HIV and AIDS

This transmission electron micrographic image shows mature forms of the human immunodeficiency virus (HIV) in a tissue sample. (SOURCE: CDC)

• HIV (human immunodeficiency virus) is a virus that most likely mutated decades ago from a virus that infected chimpanzees to one that infects humans. It began to spread beyond the African continent in the late 1970s and is now endemic worldwide. HIV causes disease because it attacks critical immune defense cells and over time overwhelms the immune system.
• Without treatment, HIV infection starts to cause symptoms in an average of eight to 10 years with AIDS-related opportunistic illnesses, or diseases that only cause illness in people with impaired immune function. This symptomatic phase has been referred to as acquired immune deficiency syndrome (AIDS) or HIV disease.
• HIV is a lifelong infection, but it is treatable and can be controlled with medications. With consistent treatment using highly specialized antiviral medications, a person with HIV may live about as long as an uninfected person.
• Statistics show that approximately 40 million people are currently living with HIV infection, and an estimated 40 million have died from this disease since the beginning of the epidemic. HIV has been particularly devastating in sub-Saharan Africa, which accounts for almost 70% of new HIV infections globally. However, infection rates in other countries also remain high.
• Globally, 85% of HIV transmission is through heterosexual intercourse.
• Worldwide, almost half of people with HIV are women, whereas in the United States, male-to-male sexual contact still accounts for more than 60% of new diagnoses.
• Approximately 20% of new diagnoses are in women. In the United States, heterosexual transmission accounts for approximately one-quarter of new diagnoses, with intravenous drug use contributing to the remaining cases in the U.S.
• Among men who have sex with men, young African-American men are most burdened, followed by Hispanic-American men.
• Infections in women have dropped 40% since 2005 in the U.S., and new HIV infections in U.S. children have fallen dramatically. This is largely a result of testing and treating infected mothers, as well as establishing uniform testing guidelines for blood products.

HIV is one of a group of viruses known as retroviruses. After getting into the body, the virus enters many different cells, incorporates its genes into the human DNA, and hijacks the cell to produce HIV virus. Most importantly, HIV attacks cells of the body's immune system called CD4 or T-helper cells (T cells). These cells are destroyed by the infection. The body tries to keep up by making new T cells or trying to contain the virus, but eventually the HIV wins out and progressively destroys the body's ability to fight infections and certain cancers. The virus structure has been studied extensively, and this ongoing research has helped scientists develop new treatments for HIV/AIDS. Although all HIV viruses are similar, small variations or mutations in the genetic material of the virus create drug-resistant viruses. Larger variations in the viral genes are found in different viral subtypes. Currently, HIV-1 is the predominant subtype that causes HIV/AIDS. HIV-2, another form of HIV, occurs almost exclusively in West Africa but has occasionally caused travel-related outbreaks elsewhere.

HIV is transmitted when the virus enters the body, usually by infected immune cells in blood, vaginal fluids, or semen. Having the following risk factors increases the chance a person may become infected with HIV.

