AIDS (Acquired Immunodeficiency Syndrome)

HIV is the blood-borne virus that causes AIDS.

Acquired immunodeficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV). HIV infection may progress without symptoms for several years before unusual infections and other evidence of declining immunity appear. There are several symptoms and signs of advanced HIV infection referred to under the “umbrella” term as AIDS. Once AIDS develops, HIV has severely harmed the immune system, but effective antiretroviral therapy (ART) against HIV can often reverse AIDS and restore health.

HIV first arose in Africa, likely evolving from simian immunodeficiency virus (SIV). It spread from non-human primates to people early in the 20th century, possibly when humans encountered infected chimpanzee blood. By testing stored blood samples, scientists have found direct evidence of a human being infected as far back as 1959.

Once introduced into humans, HIV spread primarily through sexual intercourse from person to person. As infected people migrated, the virus spread from Africa to other areas of the world. In 1981, US physicians noticed that an unusual number of young men were dying of rare, unexpected infections and cancers. Initially, US victims were regional clusters of gay men in New York and California, probably because the virus entered this population via international travel hubs. However, it is important to note that heterosexual activity and other types of contact with infected blood or secretions also efficiently transmits the virus. In Africa, which remains the center of the AIDS pandemic, most cases are heterosexually transmitted. In 1991, the news that basketball star Earvin “Magic” Johnson had acquired HIV heterosexually helped Americans understand that the infection was not limited to men who had sex with men. In the US, up to one quarter of new HIV infections are the result of heterosexual transmission. By 1992, AIDS became the number one cause of death among US men aged 25 to 44.

Other factors of transmission in the early days of AIDS were needle sharing during injection drug use (IDU) and in transfusions of blood and blood components. Before laboratory testing for the virus became available, transfusions infected numerous individuals who had hemophilia, as well as surgical patients.

In the years since HIV was first identified, it has spread to every corner of the globe and is one of the leading causes of infectious death worldwide. However, advances in testing and treatment are making a positive impact. Antiretroviral therapy (ART) is now highly effective in preventing HIV transmission.

The global target by 2025 is for 95% of people with HIV to know they are infected and for 95% of them to start on effective ART. As of 2022, 86% of infected individuals globally were aware of their HIV infection, 76% of all people living with HIV were receiving ART and 71% had undetectable HIV in their blood. As of 2022, new infections have declined by 39%, and HIV-related deaths are one-third of that from 2004.

Despite these hopeful signs, 630,000 still died globally from AIDS, 84,000 of these were children, and 64% of the world’s 39 million cases are in sub-Saharan Africa. In the US, Black and Hispanic people make up 75% of those living with HIV.

In the US, more than 1 million people have HIV infections, and approximately 40,000 are newly infected each year. In total, more than 600,000 people in the US have died from AIDS, many of them during what should have been their most productive years of life.

HIV spreads through infected blood or body fluids such as genital secretions. While HIV spreads to all cells in the body, some are affected more than others. Over time, the virus attacks specific immune cells, CD4 cells, and the number of these cells starts to fall. Eventually, the CD4 cells fall to a critical level, and the immune system can no longer defend against certain infections and cancers. This collection of symptoms and illnesses associated with advanced HIV is called AIDS.

HIV is one of a group of viruses called retroviruses. These viruses contain ribonucleic acid (RNA) as their genetic material. HIV uses a reverse transcriptase enzyme to convert its RNA to DNA, from which the cell begins making many copies of HIV. These copies are not perfect and contain small mistakes or mutations. Thus, many thousands of variant HIV viruses are produced every day. Furthermore, HIV DNA can also incorporate into the infected cell’s DNA. These unique abilities allow HIV to evade the body’s defenses and help explain why an effective cure or vaccine has not been possible. The mutations also allow HIV to become resistant to antiretroviral medications over time.

