Human Immunodeficiency Virus (HIV)

Today, most infected people who start and stay on HIV treatment never develop AIDS.

The human immunodeficiency virus (HIV) may have evolved from simian immunodeficiency virus, which infects apes. This virus is believed to have spread to humans through blood around the 1800s when chimpanzees were hunted for meat. The virus slowly spread from person to person through blood and sex until signs of human infection were first recognized in the United States in 1981. Because the illness involved “opportunistic” conditions that typically affect those with severely reduced immunity, the condition was called “acquired immunodeficiency syndrome” (AIDS). In 1983, researchers in the US and France described the virus, now known as HIV, as part of the retrovirus group.

HIV is a lifelong infection of the body’s immune cells, specifically targeting the CD4 cells. The genome of the virus becomes incorporated into these cells and hijacks them. They begin producing HIV virus until they die and release the new viruses. These viruses infect more and more CD4 cells. Eventually, the immune system is exhausted, the CD4 cells start to decline below normal, and unusual infections and complications begin to appear. These signs and symptoms of advanced, untreated HIV are then recognized as AIDS. Today, most infected people who start and stay on treatment never develop AIDS.

HIV is transmitted through the blood and genital secretions of untreated individuals infected with HIV, even if they have no symptoms. The most common ways that HIV spreads include sexual contact, sharing used hypodermic needles, and mother-to-child transmission during pregnancy, labor and delivery, or breastfeeding.

It’s important to know that HIV is not transmitted by casual interactions in the household, workplace, or classroom.

• HIV can be transmitted when certain mucous membranes come in contact with infected fluids. These membranes include the thin, moist parts of the vagina, penis, rectum, mouth, or eyes. Infected fluids may also transmit HIV through a break in the skin, such as a cut or needle puncture.
• Sexual transmission of HIV has been described regardless of the gender of partners, through vaginal, anal, and oral sex. Kissing is not a risk unless there is exposure to fresh blood or a cut in the mouth. Saliva alone contains low viral load.
• The presence of penis foreskin is a risk factor for HIV acquisition. This has most convincingly been studied and demonstrated in men who have sex with women, where the risk declines after adult male circumcision.
• HIV can be spread by sharing used hypodermic needles for street drugs or anabolic steroids. This can transmit other diseases as well, including hepatitis.
• Tattooing and body piercing can spread HIV if performed outside of a licensed, professional facility.
• At the beginning of the HIV epidemic, individuals acquired HIV infection from blood transfusions and blood products. However, because donated blood products are now thoroughly tested, the risk of acquiring HIV from blood products in the US is considered insignificant.

The stage of early infection is called primary or acute HIV and may or may not have symptoms. Acute HIV symptoms resemble those of mononucleosis or a flu-like illness. Acute HIV symptoms may last a few weeks or months. Eventually the early symptoms go away, and the infection becomes chronic HIV. In extremely rare cases, the body is able to clear the infection without treatment (the individual is known as an “elite controller” or “long-term nonprogressor”). The most common symptoms of primary HIV infection include:

• fever,
• aching muscles and joints,
• sore throat,
• swollen glands (lymph nodes).

HIV virus levels in the body are high during acute HIV, and you are likely to be infectious at this point (can spread the virus to others). However, HIV testing may still be negative (the so-called “window period”), although some tests may pick up the infection earlier than others. Early diagnosis is important, because you can start treatment, preserve your immunity, live longer, and reduce the risk of transmitting to others.

After the acute phase of infection, most people with HIV enter a period of many years where they have no symptoms at all (chronic HIV). During this time, CD4 (immune defense) cells may gradually decline, and symptoms eventually develop, such as:

• Vaginal yeast infection, often for over 1 month (candidiasis, a fungal infection)
• Oral thrush (candidiasis, a fungal infection)
• Fevers lasting more than 1 month
• Diarrhea lasting more than 1 month
• Cervical precancers or cancer
• Tiredness or fatigue

As the disease progresses and CD4 cells decline, more severe complications of HIV begin, which is commonly referred to as AIDS. The US Centers for Disease Control and Prevention (CDC) have defined AIDS as the presence of specific conditions, “opportunistic" infections, or an absolute CD4 count below 200 cells/mm³. These conditions include:

• Severe or unusual bacterial, fungal, and viral infections (opportunistic infections)
• Recurrent or unusual pneumonias like Pneumocystis jiroveci (“PJP” or “PCP”)
• Unusual cancers like Kaposi’s sarcoma and lymphomas
• Severe weight loss (wasting syndrome)
• Mental decline (HIV encephalopathy)

Fortunately, many of the symptoms of HIV can be completely reversed with HIV treatment.

