Human immunodeficiency virus (HIV) infection is a viral infection that progressively destroys certain white blood cells and can cause acquired immunodeficiency syndrome (AIDS).

• HIV is transmitted through close contact with a body fluid that contains the virus or cells infected with the virus (such as blood, semen, or vaginal fluids).
• HIV destroys certain types of white blood cells, weakening the body’s defenses against infections and cancers.
• When people are first infected, symptoms of fever, rashes, swollen lymph nodes, and fatigue may last a few days to several weeks.
• Many infected people remain well for more than a decade.
• About half of untreated people become ill and develop AIDS, defined by the presence of serious infections and cancers, within about 10 years.
• Eventually, most untreated people develop AIDS.
• Blood tests to check for HIV antibody and to measure the amount of HIV virus can confirm the diagnosis.
• HIV drugs (antiretroviral drugs)—two, three, or more taken together—can stop HIV from reproducing, strengthen the immune system, and thus make people less susceptible to infection, but the drugs cannot eliminate HIV, which persists in an inactive form.

HIV infections may be caused by one of two retroviruses, HIV-1 or HIV-2. HIV-1 causes most HIV infections worldwide, but HIV-2 causes many HIV infections in West Africa.

HIV progressively destroys certain types of white blood cells called CD4+ lymphocytes. Lymphocytes help defend the body against foreign cells, infectious organisms, and cancer. Thus, when HIV destroys CD4+ lymphocytes, people become susceptible to attack by many other infectious organisms. Many of the complications of HIV infection, including death, usually result from these other infections and not from HIV infection directly.

HIV-1 originated in Central Africa during the first half of the 20th century when a closely related chimpanzee virus first infected people. The global spread of HIV-1 began in the late 1970s, and AIDS was first recognized in 1981.

In 2016, about 36.7 million people, including 2.1 million children under age 15, were living with HIV infection worldwide. There were 1 million AIDS-related deaths, and 1.8 million people were newly infected.

Most (95%) new infections occur in the developing world. Almost 70% of new HIV infections occur in sub-Saharan Africa, with more than half occurring in women and 1 in 10 occurring in children under 15 years old. However, in many sub-Saharan African countries, the number of new HIV infections has greatly decreased, partly because of international efforts to provide treatment and strategies for prevention.

In the United States, over 1.1 million people aged 13 years or older were estimated to have HIV infection in 2015. About 15% of them do not know they have HIV infection. In 2016, 39,782 cases of HIV infection were diagnosed in the United States. Over two thirds of these infections occurred in gay and bisexual men. Among these men, most infections occurred in black men (10,223), followed by Hispanic/Latino men (7,425) and white men (7,390).

Acquired immunodeficiency syndrome (AIDS)

AIDS is the most severe form of HIV infection. HIV infection is considered to be AIDS when at least one serious complicating illness develops or the number (count) of CD4+ lymphocytes decreases substantially.

When people who are infected with HIV develop certain illnesses, AIDS is diagnosed. These illnesses, called AIDS-defining illnesses, include

• Serious infections that occur mainly in people with a weakened immune system (called opportunistic infections), including fungal infections (such as cryptococcosis and Pneumocystis jirovecii pneumonia) and severe herpes simplex infections
• Certain cancers, such as invasive cervical cancer, Kaposi sarcoma, and certain lymphomas
• Dysfunction of the nervous system
• A substantial loss of weight due to HIV infection (AIDS wasting)

Transmission of HIV Infection

The transmission of HIV requires contact with a body fluid that contains the virus or cells infected with the virus. HIV can appear in nearly any body fluid, but transmission occurs mainly through blood, semen, vaginal fluids, and breast milk. Although tears, urine, and saliva may contain low concentrations of HIV, transmission through these fluids is extremely rare, if it occurs at all.

HIV is not transmitted by casual contact (such as touching, holding, or dry kissing) or by close, nonsexual contact at work, school, or home. No case of HIV transmission has been traced to the coughing or sneezing of an infected person or to a mosquito bite. Transmission from an infected doctor or dentist to a patient is extremely rare.

HIV is usually transmitted in the following ways:

• Sexual contact with an infected person, when the mucous membrane lining the mouth, vagina, penis, or rectum is exposed to body fluids such as semen or vaginal fluids that contain HIV, as occurs during unprotected sexual intercourse
• Injection of contaminated blood, as can occur when needles are shared or a health care worker is accidentally pricked with an HIV-contaminated needle
• Transfer from an infected mother to a child before birth, during birth, or after birth through the mother’s milk
• Medical procedures, such as transfusion of blood that contains HIV, procedures done with inadequately sterilized instruments, or transplantation of an infected organ or tissues

HIV is more likely to be transmitted if skin or a mucous membrane is torn or damaged—even if minimally.

In the United States, Europe, and Australia, HIV has been transmitted mainly through male homosexual contact and the sharing of needles among people who inject drugs, but transmission through heterosexual contact accounts for about one fourth of cases. HIV transmission in Africa, the Caribbean, and Asia occurs primarily between heterosexuals, and HIV infection occurs equally among men and women. In the United States, fewer than 25% of adults who have HIV infection are women. Before 1992, most American women with HIV were infected by injecting drugs with contaminated needles, but now most are infected through heterosexual contact.

Transmission of HIV through its most common routes—sexual contact or sharing of needles—is almost completely preventable.

Through sexual activity

Risk of transmitting HIV is highest during vaginal or anal sex when a condom is not used or is used incorrectly. HIV transmission can also occur during oral sex, although transmission is less likely than during vaginal or anal sex.

