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I. Introduction – An estimated 35.0 million persons live with HIV; 2.1 million new infections occurred and 1.5 million persons died of HIV in 2013 (World Health Organization, http://www.who.int/hiv/data/epi_core_dec2014.png?ua=1 ). Despite effective combination antiretroviral therapy (cART), less than one-quarter of patients can access these life-prolonging medications; and despite its effectiveness, cART does not normalize life expectancy, as premature aging, metabolic complications and chronic inflammation complicate HIV therapy.

HIV is incurable due to the presence of a latent viral reservoir. During the life cycle of the virus, HIV integrates into the host DNA. A subset of integrated HIV provirus remains transcriptionally silent, producing neither viral proteins nor viral progeny, until reactivation by various physiologic stimuli.

This latency of HIV allows some infected cells to escape immune detection and elimination, and these latently infected cells constitute the viral reservoir. The latent viral reservoir allows viral rebound within weeks of interruption of cART, 1, 2 where the magnitude of viral replication approaches that present pre-therapy.

• Although it was once thought that viral rebound occurred universally following therapy interruption, several recent reports challenge that paradigm.
• The “Berlin patient” successfully cleared HIV after two allogeneic transplants from a donor with homozygous CCR5Δ32 mutation, 3 and he has not rebounded HIV after nearly seven years.

This case likely represents a cure from HIV; yet other cases have been described where HIV rebound has been attenuated, or delayed. The “Mississippi” baby was a perinatally HIV-infected infant who initiated cART within hours of birth, and when interrupted eighteen months later, viremia remained undetectable for nearly two years.4 The Harvard BMT cases underwent allogeneic BMT, developed undetectable HIV DNA, yet rebounded viremia within only eight months after cART discontinuation.5 Together these cases demonstrate that control of viremia in the absence of cART is possible, if not durable.4 The VISCONTI cohort of 14 HIV-infected adults who initiated antiretroviral therapy during acute infection, and in whom high level rebound viremia had not occurred several years after cessation of therapy, 6 similarly demonstrated that viral rebound following cART interruption can be attenuated.

Why is it so hard to find a cure for HIV?

June marks the 40th anniversary of the first scientific report describing pneumocystis pneumonia, which later became known as acquired immune deficiency syndrome (AIDS), More than 32 million people have died worldwide from AIDS and 38 million people are living with HIV, the virus that causes AIDS, according to the Centers for Disease Control and Prevention.

“The last 40 years of the HIV epidemic have given us an in-depth look at society, science, medicine, and socioeconomic impacts of disease on communities and countries. Forty years ago was the very first report. Still, we didn’t even know what the causative agent was,” says Dr. Stacey Rizza, a Mayo Clinic infectious diseases physician and HIV researcher.

Unfortunately, the AIDS crisis of the 1980s was steeped in misinformation and discrimination, especially against gay men who were disproportionately affected by the disease. Much progress has been made since that time, but there is still more work to be done.

Being diagnosed with HIV/AIDS has a different meaning than it did just two decades ago, says Dr. Rizza. “It’s a whole new world, and, for those of us who are a little older and started treating HIV in the ‘90s and saw that world, it was tragic. We watched wonderful people who were brave and fought their virus but unfortunately, we weren’t able to stop the virus from replicating.” HIV is a sexually transmitted infection spread through contact with infected blood, semen or vaginal fluids.

The virus also can be spread by sharing drug needles and syringes, and less commonly from mother to child. Watch: Dr. Stacey Rizza talks about 40 years of HIV/AIDS research. Journalists: Broadcast-quality sound bites with Dr. Rizza are in the downloads at the end of the post.

• Please courtesy “Stacey Rizza, M.D.
• / Infectious Diseases / Mayo Clinic.” In this Q&A, Dr.
• Rizza provides some insight to understand the research and why AIDS is such a difficult disease to cure: What did the early research find? Because of truly dedicated innovative science, within a few years, the scientific community figured out that AIDS was due to HIV.

It then took a few years to figure out how to test for that virus. Several years later, the scientific community was able to quantitate how much virus was in a person’s blood. During all this time, truly innovative research into how the virus replicates and how the immune system responds to the virus allowed bio pharmacy companies to develop what we call anti-retroviral drugs or medications to slow down the viral replication. Then several other drugs within that same class were approved in the early 1990s. In late 1995, very early 1996, the first HIV protease inhibitors were approved. At that point, it was possible to combine three different medications from two different classes and completely suppress the HIV replication.

In the last 20 years, we’ve gone from people taking multiple medicines with lots of side effects to many of my patients with HIV now take a single pill a day. That’s a combination of medicines coformulated into one pill a day that’s extremely well-tolerated and completely suppresses their virus. We know it does not eliminate the virus.

If they were to stop taking that medicine, the virus would come back. But we now have a handful of people in the world who have been what we called functionally cured of HIV, meaning they’ve gone through some research protocols that eliminated the reservoir of HIV in their body.

• The new drugs are so effective in people who have fully suppressed virus that many only need to use two medications to maintain HIV treatment and control.
• New research is investigating ways to deliver the medications differently, such as a shot that lasts several months, or maybe someday even implantable medication delivery mechanisms so that people don’t have to take the pill every day.