How long does it take to notice symptoms of HIV?

• The mononucleosis-like symptoms of acute HIV may occur within a couple of weeks and last for weeks to months or may not be noticed at all.
• If the acute HIV symptoms occur, they may last several weeks then resolve, while the chronic HIV infection progresses silently for years.
• In the absence of treatment, the time for progression from initial infection to AIDS is about 8 to 10 years.

In the 1980s, the CDC and the World Health Organization (WHO) developed separate sets of staging/classification systems. CDC stages A1 to C3 and WHO stages 1-4 listed the CD4 ranges and complications associated with each stage. These stages are no longer relevant, since highly-effective treatment prevents and reverses even advanced HIV disease. Most doctors simply refer to HIV infection as HIV disease. Currently, stages may be defined by clinical findings.

Stage:

• Acute HIV
  • Starts within 2-4 weeks and may last weeks to months
  • May or may not show symptoms
  • High level of virus (viral load) is present in blood and body fluids
  • HIV tests may not detect infection (“window period”)
• Chronic HIV
  • Occurs after the acute stage and averages 8-10 years without treatment
  • Virus in blood stabilizes at a lower, persistent level in blood and body fluids
  • No symptoms
• AIDS
  • HIV virus infection of CD4 immune cells overtakes the body’s ability to produce them
  • CD4 cell count drops below normal range (500-1800 cells/mm³)
  • Opportunistic infections and complications begin to appear

In addition to the clinical stages, the CD4 count ranges during HIV infection can help healthcare professionals predict what kinds of opportunistic infections and complications may occur and what preventive treatments (prophylaxis) may be useful.

• CDC Category A: CD4 count 500 cells/mm³ of blood or higher
  • Normal range, may last several years after the start of HIV infection
• CDC Category B: CD4 count 200-499 cells/mm³
  • Risk of yeast infections and common bacterial infections begins
• CDC Category C: CD4 count below 200 cells/mm³
  • Risk of more severe and unusual infections and cancers begins
  • Antibiotics or antifungals may be prescribed to prevent certain opportunistic infections (prophylaxis)

Does HIV have different strains? What is the difference between HIV-1 and HIV-2?

HIV virus has different subtypes. HIV-1 is the most common, “classic HIV” subtype found throughout the world. HIV-2 is related but is less transmissible and slower to progress. HIV-2 is found in people from West Africa and accounts for only 0.01% of HIV infections in the US.

HIV Antibody, Antigen/Antibody, and Nucleic Acid Tests (NAT) are the laboratory tests used for diagnosing HIV. Multiple manufacturers produce reliable HIV tests approved by the US Food and Drug Administration (FDA). Most detect both HIV-1 and HIV-2 subtypes.

• HIV Antibody – These tests detect the antibodies in blood or saliva that are produced specifically against HIV virus. Antibodies to HIV take time to develop. During this interval, a person has virus in their body but will test falsely negative for infection. This "window period” varies depending on the test.
• HIV Antigen/Antibody – In addition to the antibodies, these tests detect p24 antigen, a protein in the core of the HIV virus itself. Thus, this test allows earlier detection. These tests are only performed on blood, not saliva.
• HIV NAT – These are more sensitive and identify the HIV RNA itself. HIV NAT is the most direct evidence of infection. Thus the “window period” where HIV NAT may be falsely negative can be much shorter than HIV Antigen/Antibody tests. HIV NAT is also called HIV RNA PCR and HIV viral load test.

HIV NAT may be “qualitative” (yes or no result) for diagnostic purposes. HIV NAT may also be “quantitative” (reports the number of virus particles per mL of blood). HIV NAT gives the number of virus particles per mL of blood. This is the test most commonly referred to as “HIV viral load”, and it is used for both diagnosis and for monitoring effectiveness of treatment.

Confirmatory testing may be performed with a HIV NAT or Antigen/Antibody test, but if there is any discrepancy in any of these results, a HIV NAT may be ordered at any time. HIV NAT may even be ordered as the first test if there is an urgent need to make the diagnosis, for example, if a person is having symptoms of acute HIV infection.

Table 1. Overview of HIV Diagnostic Tests

Although the tests for detecting HIV infection continue to improve, they still require that people seek out testing or that healthcare professionals test routinely.