• Sex with an infected partner without using a condom or other barrier protection can transmit HIV. Blood, vaginal fluids, pre-seminal fluid, semen, rectal fluid, and breast milk can contain and transmit HIV virus. The virus can enter the body through the lining of the vagina, vulva, penis, rectum, or mouth during sex. Anal intercourse, followed by vaginal intercourse, are the primary risk factors. Oral sex is less likely to transmit HIV, but studies have shown that it can transmit both HIV and other sexually transmitted diseases (STDs).
• Most sexual transmission occurs between males and females or from male to male. Case reports of female-to-female transmission of HIV are rare.
• Injection-drug use with shared needles or syringes that are contaminated with blood from an infected person are another way the virus is spread.
• Mother-to-child transmission (MTCT) during pregnancy or birth, when infected maternal cells enter the baby's circulation, or through breastfeeding, is also a method of transmission.
• Health care providers in health care settings may be infected through accidental needle sticks or contact with contaminated fluids. This accounts for only 0.3% of HIV transmission.
• Rarely, transfusion of contaminated blood or blood components can transmit HIV. All blood products in the U.S. are screened to minimize this risk.
• If tissues or organs from an infected person are transplanted, the recipient may acquire HIV. Because donors are screened for HIV routinely in the United States, this is quite rare.
• People who already have a sexually transmitted infection, such as syphilis, genital herpes, chlamydia, human papillomavirus (HPV), gonorrhea, or bacterial vaginosis, are more likely to acquire HIV infection during sex with an infected partner.
• In general, the higher the level of HIV in the blood (the viral load), the more likely that person is to transmit HIV. People who have HIV but have a very low or undetectable viral load are much less likely to transmit HIV. So taking HIV medication is one way to reduce the risk of infecting others.
• Taking preventive HIV medication is highly effective and can reduce your risk of getting HIV from sex by more than 90%. This is called pre-exposure prophylaxis, or "HIV PrEP." People who inject drugs may reduce their risk by more than 70%. Using a condom is very important for highly effective PrEP and prevents other sexually transmitted infections (STI).
• Post-exposure prophylaxis (PEP) is a drug treatment that can reduce HIV infection in people recently exposed sexually or by non-occupational (injection drug use) or occupational (health care profession) exposure.

HIV cannot survive more than a few minutes outside the body. The virus does not spread through casual contact such as preparing food, sharing towels and bedding, or via swimming pools, telephones, sneezing, or toilet seats. Transmission through kissing alone is extremely rare.

Because of licensing and public health inspection, it is unlikely to get HIV by getting a tattoo in a commercial shop. However, it is possible to get HIV from a reused or improperly sterilized tattoo or piercing needle or other equipment, or from contaminated ink. So it's important to know that your tattoo artist is licensed, working in a licensed and inspected facility, and posts information about their equipment sterility and procedures.

Many people with HIV do not know they are infected. In the United States, it is likely that 14% of HIV-positive individuals are unaware of their infection. HIV infection progresses in three very general stages.

Stage 1: Acute HIV Infection

Many people do not develop symptoms or signs at all after they are infected with HIV. Others will have signs and symptoms in the first two to four weeks after HIV infection, referred to as primary or acute HIV infection.

The most common symptoms are similar to a flu-like or mononucleosis-like illness within several days to weeks after exposure to the virus, including

• fever;
• headache;
• open sores or ulcers in the mouth (like canker sores, also known as aphthous ulcers);
• fatigue;
• weight loss;
• sweating or night sweats;
• appetite loss;
• rash that may come and go quickly;
• sore throat; and
• swollen lymph nodes (glands) in the neck and groin.

These HIV-associated symptoms usually disappear within a few weeks.

Stage 2: Clinical Latency Stage (HIV Dormancy)

After acute infection, the virus appears to become dormant, and the person feels normal. This stage of HIV infection may last an average of eight to 10 years, but it can vary among individuals and strains of HIV. A recently identified aggressive HIV strain from Cuba has been found to progress to AIDS in as little as three years.

During the latent period, the virus continues to multiply actively. It infects and kills critical infection fighting cells, a type of white blood cell called CD4 cells or T helper cells (T cells). Even though the person has no symptoms, he or she is contagious and can pass HIV to others through the routes described above. At the end of this phase, as the virus overwhelms the CD4 cells, the HIV viral load starts to rise, and the CD4 count begins to drop. As this happens, the person may begin to have symptoms as the virus levels increase in the body. This is stage 3.

Stage 3: Acquired Immunodeficiency Syndrome (AIDS)

AIDS is the later stage of HIV infection, when the body is losing T cells and its ability to fight infections. Once the CD4 count falls low enough (under 500 cells/mL), an infected person is said to have AIDS or HIV disease. Sometimes, the diagnosis of AIDS is made because the person has unusual infections or cancers that signal how weak the immune system is.