It is very exciting that HIV therapy is moving that direction. Why isn’t there a cure for HIV? The reason why it is so difficult to cure HIV is that once HIV infects a person’s body, it integrates into the host genome of several cell types. Those cells then hide in any of the lymphoid tissue, such as the lymph nodes, the liver and the spleen.

1. And they lay there as what we call “latent” or “hiding”, as long as the person is on HIV therapy.
2. Anytime a virus does leave a cell, it gets taken care of by HIV therapy.
3. But if the infected individual stops the HIV therapy, that latent virus will come back.
4. To cure HIV, you have to eliminate those hiding viruses in the cells or that latent viral reservoir, which is the term.

There are many ways you can approach eliminating the reservoir. Where is the research now? One of the more popular ways that have been investigated is something called — and there are many different terms for it — “prime, shock, and kill” or “kick, and kill”, which is essentially giving medications that first wake the virus up from latency and then find ways to make the cells that have the virus susceptible to dying. Model of the HIV-specific cell death stimulus Casp8p41 binding to BH3 groove in Bc12 Essentially, it specifically targets the HIV-infected cells and eliminates them without hurting anything else. This new science is exciting. It’s getting closer and closer to understanding how to do this effectively.

And if you can do that with oral medications rather than fancy therapies like gene therapy or bone marrow transplant, it’s scalable to large parts of the world, and you can touch millions of people that way. That’s where the area of research is on how to make those hiding cells wake up, how to make them sensitive to die, and how to target just the HIV-infected cell.

Will we see a vaccine for HIV? HIV has been a very hard vaccine to develop. In the world of viruses, vaccines fall into one of three buckets. They fall into the bucket where they respond to antibodies induced by the vaccine, and the vaccines are outstanding.

1. Such viruses include polio, mumps, and lucky for us, SARS-CoV-2,
2. Then we have the second category, like the influenza vaccine, which is about 60% effective.
3. It certainly saves lives and makes a difference, but it’s not perfect.
4. And then we have the third bucket, which quite frankly is the vast majority of viruses that infect humans.

And HIV is in that category, where simply forming an antibody to the virus is not adequate to prevent infection. You have to do very sophisticated engineering to induce T cell effects, as well as innate effects and antibody effects. Even then, sometimes it’s very hard to decide what is the part of the virus to target.

• After decades, and billions of dollars of research, we’re still not there for HIV.
• There have been many approaches of how to do this science.
• Many different scientific delivery mechanisms, many different areas of the viruses targeted, many different parts of the immune system targeted, and so far, none of them have been effective at preventing HIV infection.

What needs to happen next? We still need to slow down the number of people getting infected through good public health measures and good education to stop the HIV epidemic. We still need to get more people who are infected on therapy. We know we can do it with public health measures.

• But we also need to find out more about how we eliminate that reservoir and get people cured of the virus in a simple and effective way so that we can cure more people.
• And the last major hurdle we have is to develop an effective vaccine.
• We still don’t have a vaccine that can prevent infection, a preventive vaccine, or a therapeutic vaccine where you give it to people who already have the virus that can help them control the infection.

A huge amount of research has happened, but we’re still not there yet. Read more:

HIV research at Mayo Clinic, Learn more about clinical trials. HIV testing

For the safety of its patients, staff and visitors, Mayo Clinic has strict masking policies in place. Anyone shown without a mask was recorded prior to COVID-19 or recorded in an area not designated for patient care, where social distancing and other safety protocols were followed.

Will we ever be able to cure HIV?

This article was originally published in April 2020 and has since been updated to reflect the latest developments in HIV research. HIV research has come a long way since the virus was discovered in the 1980s. Antiretroviral therapy was a major milestone that has changed the lives of millions; the goal now is to find an HIV cure.

Back in 2008, Timothy Ray Brown was the first person to be cured of HIV. Known as the “Berlin patient”, Brown received two bone marrow transplants from a donor who was naturally resistant to HIV to treat his leukemia. He remained off antiretroviral therapy until his death in 2020. When the case was announced, the medical world went nuts.

Had we finally achieved an HIV cure? Unfortunately, the answer remains not yet. Since then only four other people have been reported to remain off antiretroviral therapy thanks to a similar transplant. However, bone marrow transplants carry very high risks for HIV-positive patients, and HIV-resistant donors are rare.

How close are they to a cure for HIV?

CONCLUSION – There are many other trials that are also going on throughout the world. Enumerating all is beyond the purview of this article. Newer reports coming daily have encouraging outcome. Some of these trials are nearing the winning post. We could expect a sterilizing cure for HIV disease within another 5–10 years.

Why is HIV forever?

HIV and AIDS: Know the Facts Treatments Work, but Prevention Is Key It’s been more than 30 years since a disease now called AIDS was first recognized in the United States. Back then, it was considered a death sentence. No treatments were available, its cause was unknown, and people often died within a few months after being diagnosed.