About 15% of Americans infected with HIV are unaware of their infection because they have never been tested. In order to decrease the number that are unaware of their HIV infection status, in 2006, the CDC recommended that all people between 13 and 64 years of age be provided HIV testing at least once and at each visit that a sexually transmitted infection is suspected. In addition, those with ongoing risk factors for HIV infection should be screened yearly. Local HIV testing centers can be found online (https://gettested.cdc.gov).

HIV screening is now considered a routine laboratory test but is voluntary and usually offered on an “opt-out” basis. In other words, if HIV testing will be ordered as part of other routine tests, the person is informed of this when signing permission for laboratory tests and has the option to decline (opt out).

Two blood tests are routinely used to monitor HIV infections, the CD4 count and the HIV viral load.

The CD4 cell count shows the status of the immune defenses. The absolute CD4 count in the blood is normally above 400 cells per mm³ of blood. A declining number of CD4 cells means that HIV infection is worsening and the immune system is being damaged.

Once CD4 cells are below 200 cells per mm³, the person is severely immunosuppressed and at risk for life-threatening opportunistic infections. The level of CD4 cell count helps determine when to start preventive (prophylaxis) therapies for these infections.

The viral load measures the amount of virus circulating in the blood. The viral load is used to determine the response to drug therapy. The goal of therapy is an “undetectable” viral load of less than 20 to 50 copies per mL of blood. Once undetectable in blood, HIV is not transmittable to others (“Undetectable = Untransmittable” or “U=U”). Viral suppression lasts for as long as the patient consistently takes their medications.

Lastly, drug resistance can be acquired during treatment or transmitted from a person on treatment. Thus resistance testing is used before a starting any new regimen, whether a newly diagnosed person or one experiencing poor response to HIV therapy.

In general, “treatment failure” may include:

• failure of viral load to decline approximately one hundredfold in the first weeks,
• a viral load more than 500 copies per mL by week 12,
• a viral load more than 50 copies per mL by week 24, or,
• a rise in undetectable viral load in a person who is consistently taking their medications.

When should antiviral therapy be started?

Antiretroviral therapy (ART) can halt progression to long-term immune damage. It can also prevent the chronic inflammation that leads to complications like diabetes and cardiovascular disease. Even people who have very low or no detectable HIV without ART (“long-term nonprogressors” or “elite controllers”) benefit from ART, because progression to detectable virus and chronic inflammation still occurs without treatment over time.

Treatment for HIV should start at the time of diagnosis regardless of the CD4 cell count, even the same day, if the person is ready. They should be able to stick to the regimen and follow up with their healthcare specialist to monitor whether medications are tolerated and working. Current medications are easy to take and well-tolerated. In addition, early therapy reduces the risk of sexual transmission to uninfected partners.

Fortunately, like other chronic illnesses, HIV can be well-controlled, lifelong, with antiretroviral medications. Starting ART is a lifelong, lifesaving commitment. With ART, a person can enjoy a healthy life, relationships, and lifespan despite having HIV.

Should patients with the flu- or mono-like illness of primary (acute) HIV infection be treated?

ART treatment should be offered on the same day of diagnosis regardless of how long the patient may have had HIV. People with acute HIV mono-like illness have high levels of virus in their blood and genital secretions. Early treatment reduces their risk of transmitting HIV to others and halts spread of HIV in their immune system.

Can HIV be cured naturally?

There are no natural cures or effective treatments for HIV infection.

The highest risk of HIV transmission is at birth. Before ART was available, the risk of HIV transmission during pregnancy was 25-35%. The breakthrough came with giving zidovudine (ZDV) after the first trimester of pregnancy, then intravenously during the delivery process, and then after delivery to the newborn for six weeks. This treatment reduces the risk of transmission to below 10%. Aside from counseling about the unknown side effects of ART on the fetus, a pregnant individual with HIV should be treated with ART just as any other person with HIV. Undetectable viral load by the time of delivery reduces the risk of transmission to below 1%.

Pregnant patients with HIV should be managed by an obstetrician experienced in managing a patient with HIV. Special precautions are taken to minimize transmission during delivery. Caesarean section (C-section) is considered, especially in those with detectable or unsuppressed viral load, where the risk of transmission is higher. HIV may be transmitted during breastfeeding, thus formula feeding is recommended. Updated guidelines for managing HIV-infected women are updated on a regular basis and can be found at https://clinicalinfo.hiv.gov/en/guidelines/perinatal/.

