV therapies such as HAART, however, have produced dramatic responses in patients. These therapies often allow the immune system to recover, sustain, and protect the body from other infections. Hence, antiretroviral drugs provide a way for the immune system to remain effective, thereby improving the quality and length of life for people with HIV.

HIV Transmission and Antiretroviral Drugs

Although the use of HAART has greatly reduced the number of deaths due to HIV/AIDS, and possibly the transmission of HIV/AIDS as well, this powerful combination of drugs cannot suppress the virus completely. Therefore, people infected with HIV who take antiretroviral drugs can still transmit HIV to others through unprotected sex and needle-sharing.

Highly Active Antiretroviral Therapy (HAART) Counters Drug Resistance

As HIV reproduces itself, variants of the virus emerge, including some that are resistant to antiretroviral drugs. Therefore, health care providers recommend that people infected with HIV take a combination of antiretroviral drugs known as highly active antiretroviral therapy, or HAART. This strategy, which typically combines drugs from at least two different classes of antiretroviral drugs, has been shown to effectively suppress the virus when used properly. Developed by NIAID-supported researchers, HAART has revolutionalized how people infected with HIV are treated. HAART works by suppressing the virus and decreasing the rate of opportunistic infections.

Drugs for HIV/AIDS

Currently, there are 30 antiretroviral drugs approved by the Food and Drug Administration to treat people infected with HIV. These drugs fall into four major classes.

1. Reverse transcriptase (RT) inhibitors interfere with the critical step during the HIV life cycle known as reverse transcription. During this step, RT, an HIV enzyme, converts HIV RNA to HIV DNA. There are two main types of RT inhibitors.
• Nucleoside/nucleotide RT inhibitors are faulty DNA building blocks. When these faulty pieces are incorporated into the HIV DNA (during the process when the HIV RNA is converted to HIV DNA), the DNA chain cannot be completed, thereby blocking HIV from replicating in a cell.
• Non-nucleoside RT inhibitors bind to RT, interfering with its ability to convert the HIV RNA into HIV DNA.
2. Protease inhibitors interfere with the protease enzyme that HIV uses to produce infectious viral particles.
3. Entry and fusion inhibitors interfere with the virus' ability to fuse with the cellular membrane, thereby blocking entry into the host cell.
4. Integrase inhibitors block integrase, the enzyme HIV uses to integrate genetic material of the virus into its target host cell.
5. Multidrug combination products combine drugs from more than one class into a single product.

Currently available drugs do not cure HIV infection or AIDS. They can suppress the virus, even to undetectable levels, but they cannot eliminate HIV from the body. Hence, people with HIV need to continuously take antiretroviral drugs.

Treatment of HIV Infection

In the early 1980s when the HIV/AIDS epidemic began, people with AIDS were not likely to live longer than a few years. With the development of safe and effective drugs, however, people infected with HIV now have longer and healthier lives.

The discovery and development of new therapeutic strategies against HIV is a high priority for the National Institute of Allergy and Infectious Diseases (NIAID). Research supported by NIAID has already greatly advanced our understanding of HIV and how it causes disease. This knowledge provides the foundation for NIAID's HIV/AIDS research effort and continues to support studies designed to further extend and improve the quality of life of those infected with HIV.

Diagnosis in Babies

Babies born to mothers infected with HIV may or may not be infected with the virus, but all carry their mothers’ antibodies to HIV for several months. If these babies lack symptoms, healthcare providers cannot make a definitive diagnosis of HIV infection using standard antibody tests. Instead, they are using new technologies to detect HIV and more accurately determine HIV infection in infants between ages 3 months and 15 months. Researchers are evaluating a number of blood tests to determine which ones are best for diagnosing HIV infection in babies younger than 3 months.

Diagnosis

Because early HIV infection often causes no symptoms, a healthcare provider usually can diagnose it by testing blood for the presence of antibodies (disease-fighting proteins) to HIV. HIV antibodies generally do not reach noticeable levels in the blood for 1 to 3 months after infection. It may take the antibodies as long as 6 months to be produced in quantities large enough to show up in standard blood tests. Hence, to determine whether a person has been recently infected (acute infection), a healthcare provider can screen blood for the presence of HIV genetic material. Direct screening of HIV is extremely critical to prevent transmission of HIV from recently infected individuals.

Anyone who has been exposed to the virus should get an HIV test as soon as the immune system is likely to develop antibodies to the virus—within 6 weeks to 12 months after possible exposure to the virus. By getting tested early, a healthcare provider can give advice to an infected person about when to start treatment to help the immune system combat HIV and help prevent the emergence of certain opportunistic infections (see section on treatment). Early testing also alerts an infected person to avoid high-risk behaviors that could spread the virus to others.

Most healthcare providers can do HIV testing and will usually offer counseling at the same time. Of course, testing can be done anonymously at many sites if a person is concerned about confidentiality.

Healthcare providers diagnose HIV infection by using two different types of antibody tests: ELISA (enzyme-linked immunosorbent assay) and Western blot. If a person is highly likely to be infected with HIV but has tested negative for both tests, a healthcare provider may request additional tests. A person also may be told to repeat antibody testing at a later date, when antibodies to HIV are more likely to have developed.

Later symptoms

More persistent or severe symptoms may not appear for 10 years or more after HIV first enters the body in adults, or within 2 years in children born with HIV infection. This period of asymptomatic infection varies greatly in each person. Some people may begin to have symptoms within a few months, while others may be symptom-free for more than 10 years.

Even during the asymptomatic period, the virus is actively multiplying, infecting and killing cells of the immune system. The virus can also hide within infected cells and be inactive. The most obvious effect of HIV infection is a decline in the number of CD4 positive T (CD4+) cells found in the blood—the immune system’s key infection fighters. The virus slowly disables or destroys these cells without causing symptoms.

As the immune system becomes more debilitated, a variety of complications start to take over. For many people, the first signs of infection are large lymph nodes, or swollen glands, that may be enlarged for more than 3 months. Other symptoms often experienced months to years before the onset of AIDS include

• Lack of energy
• Weight loss
• Frequent fevers and sweats
• Persistent or frequent yeast infections (oral or vaginal)
• Persistent skin rashes or flaky skin
• Pelvic inflammatory disease in women that does not respond to treatment
• Short-term memory loss

Some people develop frequent and severe herpes infections that cause mouth, genital, or anal sores, or a painful nerve disease called shingles. Children may grow slowly or get sick frequently.