Risk of HIV infection is increased when semen or vaginal fluids contain a large amount of HIV and/or when there are tears or sores, even small ones, in the skin or membranes lining the genitals, mouth, or rectum. Thus, transmission is much more likely during the following:

• The first weeks after people are infected because at that time, the blood and body fluids contain very large amounts of HIV
• Vigorous sexual activities that damage the skin or membranes lining the genitals, mouth, or rectum
• Sexual intercourse when either partner has a genital herpes infection, syphilis, or another sexually transmitted disease (STD) that can cause sores or tears in the skin or inflammation of the genitals

HIV (antiretroviral) drugs can reduce the amount of HIV in semen and vaginal fluids. Thus, treatment of HIV infection with these drugs can dramatically reduce the likelihood of transmission.

Sexual activities that can damage the membranes lining the genitals, mouth, or rectum include fisting (inserting most or all of the hand into the rectum or vagina) and using sex toys.

The risk of being infected with HIV during heterosexual intercourse is higher for young people partly because they have less control over their impulses and thus are more likely to engage in risky sexual behavior, such as having several sex partners and not using condoms.

Recent evidence shows that HIV infected people in whom antiretroviral therapy has reduced their viral load below the current detectable level (virally suppressed) do not sexually transmit the virus to their partners.

Through needles or other instruments

Health care workers who are accidentally pricked with an HIV-contaminated needle have about a 1 in 300 chance of contracting HIV unless they are treated as soon as possible after exposure. Such treatment reduces the chance of infection to less than 1 in 1,500. The risk increases if the needle penetrates deeply or if the needle is hollow and contains HIV-contaminated blood (as with a needle used to draw blood or to inject street drugs) rather than simply being coated with blood (as with a needle used to stitch a cut).

Infected fluid splashing into the mouth or eyes has less than a 1 in 1,000 chance of causing infection.

From mother to child

HIV infection in a large number of women of childbearing age has led to an increase in HIV infection among children.

HIV infection can be transmitted from an infected mother to her child in the following ways:

• To the fetus through the placenta
• To the baby during passage through the birth canal
• To the baby after birth through breast milk

If infected mothers are not treated, about 25 to 35% of their babies are likely to be infected at birth, and if they breastfeed, about another 10 to 15% of the babies are likely to be infected.

Treating infected women with HIV drugs can dramatically reduce the risk of transmission. Infected pregnant women should be treated during the 2nd and 3rd trimesters of pregnancy, during delivery, and during breastfeeding. Doing a cesarean delivery and treating the baby for several weeks after birth also reduce the risk.

Infected mothers should not breastfeed if they live in countries where formula feeding is safe and affordable. However, in countries where infectious diseases and undernutrition are common causes of infant death and where safe, affordable infant formula is not available, the World Health Organization recommends that mothers breastfeed. In such cases, the protection provided by breastfeeding from potentially fatal infections may counterbalance the risk of HIV transmission.

Because many pregnant women with HIV infection are treated or take drugs to prevent HIV infection, the number of children getting AIDS is decreasing in many countries.

Through blood transfusions or organ transplants

Currently, HIV infection is rarely transmitted through blood transfusions or organ transplants.

Since 1985 in most developed countries, all blood collected for transfusion is tested for HIV, and when possible, some blood products are treated with heat to eliminate the risk of HIV infection. The current risk of HIV infection from a single blood transfusion (which is carefully screened for HIV and other bloodborne viruses) is estimated to be less than 1 in about 2 million in the United States. However, in many developing countries, blood and blood products are not screened for HIV or are not screened as stringently. There, the risk remains substantial.

HIV has been transmitted when organs (kidneys, livers, hearts, pancreases, bone, and skin) from infected donors were unknowingly used as transplants. HIV transmission is unlikely to occur when corneas or certain specially treated tissues (such as bone) are transplanted.

Artificial insemination

HIV transmission is also possible when sperm from an infected donor is used to inseminate a woman. In the United States, measures have been taken to reduce this risk. Fresh semen samples are no longer used. Sperm from donors is frozen for 6 months or more. Then the donors are retested for HIV infection before the sperm is used.

If a sperm donor is known to have HIV infection, washing sperm is an effective way to remove HIV from sperm.

Mechanism of HIV Infection

Once in the body, HIV attaches to several types of white blood cells. The most important are certain helper T lymphocytes (T cells). Helper T lymphocytes activate and coordinate other cells of the immune system. On their surface, these lymphocytes have a receptor called CD4, which enables HIV to attach to them. Thus, these helper lymphocytes are designated as CD4+.

HIV is a retrovirus. That is, it stores its genetic information as ribonucleic acid (RNA). Once inside a CD4+ lymphocyte, the virus uses an enzyme called reverse transcriptase to make a copy of its RNA, but the copy is made as deoxyribonucleic acid (DNA). HIV mutates easily at this point because reverse transcriptase is prone to making errors during the conversion of HIV RNA to DNA. These mutations make HIV more difficult to control because the many mutations increase the chance of producing HIV that can resist attacks by the person’s immune system and/or antiretroviral drugs.

The HIV DNA copy is incorporated into the DNA of the infected lymphocyte. The lymphocyte’s own genetic machinery then reproduces (replicates) the HIV. Eventually, the lymphocyte is destroyed. Each infected lymphocyte produces thousands of new viruses, which infect other lymphocytes and destroy them as well. Within a few days or weeks, the blood and genital fluids contain a very large amount of HIV, and the number of CD4+ lymphocytes may be reduced substantially. Because the amount of HIV in blood and genital fluids is so large so soon after HIV infection, newly infected people transmit HIV to other people very easily.