ART drugs target different steps in HIV reproduction and can be dosed once or twice a day, even as a single tablet. In addition, long-acting injectable ART combinations may be dosed weeks to months apart. ART regimens are selected based on the individual’s needs.

ART resistance is a critical problem in managing HIV. As HIV rapidly reproduces and spreads to more and more CD4 cells, it can develop mutations in the replication steps that cause resistance and treatment failure. Consistent dosing and combinations of drugs with different targets work best. The best combination of drugs are also well tolerated and simple to take. This allows people to take the medications consistently without missing doses.

In the US, guidelines for using antiviral therapy have been developed for healthcare professionals who manage HIV. These are updated on a regular basis by expert panels assembled by the National Institutes of Health (NIH) and Department of Health and Human Services (HHS) and available at their websites. A similar guideline is regularly updated by the International AIDS Society USA (IAS-USA) and available at its website.

An up-to-date overview of HIV treatment for the non-medical person is available at https://www.hiv.gov/hiv-basics/staying-in-hiv-care/hiv-treatment. 

In general, ART regimens include:

• 1 nucleoside-reverse transcriptase inhibitor (NRTI) + 1 nucleotide-reverse transcriptase inhibitor (NRTI) drug, often referred to as "dual nuc" (pronounced dual nook), plus
• 1 protease inhibitor (PI), OR 1 non-nucleoside reverse transcriptase inhibitor (NNRTI,  "non-nuc"), OR 1 integrase strand transfer inhibitor (INSTI)

What are nucleoside and nucleotide analog reverse transcriptase inhibitors (NRTIs)?

When HIV infects CD4 cells, it converts its RNA to DNA using its HIV reverse transcriptase enzyme. It then inserts HIV DNA into the cell’s human DNA. The human-like DNA of HIV then becomes part of the infected person's own cells, hijacking the cell to produce more HIV virus. NRTIs cannot remove the incorporated HIV DNA, but they can incorporate into the HIV DNA and block the action of HIV reverse transcriptase.

In general, most antiviral regimens for HIV disease contain a backbone combination of at least two NRTIs.

What are non-nucleoside analogue reverse transcriptase inhibitors (NNRTIs)?

NNRTIs target HIV reverse transcriptase itself and block its action. NNRTIs are typically used in combination with NRTIs.

What are protease inhibitors (PIs)?

PIs target another HIV enzyme called protease that allows HIV-infected CD4 cells to produce HIV proteins. PIs are often “boosted” with a second drug that boosts their blood level. This makes them more effective. PIs are generally avoided in pregnancy.

What are integrase strand transfer inhibitors (INSTIs)?

INSTIs block the action of the HIV integrase enzyme, which inserts (“integrates”) the HIV DNA into the human DNA of CD4 cells. This prevents HIV reproduction and spread to other cells. INSTIs are used in combination with NRTIs. INSTIs are preferred in pregnancy.

What are fusion inhibitors?

HIV fusion inhibitors block attachment to the envelope surrounding the virus and prevents it from entering the CD4 cells. This is used in individuals who have developed resistance to other classes of drugs in order to create a new potent combination.

What is a CCR5 antagonist?

CCR5 antagonists block entry of HIV into the CD4 cell by binding the CCR5 molecule. This is only an effective treatment in those whose HIV is only able to bind CCR5. Up to 50% of patients have HIV that is able to use a different entry point, the CXCR4 receptor. A tropism assay test is done to determine whether the patient has detectable CXCR4-using virus, in which case the patient would not be a candidate for this treatment.

What is a CYP450 inhibitor?

CYP450 are enzymes that control how fast or slowly many drugs are eliminated from the body. Many types of drugs can inhibit CYP450 enzymes, which makes them useful as “boosters” for other drugs to increase or maintain effective levels.

What is an entry inhibitor (attachment inhibitor)?

These are monoclonal antibodies that block HIV attachment and entry into the CD4 cell. They are used for patients with highly-resistant HIV virus who have treatment failure or cannot tolerate other ART.

What is a capsid inhibitor?

Capsid inhibitors bind to the HIV virus capsid and block multiple steps in HIV reproduction. They are used for patients with highly-resistant HIV virus who have treatment failure or cannot tolerate other ART.

What are the single tablet treatment regimens for HIV?

Combination pills allow for a full regimen to be taken as a single pill once per day.

