April 18, 17
Frequently Asked Questions
Human Immunodeficiency Virus (HIV) is a viral infection which, left untreated, leads to Acquired Immunodeficiency Syndrome (AIDS), the final stage of an HIV infection. Once you are infected with HIV, the virus integrates itself into the human genome. Thus, once you have HIV, you have it for the rest of your life. HIV attacks the body’s immune system, specifically CD4+ cells (otherwise known as helper T cells) which help the human body fight off infections and tumors. HIV can destroy so many of these cells that the immune system is rendered nonfunctional, leaving you extraordinarily prone to infections and cancers; even ones that can’t infect humans normally.
The onset of these “opportunistic infections” signals that the HIV infection has progressed to AIDS. A person is also considered to have AIDS once the concentration of CD4+ cells in their blood falls below 200 cells per cubic millimeter of blood (normal CD4+ cell counts are between 500 and 1200 cells/mm3). AIDS is the final stage of an HIV infection and typically leads to death in 1 to 3 years if left untreated. There are approximately 37 million people in the world with HIV and about 2 million people are infected each year. Sub-Saharan Africa accounts for 70% of new cases. 
HIV can be transmitted whenever a bodily fluid (specifically blood, semen, pre-seminal fluid, rectal fluid, vaginal fluid, or breast milk) of an HIV-positive individual comes into contact with a mucous membrane (mucous membranes can be found in the rectum, penis, vagina, and mouth), damaged tissue, or blood of an uninfected individual (e.g. from a needle or syringe).
In the United States, HIV is most commonly transmitted through having anal or vaginal sex without using a condom or by sharing needles. In extremely rare cases HIV can be transmitted through oral sex, contact between broken skin and/or open wounds, or open mouth kissing in which both individuals have open sores in their mouths (HIV can not be spread by saliva). HIV can also be transmitted via blood transfusions though this is incredibly uncommon due to the strict regulations and testing of blood donations in the United States. In addition, HIV can be transmitted from mother to child during pregnancy, childbirth, or breastfeeding; though with proper medical care during pregnancy this is also extremely rare.
It is important to note that HIV is not a highly contagious disease and can only be transmitted through intimate contact (that is, having sex of any kind, giving birth, breastfeeding, or sharing needles) and can not be transmitted through hugging, kissing, sneezing, coughing, sweat, tears, a toilet seat used by someone with HIV, or insects such as mosquitoes.
Once HIV gets into the human body it immediately begins to attack the immune system, specifically CD4+ cells or helper T cells (CD4+ is the name of a protein on the surface of T helper cells). The virus gets inside the CD4+ cell without hurting it, though once it gets inside the cell it inserts its genetic material into the cell’s DNA. The virus then creates thousands of other HIV cells using the host cell’s replication machinery. HIV continues to hijack the cell until the cell either ruptures or self-destructs. CD4+ cells are integral to how we fight off infections because they send out the signal that there is an invader in the body and recruit other types of immune cells to fight off the infection. Therefore, because of lower CD4+ cell counts in the body the immune system is compromised. As the HIV infection progresses it increasingly destroys CD4+ cells until the host has no functional immune system. This indicates that the infection has progressed to Acquired Immune Deficiency Syndrome (AIDS).
There are three main stages of an HIV infection:
1.) Acute HIV (3-12 weeks): When someone gets infected with HIV they often do not show symptoms for three to four weeks, reinforcing why it is so important to get tested for HIV regularly. About a month into the infection flu-like symptoms develop, marking the primary infection of HIV. These flu-like symptoms can range anywhere between mild and severe, with some people not experiencing any symptoms at all. At this point, CD4+ counts plummet and the viral load (how many viruses are in the body) soars. Persons infected with HIV are most likely to transmit the disease to others at this point due to their high viral load.
2.) Latent Asymptomatic HIV (8-10 years if left untreated): Within a few weeks of the primary HIV infection the body starts making anti-HIV antibodies which begin to fight off the infection. As the immune system fights off the infection CD4+ counts rise and the viral load decreases until they reach an equilibrium. During this stage there are no symptoms of HIV detectable. This indicates that the infection has progressed to the asymptomatic stage. An individual in the latent/asymptomatic stage of HIV is considered to have chronic HIV because they will stay in this stage for 8-10 years before progressing to AIDS if they are not treated. People undergoing a treatment such as highly active antiretroviral therapy (HAART) essentially stay in this stage of the infection for the rest of their lives. Although there are no symptoms of HIV during this stage, HIV can still be transmitted.
