Merck Manual

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Human Immunodeficiency Virus (HIV) Infection


Edward R. Cachay

, MD, MAS, University of California, San Diego School of Medicine

Topic Resources


  • 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).



  • Many infected people remain well for more than a decade.


  • Eventually, most untreated people develop AIDS.


  • 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.

What Is a Retrovirus?

When HIV enters a human cell, it releases its RNA, and an enzyme called reverse transcriptase makes a DNA copy of the HIV RNA. The resulting HIV DNA is integrated into the infected cell’s DNA. This process is the reverse of that used by human cells, which make an RNA copy of DNA. Thus, HIV is called a retrovirus, referring to the reversed (backward) process.

Other RNA viruses (such as polio, influenza, or measles), unlike retroviruses, do not make DNA copies after they invade cells. They simply make RNA copies of their original RNA.

Each time an HIV-infected cell divides, it makes a new copy of the integrated HIV DNA as well as its own genes. The HIV DNA copy is either

  • Inactive (latent): The virus is present but does no damage.

  • Activated: The virus takes over the functions of the infected cell, causing it to produce and release many new copies of HIV, which then invade other cells.

HIV progressively destroys certain types of white blood cells called CD4+ lymphocytes. Lymphocytes Lymphocytes One of the body's lines of defense ( immune system) involves white blood cells (leukocytes) that travel through the bloodstream and into tissues, searching for and attacking microorganisms and... read more 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.


In 2019, about 38 million people, including 1.8 million children under age 15, were living with HIV infection worldwide. In 2019, about 690,000 people died from AIDS-related illnesses worldwide, compared to 1.9 million in 2004 and 1.4 million in 2010. In 2019, about 1.7 million people, including 150,000 children, were newly infected with HIV, compared to 3.4 million new infections in 1996.

Most (86%) new infections occur in the developing world; over half are in women in sub-Saharan Africa. 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 in 2018, over 1.21 million people aged 13 years or older were estimated to have HIV infection. About 14% of them do not know they have HIV infection. There were 22% fewer cases in 2018 than 2008 and 7% fewer than in 2014. Over two thirds of these new infections occurred in men who have sex with men. Among these men, most infections occurred in black/African-American men (9,400), followed by Hispanic/Latino men (8,000) and white men (5,700).

Acquired immunodeficiency syndrome (AIDS)


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

Transmission of HIV Infection



HIV is usually transmitted in the following ways:



Did You Know...


Through sexual activity



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



From mother to child


  • To the fetus through the placenta

  • To the baby during passage through the birth canal

  • To the baby after birth through breast milk




Through blood transfusions or organ transplants

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



Artificial insemination


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 T cells One of the body's lines of defense ( immune system) involves white blood cells (leukocytes) that travel through the bloodstream and into tissues, searching for and attacking microorganisms and... read more 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 What Is a Retrovirus? What Is a Retrovirus? . That is, it stores its genetic information as ribonucleic acid ( RNA Transcription and translation Genes are segments of deoxyribonucleic acid (DNA) that contain the code for a specific protein that functions in one or more types of cells in the body. Chromosomes are structures within cells... read more Transcription and translation ). 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 DNA Genes are segments of deoxyribonucleic acid (DNA) that contain the code for a specific protein that functions in one or more types of cells in the body. Chromosomes are structures within cells... read more 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.


Simplified Life Cycle of the Human Immunodeficiency Virus


  • HIV first attaches to and penetrates its target cell.


  • The viral DNA enters the cell’s nucleus.







Simplified Life Cycle of the Human Immunodeficiency Virus


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


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 Causes ). 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.


Viral load



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.


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

Did You Know...


Symptoms of HIV Infection

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:

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.


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 Vaginal Yeast Infection (Candidiasis) The vagina is infected by a yeast called Candida, usually Candida albicans, resulting in a yeast infection called candidiasis. Being pregnant or having diabetes or a weakened immune... read more ). Shingles Shingles Shingles is a painful skin rash caused by a viral infection that results from reactivation of the varicella-zoster virus, the virus that causes chickenpox. What causes the virus to reactive... read more Shingles (herpes zoster) may cause pain and a rash.