When HIV infection destroys CD4+ lymphocytes, it weakens the body’s immune system, which protects against many infections and cancers. This weakening is part of the reason that the body is unable to eliminate HIV infection once it has started. However, the immune system is able to mount some response. Within a month or two after infection, the body produces lymphocytes and antibodies that help lower the amount of HIV in the blood and keep the infection under control. For this reason, untreated HIV infection may cause no symptoms or only a few mild symptoms for an average of about 10 years (ranging from 2 to more than 15 years).

HIV also infects other cells, such as cells in the skin, brain, genital tract, heart, and kidneys, causing disease in those organs.

CD4 count

The number of CD4+ lymphocytes in blood (the CD4 count) helps determine the following:

• How well the immune system can protect the body from infections
• How severe the damage done by the HIV is

Most healthy people have a CD4 count of 500 to 1,000 cells per microliter of blood. Typically, the number of CD4+ lymphocytes is reduced during the first few months of infection. After about 3 to 6 months, the CD4 count stabilizes, but without treatment, it usually continues to decline at rates that vary from slow to rapid.

If the CD4 count falls below about 200 cells per microliter of blood, the immune system becomes less able to fight certain infections (such as Pneumocystis jirovecii pneumonia). Most of these infections are rare in healthy people. However, they are common among people with a weakened immune system. Such infections are called opportunistic infections because they take advantage of a weakened immune system.

A count below about 50 cells per microliter of blood is particularly dangerous because additional opportunistic infections that can rapidly cause severe weight loss, blindness, or death commonly occur. These infections include

• Cytomegalovirus infections
• Mycobacterium avium complex infections

Viral load

The amount of HIV in the blood (specifically the number of copies of HIV RNA) is called the viral load.

Viral load represents how quickly HIV is replicating. When people are first infected, the viral load increases rapidly. Then, after about 3 to 6 months, even without treatment, it drops to a lower level, which remains constant, called the set point. This level varies widely from person to person—from as little as a few hundred to over a million copies per microliter of blood.

Viral load also indicates

• How contagious the infection is
• How fast the CD4 count is likely to decrease
• How fast symptoms are likely to appear

The higher the set point of the viral load, the more quickly the CD4 count decreases to the low levels (less than 200) that increase risk of opportunistic infections, even in people without symptoms.

During successful treatment, the viral load decreases to very low or undetectable levels (less than about 20 to 40 copies per microliter of blood). However, inactive (latent) HIV is still present within cells, and if treatment is stopped, HIV starts replicating and the viral load increases.

An increase in the viral load during treatment may indicate the following:

• The HIV has developed resistance to drug treatment.
• The person is not taking the prescribed drugs.
• Both

Symptoms

Initial infection

When initially infected, many people have no noticeable symptoms, but within 1 to 4 weeks, fever, rashes, sore throat, swollen lymph nodes, fatigue, and a variety of less common symptoms develop in some people. Symptoms of initial (primary) HIV infection usually last from 3 to 14 days.

Interval of mild or no symptoms

After the first symptoms disappear, most people, even without treatment, have no symptoms or only occasionally have a few mild symptoms. This interval of few or no symptoms may last from 2 to 15 years. The symptoms that most commonly occur during this interval include the following:

• Swollen lymph nodes, felt as small, painless lumps in the neck, under the arms, or in the groin
• White patches in the mouth (thrush) due to candidiasis (a yeast infection)
• Shingles
• Diarrhea
• Fatigue
• Fever sometimes with sweating
• Progressive loss of weight
• Anemia

Some people progressively lose weight and have a mild fever or diarrhea.

These symptoms may result from HIV infection or from opportunistic infections that develop because HIV has weakened the immune system.

More severe symptoms

For some people, the first symptoms are those of AIDS.

AIDS is defined as the development of very serious opportunistic infections or cancer—the ones that usually develop only in people with a CD4 count of less than 200 cells per microliter of blood.

The specific opportunistic infections and cancers that develop cause many of the symptoms. These infections occur more frequently or are more severe in people with HIV infection than in those without the infection. For example, an infection with the fungus Candida may cause white patches in the mouth and sometimes pain when swallowing (called thrush) or a thick, white discharge from the vagina that resembles cottage cheese (a vaginal yeast infection). Shingles (herpes zoster) may cause pain and a rash.

More serious opportunistic infections may cause various symptoms depending on the organ affected:

• Lungs: Fever, cough, or shortness of breath
• Brain: Headache, weakness, loss of coordination, or deterioration of mental function
• Digestive tract: Pain, diarrhea, or bleeding

HIV can also cause symptoms when it directly infects and damages organs such as the following:

• Brain: Brain damage with memory loss, difficulty thinking and concentrating, or both, eventually resulting in dementia if HIV infection is not treated, as well as weakness, tremor, or difficulty walking
• Kidneys: Kidney failure with swelling in the legs and face, fatigue, and changes in urination (more common in blacks than in whites), but often not until the infection is severe
• Heart: Heart failure with shortness of breath, cough, wheezing, and fatigue (uncommon)
• Genital organs: Decreased levels of sex hormones, which may cause fatigue and sexual dysfunction in men

HIV is probably directly responsible for a substantial loss of weight (AIDS wasting) in some people. Wasting in people with AIDS may also be caused by a series of infections or by an untreated, persistent digestive tract infection.

Cause of death

Usually, death is caused by the cumulative effects of opportunistic infections or cancers, wasting, and/or dementia.

Diagnosis

• Tests to detect antibodies to the HIV virus in a sample of blood or saliva
• Tests to detect HIV RNA in a sample of blood

Early diagnosis of HIV infection is important because it makes early treatment possible. Early treatment enables infected people to live longer, be healthier, and be less likely to transmit HIV to other people.