3.) Acquired Immunodeficiency Syndrome (1-3 years if left untreated): Although there are no symptoms of an infection during the latent stage of HIV, the body is slowly losing its battle against the virus. If left untreated, within 8 to 10 years of the primary infection CD4+ cell counts will drop to a point where the person infected is considered to have no functional immune system leaving the person especially prone to infections and cancers. A person is considered to have acquired immunodeficiency syndrome (AIDS) at the onset of an AIDS defining illness or when their CD4+ cell count drops lower than 200 cells per square millimeter of blood. An AIDS defining illness is an opportunistic infection that would not be able to infect a healthy individual but can infect those with AIDS, e.g. fungal pneumonia which is harmless to healthy humans but 90% lethal to those with AIDS.
Our immune systems come into contact with opportunistic pathogens every day, and while healthy immune systems can easily fight them off they can be lethal to those with an immunodeficiency disorder such as AIDS. People with AIDS often experience fevers, chills, night sweats, swollen glands and lymph nodes, severe vomiting and diarrhea, sores on the mouth and genitals, and severe weight loss and fatigue due to the body expending extraneous amounts of energy to fight off the infection. Those with AIDS typically die within 1 to 3 years of diagnosis due to a lethal opportunistic infection
Once you are infected with HIV the virus immediately incorporates itself into your own genetic material, so once you are diagnosed with HIV you have it for life. However, there are several therapies that can greatly reduce the effects of HIV, improve quality of life for HIV-positive individuals, and prevent the development of AIDS.
Post exposure prophylaxis drugs (PEP’s) offer a single to chance to protect yourself from an HIV infection after an exposure. PEP therapy must start very soon after the initial exposure to HIV and requires taking antiretroviral drugs (ARV’s) every day for a month. Strict adherence to each daily regimen of ARV’s is critical to the success of PEP therapy, otherwise the virus may begin to replicate and spread. If PEP’s are unsuccessful, you may be diagnosed with HIV. If started within three days of the initial exposure, a completed 28 day regimen of PEP’s can reduce the chance of infection by as much as 80%.
Most commonly, chronic HIV is treated with highly active antiretroviral therapy (HAART). HAART is a long term therapy for HIV which involves taking several combinations of HIV drugs, such as ARV’s, which prevent the virus from replicating within the immune system. This lowers the amount of viruses and increases the amount of CD4+ cells in your body. Even though your body still retains HIV in HIV reservoirs (places in your body where HIV can lay dormant indefinitely), HAART gives your immune system enough of a break that it is able to proficiently fight off infections and cancers. Additionally, lower amounts of HIV in your body during HAART treatment also lowers your chances of transmitting HIV to others.Essentially, HAART suspends HIV-infected individuals in the latent stage of HIV, preventing the infection from progressing to AIDS. Just as with post exposure prophylaxis drugs, if you are diagnosed with HIV is is imperative to strictly adhere to each daily regimen of ARV’s or else the infection may spread or progress towards AIDS.
There is currently no cure for HIV/AIDS so once you are infected it is imperative that you adhere to your therapeutic regimens so that the infection does not progress more rapidly. Some people may experience severe side effects while taking PEP’s or undergoing HAART. Even if a drug works initially it may weaken over time or stop working all together for some people. However, these treatments work successfully for the vast majority of people without any side effects. People undergoing HAART who stick to their regimens most often have normal or even above average life expectancies.
HIV can be transmitted whenever intimate contact is made with someone who has HIV. Intimate contact is defined as sex of any kind, pregnancy, childbirth, breastfeeding, or sharing needles/any equipment used to prepare drugs for injection. If you are sexually active you can protect yourself from HIV by:
1.) Always using a condom and using condoms correctly
2.) Using water-based lubricants instead of oil-based lubricants (oil based lubricants weaken latex, increasing the chances of a condom rupturing)
3.) Limiting your number of sexual partners, therefore reducing the risk of having an HIV-positive sexual partner, and
4.) Getting tested for HIV regularly (once a year or whenever you have sex with someone who is HIV-positive).
In addition to practicing safe sex, it is imperative to practice safe drug use by never sharing anything used to prepare drugs for injection (needles, syringes, spoons, eyedroppers, etc.). Persons who are especially prone to HIV may also be prescribed a pre-exposure prophylaxis (PrEP) drug such as TruvadaⓇ which can greatly reduce one’s risk of contracting HIV. If you think you recently have been exposed to HIV, post-exposure prophylaxis drugs (PEP’s) can be effective in emergency situations if administered within 72 hours of exposure.
1 in 8 people who have HIV in the United States are unaware that they are infected. During the first stage of an HIV infection, people can experience mild to severe flu-like symptoms for two to three weeks that often go unnoticed. After that, HIV-positive persons can experience no symptoms for up to 10 years before developing AIDS. Thus, if you think you may have been exposed to HIV at any point the only way to know for sure if HIV was transmitted to you is to get tested. It is suggested that you get tested for HIV after having sex with an HIV-positive individual and at least once a year if you are sexually active. Although the Ragon Institute does NOT offer HIV testing there are several ways to find a place near you that offers confidential HIV testing.