Symptoms

Early symptoms

Many people will not have any symptoms when they first become infected with HIV. They may, however, have a flu-like illness within a month or two after exposure to the virus. This illness may include

• Fever
• Headache
• Tiredness
• Enlarged lymph nodes (glands of the immune system easily felt in the neck and groin)

These symptoms usually disappear within a week to a month and are often mistaken for those of another viral infection. During this period, people are very infectious, and HIV is present in large quantities in genital fluids.

Transmission

HIV is primarily found in the blood, semen, or vaginal fluid of someone who is infected with the virus and is transmitted in four ways:

• Having unprotected sex (anal, oral or vaginal) with someone infected with HIV
• Sharing needles and syringes with someone infected with HIV
• Being exposed to the virus as a fetus or infant before or during birth or through breastfeeding from an HIV-infected mother
• Receiving a transfusion of HIV-infected blood or blood products. In the United States, all donated blood and blood products have been screened for HIV since 1985; therefore, the risk of transmission in this way is extremely low in the U.S.

HIV cannot survive for very long outside of the body. The virus cannot be transmitted through routine daily activities such as using a toilet seat, sharing food utensils or drinking glasses, shaking hands, or through kissing. The virus also cannot be spread by bloodsucking insects, such as mosquitoes.

How HIV Causes AIDS

HIV destroys CD4 positive (CD4+) T cells, which are white blood cells crucial to maintaining the function of the human immune system. As the virus attacks those cells, the person infected with HIV is less equipped to fight off infection and disease ultimately resulting in the development of AIDS.

Most people who are infected with HIV can carry the virus for years before sufficient damage to the immune system results in the development of AIDS. However, there is a strong connection between high levels of HIV in the blood and the decline in CD4+ T cells and the development of AIDS. Antiretroviral medicines can reduce the amount of virus in the body, preserve CD4+ T cells and dramatically slow the destruction of the immune system.

Why is there overwhelming scientific consensus that HIV causes AIDS?

Before HIV infection became widespread in the human population, AIDS-like syndromes occurred extremely rarely, and almost exclusively in individuals with known causes of immune suppression, such as chemotherapy and underlying cancers of certain types. A marked increase in unusual infections and cancers characteristic of severe immune suppression was first recognized in the early 1980s in homosexual men who had been otherwise healthy and had no recognized cause for immune suppression. An infectious cause of AIDS was suggested by geographic clustering of cases, links among cases by sexual contact, mother-to-infant transmission, and transmission by blood transfusion. Isolation of the HIV from patients with AIDS strongly suggested that this virus was the cause of AIDS. Since the early 1980s, HIV and AIDS have been repeatedly linked in time, place and population group; the appearance of HIV in the blood supply has preceded or coincided with the occurrence of AIDS cases in every country and region where AIDS has been noted. Individuals of all ages from many risk groups – including men who have sex with men, infants born to HIV-infected mothers, heterosexual women and men, hemophiliacs, recipients of blood and blood products, healthcare workers and others occupationally exposed to HIV-tainted blood, and male and female injection drug users – have all developed AIDS with only one common denominator: infection with HIV.

The HIV-AIDS Connection

The acquired immunodeficiency syndrome (AIDS) was first recognized in 1981 and has since become a major worldwide pandemic. Abundant evidence indicates that AIDS is caused by the human immunodeficiency virus (HIV) , which was discovered in 1983. By leading to the destruction and/or functional impairment of cells of the immune system, notably CD4+ T cells, HIV progressively destroys the body's ability to fight infections and certain cancers.

Testing

Pubic lice is visable upon inspection.

Transmission

The most common form of transmission is through sexual intercourse. It can also be transmitted through bed clothing and other clothing of the infected person.

Treatment

1. Buy Nix anti-lice creme rinse (permethrin). · Pour about 2 ounces of the creme into previously washed and towel-dried pubic hair. Add a little warm water to work up a lather. Be sure to work the creme into all the hair down to the roots. · Leave the Nix on for a full 20 minutes or it won't kill all the lice (10 minutes is not enough). · Then rinse the hair thoroughly and dry it with a towel. Repeat the Nix treatment in 1 week to kill any nits that were missed.

2. Dead Nits: Wait 3 or more hours after Nix treatment is completed before removing the dead nits. (Reason: let Nix permeate the nits) The nits can be loosened using a mixture of half vinegar and half warm water. After wetting the hair with this solution, cover the hair with a towel for 30 minutes. Then remove the dead nits by backcombing with a fine-tooth comb or pull them out individually.

3. Pregnancy and Breastfeeding: Women who are pregnant or who are breastfeeding can be treated with products containing permethrin (e.g. NIX) according to the Centers for Disease Control.

4. Contagiousness: Pubic lice are very contagious. Pubic lice are transmitted by skin to skin contact during sexual intercourse (they cannot jump). You should have no sexual intercourse until 2 weeks after successful treatment.

5. Sexual Contacts: Any sexual partners that you have had during the last month will also need treatment, even if they don't see any obvious lice.

6. Expected Course: With 2 treatments, all lice and nits should be killed. A recurrence usually means that there has been another contact with an infected person; the shampoo wasn't left on for 20 minutes; or the treatment wasn't repeated in 7 days. There are no lasting problems from having lice and they do not carry other diseases. Even after successful treatment, itching of the pubic area may persist for 1-2 weeks.

7. Other Shampoos: If any of the pyrethrin anti-lice shampoos (A-200 Clear, R & C, Pronto or RID) are used, they must be applied to dry hair. Reapplication in 7 days to prevent re-infection is also required. Do not use these products if you are pregnant or breastfeeding

Symptoms

It may take several weeks for you to find out that you have pubic lice, because it takes them a while to breed. The most obvious symptom is itching, which usually occurs at night.

Pubic Lice/ Crabs

Pubic Lice which is also known as crabs is not necessarily a sexually transmitted disease. The lice are six-legged parasites that live and lay eggs in the pubic area.

Testing

The way you test for this disease is to get some of the discharge, which the doctor puts under the microscope to confirm if you have the disease.

Treatment

This disease can occasionally be mistaken for gonorrhea, so the doctor will prescribe penicillin which does not treat NSU. It must be treated by tetracycline or another antibiotic.

Symptoms

In men the symptoms can be similar to gonorrhea, but usually milder. The incubation period varies but it is between one week to one month. The discharge form the urethra is thin and clear. In women the symptoms are like those of a urinary tract infection.

If nonspecific urethritis if left untreated in men, it may cause difficulty in urination and perhaps some bleeding. It can also cause the testicles to swell and be tender. If it spreads to the prostate it can cause pain in the groin.

Nonspecific Urethritis

Nonspecific Urethritis is an infection to the urethra, which is the urine tube that goes through to pass from the bladder to outside the body. This disease is caused by some bacteria which can be picked up from the rectum or the mouth of your partner. In some cases' people have allergic reaction to latex or spermicide and can get the disease this way. This disease is caused by several other diseases.