  • Lungs: Fever, cough, or shortness of breath


  • Digestive tract: Pain, diarrhea, or bleeding


  • 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






Cancers common in people with HIV infection

Kaposi sarcoma Kaposi Sarcoma Kaposi sarcoma is a skin cancer that causes multiple flat pink, red, or purple patches or bumps on the skin. It is caused by human herpesvirus type 8 infection. One or a few spots may appear... read more Kaposi Sarcoma , a cancer caused by a sexually transmitted herpesvirus, appears as painless, red to purple, raised patches on the skin. It occurs mainly in men who have sex with men.

Cancers of the immune system (lymphomas, typically non-Hodgkin lymphoma Non-Hodgkin Lymphomas Non-Hodgkin lymphomas are a diverse group of cancers of types of white blood cell called lymphocytes. Often, lymph nodes in the neck, under the arms, or in the groin enlarge rapidly and painlessly... read more Non-Hodgkin Lymphomas ) may develop, sometimes first appearing in the brain. When the brain is affected, these cancers can cause weakness of an arm or a leg, headache, confusion, or personality changes.

Having AIDS increases the risk of other cancers. They include cancer of the cervix, anus, testes, and lungs as well as melanoma and other skin cancers. Men who have sex with men are prone to developing cancer of the rectum due to the same human papillomaviruses Human Papillomavirus (HPV) Infection Human papillomavirus (HPV) causes warts. Some types of HPV cause skin warts, and other types cause genital warts (growths in or around the vagina, penis, or rectum). Infection with some HPV... read more Human Papillomavirus (HPV) Infection (HPV) that cause cancer of the cervix in women.

Cause of death

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

Diagnosis of HIV Infection

  • 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 Transmission of HIV Infection 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... read more Transmission of 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).


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 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 (known as the "window period" of acute HIV infection). 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.


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

  • CD4 count

  • Viral load


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


Diagnosis of AIDS


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 of HIV Infection

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 Prevention Sexually transmitted (venereal) diseases are infections that are typically, but not exclusively, passed from person to person through sexual contact. Sexually transmitted infections may be caused... read more Prevention 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.

Strategies for Preventing the Transmission of HIV

  • Abstain from sexual activity.

  • Use a latex condom for each act of intercourse with an infected partner or a partner whose HIV status is unknown (vaginal spermicides and sponges do not protect against HIV infection).

  • For men engaging in oral sex, withdraw before ejaculation.

  • For men, get circumcised (circumcision reduces a man's risk of being infected with HIV during vaginal sex with an infected woman).

  • For newly monogamous couples, get tested for HIV infection and other sexually transmitted infections (STIs) before engaging in unprotected sexual intercourse.

  • Never share needles or syringes.

  • Wear rubber gloves (preferably latex) when touching body fluids of another person .

  • If accidentally exposed to fluids containing HIV (for example, after a needlestick), seek treatment with antiretroviral drugs to prevent infection.

Condoms made of latex provide good protection against HIV (as well as other common sexually transmitted infections), 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.


Universal precautions


  • People with HIV may not know that they are infected.




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.

  • 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


Preventive treatment after exposure



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.


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

The herpes zoster vaccine Herpes Zoster Vaccine There are two herpes zoster vaccines. The newer herpes zoster vaccine is preferred over the older herpes zoster vaccine because it provides better and longer-lasting protection. The newer vaccine... read more 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 of HIV Infection

  • 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


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 of HIV 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:


  • Each year thereafter: 5 to 6%

  • Within 10 to 11 years: 50%





End-of-Life Issues

Because death rarely occurs suddenly in people with AIDS, people usually have time to make plans for the kind of their health care they want if their condition worsens. Nonetheless, people should record such plans in a legal document early and should include clear instructions about the kind of care they want (called advance directives Advance Directives Health care advance directives are legal documents that communicate a person’s wishes about health care decisions in the event the person becomes incapable of making health care decisions. There... read more ). Other legal documents, including powers of attorney and wills, should be prepared. These documents are particularly important for those patients whose partners, loved ones, or caregivers are not legally recognized, which may result in those partners or other loved ones being unable to visit or be involved in decision-making or carry out funeral and burial wishes, being excluded from inheriting assets, possibly including the family home, or other dire consequences.

Near the end of life, many people have pain and other distressing symptoms (such as agitation) and usually lose their appetite. Hospice programs Hospice Care Hospice is a concept and a program of care that is specifically designed to minimize suffering for dying people and their family members. In the United States, hospice is the only widely available... read more are particularly equipped to deal with such problems. They can provide comprehensive support and care, which focuses on managing symptoms, helping dying people maintain their independence, and supporting their caregivers.

More Information about HIV Infection


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