The infections that occur with AIDS are called opportunistic infections because they take advantage of the opportunity to infect a weakened host. A person diagnosed with AIDS may need to be on antibiotic prophylaxis to prevent certain opportunistic infections from occurring. The AIDS-defining infections include (but are not limited to) the following:

• Pneumonia caused by Pneumocystis jiroveci, which causes severe shortness of breath and dry cough
• Toxoplasmosis, a brain infection which can cause problems with thinking, headache, or symptoms that mimic a stroke
• Widespread (disseminated) infection with a bacteria called Mycobacterium avium complex (MAC), which can cause fever, diarrhea, and weight loss
• Yeast (Candida) infection of the mouth and swallowing tube (esophagus), which causes pain with swallowing
• Disseminated diseases with certain fungi: Cryptococcus neoformans is a typical example and causes a slowly progressing meningitis.
• Polyoma virus or JC virus can cause progressive multifocal leukoencephalopathy, an incurable brain infection that leads to death.

A weakened immune system can also lead to other unusual conditions:

• Lymphoma (a form of cancer of the lymphoid tissue) can cause fever and swollen lymph nodes throughout the body.
• A cancer of the soft tissues called Kaposi's sarcoma causes brown, reddish, or purple lumps that develop on the skin or in the mouth.

All sexually active adults should know their HIV status and should be tested for HIV routinely at least once. This is the only way to know whether one is HIV infected. It is not unusual for a person to get HIV from a person they never knew could have HIV; again, most people with HIV do not know it for years. Testing is important yearly or more often if a person has risk factors for HIV. If someone has a history of engaging in unprotected sex outside of a mutually monogamous relationship (meaning both partners have sex only with each other) or sharing needles while using drugs, he or she should have an HIV test. Early testing, recognition of the signs and symptoms of HIV infection, and starting treatment for HIV as soon as possible can slow the growth of HIV, prevent AIDS, and decrease the risk of transmission to another person. If a woman is pregnant and infected with HIV, she can greatly reduce the risk of mother-to-child transmission by getting treatment. HIV testing is routinely offered at the first prenatal visit.

HIV testing is available through any health care provider, as well as anonymously and confidentially. Home tests for HIV are available for purchase in most pharmacies and online. The U.S. Centers for Disease Control and Prevention (CDC) offers a tool to help the public find their nearest HIV testing site by zip code at https://gettested.cdc.gov. You can also text your ZIP code to KNOW IT (566948), or call 1-800-CDC-INFO (1-800-232-4636). Knowing one's status is the first step to avoiding AIDS.

People who are at risk for HIV infection can take daily PrEP to dramatically reduce the likelihood of getting infected. Taking PEP after sexual intercourse, injection drug use, or health professional exposure can also prevent HIV transmission. Any health care professional licensed to prescribe medication can prescribe PrEP and PEP.

People known to have HIV infection should go to the hospital any time they develop high fever, shortness of breath, coughing up blood, severe diarrhea, severe chest or abdominal pain, generalized weakness, severe headache, seizures, confusion, or a change in mental status. These may indicate a life-threatening condition for which an urgent evaluation in the hospital's emergency department is recommended. All infected people should be under the regular care of a physician skilled in the treatment of HIV and AIDS.

HIV infection is commonly diagnosed by blood tests. Testing for HIV is usually a two-step process. First, a screening test is done. If that test is positive, a second test (Western blot) is done to confirm the result.

There are three common types of screening tests that use a blood specimen:

1. HIV antibody tests;
2. a fourth-generation combination antibody/antigen test that detects both antibodies and a piece of the virus called the p24 antigen;
3. RNA tests (HIV RT PCR or viral load);
4. in addition, a blood test called a Western blot is necessary to confirm the diagnosis.

No test is perfect. Tests may be falsely positive or falsely negative. For example, it can take some time for the immune system to produce enough antibodies for the antibody test to turn positive. This time period is commonly referred to as the "window period" and may last six weeks to three months following infection. The antigen/antibody assay is most sensitive and may be positive within two weeks after infection. If the initial antibody test is negative or unclear, a repeat test should be performed three months later.