Testing

Testing is by a blood sample.

Transmission

Transmission is through sexual contact or sharing hypodermic needles of drug users and blood transfusions, which is rare. You can also get it by sharing a tooth brush or shaving kit. If the person that has the disease and you have an open sore and you come in contact with them than you can get the disease.

Treatment

Unfortunately there is no cure for Hepatitis B. There is a treatment called alpha interferon which decreases the viral activity. It is a natural product of the human body, which interferes with the reproduction of a virus after it has interred the body. Most people who get hepatitis B will carry it for the rest of their lives

Symptoms

The incubation period is two to six weeks after being infected. The symptoms are feeling very tired, loss of appetite, and jaundice, which is a yellowing of the skin. You may also have symptoms such as skin rashes, nausea, and abdominal pain.

Hepatitis B

Hepatitis B is inflammation of the liver caused by viruses and toxic substances.

Testing

If you have the symptoms go to the doctor and he will take a sample of the sores and test to see if you have herpes.

Herpes is a virus that multiplies when it gets into the cells of the skin. The skin becomes red and irritable and afterwards the blisters begin to appear. Then the blisters open and heal forming new skin. In the first outbreak the area is usually painful and may itch and burn. Flu like symptoms are also common.

Transmission

The most common form of transmission is through sexual intercourse and oral sex.

Treatment

There is no medical cure, at this time for herpes, but your doctor can prescribe a drug called acyclovir, which reduces the pain and the outbreaks.

Symptoms

Symptoms usually appear between 2-20 days after contact with an infectious person. The symptoms are clusters of painful blisters on the genitals. After a few days they burst, leaving small ulcers.

In men, the blisters usually appear on the penis, but can also be in the urethra.

In women the blisters usually appear on the labia and can appear in the cervix.

First outbreaks can be accompanied by fever, headache, and muscle soreness. Other symptoms are painful urination discharge from the vagina or the urethra.

The symptoms usually disappear within a couple of weeks. And the person may never have another occurrence or the virus can lay dormant in the person's body. Some people may have the virus and never experience the symptoms, but can transmit it to other people.

Genital Herpes

Genital Herpes are clusters of painful blisters on the genitals.

Testing

Usually the physician can tell just by looking at the infected area whether or not you have genital warts. The doctor can also pour a diluted vinegar solution on the warts and they will turn white, which lets him know that they are present. If it is not clear than he may use a diagnostic procedure called colposcopy, which is a magnifying procedure. Also when you have an abnormal pap smear, it may indicate that you have genital warts.

Transmission

The most common form of transmission is through sexual intercourse. Warts are very contagious even in people who show no symptoms.

Treatment

The warts are treatable. The doctors can use a solution called Podophllin solution, trichloracetic acid, and fluorouracil cream. These are used to burn the warts off the skin. Liquid nitrogen or lasers are used sometimes. A six-month check up is necessary to confirm that all of the warts are destroyed.

Symptoms

When symptoms are present, they are small, visible warts appearing at the tip of the penis or at the opening of the vagina. Warts can occur anywhere on the column of the penis, in the urethra, or the testicles of the male, and inside the vagina of the woman. They can also occur on the rectum.

Genital Warts

Genital warts which appear several months or more after exposure are skin-colored, cauliflower-shaped eruptions and are sometimes accompanied by itching and irritation.

Testing

The disease is detected by a blood test.

Transmission

The most common form of transmission is through sexual intercourse. Syphilis can also be acquired by blood transfusion or from passed from an infected mother to her fetus.

Treatment

Treatment is by penicillin injection, or a two-week regimen of tetracycline, which is the standard treatment for syphilis. All stages of syphilis are treatable and can be stopped.

Treatment

Treatment is by penicillin injection, or a two-week regimen of tetracycline, which is the standard treatment for syphilis. All stages of syphilis are treatable and can be stopped.

Symptoms

If Syphilis if not treated, it can occur in three stages. The symptoms are slow to appear usually 10 -90 days after exposure.

The first stage can occur any time between two to four weeks after infection has occurred. A painless ulcer develops at this site most of the time. The ulcer starts as a red spot, turns into a pimple, which ulcerates, forming a sore. The ulcer is usually found on the genitals or anus, but can appear on any part of the skin, including the mouth. It usually heals in 4-6 weeks, leaving a thin scar. During this period the bacterium is circulating in the blood throughout the body.

The second stage appears one to six months after the ulcer heals, you feel generally ill, you have a fever and a headache and lose your appetite. The glands in your neck, armpit and groin may swell. Most people develop a skin rash that does not itch. The spots appear on the palms of the hands and the bottom of the feet.

The symptoms usually last three to six months. There is what you call a latent period where there are no apparent symptoms, and the carrier is no longer contagious. However, the organism is working itself into the host's tissues. There are 50 to 70 percent of the carriers that can live the rest of their lives in this stage, without passing into the syphilis stage.

The last stage is the serious stage. It flares up without warning. It can cause heart problems, eye problems, brain and spinal cord damage, with a high probability of paralysis, insanity, blindness or death.

Syphilis

Syphilis is another sexually transmitted disease. It can be transmitted from an infected sex organ to an open cut in the skin of another person. It usually penetrates the moist mucous membranes of the mouth, the vagina, and the penis urethra, through which urine passes from the bladder to the outside.

Testing

There are two types of testing to show if you have gonorrhea. One is called gram strain, which is usually more accurate for men then for women. The test consists of placing a smear of the discharge on a slide that has a dye in it and when examined under a microscope shows the presence of gonorrhea.

The next test is a culture test, this one is usually used to tell if women have gonorrhea or not. It involves taking a sample of the discharge and placing it on a culture plate to incubate for two days, to allow the bacteria to multiply. Cervical samples are more accurate, to tell if the woman has gonorrhea or not.

Transmission

The bacterium that causes gonorrhea can be passed through intercourse, anal sex, and cunnilingus. The transmission is by contact of fluids from mucous membranes of infected people and it usually is through sexual activity. Most frequently, these bacteria infect the man's urethra, the tube that carries urine and semen through the penis, and the woman's cervix, the canal into the uterus.

Treatment

There is treatment for gonorrhea, since it is a bacterial infection, and the name of the drug is Ceftriaxone.

Symptoms

The symptoms in males include a yellowish discharge from the penis, which causes painful, frequent urination. Symptoms can develop from two to thirty days after infection. A few percent of infected men have no symptoms. The infection may move into the prostate, seminal vesicles, and epididymis, causing pain and fever. Untreated, gonorrhea can lead to sterility.