1.) Visit GetTested.cdc.gov
2.) Text your ZIP code to KNOW IT (566948), or
3.) Call 1-800-CDC-INFO (1-800-232-4636).
HIV most likely evolved from SIV (simian immunodeficiency virus) which infects the immune systems of chimpanzees much in the same way that HIV infects the immune systems of humans. In 1999 scientists discovered a strain of SIV (SIVcpz) in chimpanzees in West Africa that is almost identical to HIV-1, the strain of HIV responsible for the global HIV pandemic.  HIV-2, the less common and less infectious strain of HIV comes from SIVsmm which can be found in sooty mangabey monkeys.
Most scientists accept the “hunter theory” of the jump from SIV to HIV. Most likely, SIV crossed from chimps and mangabeys to humans through the hunting, butchering, and consumption of these animals (processes which allow for the exchange of blood). In most cases the human immune system would easily fight off SIV, but in a few people the virus mutated into what we now know as HIV.
The virus was most likely first transmitted to humans around 1920 in Kinshasa, the capital of the Democratic Republic of Congo. As a result, Kinshasa now has the most genetically diverse strains of HIV in the world. Since its inception in the 1920’s, HIV has spread to every human-inhabited continent and has infected over 75 million people.
The innovation of antiretroviral therapy (ART) coupled with increased accessibility to treatment in the areas most affected by HIV has saved the lives of an estimated 7.8 million people between 2000 and 2014. Nevertheless, in 2014 1.2 million people died from HIV, sub-Saharan Africa contributing to about 70% of the deaths.
Creating an HIV vaccine has remained elusive to immunologists since HIV research began over thirty years ago. Most vaccines take anywhere between ten to twenty years to create and refine before being distributed to the general public. However, HIV has several components that has made creating an HIV vaccine virtually impossible over the past three decades.
First, upon transmission HIV immediately incorporates its genome into your DNA. So, once you are infected with HIV, it is inextricably weaved into your DNA for the rest of your life. Furthermore, your body can not build up a natural immunity to HIV like it can for diseases such as chickenpox. When you are initially infected with chickenpox your body can easily overcome the infection after about one week. After that you are immune to chickenpox for the rest of your life. Unlike chickenpox, your body cannot create a natural immunity to HIV. Although you may be able to control an HIV infection using antiretroviral therapy, there is no way to eradicate the virus from your system or prevent it from ever coming back completely.
Even after HAART is discontinued, HIV can lay hidden in the DNA of certain cells throughout the body called HIV reservoirs. HIV reservoirs can be found in the brain, lymphoid tissue, bone marrow, and the genital tract, and while HAART depletes these reservoirs, it does so very slowly. Some researchers predict that it can take up to 80 years of constant HAART to fully deplete all HIV reservoirs. HIV also infects and destroys CD4+ cells which play an integral role in the immune system. Thus, HIV poses a confounding catch-22 to the immune system. As the infection intensifies and kills more CD4+ cells there are less CD4+ cells to fight off the infection.
In addition to HIV’s astounding ability to escape the human immune system, HIV has many subsets of viruses which vary dramatically by geographic region. For frame of reference, the gargantuan genetic diversity of influenza pales in comparison to that of HIV. Nevertheless, a new influenza vaccine must be made every year to fight new strains of the virus (and many times those vaccines do not work well). Thus, it should come as no surprise that an HIV vaccine has remained elusive to immunologists since the start of the epidemic thirty years ago. Scientists have also yet to discover a model organism for studying HIV that accurately predicts vaccine efficiency in humans. Most of the time treatments that are successful in mice and non-human primates do not translate to humans.
Founded with a commitment of $100 million from Mr. and Mrs. Ragon, the Ragon Institute of MGH, MIT, and Harvard has dual missions to contribute to the accelerated discovery of an HIV/AIDS vaccine and subsequently to establish itself as a world leader in the collaborative study of immunology. The Ragon Institute creates a singular opportunity and environment to engage scientists, engineers and clinicians in challenging research for which there may be no greater benefit–saving lives and curing the ill.
Unlike most institutions, the Ragon Institute creates nontraditional partnerships among experts with different yet complementary backgrounds including engineers, immunologists, clinicians, computational biologists, and immunogeneticists allowing for the integration of key facets of current vaccine development efforts that have tended to follow separate tracks (e.g. a combined T cell and antibody solution to HIV). Furthermore, the Ragon Institute provides a means for rapidly funding promising studies and emerging concepts in the field such as elite controllers, innovative viral vectors, and innate immune system memory. In summary, the Ragon Institute provides a substantial pool of accessible, flexible funding that allows scientists to pursue risky, unconventional avenues of study that are unlikely to attract funding from traditional sources. Such funding combined with the backing of nontraditional interdisciplinary partnerships in HIV/AIDS research encourages innovation and compresses the time it takes to conduct translational research towards a cure for HIV.
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