AIDS is an advanced stage of HIV infection. People with AIDS often develop symptoms and signs of specific types of infections or cancers caused by destruction of the CD4 immune cells. These infections or cancers are so typical in AIDS that they are referred to as "AIDS-defining conditions” (See AIDS-Defining Conditions section below) that should alert healthcare professionals to consider HIV testing.   

Depending on how far the CD4 cells (”CD4 count”) have dropped, people with AIDS may develop unusual or unusually severe infections. Because these infections take advantage of the weakened immune system, healthcare professionals refer to them as "opportunistic infections."

Because the CD4 system also defends against certain cancers, people with AIDS can develop cancers like lymphoma (a type of cancer involving white blood cells) or Kaposi’s sarcoma.

AIDS-Defining Conditions

• Pneumonia caused by Pneumocystis jiroveci
• Recurrent severe bacterial pneumonia
• Recurrent blood infections caused by Salmonella bacteria
• Candida infection of the esophagus (swallowing tube) or lungs
• Cytomegalovirus infections including retinitis or infection of other organs
• Invasive cervical cancer
• Kaposi sarcoma
• Selected types of lymphoma, including Burkitt, immunoblastic, or lymphomas that start in the brain
• Wasting syndrome caused by HIV
• Certain parasites in the intestinal tract that cause intractable diarrhea: cryptosporidiosis, isosporiasis
• Certain fungal infections if found outside of the lungs: coccidioidomycosis, cryptococcosis, histoplasmosis
• Tuberculosis in the lungs or outside the lungs (disseminated)
• Herpes simplex infections that cause continuous sores, especially in the lung or esophagus
• Infections with selected mycobacterium (relatives of the tuberculosis bacterium) outside the lung
• Brain infection or infection of any internal organ with the parasite toxoplasmosis
• Encephalopathy (brain infection) due to HIV
• A virus-caused brain disease called progressive multifocal leukoencephalopathy

The risk that HIV infection will progress to AIDS increases with time if the HIV infection is undiagnosed or untreated. Fifty percent of people will develop AIDS within 10 years. However, some develop AIDS in the first year or two and others remain completely asymptomatic for decades after infection. Generally, AIDS develops once the “CD4 count” drops below 200 cells/microliter. As the CD4 count drops further and immunity worsens, more and more conditions and symptoms will begin to appear.

ART is highly effective in preventing progression to AIDS. In countries with the greatest access to healthcare resources, the use of ART has turned HIV into a chronic disease. On the other hand, infected people who do not have access to care, are not able to take their medications, or have a virus that has developed resistance to ART, are at increased risk for progression to AIDS.

Merely having HIV does not mean a person has AIDS. AIDS is the advanced stage of HIV infection and requires that the person have evidence of immune damage.

The diagnosis of AIDS requires:

• a confirmed, positive test for HIV ("HIV positive" test) AND
  • evidence of an AIDS-defining condition OR
  • CD4 count below 200 cells/microliter OR
  • CD4 percentage  < 14% of total lymphocyte count.

Testing for HIV is a two-step process involving a screening test and a confirmatory test. Current guidelines recommend that the first step is a screening test that looks for a component of the virus, called p24 antigen, as well as antibodies against HIV. Specimens for testing come from blood obtained from a vein or a finger stick, an oral swab, or a urine sample. Results can come back in minutes (rapid tests), or can take several days, depending on the method that is used. If the screening HIV test is positive, an antibody test will confirm the results. This second test looks for antibodies to HIV-1, the most common form of this virus worldwide, and/or HIV-2, a strain found in West Africa. If one of these tests is positive, it confirms infection with that particular type of HIV. Sometimes antibodies can take some time to develop after infection and may not be detected if testing is too early. If medical professionals strongly suspect HIV infection, but antibody tests are negative, they can perform a more specific test to detect HIV itself in the blood.

Antiretroviral therapies (ART) are medications that fight HIV. Different antiretroviral medications target the virus in different ways. When used in combination with each other, they are highly effective, but there is no cure for HIV.