Less than half the women with gonorrhea show any symptoms, or symptoms so mild they just ignore. Early symptoms include a discharge from the vagina, some discomfort in the lower abdomen, irritation of the genitals, pain or burning during urination and some abnormal bleeding. Women, who leave these symptoms untreated, develop severe complications. The infection will usually spread to the uterus, fallopian tubes, and ovaries, causing Pelvic Inflammatory Disease (PID). Gonorrhea is the most common cause of female infertility.

Some early symptoms of this infection are lower abdomen pain, fever, nausea, and pain during intercourse.

In both men and women if gonorrhea is left untreated, it may spread throughout the body, affecting joints and even heart valves.

Gonorrhea/Clap

Gonorrhea also known as the clap, is a sexually transmitted bacterial disease, which differs in males and females.

Testing

There are two methods to test for chlamydia. One involves taking a cotton swab sample from the infected area and the other is with a urine test. The urine test is most common.

Transmission

The most common form of transmission is through sexual intercourse and oral sex.

Treatment

There is treatment for chlamydia with antibiotics. A single dose of azithromycin or a week long treatment with doxycycline taken twice daily are the most common treatments.

Symptoms

Possible symptoms include discharge from the penis or vagina and some burning sensations during urination. Additional symptoms for women include lower abdominal pain or pain during intercourse and bleeding between menstrual periods. Men may experience burning and itching around the opening of the penis and pain or swelling in the testicles. The males are more likely to have symptoms, than women. Men may also have a discharge from the penis.

Some men think they have gonorrhea, but it is not. The incubation period for chlamydia is longer and the discharge is lighter in color. Pelvic inflammatory disease (PID), which can be caused by chlamydia, is a cause of infertility when left untreated.

Chlamydia

Chlamydia is the No. 1 sexually transmitted disease in the US. Chlamydia is known as the "silent epidemic" because most of the women and many men with the disease have no symptoms.

Sexually Transmitted Disease

Symptoms
HIV causes the destruction of the immune system. It destroys the body's white blood cells which are called the T-cells. The T-cells is essential to the effectiveness of the body's immune system. So, consequently the body's natural defense system is impaired. The early symptom of HIV includes weight loss, fever, swollen lymph nodes, fatigue, minor illnesses and infections. Some other signs may be pneumonia and Kaposi's sarcoma, a rare skin cancer.

HIV/AIDS

One of the most severe transmitted diseases is HIV, which stands for Human Immunodeficiency Virus. This is the virus which ultimately causes AIDS. If someone is HIV positive, they have been infected with the virus that causes AIDS. Most people who are HIV positive go on to develop AIDS, but it may take many years before they have full-blown AIDS. During this time they may feel well, but still can infect other people, by giving blood or having sex with someone. AIDS stands for Acquired Immunodeficiency Syndrome which is a collection of symptoms associated with HIV infection.

Government of Canada's Role

In January 2005, the Government of Canada launched the Federal Initiative to Address HIV/AIDS in Canada and committed to pursuing a Government of Canada-wide approach to addressing HIV/AIDS. The Federal Initiative to Address HIV/AIDS in Canada signals a renewed and strengthened federal role in the Canadian response to HIV/AIDS. The Federal Initiative, a partnership of the Public Health Agency of Canada (PHAC), Health Canada, the Canadian Institutes of Health Research and Correctional Service Canada, will focus on addressing the complex social, human rights, biological and community barriers that continue to fuel the epidemic.

Recommendations from program reviews, evaluations and other consultative exercises, have signalled the need for the federal government to:

• Develop discrete approaches to addressing the epidemic for people living with HIV/AIDS, gay men, injection drug users, Aboriginal people, prison inmates, youth and women at risk for HIV infection, and people from countries where HIV is endemic;
• Increase government collaboration at all levels - federal, provincial, territorial and municipal;
• Support the use of social marketing initiatives to increase public awareness of HIV/AIDS and encourage those who may be part of the hidden epidemic to access HIV/AIDS programs;
• Encourage greater integration of HIV/AIDS prevention, care and treatment interventions with those of other diseases, as appropriate;
• More broadly engage federal departments and agencies in the response, such as Citizen and Immigration Canada, and those that have mandates related to housing, disability, social justice, employment and other determinants of health;
• Increase its engagement in the global response to the epidemic; and
• Improve the communication of outcomes achieved from federal investments in HIV/AIDS.

Canada has also responded to the global HIV/AIDS crisis. In May 2004, the Government committed funds to the World Health Organization's 3 by 5 initiative, to help provide anti-retroviral treatment to 3 million people with HIV/AIDS by the end of 2005. The Government is also extending its contribution in 2005 to the Global Fund to Fight AIDS, Tuberculosis and Malaria. In addition to these contributions, the Government has passed a bill to make less-expensive generic drugs available to developing and least developed countries facing public health challenges such as HIV/AIDS.

HIV cannot be transmitted through:

• Casual, everyday contact;
• Shaking hands, hugging, kissing;
• Coughs, sneezes;
• Giving blood;
• Swimming pools, toilet seats;
• Sharing eating utensils, water fountains; or
• Mosquitoes, other insects, or animals.

HIV is transmitted through:

• Unprotected sexual intercourse (vaginal, anal, oral);
• Shared needles or equipment for injecting drugs;
• Unsterilized needles for tattooing, skin piercing or acupuncture;
• Pregnancy, delivery and breast feeding (from an HIV-infected mother to her infant); and
• Occupational exposure in health care settings.

Diseases and Conditions

HIV and AIDS

The Human Immunodeficiency Virus (HIV) is the virus that causes Acquired Immunodeficiency Syndrome (AIDS). HIV attacks the immune system, resulting in a chronic, progressive illness and leaving infected people vulnerable to opportunistic infections and cancers. The median time from infection to AIDS diagnosis now exceeds 10 years. AIDS is fatal. There is no cure.

What about home testing?

Using an HIV test kit at home means that the results are learned on the spot without any counselling. Reactive test results must be confirmed by further testing at a clinic. If purchased over the internet, there is no guarantee that the test kit is genuine or will provide accurate results. In the event of an incorrect result, there may be no legal recourse.

In many countries it is illegal to sell HIV test kits to the public. There is currently some debate about allowing them to be sold in the USA and the UK. AVERT opposes the legalisation of the sale of home testing kits in the UK because of the lack of post-test counselling.

What is HIV home sampling?

It is generally recommended that the HIV test is done in a health care setting. However, in some countries 'home sampling' kits are available. With a home sampling kit, a person can take a sample (usually a blood sample) and then send it to a laboratory for testing. A few days later, the person phones up a special number, gives their individual identification code, and is given the result over the phone. If the result is positive then a professional counsellor will provide emotional support and referrals.

