Understanding the Risks and Implications of HIV Superinfection

HIV superinfection (HIV-SI) is an emerging concern for people who already have established human immunodeficiency virus (HIV). Superinfection occurs when an HIV-infected individual is infected with a distinct HIV viral strain. Incidence rates of superinfection vary between 0% and 7.7% annually. 

If you have HIV, understanding the risks and implications of HIV superinfection can help you stay informed about your sexual health. You can take steps to prevent superinfection or dual infection.

Learning how superinfection occurs is the first step in preventing it. Practicing safe sex and following a treatment regimen for your established HIV can also help you prevent superinfection. 

Continue reading for everything you need to know about HIV superinfection: how it occurs, its prevalence, how to manage it, and more. Then, request your rapid STD test to stay on top of your sexual health and plan the correct treatment regimen, if needed. 

The Science of HIV Superinfection: How It Happens

HIV superinfection occurs when someone who is currently infected with HIV becomes infected with a second, distinct strain of the human immunodeficiency virus.

HIV generally spreads through sexual contact or needle use. Researchers have determined that these same methods of initial HIV transmission can also lead to HIV superinfection. When a person who is infected with HIV does not practice safe sex or shares needles with a person who has a different strain of HIV, they can become infected with that strain as well. 

Superinfection is a type of dual infection, but not all dual infections are superinfections. The two main types of dual infections include: 

• Coinfection, which occurs when a person becomes infected with two separate strains simultaneously or close in time
• Superinfection, which is a sequential infection that occurs after the person has developed an immune response to the initial strain 

A superinfection is not necessarily stronger or more virulent than the initial infection. It is just the term to describe this type of dual infection. 

Superinfection differs from reinfection. Reinfection occurs when an infected individual has poor adherence to treatment, eventually leading to treatment failure. The person develops a resistance to their drug treatment, preventing that treatment from effectively treating their HIV again. 

There are several strains of HIV out there. The two most common are HIV-1 and HIV-2, but both have multiple groups and subtypes. While you may develop immunity to one strain of HIV after contracting it, you may not be immune to other strains. 

The first instances of HIV superinfection were discovered when researchers observed a coinfection of HIV-1 and HIV-2 in an individual. These strains are evolutionarily distinct. 

Superinfection can also occur with two HIV-1 recombinant forms, which contain separate genomic sections. 

Researchers are still determining how HIV superinfection affects the body. Some studies show that HIV superinfection can lead to accelerated disease progression or abrupt deterioration of clinical status. However, other studies show that superinfection had no significant effect on the person’s health. 

HIV superinfection is relatively challenging to identify, and researchers are still determining the best ways to pinpoint superinfection vs. coinfection. One popular method for identifying superinfection is through next-generation sequencing (NGS). This is a relatively new technology for DNA and RNA sequencing that identifies variants and mutations. 

One study of NGS for detecting HIV superinfection identified nine cases of HIV superinfection in a pool of 142 women with HIV infection. The study was able to obtain approximately 1.7 million raw sequencing readings, with 1.25 million of them passing quality filtering. 

Epidemiology and Transmission: Understanding the Spread

Until recent years, HIV superinfection was not understood well because it is widely underreported. Additionally, many clinicians have not distinguished between HIV superinfection and coinfection, potentially skewing data. The hope is that further research and testing will narrow the exact risk factors and transmission methods leading to superinfection. 

Epidemiology of HIV Superinfection

Current data point to the prevalence of HIV superinfection worldwide. This type of dual infection has been reported in countries such as:

• The United States
• Canada
• The United Kingdom
• The Netherlands
• Zambia
• Burkina Faso
• Kenya
• Switzerland
• Uganda
• Thailand
• Australia

This HIV coinfection is also prevalent among multiple populations, including those who are heterosexual and homosexual. The risk of infection may be higher among men who have sex with men, people who use intravenous drugs, and women who are sex workers.

Incidence rates of HIV superinfection may be as high as 7.7% annually, but incidence varies depending on an infected person’s commitment to antiretroviral drug use. One study conducted in Uganda found that the rate of superinfection in people who are already positive for HIV may be comparable to the rate of primary HIV infection. 

Transmission of HIV Leading to Superinfection

The exact risk factors of HIV superinfection are not yet clearly defined. However, it appears that the same risk factors for initial HIV infection may also be true for HIV superinfection, such as:

• Increased number of sexual partners
• Non-marital relationships
• Absence of male circumcision
• Limited condom use
• Lack of antiretroviral therapy (ARV) use

HIV typically doesn’t pass between people who have an undetectable viral load. If you are HIV-positive, sticking to a treatment regimen may prevent you from passing HIV to another person.  

Initially, researchers hypothesized that HIV superinfection was most common during the initial stage of primary HIV infection, which is six months after infection. Numerous studies supported this assumption, but further research has shown that HIV superinfection can occur more than two years after the primary infection. 

It appears that HIV superinfection occurs due to a loss of immune control in individuals infected with primary HIV. Initial infection causes the CD8+ T cells to maintain a viral set point and control viral replication. But when an individual becomes infected with a secondary strain, the T-cells lose control over replication and deviate from the set point. Researchers are still unsure why this happens. 

The weakened T-cell response allows the superinfecting strain to resist immune control, and the superinfecting strain recombines quickly. 

Preventing HIV Superinfection 

Though researchers are still determining the exact causes and methods of transmission of HIV superinfection, there are a few measures you can take to prevent this type of dual infection. 