ART suppresses reproduction of the virus and stops or delays the disease from progressing to AIDS. Most guidelines recommend that HIV-infected people begin ART as soon as possible, even the same day, after their HIV diagnosis. This delays or prevents disease progression, improves the long-term health of an infected person, and reduces transmission to their partners.

There are currently seven major classes of antiretroviral medications:

1. nucleoside reverse transcriptase inhibitors (NRTIs),
2. non-nucleoside reverse transcriptase inhibitors (NNRTIs),
3. protease inhibitors (PIs),
4. fusion inhibitors,
5. integrase strand transfer inhibitors (INSTIs),
6. CCR5 antagonists, and
7. entry inhibitors.

Doctors prescribe these drugs in different combinations according to the patient’s needs and depending on whether the virus has become resistant to a specific drug or class of drugs. Treatment regimens usually consist of three to four medications at the same time. Combination treatment is essential because taking only one class of medication allows the virus to become resistant to the medication. There are now pills that contain multiple drugs in a single pill, so many people take a single pill per day.

When starting ART, medical professionals may perform blood tests to make sure the virus is not already resistant to the chosen medications. They may repeat resistance tests if it appears the drug regimen is not working or stops working.

People with HIV must take all of their medications as directed. ART is an "all or nothing" treatment. Never stop only one ART pill in a combination regimen. If a person is on more than one ART pill and cannot tolerate one of the them, they should call their medical professional as soon as possible so they can prescribe a better-tolerated combination. If unable to reach their prescriber, it is best to stop all the ART pills at one time, not just one.

Missing ART doses, even once a week, is the most common cause of treatment failure and resistance to ART.

There are three goals of treatment for pregnant individuals with HIV infection:

• to prevent HIV infection before pregnancy (PrEP),
• to treat maternal HIV infection, and
• to reduce the risk of HIV transmission to the fetus or newborn.

HIV PrEP is safe and should be offered to everyone at risk for HIV transmission, including those who may become pregnant or breastfeed. In the event of pregnancy, doctors review the most current safety data to determine which medications and combinations to use.

HIV testing is considered part of routine prenatal care regardless of risk factors and is repeated in the third trimester if risk factors are high. HIV can be transmitted during pregnancy, during delivery, or after delivery through breastfeeding. The risk of transmission to the newborn is about 25% without any ART treatment during pregnancy. In addition, vaginal delivery poses greater risk of transmission than Cesarean section. After delivery, breastfeeding poses a risk of transmission as well.

Of all risk factors, the most critical in preventing HIV transmission to a newborn is whether maternal HIV level in the blood is below 1,000 copies/mL at the time of delivery and breastfeeding. ART treatment should be offered as early as possible during pregnancy (perinatal ART) regardless of CD4 cell count. Perinatal ART reduces the risk to below 1% in the U.S. and Europe. Despite ART, however, breastfeeding still poses up to a 1% risk, and feeding infant formula or pasteurized human milk from a milk bank is encouraged. Depending on status of HIV at the time of delivery, breastfeeding may be considered, while understanding that the risk to the infant is not zero.

Perinatal ART is given as early as possible and throughout pregnancy, labor, and delivery. If the opportunity to start ART was missed during pregnancy, it is still beneficial during labor. In addition to oral ART, additional intravenous medication is appropriate during labor if  HIV viral load is above 1,000 copies/mL within 4 weeks of delivery.

Furthermore, if the quantity of HIV in the mother's blood (“viral load”) is known or suspected to be above 1,000 copies/mL near the time of delivery, doctors will typically schedule a Cesarean delivery at 38 weeks to reduce the risk of transmission added by vaginal delivery. 

After delivery, the newborn receives ART for two to six weeks, depending on how well HIV was controlled before and during delivery. The infant is re-tested periodically in the first six months to ensure they have not acquired HIV.