HIV itself may cause arthritis and muscle pain. However, it is also associated with a number of rheumatic diseases. These conditions may be triggered by a person’s genetic predisposition and/or the immune response to HIV infection itself. Fortunately with ART, these disorders have declined in numbers and severity for people living with HIV.

Rheumatologic disorders associated with HIV infection include:

• psoriasis and psoriatic arthritis
• rheumatoid arthritis
• reactive arthritis
• polymyositis
• vasculitis
• fibromyalgia
• septic arthritis (bacterial joint infection)

What are the opportunistic infections associated with HIV?

Depending on the CD4 count, advanced HIV can pose risks for mild to life-threatening certain opportunistic infections (see AIDS). Opportunistic infections associated with HIV may include:

• Candida (oral thrush, genital yeast infection)
• Pneumocystis jerovici pneumonia (PJP, PCP)
• Tuberculosis (TB)
• Histoplasmosis
• Cryptococcus
• Cytomegalovirus (CMV)
• Mycobacterium avian complex (MAC)

There are potential side effects associated with antiviral therapies. The most common ones for each class of drug are summarized in readily available product information.

People with untreated HIV and CD4 below 400 cells per mm³ may have early opportunistic infections with few or no symptoms. Because current ART is potent, these infections may flare up and become apparent when ART is started. This is called “immune reconstitution syndrome.” It is not a side effect but a sign that ART is actually working well and immunity is being restored quickly.

Monitoring antiviral therapy

The viral load and the CD4 cell count are checked before starting ART. The viral load is repeated after approximately four weeks of treatment. It is expected that the viral load should drop by at least a hundredfold during this interval. The goal is for the viral load to decrease to undetectable levels by approximately 12-24 weeks. Once the patient's viral load is stable and fully suppressed, they can often have viral load and CD4 cell counts performed less frequently (for example, every six months or even less).

What happens if viral load increases while on HIV therapy?

The most common reason for a rise in viral load is that doses are being missed. If drug side effects are causing missed doses, side effects must be addressed or a better-tolerated regimen may be needed. Options include using a pillbox, taking doses with daily activities such as tooth brushing, or possibly changing the regimen. Finally, missed doses may be due to depression, substance abuse, or another issue that must be managed.

Sometimes, the viral load can briefly rise due to an illness, immunization, or an unknown cause. However, persistently elevated viral load, especially greater than 200 copies per mL, may be due to resistance.

If this is the case, ART resistance testing is ordered to determine a more effective ART regimen. Two types of resistance tests are available:

• HIV genotype assay - HIV genotype looks for mutations in the virus that predict resistance to different ART. An HIV genotype test is best used to screen before start of treatment and for those with failure of their first one or two treatment regimens.
• HIV phenotype assay - HIV phenotype measures the actual amount of drug it takes to block infection by the patient's virus. The HIV phenotype is most useful in those who have been on multiple regimens and have substantial drug resistance.

What are the risks of missing doses or stopping antiviral therapy?

Although every missed dose increases the chance that the virus will develop resistance, a single missed dose is not a complete failure. It is an opportunity to learn what can be done to minimize missing future doses. When a dose is missed, the patient should contact their HIV specialist without delay to discuss the course of action.

If the ART regimen must be stopped before discussing with the HIV specialist, it is best to stop all of the drugs in the combination rather than staying on one or two. Taking only part of the drug combination in a multiple pill regimen is especially risky for ART resistance.

What can be done for people who have severe immunosuppression?

Some individuals are already immunosuppressed when they first seek medical care. Others may progress to that stage due to resistance to ART. Resistance testing helps ensure that patients are on the best possible ART regimen. Active infections should be treated.

Because immune response is restored so rapidly when ART is started, some opportunistic infections may flare up and become life-threatening if ART is started before an infection is under control. This is called immune reconstitution syndrome or IRIS. For example, starting a new ART regimen should be delayed by 2 weeks to 2 months if the patient has active tuberculosis or cryptococcal meningitis. Depending on the of CD4 count, prophylactic (preventive) therapy may be started for other opportunistic infections. Once CD4 count has risen and remains stable on ART, prophylactic antibiotics may be stopped.

Guidelines for the prevention of opportunistic infections can be found at https://aidsinfo.nih.gov/.

How long can you live with HIV?

Prognosis is excellent once ART is started, even for those who are diagnosed and treated late in disease, after they have developed severe immune deficiency and very low CD4 counts. In fact, it is not unusual for a low CD4 count to revert to normal on ART within a few weeks to months. Health can be rapidly restored even for those who are very ill with advanced HIV/AIDS.