Doctors usually ask about risk factors for HIV infection (such as possible exposure in the workplace, high-risk sexual activities, and use of injected street drugs) and about symptoms (such as fatigue, rashes, and weight loss).

Doctors also do a complete physical examination to check for signs of opportunistic infections, such as swollen lymph nodes and white patches inside the mouth (indicating thrush), and for signs of Kaposi sarcoma of the skin or mouth.

Screening and diagnostic tests

If doctors suspect exposure to HIV infection, they do a screening test for HIV. Doctors also recommend that all adults and adolescents, particularly pregnant women, have a screening test regardless of what their risk appears to be. Anyone who is concerned about being infected with HIV can request to be tested. Such testing is confidential and often free of charge.

The current (4th-generation) combination screening test tests for two things that suggest HIV infection:

• Antibodies to HIV
• HIV antigens (p24 antigen)

Antibodies are proteins produced by the immune system to help defend the body against a particular attack, such as that by HIV. Antigens are foreign substances that can trigger an immune response.

The body takes several weeks to produce enough antibodies to be detected by the test, so results of the antibody test are negative during the first few weeks after the virus enters the body. However, results of the p24 antigen test can be positive as early as 2 weeks after the initial infection. The combination tests can be done quickly by a laboratory. Also, a version of these tests can be done in a doctor’s office or clinic (called bedside testing). If results are positive, doctors do a test to distinguish HIV-1 from HIV-2 and a test to detect the amount of HIV RNA in the blood (the viral load).

The newer combination screening test is quicker and less complex than older screening tests, which use enzyme-linked immunosorbent assay (ELISA) to detect HIV antibodies and then confirm positive results using a separate, more accurate, specific test such as the Western blot test.

Other, older rapid bedside tests are also available. These tests can be done using a sample of blood or saliva. If results of these rapid screening tests are positive, they are confirmed by ELISA (with or without Western blot) or by repetition of one or more other rapid tests.

If people at low risk have a negative test result, the screening test is not repeated unless their risk status changes. If people at the highest risk have a negative test result (especially if they are sexually active, have several sex partners, or do not practice safe sex), testing should be repeated every 6 to 12 months.

HIV RNA tests can confirm positive results of an antibody test or detect evidence of HIV infection when antibody test results are negative. HIV RNA tests often use techniques to produce many copies of an organism’s genetic material (called nucleic acid amplification). These tests can detect very small amounts of HIV RNA in blood and are very accurate.

Monitoring

If HIV infection is diagnosed, blood tests should be done regularly to measure the following:

• CD4 count
• Viral load

If the CD4 count is low, people are more likely to develop serious infections and other complications of HIV such as certain cancers. Viral load helps predict how fast the CD4 count is likely to decrease over the next few years.

These two measurements help doctors determine

• How soon to start antiretroviral drugs
• What effects treatment is likely to have
• Whether other drugs may be needed to prevent complicating infections

With successful treatment, the viral load falls to very low levels within weeks, and the CD4 count begins a slow recovery toward normal levels.

Diagnosis of AIDS

AIDS is diagnosed when the CD4 count falls below 200 cells per microliter of blood or when extreme wasting or certain serious opportunistic infections or cancers develop.

Diagnosis of HIV-related conditions

Various tests may be done to check for conditions that can accompany HIV infection. These tests include the following:

• Bone marrow aspiration and biopsy: To check for low blood cell counts (including anemia), which may be due to lymphomas, cancers, and opportunistic infections
• Computed tomography (CT) with a contrast agent or magnetic resonance imaging (MRI): To check for damage to the brain or spinal cord

Prevention

At present, there is no effective HIV vaccine to prevent HIV infection or slow the progression of AIDS in people who are already infected. However, treating people who have HIV infection reduces the risk of their transmitting the infection to other people.

Transmission of HIV through its most common routes—sexual contact or sharing of needles—is almost completely preventable. However, the measures required for prevention—sexual abstinence or consistent condom use and access to clean needles—are sometimes personally or socially unpopular. Many people have difficulty changing their addictive or sexual behaviors, so they continue to put themselves at risk of HIV infection. Also, safe sex practices are not foolproof. For example, condoms can leak or break.

Condoms made of latex provide good protection against HIV (as well as other common sexually transmitted diseases), but they are not foolproof. Oil-based lubricants (such as petroleum jelly) should not be used because they may dissolve latex, reducing the condom’s effectiveness.

Other measures can help. For men, circumcision, an inexpensive, safe procedure, reduces the risk of becoming infected during vaginal intercourse with an infected woman by about half. Whether circumcision reduces the risk of HIV infection in other circumstances is unclear. Because circumcision provides only partial protection against HIV infection, people should also use other measures to prevent HIV infection. For example, if either partner has a sexually transmitted disease or HIV infection, it should be treated, and condoms should be used correctly and consistently.

Universal precautions

People who are likely to come into contact with blood or other body fluids at their job should wear protective latex gloves, masks, and eye shields. These precautions apply to body fluids from all people, not just those from people with HIV, and are thus called universal precautions. Universal precautions are taken for two reasons:

• People with HIV may not know that they are infected.
• Viruses that cause other serious disorders (such as hepatitis B and C) can be transmitted by body fluids.

Surfaces contaminated with HIV can easily be cleaned and disinfected because HIV is inactivated by heat and by common disinfectants such as hydrogen peroxide and alcohol.

Because HIV is not transmitted through the air or by casual contact (such as touching, holding, or dry kissing), hospitals and clinics do not isolate HIV-infected people unless they have another contagious infection.