Other tests can detect antibodies in body fluids other than blood, such as saliva, urine, and vaginal secretions. Some of these are designed to be rapid HIV tests that produce results in approximately 20 minutes. These tests have accuracy rates similar to traditional blood tests. OraQuick is an at-home test that uses an oral swab to detect HIV antibodies in oral fluid. Clearview is another rapid HIV test that can detect HIV antibodies in blood or plasma. HIV home-testing kits are available at many local drugstores. Blood is obtained by a finger prick and blotted on a filter strip. Other test kits use saliva or urine. The filter strip is mailed in a protective envelope to a laboratory to be tested. Results are returned by mail within one to two weeks.

All positive HIV screening tests must be confirmed with a confirmatory blood test called the Western blot to make a positive diagnosis. If the screening test and the Western blot are both positive, the likelihood of a person being HIV infected is >99%. Sometimes, the Western blot is "indeterminate," meaning that it is neither positive nor negative. In these cases, the tests are usually repeated at a later date. In addition, an RNA test for the virus might be done. Because the p24 antigen is present in the blood before the body forms antibodies, the antibody/antigen screening test may decrease the "window period" and allow for earlier detection of HIV infections.

RNA testing (viral load test) detects HIV RNA in the blood. It is not commonly used for screening but can be helpful in detecting early HIV infection when a person is in the window period or if the screening tests are unclear.

Many drugs have become available to fight both the HIV infection and its associated infections and cancers. These drugs have been called highly active antiretroviral therapy (HAART). More commonly, they are simply referred to as ART. Although these medications do not cure HIV/AIDS, antiretrovirals have greatly reduced HIV-related complications and deaths.

Therapy is initiated and individualized under the supervision of a physician who is an expert in the care of HIV-infected patients. A combination of at least three ART drugs is needed to suppress the virus from replicating and boost the immune system. How these drugs are combined depends on the most current treatment guidelines, individual patient preferences, other medical conditions, past treatment history, and any resistance mutations in the individual's virus. Resistance mutations may already be present at the time of infection, thus most clinicians will test the patient's virus for resistance mutations prior to starting or changing a regimen.

The earliest class of highly active antiretroviral therapy, reverse transcriptase inhibitor drugs, inhibit the ability of the virus to make copies of itself. The following are examples:

• Nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs): These include medications such as zidovudine (AZT, Retrovir), didanosine (ddI, Videx), stavudine (d4T, Zerit), lamivudine (3TC, Epivir), abacavir (ABC, Ziagen), emtricitabine (FTC, Emtriva), tenofovir disoproxil fumarate (TDF, Viread), and tenofovir alafenamide (TAF).
• Combination NRTIs include tenofovir/emtricitabine (TDF/FTC, Truvada), emtricitabine/tenofovir alafenamide (TAF/FTC, Descovy), zidovudine/lamivudine (Combivir), abacavir/lamivudine (Epzicom or Kivexa), and abacavir/zidovudine/lamivudine (Trizivir).

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are commonly used in combination with NRTIs to help keep the virus from multiplying. Examples of NNRTIs are efavirenz (Sustiva), nevirapine (Viramune), extended-release nevirapine (Viramune XR) delavirdine (Rescriptor), etravirine (Intelence), rilpivirine (Edurant), and doravirine (Pifeltro). Complete HIV treatment regimens that combine two NRTIs and one NNRTI in one pill taken once a day are available for convenience; these include Atripla (efavirenz/TDF/FTC), Complera (rilpivirine/TDF/FTC), Odefsey (rilpivirine/TAF/FTC), and doravirine/TDF/lamivudine (Delstrigo).

Protease inhibitors (PIs) interrupt virus replication at a later step in the HIV life cycle, preventing cells from producing new viruses. Currently, these include ritonavir (Norvir), darunavir (Prezista), and atazanavir (Reyataz). Using PIs with NRTIs reduces the chances that the virus will become resistant to medications. Atazanavir and darunavir are available in combination with cobicistat as atazanavir/cobicistat (Evotaz) and darunavir/cobicistat (Prezcobix). Cobicistat and ritonavir inhibit the breakdown of other drugs, so they are used as boosters to reduce the number of pills needed. A PI-based one-pill regimen is darunavir/cobicistat/TAF/FTC (Symtuza).