This is a general summary of the approach to perinatal ART and prevention of HIV transmission. Individual cases may be more complex, and the best approach is carefully determined by the person’s healthcare team.

The complications of HIV infection are caused by weakened immunity and chronic inflammation caused by chronic HIV infection. This makes the person more vulnerable to certain types of conditions and infections (See AIDS-Defining Conditions section above). In addition to the immune system, the virus infects the nervous system and may cause degeneration, problems with thinking, or even dementia. Some patients on ART may be at risk for developing long-term cholesterol or blood-sugar problems, like heart disease and diabetes. Treatment with ART can prevent, reverse, or reduce these complications.

Many effective ART combinations are available, yet the virus can become resistant to one or more of them. This can be a serious complication if it means that a patient must use a less effective combination or a difficult regimen. To reduce the risk of resistance, patients should take their medications as prescribed and call their prescriber immediately if they feel they need to stop one or more drugs.

Left untreated, HIV is almost always a fatal illness, with half of infected people dying within nine months of diagnosis of an AIDS-defining condition. The use of ART has dramatically changed this grim picture. People who are on an effective ART regimen have life expectancies that are similar to the uninfected population. Unfortunately, some people with HIV may deal with poor access to healthcare, social and economic burdens, substance-abuse problems, or other problems that interfere with their ability or desire to take medications.

There is no cure for HIV/AIDS at this time, but there are highly effective treatments. Scientists have a detailed knowledge of HIV genes and proteins and understand how it functions. The combinations of drugs that make up ART therapy are designed to attack different parts of the virus life cycle, causing it to stop reproducing. People with HIV must take ART for life. Even when viral levels are fully suppressed, the virus is still present in the body and begins reproducing again as soon as treatment stops.

One of the problems with finding a cure is that HIV DNA incorporates into the person’s own DNA and can persist in cells throughout the body. HIV in the person’s DNA may not reproduce for a long time. During this “latent period” of HIV infection, the person can remain asymptomatic for months to years while the virus hides from the immune system. Secondly, there are “protected compartments” in the body that are poorly accessible to immune defenses. In addition, ART medications may not achieve high enough levels in these “protected compartments” to control the virus. Thus HIV can maintain active in the brain, bone marrow, and reproductive organs. New research is helping us understand how to treat viruses effectively in these secluded areas.

Avoiding sexual activity (sexual abstinence) is completely effective in eliminating sexual transmission of HIV and preventing AIDS. That said, sex is a normal part of life. It is not easy for everyone to remain abstinent. Educational campaigns have not been successful in reducing HIV transmission in at-risk populations. In addition, the desire for having children and a family makes abstinence impractical at best.

Monogamous sexual intercourse between two uninfected partners is one way to avoid sexual transmission of the virus. Barrier methods that prevent contact with blood and genital fluids, such as male and female condoms, markedly reduce the risk of HIV transmission. ART taken within 4 to 72 hours after exposure (the earlier the better) may also reduce the risk of HIV infection; this is called “post-exposure prophylaxis” (PEP). PEP is typically used when barrier methods fail or were not used during sex with a person with known or high risk factors for HIV.

ART taken before sex as “pre-exposure prophylaxis” (PrEP) is highly effective when added to barrier methods.

Perhaps the most effective way to reduce HIV transmission and prevent AIDS is for the HIV-infected partner to be on ART with undetectable levels of virus in their blood. This has prompted the slogan “Undetectable is untransmittable” or “U=U”. As above, ART can prevent pregnancy-related transmission as well. Use of infant formula in place of breast milk also reduces transmission to the newborn.

For people who inject drugs, the use of sterile needles and the elimination of needle sharing reduces the risk of transmission. Syringe services and harm reduction programs are available in many areas that provide users of injected drugs with sterile needles, personal injection equipment, and education on how to avoid infections including HIV. These programs have been shown to successfully reduce HIV transmission and the associated societal and healthcare costs of IV drug use.