Preventing transmission by blood transfusions and organ transplants

In the United States, the following have almost eliminated transmission of HIV infection by organ transplantation or blood transfusion:

• Screening donors of organs or blood for risk factors for HIV infection
• Screening donated blood for HIV

Risk is reduced further by asking people with risk factors for HIV infection, regardless of their test results for HIV, not to donate blood or organs for transplantation.

However, developing countries have not consistently used sensitive HIV screening tests and have not restricted donors. Consequently, transmission by these routes is still a problem in these countries.

Preventing transmission from mother to newborn

Pregnant women infected with HIV can transmit the virus to the newborn.

The following can help prevent HIV transmission from mother to newborn:

• Testing pregnant women to determine whether they are infected with HIV
• If they are infected, treating them with antiretroviral drugs during pregnancy and labor (treatment during labor is especially important)
• Delivering the baby by cesarean rather than by vaginal delivery
• After birth, treating the newborn with zidovudine, given intravenously, for 6 weeks
• If possible, using formula instead of breastfeeding (HIV can be transmitted in breast milk)

Preventive treatment before exposure

Taking an antiretroviral drug before being exposed to HIV can reduce the risk of HIV infection. Such preventive treatment is called preexposure prophylaxis (PrEP). However, PrEP is expensive and is effective only if people take the drug every day. Thus, PrEP is recommended only for people who have a very high risk of becoming infected, such as people who have a partner who is infected with HIV.

PrEP may also be recommended for people who engage in high-risk sexual activities, such as the following:

• Men who have anal sex with men without using a condom
• Heterosexual men and women who do not regularly use condoms during sex with partners whose HIV status is unknown and who are at increased risk of HIV infection

People who use PrEP still need to use other methods to prevent HIV infection, including consistent use of condoms and not sharing needles to inject drugs.

Preventive treatment after exposure

People who have been exposed to HIV from a blood splash, needlestick, or sexual contact may reduce the chance of infection by taking antiretroviral drugs for 4 weeks. These drugs are more effective when they are started as soon as possible after the exposure. Taking two or more drugs is currently recommended.

Doctors and the person who was exposed typically decide together whether to use these preventive drugs. They base the decision on the estimated risk of infection and the possible side effects of the drugs. If they do not know whether the source is infected with HIV, they consider how likely the source is to be infected. However, even when the source of the exposure is known to be infected with HIV, the risk of infection after exposure varies, depending on the type of exposure. For example, risk from a blood splash is less than that from a needlestick.

Immediately after exposure to HIV infection, what is done depends on the type of exposure:

• If skin is exposed, it is cleaned with soap and water.
• Puncture wounds are cleaned with antiseptic.
• If mucous membranes are exposed, they are flushed with large amounts of water.

Immunization

People with HIV infection should have the following vaccinations (for more information, see CDC immunization recommendations):

• Conjugate pneumococcal vaccine (PCV13) and polysaccharide pneumococcal vaccine (PPSV23) if they have not had them before (PCV13 is given first, followed by PPSV23 at least 8 weeks later)
• Influenza vaccine every year
• Hepatitis B vaccine if they have not had the vaccine before or have not completed the series of 3 vaccinations
• Hepatitis A vaccine if they are at increased risk of or desire protection from hepatitis A
• Human papillomavirus (HPV) vaccine to prevent HPV-related cervical and anal cancers (given to females and males at the recommended ages)
• Meningococcal vaccine if adults have not had the vaccine before (doses are given at least 2 months apart)
• Tetanus-diphtheria vaccine (Td) with a booster every 10 years (if people have not previously received the tetanus-diphtheria-pertussis vaccine [Tdap], Tdap is substituted for one Td booster)

The herpes zoster vaccine may be useful. However, the original live-attenuated zoster vaccine is not given in people with a weakened immune system and if the CD4 count is below 200 cells per microliter of blood. However, recommendations regarding use of the newer recombinant zoster vaccine in people with HIV have not yet been made.

Treatment

• Antiretroviral drugs 
• Drugs to prevent opportunistic infections
• Drugs to relieve symptoms 

Treatment with antiretroviral drugs is recommended for almost all people with HIV infection because without treatment, HIV infection can lead to serious complications and because newer, less toxic drugs have been developed. For most people, early treatment has the best results. Research has shown that people who are promptly treated with antiretroviral drugs are less likely to develop AIDS-related complications and to die of them.

Treatment cannot eliminate the virus from the body, although the HIV level often decreases so much that it cannot be detected in blood or other fluids or tissues. The goals of treatment are

• Reducing HIV level to undetectable
• Restoring CD4 count to normal

If treatment is stopped, the HIV level increases, and the CD4 count begins to fall. Thus, people need to take antiretroviral drugs for their lifetime.

Before starting a treatment regimen, people are taught about the necessity of the following:

• Taking drugs as directed
• Not skipping any doses
• Taking the drugs for the rest of their life

Taking the drugs as directed for a life time is demanding. Some people skip doses or stop taking the drugs for a time (called a drug holiday). These practices are dangerous because they enable HIV to develop resistance to the drugs.

Because taking HIV drugs irregularly often leads to drug resistance, health care practitioners try to make sure that people are both willing and able to adhere to the treatment regimen. To simplify the drug schedule and to help people take the drugs as directed, doctors often prescribe treatment that combines two or more drugs in one tablet that can be taken only once a day.

Prognosis

Exposure to HIV does not always lead to infection, and some people who have had repeated exposures over many years remain uninfected. Moreover, many HIV-infected people remain well for more than a decade. A very few HIV-infected, untreated people have remained well for over 20 years. Why some people become ill so much sooner than others is not fully understood, but a number of genetic factors appear to influence both susceptibility to infection and progression to AIDS after infection.