Older PIs no longer commonly used due to pill burden and side effects include lopinavir and ritonavir combination (Kaletra), saquinavir (Invirase), indinavir sulphate (Crixivan), fosamprenavir (Lexiva), tipranavir (Aptivus), and nelfinavir (Viracept).

Fusion and entry inhibitors are agents that keep HIV from entering human cells. Enfuvirtide (Fuzeon/T20) was the first drug in this group and was given in injectable form like insulin. Maraviroc (Selzentry) can be given by mouth and is used in combination with other ARTs.

Integrase strand transfer inhibitors (integrase inhibitors or integrases, INSTIs) stop HIV genes from becoming incorporated into the human cell's DNA and are very well tolerated. Raltegravir (Isentress) was the first drug in this class. Elvitegravir is part of two fixed-dose combinations (elvitegravir/cobicistat/TDF/FTC, Stribild) and (elvitegravir/cobicistat/TAF/FTC, Genvoya) taken as one pill once daily. Dolutegravir (Tivicay) is also available in a once-daily combination pill with two NRTIs, abacavir and lamivudine, called Triumeq. The newest INSTI is available in a one-pill combination as Biktarvy (biktegravir/TAF/FTC).

An INSTI/NNRTI combination is available as Juluca (dolutegravir/rilpivirine) and can be used to replace a three-drug regimen after six months of successful suppression of HIV virus that has no resistance.

ART may have a variety of side effects depending on the type of drug. An expert in infectious diseases and HIV treatment should be consulted if the patient needs concomitant treatment for opportunistic infections, hepatitis B, or hepatitis C. Some medications used to treat these conditions will negatively interact with ART drugs.

Birth defects are associated with both efavirenz and dolutegravir. Both should be avoided for PEP or treating HIV-infected women of childbearing age who are not using effective birth control.

Pregnant women who are HIV-positive should seek care immediately from an obstetrician (OB) to minimize the risk of mother-to-child transmission of the virus. ART reduces the risk of transmitting the virus to the fetus, and the mother may be treated by both the OB and an infectious-disease subspecialist. Therapy can also be given during childbirth, or to the baby in the perinatal period, in order to help prevent HIV infection in the newborn. There are certain drugs, however, that are harmful to the baby. Therefore, seeing a physician as early as possible before or during pregnancy to discuss ART medications is crucial.

Although it is important to receive medical treatment for HIV/AIDS, patients may use home remedies or alternative medicine along with standard HIV treatment to improve overall health. It is important to talk to your doctor before trying alternative therapies as some can interfere with the effectiveness of or cause negative effects with HIV drugs.

People with HIV infection should be under the care of a physician who is experienced in treating HIV infection. This is often an infectious-disease subspecialist, but may be a health care provider, such as an internal medicine or pediatric specialist, who has special certification in HIV treatment. All people with HIV should be counseled about avoiding the spread of the disease. Infected individuals are also educated about the disease process, and attempts are made to improve the quality of their life.

Despite significant efforts, there is no effective vaccine against HIV. The only way to prevent infection by the virus is to avoid behaviors that put one at risk, such as sharing needles or having unprotected sex. Unprotected sex means sex without a barrier such as a condom. Because condoms break, even they are not perfect protection. Many people infected with HIV don't have any symptoms and appear healthy. There is no way to know with certainty whether a sexual partner is infected. Here are some HIV prevention strategies:

• Abstain from oral, vaginal, and anal sex. This obviously has limited appeal, but it is the only 100% effective way to prevent HIV.
• Have sex with a single partner who is known to be uninfected. Mutual monogamy between uninfected partners eliminates the risk of sexual transmission of HIV.
• Use a condom in other situations. Condoms offer protection if used properly and consistently. Occasionally, they may break or leak. Only condoms made of latex should be used. Only water-based lubricants should be used with latex condoms; petroleum jelly dissolves latex.
• Use condoms the right way every time you have sex. Learn the right way to use a male condom.
• Choose less risky sexual behaviors. Anal sex is the highest-risk sexual activity for HIV transmission, especially for the receptive partner (bottom). Oral sex is much less risky than anal or vaginal sex. Sexual activities that don't involve contact with body fluids (semen, vaginal fluid, or blood) carry no risk of HIV transmission.
• Do not inject street drugs. When people are high, they're more likely to have risky sex or share unsterile needles, which increases the chance of getting or transmitting HIV.
• If you do inject drugs, never share your needles or works. Use only sterile needles. You can get them at many pharmacies without a prescription, or from community needle-exchange programs. Use a new sterile needle and syringe each time you inject. Clean used needles with full-strength laundry bleach, making sure to get the bleach inside the needle, soak at least 30 seconds (sing the "happy birthday" song three times), and then flush out thoroughly with clean water. Use bleach only when you can't get new needles. Needles and syringes aren't designed to be cleaned and reused, but it is better than sharing uncleaned needles and works.
• Use sterile water to fix drugs.
• Clean skin with a new alcohol swab before injecting.
• Be careful not to get someone else's blood on your hands or your needle or works.
• Dispose of needles safely after one use. Put them in an old milk jug and keep used needles away from other people. Pharmacies accept used needles in containers for safe disposal.
• If you work in a health care field, follow recommended guidelines for protecting oneself against needle sticks and exposure to contaminated fluids.

The risk of HIV transmission from a pregnant woman to her baby is significantly reduced if the mother takes ART during pregnancy, labor, and delivery and her baby takes ART for the first six weeks of life. Even shorter courses of treatment are effective, though not as optimal. The key is to be tested for HIV as early as possible in pregnancy. In consultation with their physician, many women opt to avoid breastfeeding to minimize the risk of HIV transmission through breast milk after the baby is born.

PrEP is short for pre-exposure prophylaxis. People who do not have HIV can take a daily pill to reduce their risk of becoming infected. When taken daily, it is highly effective and reduces sexual transmission of the virus by over 90% and injection transmission by 70%. It is also safe and well tolerated. PrEP is not right for everyone and must still be used in combination with safer sex (condoms) and injection practices. It requires commitment to treatment and does not replace other prevention measures like condom use. It also requires very regular medical visits and frequent blood tests for kidney function, STDs (STIs) and HIV. Unknowingly continuing PrEP medication while HIV-infected can lead to resistance and severely reduce your HIV treatment options. Resistance has already been reported in a person who became infected while taking PrEP.

PEP is short for post-exposure prophylaxis and refers to preventive treatment after sexual, injection, or occupational exposure to HIV. Occupational transmission of HIV to health care workers is extremely rare, and the proper use of safety devices minimizes the risk of exposure while caring for patients with HIV. Sexual and injection exposure is a much greater risk. A person who has a possible occupational or non-occupational injection, or sexual exposure, should see a doctor immediately. PEP must be started as soon as possible, preferably within a few hours and no later than 72 hours, after a possible exposure to HIV. It is also very important after non-occupational exposures to screen and treat for other STIs, pregnancy, and hepatitis.

There is no cure for HIV infection. Before there were treatments for the virus, people with AIDS lived only for a couple of years. Fortunately, medications have substantially improved the outlook and survival rates. HIV prevention efforts have reduced infection in young children and have the potential to limit new infections in other populations.

ART extends the average life expectancy, and many people with HIV can expect to live for decades with proper treatment. An increasing number have a normal life expectancy if they adhere carefully to medication regimens. Medications help the immune system recover and fight infections and prevent cancers from occurring. If ART is not taken regularly and doses are missed, the virus may become resistant, and the manifestations of AIDS may develop.

Drugs used to treat HIV and AIDS do not eliminate the infection. Although effective ART reduces the risk of transmitting HIV, it is important for the person to remember that he or she is still contagious even when receiving effective treatment. Intensive research efforts are being focused on developing new and better treatments. Although currently there is no promising vaccine, work continues on this front.

The CDC is a good source for more information. Their online resource (http://www.cdc.gov/hiv/) includes fact sheets and extensive information for the public on symptoms, diagnosis, and treatment.