What is HIV-2 Infection?
HIV, or Human Immunodeficiency Virus, is a type of virus that comes in two variations: HIV type 1 (HIV-1) and HIV type 2 (HIV-2). Both types can lead to AIDS and spread in similar ways, but they are not identical. There are key differences between them, especially in how common they are, how they are diagnosed, and how they are treated.
HIV-2 is less common than HIV-1 worldwide, but it’s still a significant health issue in different regions. It’s most common in West Africa, but due to global travel and migration, HIV-2 has been found in other parts of Africa, Europe, India, and the United States. It’s estimated that around 1 to 2 million people have HIV-2 globally, but this number is likely to be an underestimate.
The first cases of HIV-2 in the United States were found in the late 1980s. Nowadays, it’s estimated that about 1% of people living with HIV in the US have HIV-2. However, doctors generally know less about HIV-2, and there’s limited research and data about it. This has restricted our understanding about how prevalent it is, how to treat it, and how to monitor it, compared to HIV-1.
Up until now, our approach to dealing with HIV-2 has largely been based on what we know about HIV-1, but there are significant differences. Its lower occurrence compared to HIV-1 has led to a lack of medical trials or studies on HIV-2. This has meant we don’t fully understand how to manage it. Despite this, given that HIV-2 is found worldwide, doctors need to be aware of the differences between HIV-1 and HIV-2. They also need to be on the lookout for HIV-2, especially in people from places where the virus is common.
What Causes HIV-2 Infection?
HIV-2 is a virus, similar to HIV-1, that can infect humans. Studies suggest that it originally came from a type of monkey known as the sooty mangabey, which was infected with a monkey version of HIV, called simian immunodeficiency virus (SIV). Research indicates that this virus likely jumped from monkeys to humans sometime between the 1940s and 1950s. However, the first known case of HIV-2 in humans wasn’t identified until 1986, when a man from Guinea Bissau, living in Portugal, turned up with severe immune system weakness and tested negative for HIV-1. Then in 1989, the first case was identified in the US when a woman from Cape Verde came in with a brain infection common in people with HIV-1.
The rapid, worldwide spread of HIV-2 was fueled by the colonial wars being fought in Guinea and other parts of West Africa during the 1960s and 1970s. This led to a lot of movement across West Africa and to Europe. The wartime conditions also led to the widespread use of blood products to treat injuries, the emergence of sexual networks between the military and local communities, and large-scale vaccination efforts that did not properly sterilize needles used.
These conditions helped HIV-2 spread rapidly in Guinea Bissau. From there, it moved to neighboring countries and even further to Portuguese colonies, including Cape Verde, Angola, Mozambique, India, and Brazil. This led to high levels of HIV-2 transmission in Portugal, which now has the highest rate of HIV-2 infection in Europe.
Risk Factors and Frequency for HIV-2 Infection
Most people with HIV globally have HIV-1, with an estimated 38 million people infected as of 2018. HIV-2 is less common but still impacts an estimated 1-2 million people worldwide, particularly in West Africa. Countries such as Cape Verde, Guinea-Bissau, Senegal, The Gambia, Mali, Cote d’Ivoire, Sierra Leone, and Nigeria have the highest rates. Outside of Africa, some cases of HIV-2 have been reported in Europe, South America, Asia, and the United States.
In the United States, between 2010 to 2017, there were 198 reported cases of HIV-2. Over half of these cases were in the Northeast, with an additional 30% in the South. The majority of HIV-2 cases in the US were transmitted through heterosexual contact, but there were some instances of transmission through male-to-male sexual contact and intravenous drug use. Despite these numbers, the real prevalence of HIV-2 in the US is likely higher due to limitations in testing abilities.
Overall, the spread of HIV-2 is decreasing with time. The highest global number of cases likely happened between the 1970s and 1980s, especially in Guinea-Bissau where up to 10% of people had the virus. Nowadays, similarly high rates are only seen in adults over 40 in Guinea, with younger adults having a rate of 1-2%. However, the prevalence of HIV-2 in West Africa has been steadily declining over the past several decades, at the same time as the prevalence of HIV-1 has been rising. The causes of these shifts are not entirely clear, but potential factors include decreasing viral resilience, lower transmission efficiency, and HIV-1 outcompeting HIV-2. In fact, up to 30% of the decrease in HIV-2 could be due to competitive exclusion by HIV-1, whereas the remaining 70% could be due to changes in societal behaviors and interventions.