If infected people are not treated, AIDS develops in most of them. How quickly the number of CD4 cells decreases and HIV infection progresses toward AIDS varies greatly from person to person. Generally, experts estimate that if untreated, people develop AIDS at the following rates:

• For the first several years after infection: 1 to 2% each year
• Each year thereafter: 5 to 6%
• Within 10 to 11 years: 50%
• Eventually: More than 95%, possibly all if they live long enough

However, with effective treatment, the HIV RNA level decreases to undetectable levels, CD4 counts increase dramatically, and people can continue to lead productive, active lives. The risk of illness and death decreases but remains higher than that of people who are of similar age and who are not infected with HIV. However, if people cannot tolerate or take drugs consistently, HIV infection and immune deficiency progresses, causing serious symptoms and complications.

Usually, HIV infection does not directly cause death. Instead, HIV infection leads to a substantial loss of weight (wasting), opportunistic infections, cancers, and other disorders, which then lead to death.

Cure has been thought to be impossible, although intensive research on how to eliminate all of the latent HIV from infected people continues.

The post HIV, The Human Immunodeficiency Virus and AIDS appeared first on Medika Life.

Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ T lymphocytes and impair cell-mediated immunity, increasing risk of certain infections and cancers.

This article will examine both strains and explain CD4+ T lymphocytes and AIDS in more detail.

Initial HIV infection may cause nonspecific febrile illness. Risk of subsequent manifestations—related to immunodeficiency—is proportional to the level of CD4+ lymphocyte depletion. HIV can directly damage the brain, gonads, kidneys, and heart, causing cognitive impairment, hypogonadism, renal insufficiency, and cardiomyopathy.

Manifestations range from asymptomatic carriage to acquired immune deficiency syndrome (AIDS), which is defined by serious opportunistic infections or cancers or a CD4 count of < 200/mcL. HIV infection can be diagnosed by antibody, nucleic acid (HIV RNA), or antigen (p24) testing. Treatment aims to suppress HIV replication by using combinations of 3 or more drugs that inhibit HIV enzymes; treatment can restore immune function in most patients if suppression of replication is sustained.

HIV-1 and HIV-2

HIV-1 causes most HIV infections worldwide, but HIV-2 causes a substantial proportion of infections in parts of West Africa. In some areas of West Africa, both viruses are prevalent and may co-infect patients. HIV-2 appears to be less virulent than HIV-1.

HIV-1 originated in Central Africa in the first half of the 20th century, when a closely related chimpanzee virus first infected humans. Epidemic global spread began in the late 1970s, and AIDS was recognized in 1981.

The World Health Organization (WHO) estimates that in 2017, about 36.9 million people, including 1.8 million children (younger than 15 years), were living with HIV worldwide; of the total, about 25.7 million live in sub-Saharan Africa. About 25% of people living with HIV were undiagnosed. Among people who knew they were infected, 79% were accessing treatment. 

In 2017, about 940,000 people died from AIDS-related illnesses worldwide (70% in sub-Saharan Africa), compared to 1.9 million in 2004 and 1.4 million in 2010. In 2017, about 1.8 million people, including 180,000 children, were newly infected with HIV, compared to 3.4 million new infections in 1996. Most new infections (95%) now occur in the developing world; over half are in women in sub-Saharan Africa.

In many sub-Saharan African countries, incidence of HIV infection is declining markedly from the very high rates of a decade before; nevertheless, important gaps remain to meet the World Health Organization’s Fast-Track strategy to end the AIDS epidemic by 2030.

In the United States in 2015, more than 1.1 million people aged over 13 years were estimated to be living with HIV infection; HIV was undiagnosed in about 15% of them. Overall, the number of new cases decreased by 19% from 2005 to 2014. In 2016, 39,782 cases were diagnosed. Over two thirds (67% or 26,570) of new infections occurred in gay and bisexual men. Among gay and bisexual men, the number of new infections was 10,223 in black/African American men, 7,425 in Hispanic/Latino men, and 7,390 in white men.

CD4+ T Lymphocytes

The 2 main types of lymphocytes are

• B cells (which mature in bone marrow)
• T cells (which mature in the thymus)

The main types of lymphocytes are morphologically indistinguishable but have different immune functions. They can be distinguished by antigen-specific surface receptors and molecules called clusters of differentiation (CDs), whose presence or absence define some subsets. More than 300 CDs have been identified. Each lymphocyte recognizes a specific antigen via surface receptors.

T cells

T cells develop from bone marrow stem cells that travel to the thymus, where they go through rigorous selection. There are 3 main types of T cell:

• Helper
• Regulatory (suppressor)
• Cytotoxic

In selection, T cells that react to self antigen presented by self MHC molecules or to self MHC molecules (regardless of the antigen presented) are eliminated by apoptosis, limiting the likelihood of autoimmunity. Only T cells that can recognize nonself antigen complexed to self MHC molecules survive; they leave the thymus for peripheral blood and lymphoid tissues.

Most mature T cells express either CD4 or CD8 and have an antigen-binding, Ig-like surface receptor called the T-cell receptor (TCR). There are 2 types of TCR:

• Alpha-beta TCR: Composed of TCR alpha and beta chains; present on most T cells
• Gamma-delta TCR: Composed of TCR gamma and delta chains; present on a small population of T cells

Genes that encode the TCR, like Ig genes, are rearranged, resulting in defined specificity and affinity for antigen. Most T cells (those with an alpha-beta TCR) recognize antigen-derived peptide displayed in the MHC molecule of an antigen-presenting cell. Gamma-delta T cells recognize protein antigen directly or recognize lipid antigen displayed by an MHC-like molecule called CD1. As for B cells, the number of T-cell specificities is almost limitless.