For home sampling, the major advantages are convenience, speed, privacy and anonymity. In countries where HIV tests are not free, home sampling may be a cost-effective way to get tested. But for some people the lack of face-to face counselling before and after the test may be a disadvantage. There is one company in the USA that offers an FDA-approved home sampling kit for HIV.

There is also a company in the UK that offers home sampling services using oral fluid instead of blood. However, this company only conducts a preliminary screening test instead of the full diagnostic procedure, so clients with reactive test results must visit a clinic for further testing. This service is only suitable for people at low risk of being infected.

How accurate are HIV tests?

Standard HIV antibody (ELISA) tests are at least 99.5% accurate when it comes to detecting the presence of HIV antibodies. This high level of sensitivity however means that their specificity (ability to distinguish HIV antibodies from other antibodies) is slightly lowered. Once an individual is out of the window period, it is more likely that they will receive a false positive result than a false negative.

Any HIV positive result given by an ELISA test must therefore be confirmed using a second test. Secondary tests include:

• Western Blot Assays – One of the oldest but most accurate confirmatory antibody tests. It is complex to administer and may produce indeterminate results if a person has a transitory infection with another virus.
• Indirect Immunofluorescence Assay – Like the Western blot, but uses a microscope to detect HIV antibodies.
• Line Immunoassay - Commonly used in Europe. Reduces chance of sample contamination and is as accurate as the Western Blot.
• A second ELISA – In resource-poor settings with relatively high prevalence, a second ELISA test may be used to confirm a diagnosis. The second test will usually be a different commercial brand and will use a different method of detection to the first.

When two tests are combined, the chance of getting an inaccurate result is less than 0.1%.

What does the HIV test involve?

In most countries, there are many places that you can get tested for HIV. It is recommended that you get the HIV test done at a health clinic, at the doctor's surgery, or at a specialist HIV/AIDS voluntary counselling and testing (VCT) site. When you attend to get tested, you will see a doctor, trained counsellor, a nurse or some other health professional in private. He or she will explain what the test involves and what the result means.

Normally a small sample of blood will be taken from your arm, sent to a laboratory and tested. In the USA and a number of places in Africa, the Middle East and Russia, oral tests are also available which do not require the use of needles. The test is always strictly confidential and only goes ahead if you agree. Your personal doctor will not be told about the test without your permission. Depending on the test used, it can take anything from a few days to a week or longer to get the result back.

A rapid HIV test is also an antibody test. The advantage of a rapid test is that you do not have to return to get your test result. The test results from a rapid test are usually available in approximately 30 minutes. Rapid tests are single-use, and do not require laboratory facilities or highly trained staff. This makes rapid tests very suitable for VCT in resource-poor countries.

What are the reasons to have an HIV test?

Many people who have an HIV test have been worrying unnecessarily. Getting a negative result (which means you are not infected with HIV) can put your mind at rest. If your test result is positive, many things can be done to help you to cope with the HIV positive result and look after your health. If your test is positive, then:

• A doctor can keep an eye on your health. Many people who test positive stay healthy for several years. But if you fall ill, there are many drugs called antiretrovirals that can help to slow down the virus and maintain your immune system. You can also have medicines to prevent and treat some of the illnesses that people with HIV get. You may also have access to trials of new drugs and treatments.
• If you do fall ill, the doctor is going to take your symptoms more seriously if they know that you are HIV positive.
• If you know that you are HIV positive, you can take steps to protect other people. For example, by practising safe sex and informing you past sexual partners.
• Knowing that you have HIV may affect some of your future decisions and plans, for example starting a family.

HIV testing

The standard HIV test looks for antibodies in a person's blood. When HIV (which is a virus) enters a person's body, special proteins are produced. These are called antibodies. Antibodies are the body's response to an infection. So if a person has antibodies to HIV in their blood, it means they have been infected with HIV. There are only two exceptions to this rule. Firstly, babies born to positive mothers retain their mother's antibodies for up to 18 months, which means they may test positive on an HIV antibody test, even if they are actually HIV negative. This is why babies born to positive mothers may receive a PCR test after birth. Secondly, some people who have taken part in HIV vaccine trials may have HIV antibodies even if they are not infected with the virus.

Most people develop detectable HIV antibodies within 6 to 12 weeks of infection. In very rare cases, it can take up to 6 months. It is exceedingly unlikely that someone would take longer than 6 months to develop antibodies.

Getting tested earlier than 3 months may result in an unclear test result, as an infected person may not yet have developed antibodies to HIV. The time between infection and the development of antibodies is called the window period. During the window period people infected with HIV will not yet have antibodies in their blood that can be detected by an HIV test. However, the person may already have high levels of HIV in their blood, sexual fluids or breast milk. Someone can transmit HIV to another person during the window period even though they do not test positive on an antibody test. So it is best to wait for at least 3 months after the last time you were at risk before taking the test, and abstain from unprotected sex or drug use with shared needles in the meantime. Some test centres may recommend testing again at 6 months if you're deemed to be at particularly high risk of infection.

It is also important that you are not exposed to further risk of getting infected with HIV during the window period. The test is only accurate if there are no other exposures between the time of possible exposure to HIV and testing.

A negative test at three months will almost always mean a person is not infected with HIV. If an individual's test is still negative at six months and they have not had unprotected sex or shared needles again in the meantime, it means that they do not have HIV, and will not therefore go on to develop AIDS.

The only way to know for sure whether you are infected with HIV is to have an HIV antibody test. It is not possible to tell from any symptoms.

The third type of test is a PCR test (Polymerase Chain Reaction test). The whole process of extracting genetic material and testing it with a PCR test is referred to as Nucleic Acid-amplification Testing or 'NAT'. PCR tests detect the genetic material of HIV itself, and can identify HIV in the blood within two or three weeks of infection.

PCR tests come in two forms: DNA PCR and RNA PCR. Babies born to HIV positive mothers are usually tested using a DNA PCR because they retain their mother's antibodies for several months, making an antibody test inaccurate. Blood supplies in most developed countries are screened for HIV using an RNA PCR test, which can produce positive results several days before a DNA test. When a person already knows that she or he is infected with HIV, they may also have a viral load test to detect HIV genetic material and estimate the level of virus in the blood. This can be performed using either an RNA or DNA PCR test. PCR tests are not often used to test for HIV in adults, as they are very expensive and more complicated to administer than a standard antibody or P24 test. However they may be offered in special circumstances, or by private clinics where patients are willing to pay.

Blood supplies in most developed countries are screened for HIV using an RNA PCR test, which can produce positive results several days before a DNA test.