If HIV is fully suppressed on treatment for at least 6 months, a person's lifespan and health is similar to a person without HIV infection. Current ART regimens, if taken consistently and indefinitely, completely and durably suppress HIV. In fact, well-controlled HIV is unlikely to progress to AIDS or opportunistic infections.

In addition, HIV suppression reduces the long-term chronic inflammation that causes other complications like heart disease, stroke, and diabetes.

Prognosis is poor if HIV is never diagnosed or treated. Most people will develop symptoms of AIDS and opportunistic infections about 7-8 years after getting infected. If untreated, life expectancy from that point is about 3 years.

Can the HIV virus go away on its own?

Rarely, some people may control HIV for years without treatment (“long-term nonprogressor,” “elite controller”). However, cure or elimination of the virus is extremely unlikely once a person is infected.

Does HIV have a permanent cure?

There is no treatment or medication that cures or eliminates HIV infection from the body. The viral load will rise and disease will progress again if medication is stopped.

Researchers continue to explore simplified drug regimens to reduce problems with missed doses and side effects. In addition, multiple potent drugs in new classes has made it possible to suppress viral load to undetectable even in many of the most treatment-experienced patients.

Researchers are exploring strategies to cure HIV. One strategy has been to use therapies that boost the natural immune response to HIV and allow for complete or partial control. Another area of research is to purge infected cells, which act as a "latent reservoir” of persistent virus, with various agents to eradicate it from the body.

Two cases of HIV cure after bone marrow transplant in recent years have stirred great scientific interest. The conditions in these cases were too unique, and bone marrow transplants far too risky, for this to be a realistic approach to curing HIV infection. However, these cases offer new possibilities for researchers and hope for the future.

Ways to prevent HIV transmission include:

• Avoidance of sex until it is certain that both partners in a monogamous relationship are not HIV infected via testing.
• Use of barrier precautions during sex, like male and female condoms.
  • Male condoms should be applied as soon as an erection is achieved.
  • For oral sex, male condoms should be used for fellatio (oral contact with the penis) and latex barriers (dental dams or female condom) for cunnilingus (oral contact with the vaginal area). A dental dam is any piece of latex that prevents genital or anal secretions from coming in direct contact with the mouth.
• Treatment as Prevention (TasP) - ART is highly effective in preventing transmission to uninfected partners. Once HIV virus is undetectable in blood for at least 6 months on treatment, HIV is not transmitted in genital and anal fluids.
• Pre-exposure prophylaxis (PrEP) with two oral NRTIs or 1 injectable NNRTI is highly effective in protecting a person from getting a HIV infection. In those who consistently take PrEP and have detectable drug levels in blood, protection is over 90%.
• Several large studies have shown that male circumcision along with behavioral counseling reduced the risk of heterosexual men acquiring HIV infection in parts of the world with limited access to PrEP or ART.

Should I take PrEP?

HIV can be prevented by consistently taking preventive medication, commonly called PrEP, along with avoidance of contact with infectious fluids.

PrEP is highly effective and is highly recommended in those who have risk factors for HIV infection.

In general, the CDC recommends PrEP for those who have had vaginal or anal sex in the last 6 months and have had or will have:

• sexually transmitted infections (STI) or taken post-exposure prophylaxis for HIV,
• partner(s) living with HIV whose virus is not known to be undetectable,
• partner(s) whose HIV status is unknown, especially if no barrier precautions were taken,
• partner(s) who inject drugs, and/or,
• planning pregnancy with a partner living with HIV.

The FDA has approved once-daily drugs for PrEP in HIV-uninfected adults and teens who have been or will be potentially exposed. In addition, injectable PrEP is also available.

In addition to medication, PrEP requires continued use of condoms or barrier precautions and regularly scheduled screening for HIV infection, sexually transmitted infections, and treatment adherence. PrEP has potential side effects but is generally well-tolerated.

Prevention is best, but in an accidental or emergency situation, Post-exposure Prophylaxis (PEP) with combination ART may prevent HIV infection. It must be given with 72 hours after an unprotected exposure to blood or body fluids of a person with HIV, within 4 hours if at all possible. Exposure to infected blood or body fluids may happen during work (occupational exposure). Non-occupational exposure may occur during sexual activity (rape or a broken condom) or sharing injection equipment. ART is given for 4 weeks, and testing for HIV and other potential infections is continued for several more weeks. Updated guidelines are published and available at https://aidsinfo.nih.gov.