For alpha-beta T cells to be activated, the TCR must engage with antigen-MHC. Costimulatory accessory molecules must also interact (eg, CD28 on the T cell interacts with CD80 and CD86 on the antigen-presenting cell); otherwise, the T cell becomes anergic or dies by apoptosis. Some accessory molecules (eg, CTLA-4 [cytotoxic T-lymphocyte antigen 4] on the T cell, which also interacts with CD80 and CD86 on the antigen-presenting cell, PD-1 [programmed cell death protein 1] on the T cell, which interacts with PD-L1 [programmed cell death protein ligand 1] on the antigen-presenting cell) inhibit previously activated T cells and thus dampen the immune response. Molecules such as CTLA-4 and PD-1, and their ligands, are termed checkpoint molecules because they signal that the T cell needs to be restrained from continuing its activity. Cancer cells that express checkpoint molecules may thus be protected from the immune system by restraining the activity of tumor-specific T cells.

Monoclonal antibodies that target checkpoint molecules on either T cells or on tumor cells (termed checkpoint inhibitors) are used to prevent downregulation of antitumor responses and effectively treat some heretofore resistant cancers. However, because checkpoint molecules are also involved in other types of immune response, checkpoint inhibitors can cause severe immune-related inflammatory and autoimmune reactions (both systemic and organ specific).

Polymorphisms in the CTLA-4 gene are associated with certain autoimmune disorders, including Graves disease and type I diabetes.

AIDS

AIDS is defined as one or more of the following:

• HIV infection that leads to any of certain illnesses highlighted below
• A CD4+ T lymphocyte (helper cell) count of < 200/mcL
• A CD4+ cell percentage of ≤ 14%

AIDS-defining illnesses are

• Serious opportunistic infections
• Certain cancers (eg, Kaposi sarcoma, non-Hodgkin lymphoma) to which defective cell-mediated immunity predisposes
• Neurologic dysfunction

AIDS-Defining Illnesses

The Infection Process

HIV attaches to and penetrates host T cells via CD4+ molecules and chemokine receptors. After attachment, HIV RNA and several HIV-encoded enzymes are released into the host cell.

Viral replication requires that reverse transcriptase (an RNA-dependent DNA polymerase) copy HIV RNA, producing proviral DNA; this copying mechanism is prone to errors, resulting in frequent mutations and thus new HIV genotypes. These mutations facilitate the generation of HIV that can resist control by the host’s immune system and by antiretroviral drugs.

Proviral DNA enters the host cell’s nucleus and is integrated into the host DNA in a process that involves integrase, another HIV enzyme. With each cell division, the integrated proviral DNA is duplicated along with the host DNA. Subsequently, the proviral HIV DNA can be transcribed to HIV RNA and translated to HIV proteins, such as the envelope glycoproteins 41 and 120. These HIV proteins are assembled into HIV virions at the host cell inner membrane and budded from the cell surface within an envelop of modified human cell membrane. Each host cell may produce thousands of virions.

After budding, protease, another HIV enzyme, cleaves viral proteins, converting the immature virion into a mature, infectious virion.

Infected CD4+ lymphocytes produce > 98% of plasma HIV virions. A subset of infected CD4+ lymphocytes constitutes a reservoir of HIV that can reactivate (eg, if antiviral treatment is stopped).

Virions have a plasma half-life of about 6 hours. In moderate to heavy HIV infection, about 10⁸ to 10⁹ virions are created and removed daily. The high volume of HIV replication and high frequency of transcription errors by HIV reverse transcriptase result in many mutations, increasing the chance of producing strains resistant to host immunity and drugs.

Immune system

Two main consequences of HIV infection are

• Damage to the immune system, specifically depletion of CD4+ lymphocytes
• Immune activation

CD4+ lymphocytes are involved in cell-mediated and, to a lesser extent, humoral immunity. CD4+ depletion may result from the following:

• Direct cytotoxic effects of HIV replication
• Cell-mediated immune cytotoxicity
• Thymic damage that impairs lymphocyte production

Infected CD4+ lymphocytes have a half-life of about 2 days, which is much shorter than that of uninfected CD4+ cells. Rates of CD4+ lymphocyte destruction correlate with plasma HIV level. Typically, during the initial or primary infection, HIV levels are highest (> 10⁶ copies/mL), and the CD4 count drops rapidly.

The normal CD4 count is about 750/mcL, and immunity is minimally affected if the count is > 350/mcL. If the count drops below about 200/mcL, loss of cell-mediated immunity allows a variety of opportunistic pathogens to reactivate from latent states and cause clinical disease.

Other tissues

HIV also infects nonlymphoid monocytic cells (eg, dendritic cells in the skin, macrophages, brain microglia) and cells of the brain, genital tract, heart, and kidneys, causing disease in the corresponding organ systems.

HIV strains in several compartments, such as the nervous system (brain and CSF) and genital tract (semen), can be genetically distinct from those in plasma, suggesting that they have been selected by or have adapted to these anatomic compartments. Thus, HIV levels and resistance patterns in these compartments may vary independently from those in plasma.

Disease progression

During the first few weeks of primary infection, there are humoral and cellular immune responses:

• Humoral: Antibodies to HIV are usually measurable within a few weeks after primary infection; however, antibodies cannot fully control HIV infection because mutated forms of HIV that are not controlled by the patient’s current anti-HIV antibodies are generated.
• Cellular: Cell-mediated immunity is a more important means of controlling the high levels of viremia (usually over 10⁶ copies/mL) at first. But rapid mutation of viral antigens that are targeted by lymphocyte-mediated cytotoxicity subvert control of HIV in all but a small percentage of patients.