HIV testing

here are three main types of HIV test.

The first type of test is the HIV antibody test. This test shows whether a person has been infected with HIV, the virus that causes AIDS. Information on this page concentrates mainly on HIV antibody testing. Antibody tests are also known as ELISA (Enzyme-Linked Immunosorbent Assay) tests.

The second type of test is an antigen test. Antigens are the substances found on a foreign body or germ that trigger the production of antibodies in the body. The antigen on HIV that most commonly provokes an antibody response is the protein P24. Early in the infection, P24 is produced in excess and can be detected in the blood serum by a commercial test (although as HIV becomes fully established in the body it will fade to undetectable levels). P24 antigen tests are sometimes used to screen donated blood, but they can also be used for testing for HIV in individuals, as they can detect HIV earlier than standard antibody tests. Some of the most modern HIV tests combine P24 and other antigen tests with standard antibody identification methods to enable earlier and more accurate HIV detection.

First and second line therapy

At the beginning of treatment, the combination of drugs that a person is given is called first line therapy. If after a while HIV becomes resistant to this combination, or if side effects are particularly bad, then a change to second line therapy is usually recommended.

Second line therapy will ideally include a minimum of three new drugs, with at least one from a new class, in order to increase the likelihood of treatment success.

Our continuing antiretroviral treatment page has more information about changing HIV treatment.

What does combination therapy usually consist of?

The most common drug combination given to those beginning treatment consists of two NRTIs combined with either an NNRTI or a "boosted" protease inhibitor. Ritonavir (in small doses) is most commonly used as the booster; it enhances the effects of other protease inhibitors so they can be given in lower doses. An example of a common antiretroviral combination is the two NRTIs zidovudine and lamivudine, combined with the NNRTI efavirenz.

Some antiretroviral drugs have been combined into one pill, which is known as a ‘fixed dose combination’. This reduces the number of pills to be taken each day.

The choice of drugs to take can depend on a number of factors, including the availability and price of drugs, the number of pills, the side effects of the drugs, the laboratory monitoring requirements and whether there are co-blister packs or fixed dose combinations available. Most people living with HIV in the developing world still have very limited access to antiretroviral treatment and often only receive treatment for the diseases that occur as a result of a weakened immune system. Such treatment has only short-term benefits because it does not address the underlying immune deficiency itself.

The groups of antiretroviral drugs

There are five groups of antiretroviral drugs. Each of these groups attacks HIV in a different way.

Antiretroviral drug class	Abbreviations	First approved to treat HIV	How they attack HIV
Nucleoside/Nucleotide Reverse Transcriptase Inhibitors	NRTIs, nucleoside analogues, nukes	1987	NRTIs interfere with the action of an HIV protein called reverse transcriptase, which the virus needs to make new copies of itself.
Non-Nucleoside Reverse Transcriptase Inhibitors	NNRTIs, non-nucleosides, non-nukes	1997	NNRTIs also stop HIV from replicating within cells by inhibiting the reverse transcriptase protein.
Protease Inhibitors	PIs	1995	PIs inhibit protease, which is another protein involved in the HIV replication process.
Fusion or Entry Inhibitors		2003	Fusion or entry inhibitors prevent HIV from binding to or entering human immune cells.
Integrase Inhibitors		2007	Integrase inhibitors interfere with the integrase enzyme, which HIV needs to insert its genetic material into human cells.

NRTIs and NNRTIs are available in most countries. Fusion/entry inhibitors and integrase inhibitors are usually only available in resource-rich countries.

Protease inhibitors are generally less suitable for starting treatment in resource-limited settings due to the cost, number of pills which need to be taken, and the particular side effects caused by protease drugs.

How many HIV and AIDS drugs are there?

There are more than 20 approved antiretroviral drugs but not all are licensed or available in every country. See our drugs table for a comprehensive list of antiretroviral drugs approved by the American Food and Drug Administration.

Why do people need to take more than one drug at a time?

If only one drug was taken, HIV would quickly become resistant to it and the drug would stop working. Taking two or more antiretrovirals at the same time vastly reduces the rate at which resistance would develop, making treatment more effective in the long term.

Our continuing antiretroviral treatment page has more about drug resistance.

What is combination therapy?

Taking two or more antiretroviral drugs at a time is called combination therapy. Taking a combination of three or more anti-HIV drugs is sometimes referred to as Highly Active Antiretroviral Therapy (HAART).

What is HIV antiretroviral drug treatment?

This is the main type of treatment for HIV or AIDS. It is not a cure, but it can stop people from becoming ill for many years. The treatment consists of drugs that have to be taken every day for the rest of a person’s life.

The aim of antiretroviral treatment is to keep the amount of HIV in the body at a low level. This stops any weakening of the immune system and allows it to recover from any damage that HIV might have caused already.

• antiretrovirals
• anti-HIV or anti-AIDS drugs

• HIV antiviral drugs
• ARVs

HIV AIDS treatments

Introduction to HIV and AIDS drug treatment

This is the first of a set of treatment pages that give an overview of the issues surrounding HIV and AIDS drug treatment. It is followed by starting HIV & AIDS drug treatment and continuing HIV & AIDS drug treatment.

Treatment

There is currently no vaccine or cure for HIV or AIDS.The only known method of prevention is avoiding exposure to the virus. However, a course of antiretroviral treatment administered immediately after exposure, referred to as post-exposure prophylaxis, is believed to reduce the risk of infection if begun as quickly as possible.Current treatment for HIV infection consists of highly active antiretroviral therapy, or HAART.This has been highly beneficial to many HIV-infected individuals since its introduction in 1996, when the protease inhibitor-based HAART initially became available.Current HAART options are combinations (or "cocktails") consisting of at least three drugs belonging to at least two types, or "classes," of antiretroviral agents. Typically, these classes are two nucleoside analogue reverse transcriptase inhibitors (NARTIs or NRTIs) plus either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor (NNRTI). New classes of drugs such as Entry Inhibitors provide treatment options for patients who are infected with viruses already resistant to common therapies, although they are not widely available and not typically accessible in resource-limited settings. Because AIDS progression in children is more rapid and less predictable than in adults, particularly in young infants, more aggressive treatment is recommended for children than adults.In developed countries where HAART is available, doctors assess their patients thoroughly: measuring the viral load, how fast CD4 declines, and patient readiness. They then decide when to recommend starting treatment.