Signs and Symptoms of HIV-2 Infection
Patients diagnosed with HIV-2 should receive a similar medical evaluation as those with HIV-1. This involves going through a comprehensive medical history, thorough physical examination, and laboratory tests. The aim is to confirm the HIV-2 diagnosis, check for any opportunistic infections, educate the patient about the condition, and discuss the potential benefits of antiretroviral therapy. Doctors should be aware that HIV-2 cases may present in older patients, different populations, or those without traditional risk factors. Therefore, it’s important to readily test for HIV-2, especially in those with epidemiological risk.
People with HIV-2 often experience the same sort of symptoms as those with HIV-1. This includes developing what we call an ‘acute retroviral syndrome’ or an opportunistic infection. HIV-2 patients could have any opportunistic infection, including oral thrush, pneumonia caused by Pneumocystis, cytomegalovirus, Kaposi sarcoma, tuberculosis, widespread mycobacterial infection, toxoplasmosis, and progressive multifocal leukoencephalopathy, among others.
A systematic evaluation for co-infection and concurrent opportunistic infection should be done as per the HIV-1 guidelines. It’s crucial to rule out dual infection with HIV-1 as part of the initial laboratory testing.
In a study examining HIV-2 patients in The Gambia, the most commonly seen AIDS-defining features at initial presentation were generalized wasting and pulmonary tuberculosis. However, these findings may not apply globally. Limited studies comparing frequency of opportunistic infections between HIV-1 and HIV-2 patients exist, but there’s some suggestion that encephalitis may be more prevalent in patients with HIV-2. It is not completely understood whether this disparity is due to longer survival times or differences in the ways that HIV-1 and HIV-2 affect the nervous system. Additionally, HIV-related kidney disease, which occurs in about 10% of HIV-1 patients, is seldom reported among HIV-2 cases.
Testing for HIV-2 Infection
In the past, diagnosing HIV-2, a type of Human Immunodeficiency Virus, was quite challenging. Some of these challenges had to do with identifying HIV antibodies and detecting the level of HIV-2 in the blood. Doctors used to rely on their clinical judgment to decide if someone needed to be tested for HIV-2. Some signs that might point to HIV-2 included a decrease in CD4 cells (essential components of our immune system) for someone already being treated for HIV-1, no detectable virus in the blood of an untreated HIV-positive patient, or infections often seen in West African populations.
Previous tests could identify HIV-1 and HIV-2 antibodies, but they couldn’t distinguish which type of the virus a person had. More conclusive tests, called western blots, were used to confirm diagnoses, but they often gave unclear results or wrongly identified a person with HIV-2 as having HIV-1.
Thankfully, a better HIV test, the 4th generation HIV-1/2 antigen-antibody test, is now widely used. This test can identify and distinguish between HIV-1 and HIV-2. As a result, in 2014, the Centers for Disease Control (CDC) updated guidelines for testing to improve HIV-2 diagnosis.
In 2018, the CDC made further updates to the testing guidelines that all doctors should use when interpreting HIV tests.
However, measuring the amount of HIV-2 in the blood, called viral load testing, is still not easy. Only two labs in the United States carry out this testing regularly. It’s important to note that up to 40% of people with HIV-2 have no detectable virus in their blood even without treatment, so viral load tests might not always give reliable results. They can be helpful in confirming an HIV-2 diagnosis and checking how well a treatment is working, but they can’t rule out an infection. Also, there are currently no available tests to determine the resistance of HIV-2 to different treatments.
Treatment Options for HIV-2 Infection
The aim of antiretroviral therapy (ART) in HIV-2, which is a type of HIV, is the same as HIV-1. These goals are to prevent the spreading of the disease, boost the immune system, suppress the virus for a long time, and decrease illness and death related to the disease. However, there is minimal scientific research that gives clear direction on when to start ART for HIV-2, which medications are most effective, or what combinations should be used if the virus still progresses despite treatment.
Most of the available guidance for managing HIV-2 comes from studies on HIV-1 patients. Despite this lack of direct evidence, it is evident that some of the combination therapies used for HIV-1 are also effective in treating HIV-2.
At present, it is recommended that all patients diagnosed with HIV-2 start ART as soon as possible. The first choice of treatment usually includes a combination of two types of drugs – nucleoside reverse transcriptase inhibitors (NRTIs), that block the virus’s ability to replicate, and either an integrase strand transfer inhibitor (INSTI) which blocks the virus from integrating into the cell’s DNA, or a protease inhibitor (PI) that stops the virus from assembling itself. The PI’s used are usually darunavir or lopinavir.