Plasma HIV virion levels, expressed as number of HIV RNA copies/mL, stabilize after about 6 months at a level (set point) that varies widely among patients but averages 30,000 to 100,000/mL (4.2 to 5 log₁₀/mL). The higher this set point, the more quickly the CD4 count decreases to a level that seriously impairs immunity (< 200/mcL) and results in the opportunistic infections and cancers that define AIDS.

Risk and severity of opportunistic infections, AIDS, and AIDS-related cancers are determined by 2 factors:

• CD4 count
• Exposure to potentially opportunistic pathogens

Risk of specific opportunistic infections increases below threshold CD4 counts of about 200/mcL for some infections and 50/mcL for others, as in the following:

• CD4 count < 200/mcL: Increased risk of Pneumocystis jirovecii pneumonia, toxoplasmic encephalitis, and cryptococcal meningitis
• CD4 count < 50/mcL: Increased risk of cytomegalovirus (CMV) and Mycobacterium avium complex (MAC) infections

For every 3-fold (0.5 log₁₀) increase in plasma HIV RNA in untreated patients, risk of progression to AIDS or death over the next 2 to 3 years increases about 50%.

Without treatment, risk of progression to AIDS is about 1 to 2%/year in the first 2 to 3 years of infection and about 5 to 6%/year thereafter. Eventually, AIDS almost invariably develops in untreated patients.

Transmission

Transmission of HIV requires contact with body fluids—specifically blood, semen, vaginal secretions, breast milk, saliva, or exudates from wounds or skin and mucosal lesions—that contain free HIV virions or infected cells. Transmission is more likely with the high levels of virions that are typical during primary infection, even when such infections are asymptomatic.

Transmission by saliva or droplets produced by coughing or sneezing, although conceivable, is extremely unlikely. HIV is not transmitted by casual nonsexual contact as may occur at work, school, or home.

Transmission is usually

• Sexual: Direct transmission through sexual intercourse
• Needle- or instrument-related: Sharing of blood-contaminated needles or exposure to contaminated instruments
• Maternal: Childbirth or breastfeeding
• Transfusion- or transplant-related

Sexual transmission of HIV

Sexual practices such as fellatio and cunnilingus appear to be relatively low risk but not absolutely safe. Risk does not increase significantly if semen or vaginal secretions are swallowed. However, open sores in the mouth may increase risk.

The sexual practices with the highest risks are those that cause mucosal trauma, typically intercourse. Anal-receptive intercourse poses the highest risk. Mucous membrane inflammation facilitates HIV transmission; sexually transmitted diseases, such as gonorrhea, chlamydial infection, trichomoniasis, and especially those that cause ulceration (eg, chancroid, herpes, syphilis), increase the risk several-fold. Other practices that cause mucosal trauma include fisting (inserting most or all of the hand into the rectum or vagina) and using sexual toys. When used during intercourse with an HIV-infected partner and/or with multiple concurrent sex partners, these practices increase the risk of HIV transmission.

In heterosexuals, the estimated risk per coital act is about 1/1000; however, risk is increased in the following:

• Early and advanced stages of HIV infection when HIV concentrations in plasma and genital fluids are higher
• Younger people
• People with ulcerative genital diseases

Circumcision seems to reduce the risk of males acquiring HIV infection by about 50% by removing the penile mucosa (underside of foreskin), which is more susceptible to HIV infection than the keratinized, stratified squamous epithelium that covers the rest of the penis.

Recent evidence shows that HIV infected people in whom antiretroviral therapy has reduced their viral load below the current detectable level (virally suppressed) do not sexually transmit the virus to their partners. Undetectable virus equals an untransmittable virus.

Epidemiology

HIV has spread in 2 epidemiologically distinct patterns:

• Male homosexual intercourse or contact with infected blood (eg, through sharing needles in injection drug users; before effective screening of donors, through transfusions)
• Heterosexual intercourse (affecting men and women about equally)

In most countries, both patterns occur, but the first pattern usually predominates in developed countries; the second pattern predominates in Africa, South America, and southern Asia.

In areas where heterosexual transmission is dominant, HIV infection follows routes of trade, transportation, and economic migration to cities and spreads secondarily to rural areas. In Africa, particularly southern Africa, the HIV epidemic has killed tens of millions of young adults, creating millions of orphans. Factors that perpetuate spread include

• Poverty
• Poor education
• Deficient systems of medical care that do not provide access to HIV testing and antiretroviral drugs

However, through international efforts, as of 2016, an estimated 19.5 million people living with HIV were accessing antiretroviral therapy, dramatically reducing deaths and transmission in many countries.

Many opportunistic infections that complicate HIV are reactivations of latent infections. Thus, epidemiologic factors that determine the prevalence of latent infections also influence risk of specific opportunistic infections. In many developing countries, prevalence of latent TB and toxoplasmosis in the general population is higher than that in developed countries. Dramatic increases in reactivated TB and toxoplasmic encephalitis have followed the epidemic of HIV-induced immunosuppression in these countries. Similarly in the United States, incidence of coccidioidomycosis, common in the Southwest, and histoplasmosis, common in the Midwest, has increased because of HIV infection.

Human herpesvirus 8 infection, which causes Kaposi sarcoma, is common among homosexual and bisexual men but uncommon among other HIV patients in the United States and Europe. Thus, in the United States, more than 90% of AIDS patients who have developed Kaposi sarcoma are homosexual or bisexual men.

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