HAART neither cures the patient nor does it uniformly remove all symptoms; high levels of HIV-1, often HAART resistant, return if treatment is stopped.Moreover, it would take more than a lifetime for HIV infection to be cleared using HAART.Despite this, many HIV-infected individuals have experienced remarkable improvements in their general health and quality of life, which has led to a large reduction in HIV-associated morbidity and mortality in the developed world.One study suggests the average life expectancy of an HIV infected individual is 32 years from the time of infection if treatment is started when the CD4 count is 350/µL.In the absence of HAART, progression from HIV infection to AIDS has been observed to occur at a median of between nine to ten years and the median survival time after developing AIDS is only 9.2 months.However, HAART sometimes achieves far less than optimal results, in some circumstances being effective in less than fifty percent of patients. This is due to a variety of reasons such as medication intolerance/side effects, prior ineffective antiretroviral therapy and infection with a drug-resistant strain of HIV. However, non-adherence and non-persistence with antiretroviral therapy is the major reason most individuals fail to benefit from HAART.The reasons for non-adherence and non-persistence with HAART are varied and overlapping. Major psychosocial issues, such as poor access to medical care, inadequate social supports, psychiatric disease and drug abuse contribute to non-adherence. The complexity of these HAART regimens, whether due to pill number, dosing frequency, meal restrictions or other issues along with side effects that create intentional non-adherence also contribute to this problem.The side effects include lipodystrophy, dyslipidemia, insulin resistance, an increase in cardiovascular risks and birth defects.

The timing for starting HIV treatment is still debated. There is no question that treatment should be started before the patient's CD4 count falls below 200, and most national guidelines say to start treatment once the CD4 count falls below 350; but there is some evidence from cohort studies that treatment should be started before the CD4 count falls below 350.In those countries where CD4 counts are not available, patients with WHO stage III or IV disease should be offered treatment.

Anti-retroviral drugs are expensive, and the majority of the world's infected individuals do not have access to medications and treatments for HIV and AIDS.Research to improve current treatments includes decreasing side effects of current drugs, further simplifying drug regimens to improve adherence, and determining the best sequence of regimens to manage drug resistance. Unfortunately, only a vaccine is thought to be able to halt the pandemic. This is because a vaccine would cost less, thus being affordable for developing countries, and would not require daily treatment.However, after over 20 years of research, HIV-1 remains a difficult target for a vaccine.

HIV test

Many HIV-positive people are unaware that they are infected with the virus.For example, less than 1% of the sexually active urban population in Africa have been tested and this proportion is even lower in rural populations.Furthermore, only 0.5% of pregnant women attending urban health facilities are counselled, tested or receive their test results.Again, this proportion is even lower in rural health facilities.Since donors may therefore be unaware of their infection, donor blood and blood products used in medicine and medical research are routinely screened for HIV.

HIV-1 testing consists of initial screening with an enzyme-linked immunosorbent assay (ELISA) to detect antibodies to HIV-1. Specimens with a nonreactive result from the initial ELISA are considered HIV-negative unless new exposure to an infected partner or partner of unknown HIV status has occurred. Specimens with a reactive ELISA result are retested in duplicate.If the result of either duplicate test is reactive, the specimen is reported as repeatedly reactive and undergoes confirmatory testing with a more specific supplemental test (e.g., Western blot or, less commonly, an immunofluorescence assay (IFA)). Only specimens that are repeatedly reactive by ELISA and positive by IFA or reactive by Western blot are considered HIV-positive and indicative of HIV infection. Specimens that are repeatedly ELISA-reactive occasionally provide an indeterminate Western blot result, which may be either an incomplete antibody response to HIV in an infected person, or nonspecific reactions in an uninfected person.Although IFA can be used to confirm infection in these ambiguous cases, this assay is not widely used. Generally, a second specimen should be collected more than a month later and retested for persons with indeterminate Western blot results. Although much less commonly available, nucleic acid testing (e.g., viral RNA or proviral DNA amplification method) can also help diagnosis in certain situations.In addition, a few tested specimens might provide inconclusive results because of a low quantity specimen. In these situations, a second specimen is collected and tested for HIV infection.

AIDS

When CD4⁺ T cell numbers decline below a critical level, cell-mediated immunity is lost, and infections with a variety of opportunistic microbes appear. The first symptoms often include moderate and unexplained weight loss, recurring respiratory tract infections (such as sinusitis, bronchitis, otitis media, pharyngitis), prostatitis, skin rashes, and oral ulcerations. Common opportunistic infections and tumors, most of which are normally controlled by robust CD4⁺ T cell-mediated immunity then start to affect the patient. Typically, resistance is lost early on to oral Candida species and to Mycobacterium tuberculosis, which leads to an increased susceptibility to oral candidiasis (thrush) and tuberculosis. Later, reactivation of latent herpes viruses may cause worsening recurrences of herpes simplex eruptions, shingles, Epstein-Barr virus-induced B-cell lymphomas, or Kaposi's sarcoma, a tumor of endothelial cells that occurs when HIV proteins such as Tat interact with Human Herpesvirus-8. Pneumonia caused by the fungus Pneumocystis jirovecii is common and often fatal. In the final stages of AIDS, infection with cytomegalovirus (another herpes virus) or Mycobacterium avium complex is more prominent. Not all patients with AIDS get all these infections or tumors, and there are other tumors and infections that are less prominent but still significant.

Latency stage

A strong immune defense reduces the number of viral particles in the blood stream, marking the start of the infection's clinical latency stage. Clinical latency can vary between two weeks and 20 years. During this early phase of infection, HIV is active within lymphoid organs, where large amounts of virus become trapped in the follicular dendritic cells (FDC) network.The surrounding tissues that are rich in CD4⁺ T cells may also become infected, and viral particles accumulate both in infected cells and as free virus. Individuals who are in this phase are still infectious. During this time, CD4⁺ CD45RO⁺ T cells carry most of the proviral load.

Acute HIV infection

The initial infection with HIV generally occurs after transfer of body fluids from an infected person to an uninfected one. The first stage of infection, the primary, or acute infection, is a period of rapid viral replication that immediately follows the individual's exposure to HIV leading to an abundance of virus in the peripheral blood with levels of HIV commonly approaching several million viruses per mL.This response is accompanied by a marked drop in the numbers of circulating CD4⁺ T cells. This acute viremia is associated in virtually all patients with the activation of CD8⁺ T cells, which kill HIV-infected cells, and subsequently with antibody production, or seroconversion. The CD8⁺ T cell response is thought to be important in controlling virus levels, which peak and then decline, as the CD4⁺ T cell counts rebound to around 800 cells per µL (the normal blood value is 1200 cells per µL ). A good CD8⁺ T cell response has been linked to slower disease progression and a better prognosis, though it does not eliminate the virus.During this period (usually 2-4 weeks post-exposure) most individuals (80 to 90%) develop an influenza or mononucleosis-like illness called acute HIV infection, the most common symptoms of which may include fever, lymphadenopathy, pharyngitis, rash, myalgia, malaise, mouth and esophagal sores, and may also include, but less commonly, headache, nausea and vomiting, enlarged liver/spleen, weight loss, thrush, and neurological symptoms. Infected individuals may experience all, some, or none of these symptoms. The duration of symptoms varies, averaging 28 days and usually lasting at least a week.Because of the nonspecific nature of these symptoms, they are often not recognized as signs of HIV infection. Even if patients go to their doctors or a hospital, they will often be misdiagnosed as having one of the more common infectious diseases with the same symptoms. Consequently, these primary symptoms are not used to diagnose HIV infection as they do not develop in all cases and because many are caused by other more common diseases. However, recognizing the syndrome can be important because the patient is much more infectious during this period.

