This is a part of the Sick Saturdays feature, in which we have a sick discussion on the symptoms and biology behind infectious illnesses.

Many diseases have a stigma attached to them. Since the discovery of the virus, Human Immunodeficiency Virus (HIV) has been a contentious subject in medicine and society. Stigma associated with HIV continues to this day across the world, and it contributes to the ongoing limited response to the outbreak. 

When untreated, HIV can progress to Acquired Immunodeficiency Syndrome (AIDS). An HIV infection is a complex and often misunderstood condition. Here, we aim to educate you about the biology behind HIV as well as about HIV and society.

Origins and causes

To start, let’s address the difference between HIV and AIDS. HIV is the virus that causes AIDS. AIDS is defined as a drop in CD4 cell count to below 200 cells/mm³ or the presence of one or multiple opportunistic infections associated with HIV. We’ll go over CD4 cells and opportunistic infections later. 

For now, know that HIV is contagious but AIDS itself is not. Not everyone who is HIV+ will progress to AIDS. With available treatments, AIDS and especially HIV are not death sentences. If on antiretroviral therapy (ART), a person that is HIV+ will not get AIDS. If not on medication, HIV will usually cause AIDS 10 years or more after initial infection, but it can also do so much more quickly. Both HIV transmission and progression to AIDS can be prevented. AIDS can be cured, while HIV cannot. 

HIV is closely related to simian immunodeficiency virus (SIV), which infects a number of non-human African primates. The virus originated when a certain SIV strain was transmitted from a chimpanzee to a human. HIV is a type of retrovirus, meaning it uses RNA as its genetic code (instead of DNA like most organisms). This trait of HIV means special medications are needed to treat it. Antiretroviral drugs, as their name might suggest, work against retroviruses.

AIDS was identified in 1981, and was first called Gay-Related Immune Deficiency (GRID). The current name was more commonplace a year later. The causative agent of AIDS, HIV (initially called Lymphadenopathy Associated Virus), was discovered in 1983. Also in 1983, the mode of transmission of HIV was announced to be through blood or sexual contact.

This means that you cannot get HIV from hugging or kissing a person that is HIV+, nor from sharing unchewed foods, drinks, toilets, or a living space. Animals cannot transmit HIV. However, mothers can transmit HIV to their babies during pregnancy, labor, delivery, or breastfeeding; collectively, these methods are known as mother-to-child transmission (MTCT).

For HIV infection to occur, certain fluids have to come into contact with certain body parts. The only bodily fluids that contain enough HIV to cause an infection are blood, breastmilk, and genital secretions. These fluids can only infect through open wounds, direct injection into the bloodstream, or mucous membranes, including the mouth, rectum, vagina, and penis. So if an encounter does not involve one of those fluids and one of those entry points, HIV infection will not occur!

Prevention and treatment

As with any disease, it is easier to prevent HIV infection than to treat it. The easiest way to prevent sexual HIV transmission is to not have intercourse, or to always have intercourse with a condom or dental dam. Physical barriers are needed to prevent HIV infection as spermicides only kill sperm, not viruses. Other ways to prevent HIV include limiting your number of sexual partners and not sharing needles or using dirty needles. 

In high-risk individuals, pre-exposure prophylaxis (PrEP) may be recommended. PrEP involves taking a regimen of ART to prevent HIV infection. When taken correctly, PrEP is more than 99% effective at stopping sexual HIV transmission. 

A similar medication can be taken soon after exposure to HIV to hinder the virus from taking hold. Known as post-exposure prophylaxis (PEP), this therapy should be initiated within 72 hours of a potential HIV exposure. If prescribed PEP, you must take an antiretroviral medication once or twice daily for 28 days. PEP should not be used as a regular form of HIV protection, as it is less effective than PrEP at preventing an infection.

If you are HIV+, you can prevent transmitting the virus to others by following your ART as prescribed. ART lowers the amount of virus (the viral load) in your blood, sometimes to such a low level that it is undetectable on an HIV test. Having an undetectable viral load means that you cannot transmit HIV through blood, sexual contact, or MTCT. By taking ART you also control your HIV infection.

Antiretroviral drugs fall into one of seven different classes based on their mechanism of action. Because HIV rapidly evolves, people that are HIV+ usually take a combination of at least two antiretrovirals, each in a separate class. A certain threshold of the drugs must be present in the blood for HIV to be suppressed. To maintain that necessary drug concentration, ART must be taken daily.

