The Relationship Between Genetics and HIV Infections

Genes play a role in a person's susceptibility to HIV infection, the progression of HIV into AIDS, and the effectiveness of different treatments.

Millions of people are exposed to HIV each year, but not everyone will become infected. Researchers estimate DNA accounts for 28% to 42% of an individual's risk for contracting HIV.

Multiple genetic variations have been identified that either protect against HIV and AIDS or are associated with a greater risk. Genes may also impact the course of the disease and the effectiveness of different treatments.

This article discusses genetics and HIV. It explores the recent advances in the field of HIV and genes and explains how different genes may affect the immune system's response to the HIV.

Genes May Protect Against HIV

Over the past several decades, researchers have identified a few different genes that are associated with a decreased risk of contracting HIV.

The first genetic mutation related to HIV was identified in the mid-1990s as CCR5-Delta32. Research shows people with a homozygous 32 bp deletion in CCR5 are less likely to contract HIV.

Scientists estimate that 10% to 14% of Europeans carry this gene, which appears to have a protective effect against HIV. The gene is rarely found in people of African or Asian heritage.

Researchers suspect this genetic variant may have developed in response to the Bubonic plague or smallpox. HIV and smallpox affect the immune system in similar ways—by causing cellular immune dysfunction and entering leukocytes using chemokine receptors. Experts theorize if your ancestors survived smallpox, you may have an evolutionary advantage against HIV.

Other genes, like EFCAB14, are also being investigated for potential protective effects against HIV infection.

Genes May Increase HIV Risk

Researchers have also identified two genes associated with an increased risk of contracting HIV. People with mutations in CD101 and UBE2V1 are four times more likely to contract HIV than people without these genetic variants.

Researchers are uncertain exactly how these genes increase HIV risk. Both genes play a role in immune system functioning and are known to impact inflammatory pathways.

The CD101 gene is responsible for encoding antibodies implicated in regulatory T-cell function. Variations in this gene appear to lower immunity to HIV by inhibiting the ability of regulatory T cells to suppress T cell cytokine production.

The UBE2V1 gene is associated with enzymes involved in pro-inflammatory cytokine expression. In addition to increasing susceptibility to HIV infections, mutations in this gene are also associated with increased risk of heart disease, kidney disease, and certain cancers.

More research is needed to understand exactly how these genetic variants increase HIV risk. For now, investigators hope these new findings will help in the development of new pre-exposure prophylaxis (PrEP) therapies.

Genes May Delay AIDS Onset

HIV is treated with antiretroviral therapy to prevent progression to AIDS. However, researchers identified a subset of HIV-positive individuals whose HIV RNA load remains low even without treatment. These people are known as HIV controllers.

Genetic testing of HIV controllers identified chromosomes in the human leukocyte antigen (HLA) complex that may protect against or delay the onset of AIDS: HLA-B57, HLA-B27, HLA-B52, and HLA-B39.

Several alleles associated with a faster progression to AIDS were also identified. These include HLA-B35, HLA-B18, HLA-A24, HLA-B08, and HLA–A29.

It is unclear the precise role these different genetic variations play in either suppressing or accelerating HIV replication and progression to AIDS. Researchers suspect these interact with other genes involved in the immune response, such as IL28B, LAG3, CTLA4, CD28, and CD3.

While more research is needed to fully understand the role these genes play, scientists are hopeful that studying the genetic code of HIV controllers will unlock new therapeutic targets and treatments for HIV.

Genes, Blood Types, and HIV

Various blood group antigens have been studied for their potential role in promoting or protecting against HIV infection. To date, researchers have not found any clear associations between blood antigens and HIV risk.

Blood group antigens that have been investigated for their role in HIV include:

• ABO blood type: Early HIV and AIDS research explored the idea that some blood types are more susceptible to HIV infection than others. However, this theory is unproven and controversial. Initially, it was thought type O blood increased HIV risk. This was contradicted by other studies that found HIV was more common in people with type AB or B blood. To date, it's unclear what, if any, role ABO blood typing has in HIV infection. 
• Duffy blood group antigen: Found on the surface of red blood cells and other tissue, the Duffy antigen is a receptor for chemokines, small signaling proteins involved in the immune response. Scientists suspect people who do not have the Duffy antigen (Duffy-null) may be more susceptible to HIV infection. However, to date, studies have been mixed on whether the Duffy antigen plays a role in HIV infection. 
• Rh blood groups: Rh factor, commonly noted along with your ABO blood type as either positive or negative, was once thought to play a role in HIV infection. Rh proteins are found on the surface of red blood cells. The initial theory was Rh positivity protected against HIV and Rh negativity increased the risk. However, research has been unable to confirm any association between Rh type and HIV status.
• Pk antigen: Pk is a very rare blood group antigen found on the surface of red blood cells. In laboratory studies, cells with high levels of Pk were significantly harder to infect with HIV than cells with no Pk. Investigators suspect Pk provides genetic resistance to HIV and suspect it could be useful in the development of new HIV prevention therapies. 

Genes and HIV Treatments

DNA is also being used to identify new therapies for the prevention and treatment of HIV. Genetics can also help determine the best treatments for individuals. 

Human genetic variability has been found to have an impact on your response to treatment and potential side effects. For example: 

• Ziagen (abacavir) is linked to hypersensitivity reactions in people with certain HLA-B variants.
• Reyataz (atazanavir) may cause hyperbilirubinemia (jaundice) in people with UGT1A1 variations. 
• Sustiva (efavirenz) can lead to high drug plasma levels in people with some CYP2A6 or CYP2B6 alterations. 
• Viramune (nevirapine) can also cause high drug plasma levels in people with some CYP2B6 alterations. 
  

The interplay between genes and HIV infection and treatments is still being explored. Scientists are hopeful that this line of research may one day lead to a cure for HIV and AIDS.