The clinical course of infection

Infection with HIV-1 is associated with a progressive decrease of the CD4⁺ T cell count and an increase in viral load. The stage of infection can be determined by measuring the patient's CD4⁺ T cell count, and the level of HIV in the blood.

HIV infection has basically four stages: incubation period, acute infection, latency stage and AIDS. The initial incubation period upon infection is asymptomatic and usually lasts between two and four weeks. The second stage, acute infection, which lasts an average of 28 days and can include symptoms such as fever, lymphadenopathy (swollen lymph nodes), pharyngitis (sore throat), rash, myalgia (muscle pain), malaise, and mouth and esophageal sores. The latency stage, which occurs third, shows few or no symptoms and can last anywhere from two weeks to twenty years and beyond. AIDS, the fourth and final stage of HIV infection shows as symptoms of various opportunistic infections.

Genetic variability

HIV differs from many viruses in that it has very high genetic variability. This diversity is a result of its fast replication cycle, with the generation of 10⁹ to 10¹⁰ virions every day, coupled with a high mutation rate of approximately 3 x 10^-5 per nucleotide base per cycle of replication and recombinogenic properties of reverse transcriptase.This complex scenario leads to the generation of many variants of HIV in a single infected patient in the course of one day.This variability is compounded when a single cell is simultaneously infected by two or more different strains of HIV. When simultaneous infection occurs, the genome of progeny virions may be composed of RNA strands from two different strains. This hybrid virion then infects a new cell where it undergoes replication. As this happens, the reverse transcriptase, by jumping back and forth between the two different RNA templates, will generate a newly synthesized retroviral DNA sequence that is a recombinant between the two parental genomes.This recombination is most obvious when it occurs between subtypes.

The closely related simian immunodeficiency virus (SIV) exhibits a somewhat different behavior: in its natural hosts, African green monkeys and sooty mangabeys, the retrovirus is present in high levels in the blood, but evokes only a mild immune response,does not cause the development of simian AIDS,and does not undergo the extensive mutation and recombination typical of HIV.By contrast, infection of heterologous hosts (rhesus or cynomologus macaques) with SIV results in the generation of genetic diversity that is on the same order as HIV in infected humans; these heterologous hosts also develop simian AIDS.The relationship, if any, between genetic diversification, immune response, and disease progression is unknown.

Three groups of HIV-1 have been identified on the basis of differences in env: M, N, and O.Group M is the most prevalent and is subdivided into eight subtypes (or clades), based on the whole genome, which are geographically distinct.The most prevalent are subtypes B (found mainly in North America and Europe), A and D (found mainly in Africa), and C (found mainly in Africa and Asia); these subtypes form branches in the phylogenetic tree representing the lineage of the M group of HIV-1. Coinfection with distinct subtypes gives rise to circulating recombinant forms (CRFs). In 2000, the last year in which an analysis of global subtype prevalence was made, 47.2 percent of infections worldwide were of subtype C, 26.7 percent were of subtype A/CRF02_AG, 12.3 percent were of subtype B, 5.3 percent were of subtype D, 3.2 percent were of CRF_AE, and the remaining 5.3 percent were composed of other subtypes and CRFs.Most HIV-1 research is focused on subtype B; few laboratories focus on the other subtypes.The genetic sequence of HIV-2 is only partially homologous to HIV-1 and more closely resembles that of SIV than HIV-1.

Assembly and release

The final step of the viral cycle, assembly of new HIV-1 virons, begins at the plasma membrane of the host cell. The Env polyprotein (gp160) goes through the endoplasmic reticulum and is transported to the Golgi complex where it is cleaved by protease and processed into the two HIV envelope glycoproteins gp41 and gp120. These are transported to the plasma membrane of the host cell where gp41 anchors the gp120 to the membrane of the infected cell. The Gag (p55) and Gag-Pol (p160) polyproteins also associate with the inner surface of the plasma membrane along with the HIV genomic RNA as the forming virion begins to bud from the host cell. Maturation either occurs in the forming bud or in the immature virion after it buds from the host cell. During maturation, HIV proteases cleave the polyproteins into individual functional HIV proteins and enzymes. The various structural components then assemble to produce a mature HIV virion.This cleavage step can be inhibited by protease inhibitors. The mature virus is then able to infect another cell.

This integrated viral DNA may then lie dormant, in the latent stage of HIV infection.To actively produce the virus, certain cellular transcription factors need to be present, the most important of which is NF-κB (NF kappa B), which is upregulated when T-cells become activated.This means that those cells most likely to be killed by HIV are those currently fighting infection.

In this replication process, the integrated provirus is copied to mRNA which is then spliced into smaller pieces. These small pieces produce the regulatory proteins Tat (which encourages new virus production) and Rev. As Rev accumulates it gradually starts to inhibit mRNA splicing.At this stage, the structural proteins Gag and Env are produced from the full-length mRNA. The full-length RNA is actually the virus genome; it binds to the Gag protein and is packaged into new virus particles.

HIV-1 and HIV-2 appear to package their RNA differently; HIV-1 will bind to any appropriate RNA whereas HIV-2 will preferentially bind to the mRNA which was used to create the Gag protein itself. This may mean that HIV-1 is better able to mutate (HIV-1 infection progresses to AIDS faster than HIV-2 infection and is responsible for the majority of global infections).

Replication and transcription

Shortly after the viral capsid enters the cell, an enzyme called reverse transcriptase liberates the single-stranded (+)RNA from the attached viral proteins and copies it into a complementary DNA.^[77] This process of reverse transcription is extremely error-prone and it is during this step that mutations may occur. Such mutations may cause drug resistance. The reverse transcriptase then makes a complementary DNA strand to form a double-stranded viral DNA intermediate (vDNA). This vDNA is then transported into the cell nucleus. The integration of the viral DNA into the host cell's genome is carried out by another viral enzyme called integrase.^[77]