Today, people infected with HIV—the virus that causes AIDS—can live full, healthy lives, in large part because of medicines and other discoveries made with NIH support. The terms HIV and AIDS can be confusing, because they’re related but different. HIV is a virus that harms your immune system The cells and tissues that protect your body from invading viruses, bacteria, and other microscopic threats.

by invading and then destroying your infection-fighting white blood cells. AIDS is the final stage of an untreated HIV infection. People with AIDS can have a range of symptoms, because their weakened immune systems put them at risk for life-threatening infections and cancers.

1. HIV virus passes from one person to another through certain body fluids, such as blood and semen.
2. About 90% of new HIV infections in the U.S.
3. Occur during sex.
4. Shared needles and injection drug use is the second most common route of infection.
5. HIV can also spread from an infected mother to her newborn.
6. HIV isn’t spread through casual contact, such as shaking hands, hugging, sneezing, sharing utensils, or using bathrooms.

Today, by taking a combination of HIV-fighting medicines (called antiretroviral therapy), fewer Americans with HIV are developing AIDS. And some HIV infections can now be prevented by taking daily medications (called PrEP). Because of these advances, some people may think that there’s little need to be concerned about HIV and AIDS.

But nothing could be further from the truth. Nationwide, more than 1 million people are infected with HIV, and each year over 50,000 more become newly infected. About 1 in 7 Americans who have HIV don’t even realize they’re infected, so they may be unknowingly spreading the virus to others. The problem is even more severe in developing nations, especially in parts of Africa.

Even though treatments and prevention strategies can keep HIV in check, there’s still no cure and no vaccine to prevent HIV infections. That’s why NIH-funded scientists continue to search for new, more effective ways to halt HIV infections. “If you get a diagnosis of HIV infection, and you begin antiretroviral therapy in a timely fashion, before your immune system becomes substantially compromised, your prognosis The likely outcome of a disease, including your chances for survival.

Is excellent,” says Dr. Anthony S. Fauci, NIH’s infectious disease chief, who first began treating AIDS patients in the early 1980s. Studies show that with early treatment, HIV levels may become so low that the virus becomes undetectable in the blood. That lengthens life and reduces the risk of spreading HIV to others.

“If those who are infected stay on therapy, they can save their own lives and also help keep HIV from infecting their sexual partners,” Fauci says. Keeping HIV infections in check requires early diagnosis and taking daily HIV medications for life. Even if it’s undetectable in the blood, once a person’s been infected with HIV, it remains forever hidden in the body.

1. HIV has the ability to integrate itself into your cells and hide in an inactive form, called a reservoir,” says Fauci.
2. Although medicines can keep virus levels low, they don’t clear out the viral reservoir.
3. So if treatment lapses, HIV comes out of hiding and rushes back into the bloodstream.
4. For some people, keeping up with this daily health regimen can be a challenge.

Nationwide, fewer than 1 in 3 people with HIV takes antiretroviral medicines regularly enough to reduce the virus to undetectable levels. That’s why ongoing NIH-funded studies are creating and evaluating medications that might be taken less often, such as once a month.

1. This approach will be tested in a large clinical trial expected to begin in Africa later this year.
2. Other approaches that don’t depend on daily anti-HIV drugs are also being tested.
3. Research over the past few decades has identified preventive strategies that work: limit your number of sexual partners, never share needles, and use condoms correctly and regularly.

NIH is also exploring new ways to prevent HIV infections, including experimental vaccines. One preventive approach for people at increased risk for HIV infection involves taking a daily dose of an antiretroviral drug. “In terms of prevention, a game-changer that we’ve got right now is pre-exposure prophylaxis, or PrEP,” says Dr.

Carl W. Dieffenbach, who heads NIH’s global research efforts in HIV/AIDS. “This strategy protects you from getting infected with HIV if you take the medication daily.” A pill form of PrEP (called Truvada) is approved by the U.S. Food and Drug Administration for people at high risk of getting HIV. Truvada combines 2 antiretroviral drugs already used to treat HIV infections.

When it comes to treatment and prevention, Dieffenbach says, “the most important activity that you can engage in is first getting an HIV test.” Your health care provider, community health clinic, and others may offer quick HIV tests, often at no cost to you.

1. The U.S. Centers for Disease Control and Prevention recommends at least a yearly HIV screening for people considered at high risk for infection.
2. Testing is especially important for young people from ages 13 to 24, because more than half in that age group who tested positive for HIV didn’t know they’d been infected.

Some people avoid getting tested because they’re afraid of the possibility of being HIV-positive. Others may feel embarrassed or uncomfortable talking about sexual issues, and so they don’t get tested. But the earlier HIV is diagnosed and treated, the better the outcome.

The stigma Being viewed in a negative way because of a medical condition or other characteristic. associated with HIV infection makes it difficult for some people who are at risk to come forward and either be counseled about how to avoid infection, or if they are infected, to get into a health care system and stay in the health care system,” Fauci says.

But studies show that open communication can help people treat and prevent HIV. “The stigma problem can only be solved one person or one family at a time, because each person’s situation is unique,” Dieffenbach says. “It’s about continuing a conversation with openness and acceptance in communities.