First, if you have HIV, be diligent about taking your antiretroviral drug therapy. Keeping your viral load low can help you maintain an adequate immune response to HIV, preventing you from contracting another strain of the virus. 

Always use a condom when having sex with a person whose sexual health you are unsure of. HIV spreads through sexual contact and shared needles, and taking measures to prevent bodily fluids from spreading in both activities can help prevent a secondary infection. 

If you haven’t recently, take a 10-panel STD test to stay informed about your sexual health. Beginning treatment for any new STDs quickly can keep your immune system going strong. 

Clinical Implications: Managing HIV Superinfection

While the term “superinfection” does not necessarily indicate a more severe infection than primary HIV, this type of dual infection could have serious consequences for infected individuals. The main concern is that superinfected patients often develop drug resistance to known HIV treatments. 

Drug Resistance

Superinfection involves viral recombination, which is what happens when two or more genomes co-infect the same host cell and exchange genetic segments. As a result, the HIV infection becomes more complex, turning into a mosaic recombinant strain that cannot be treated with a typical drug therapy. 

Antiretroviral therapy is the leading treatment for HIV. When successful, this therapy suppresses HIV replication and lowers the viral load. People with undetectable viral loads are not at risk of passing HIV to sexual partners, allowing them to live mostly normal lives. 

Superinfection lowers the potential success of antiretroviral therapy. As a result, people with superinfection can often pass HIV to others through bodily fluids. They may also experience more noticeable symptoms, including:

• Fever
• Headache
• Sore throat
• Chills
• Night sweats
• Diarrhea
• Swollen lymph glands 

When HIV treatment begins not working, HIV can turn into AIDS. The prognosis for people with HIV superinfection is potentially worse than those with primary HIV infection. 

Challenges in Diagnosing Superinfection 

HIV superinfection isn’t only challenging to treat; it’s also difficult to diagnose. 

Superinfection is diagnosed by detecting viral recombinants for phylogenetically distinct parent strains. However, the current detection methods aren’t always accurate or easily accessible.

Initially, clinicians used bulk sequencing to amplify viral DNA and detect new phylogenetic species. However, this method cannot accurately detect genetic differences that are lower than 20%, leaving some cases of superinfection undetected. 

Next-generation sequencing is currently the most accurate method of detecting genetic differences, as it can identify differences of 1% or less. The biggest problem is that people with HIV superinfection often do not suspect that they have a dual infection, so they don’t undergo the proper testing to identify it.

Superinfection may have the same symptoms as primary HIV infection and may not initially feel worse, making it trickier to recognize and identify as such in the early stages. 

Other Potential Impacts 

Untreated HIV often causes immunosuppression, making infected individuals more likely to contract other viral illnesses. As a result, people with HIV superinfection who have developed drug resistance may be at a higher risk of contracting other STDs from sexual partners. 

People who are HIV positive and anyone with multiple sexual partners should participate in same-day STD testing regularly to catch new infections as early as possible. The earlier you treat an STD, the better the prognosis. 

Superinfection and HIV Vaccine Research: A New Challenge 

HIV superinfection also poses concerns for public health and HIV vaccine development. Current vaccines may not adequately protect against superinfection. 

Existing HIV Vaccine Research

First, it’s important to understand that there is currently no available vaccine that will prevent HIV infection. Scientists have been working toward an HIV vaccine for some time, but developing one is challenging for several reasons:

• HIV mutates rapidly and evades the immune system in unique ways.
• There are no documented cases of a person developing an immune response to HIV that clears the infection. 
• Inactivated HIV cannot effectively elicit an immune response. 
• People in high-risk groups are exposed to HIV daily. 

The National Institutes of Health is close to developing a vaccine. The most promising vaccine technology thus far uses antigens, which stimulate specific immune responses. An ideal vaccine would induce an uninfected individual’s immune system to produce broadly neutralizing antibodies (bNAbs).

Unfortunately, HIV superinfection may complicate vaccine development. 

Challenges With HIV Superinfection Vaccination

Case studies have shown that the strains of HIV leading to superinfection have distinct viral epitopes from the virus that initially causes the HIV infection. As a result, a vaccine that creates an immune response to the initial HIV infection would not protect against that secondary superinfecting strain. The superinfecting strain would proliferate, causing an infection. 

Any HIV vaccines designed to recognize specific viral epitopes would not adequately protect against other strains of HIV that have distinct epitopes. Worse, individuals who have received these ineffective vaccines may experience a faster progression of HIV infection than those who do not receive the vaccine. 

Researchers aim to develop a vaccine that protects against the viral epitopes of several viral subtypes, providing adequate protection against the epitope that causes superinfection. While no approved HIV vaccines exist at the time of this writing, researchers may need to alter their methods and backtrack slightly to develop a vaccine that fits the unique requirements of HIV superinfection. 

Protect Your Sexual Health With Rapid STD Testing

HIV superinfection is a serious condition that researchers are still working to understand. If you have HIV, rest assured that hard-to-treat superinfection is rare. You can protect yourself against superinfection by following your prescribed treatment regimen, avoiding sharing needles, and using protection whenever you have sex. 

If your HIV symptoms return or you think you have been exposed to HIV while infected, don’t hesitate to talk to your doctor about HIV superinfection. Because superinfection is not understood well, your doctor may not suspect superinfection initially or conduct next-generation sequencing to test for it. 

Staying informed about your sexual health can help you take the appropriate measures to protect it. At Rapid STD Testing, we make testing for STDs simple and easy. Contact us today to find a clinic near you and schedule testing, then learn the answer to “Can undetectable HIV become detectable?“