Once AIDS sets in, ART should be prescribed if not already, but other relevant symptoms and opportunistic diseases must also be addressed. Opportunistic diseases associated with HIV include tuberculosis, candidiasis (thrush), toxoplasmosis, and Salmonella infections. The treatment of those aspects of AIDS is specific to each medical issue. If not treated, conditions related to AIDS will cause death in an average of three years.

diagram of seven steps of hiv life cycle

Infection and spread

The HIV life cycle is usually divided into seven stages:

  1. During the first stage, called binding, receptors on the outside of an HIV virion bind to receptors on the surface of a CD4+ T-cell. HIV must bind to a CD4 receptor as well as to one of two coreceptors, CXCR4 or CCR5. Two classes of ARTs target binding: CCR5 antagonists and post-attachment inhibitors. Post-attachment inhibitors prevent HIV from binding to the CD4 receptor, while CCR5 inhibitors block the CCR5 receptor specifically.
  2. The second step of HIV infection, fusion, involves the fusing of the HIV envelope with the CD4+ cell membrane so that HIV can enter the cell. Fusion inhibitors are a kind of ART that prevent fusion by altering the structure of an HIV envelope protein needed for it to join to the CD4+ cell membrane. 
  3. Reverse transcription is the next stage, in which HIV uses a special enzyme (reverse transcriptase) to turn its RNA into DNA. This change is needed in order for HIV’s genome to combine with host cell DNA. Two types of ART target this stage. Nucleoside reverse transcription inhibitors (NRTIs) are identical to nucleosides used in DNA transcription, so when exposed to HIV, NRTIs bind in place of HIV nucleosides and terminate transcription. On the other hand, non-nucleoside reverse transcription inhibitors (NNRTIs) primarily attach to reverse transcriptase and inactivate it.
  4. After reverse transcription, the newly made HIV DNA enters the nucleus of the host CD4+ cell and integrates into host DNA using an enzyme called integrase, during integration. Integrase inhibitors block integrase, preventing HIV from replicating
  5. If not yet disrupted, HIV continues its life cycle by beginning replication. No class of ART works against replication.
  6. In the assembly step, once all the parts of the virus have been reproduced, they migrate back to the cell membrane to form non-infectious HIV particles. Similar to replication, no ART drugs prevent assembly.
  7. Budding is the final stage. Immature HIV leaves the CD4+ cell, then releases numerous proteases, which make HIV protein chains into smaller proteins. These proteins assemble to become infectious HIV, which can then infect a new cell. A type of ART that functions during budding are the protease inhibitors (PIs). PIs bind to proteases which stops protein cleavage from happening.

A common ART regimen is two NRTIs with one PI. Other ART drug combinations exist, but they almost always involve an NRTI; this type of ART is important because if reverse transcription can’t occur, HIV can’t integrate its DNA with that of the host cell and therefore can’t replicate.

If left untreated, an HIV infection will cause very low CD4+ T-cell levels. CD4+ cells are important in immunity to pathogens, and their numbers are somewhat indicative of immune function. Low CD4+ levels makes a person more susceptible to opportunistic infections, and people with levels below 200 cells/mm³ are said to have AIDS. 

Society and stereotypes

HIV is considered to be a global pandemic. Across the world in 2019, 38 million people were HIV+. Of all people living with HIV in the United States, about 1 in 7 don’t know they have it

In the United States in 2018, HIV was more common in males, particularly gay and bisexual males. HIV was largely contracted through male-to-male sexual contact. The age range that HIV was most frequently diagnosed during was 25 to 34 years old. 

HIV disproportionately affects BIPOC; the rate of HIV diagnoses in 2018 amongst Blacks was 39.2 per 100,000 and that of Hispanic/Latinos 16.4 per 100,000, whereas amongst whites it was 4.8 per 100,000. Moreover, HIV is more common in people with mental illnesses and people that are homeless. Most members of those groups already deal with hardships, and becoming HIV+ only heightens the challenges they face. 

Stigma in the US regarding HIV/AIDS began with its emergence in primarily gay individuals as well as with its related initial name of GRID. In the United States, HIV/AIDS stigma is still very connected to sexuality. The many misconceptions associated with HIV/AIDS only further the stigma attached to the infection. 

HIV/AIDS stigma is especially common in sub-Saharan Africa. Notably, unlike in the US, HIV is most often spread through heterosexual contact in sub-Saharan Africa.

Religion and beliefs on gender and sexuality are common contributors to stigma in the region. Some religious people see people who are HIV+ as being impure or immoral. Others believe that women are expected to be subservient to their husbands and a diagnosis of HIV suggests that they were unfaithful. Stigma is also perpetuated in the way that HIV/AIDS is discussed. In Malawi, physicians sometimes refer to HIV/AIDS as ELISA disease or immunosuppression

All throughout the world, stigma and stereotypes linked to HIV/AIDS are the cause of discrimination and denial of services for many people living with HIV. In fact, about 1 in every 8 people that are HIV+ in the world have been denied medical assistance due to their HIV status

How have you helped those who are HIV+ in your community? Be it through volunteering or educating a friend about HIV/AIDS, there are many simple ways you can contribute to elimination and eradication of the infection.

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Delaney

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