However, it is critical to know that HIV-2 is naturally resistant to all non-nucleoside reverse transcriptase inhibitors (NNRTI), another type of drug that blocks the virus’s ability to replicate, rendering them ineffective. Similarly, most PIs, besides darunavir, lopinavir, and saquinavir, are ineffective too. The fusion inhibitor (prevents the HIV virus from entering the cell) enfuvirtide also does not work against HIV-2 and should not be used. This resistance to certain drugs occurs because of natural variations in HIV-2 that result in the drugs not binding effectively to the sites they target in HIV-1, thus making them less effective or not effective at all.
When patients with HIV-2 start their treatment, they should be monitored the same way as those with HIV-1, except they don’t need a baseline resistance test. Doctors can monitor treatment progress by regularly checking the count of CD4 cells (a type of immune cell that the HIV virus attacks) and the amount of HIV-2 virus in the body, if this test is available. But, if the patient’s disease continues to progress or their CD4 count continues to decline, even though initial tests couldn’t detect the virus, this might indicate that the treatment is not working.
What else can HIV-2 Infection be?
When considering a diagnosis of HIV-2, various other conditions that may share risk factors or clinical signs need to be excluded. This list includes illnesses caused by sexually transmitted pathogens as well as infections that commonly happen in people with suppressed immune systems. Here are some of these conditions:
- HIV-1 infection
- Dual infection with HIV-1 and HIV-2
- Hepatitis B
- Hepatitis C
- Pneumonia caused by Pneumocystis jiroveci
- Encephalitis caused by Toxoplasma gondii
- Cryptosporidiosis
- Tuberculosis
- Non-tuberculosis mycobacterial Infection
- Bartonellosis
- Syphilis
- Mucocutaneous candidiasis
- Cryptococcosis
- Histoplasmosis
- Coccidioidomycosis
- Aspergillosis
- Cytomegalovirus infection
- Herpes simplex virus infection
- Varicella zoster virus infection
- Kaposi sarcoma (caused by Human herpesvirus-8)
- Progressive multifocal leukoencephalopathy
What to expect with HIV-2 Infection
There is limited information available concerning the long-term outcomes and quality of life for those living with HIV-2, as most studies conducted so far have been small. However, what research has been conducted indicates that patients with HIV-2 whose CD4 cell counts (which are a type of white blood cell that fights infection) remain above 500 cells/µL typically fare better than those with HIV-1 of the same age.
Addition studies reveal that when individuals with HIV-2 develop advanced disease, their mortality rates become similar to those with HIV-1 when adjusted for factors like CD4 cell count, age, and population demographics. What remains unclear presently due to limited data is whether the long-term mortality rates or non-AIDS-related health conditions are the same when comparing HIV-2 and HIV-1 patients who are on antiretroviral therapy (medication to manage HIV).
Possible Complications When Diagnosed with HIV-2 Infection
People with chronic HIV-2 infection typically experience similar complications to those with HIV-1. When the number of CD4 cells (important immune cells) drops below 200 cells per micro-liter in HIV-2 patients, they are vulnerable to opportunistic infections, just like those with HIV-1. Opportunistic infections are infections that take advantage of a weakened immune system and can be caused by organisms like Pneumocystis jiroveci and Toxoplasma gondii.
Starting antiretroviral therapy (ART) helps to rebuild the immune system and lowers the risk of these infections. Generally, the same preventative treatment is suggested for HIV-2 patients with CD4 counts under 200 cells per micro-liter. This is to prevent opportunistic infections, although there is no specific data from HIV-2 patient research.
So, in case of HIV-2, we can expect the following potential complications:
- Decreased CD4 cell count (below 200 cells/µL)
- Risk of developing opportunistic infections
- Specific infections by pathogens like Pneumocystis jiroveci and Toxoplasma gondii
To manage these complications, the following steps are usually advised:
- Initiating antiretroviral therapy (ART)
- Taking preventative treatment when CD4 count is below 200 cells/µL
Preventing HIV-2 Infection
The main way HIV-2 spreads is through sexual contact. If you’re at risk, it’s important to learn about safe ways to have sex and to get tested regularly. You’ll want to speak with someone who understands your background and respects you, so they can discuss ways you can reduce the risk based on your specific situation. If you use intravenous drugs – those that are taken by injecting into a vein – you should be offered additional advice to keep you from getting HIV-2 through the equipment you use.
Pre-exposure prophylaxis, known as PrEP, is a method used to prevent HIV infection. It involves taking medicines before being exposed to HIV. Even though there isn’t specific research on using PrEP for HIV-2, the drugs that are used in PrEP can work against both HIV-1 and HIV-2. So, it’s likely that it could be equally effective in preventing HIV-2. At present, we don’t know much about the success of using long-lasting injectable PrEP – a shot that’s administered to the body – for HIV-2. Still, recent experiments have shown that a drug called cabotegravir can work against HIV-2.
