Information

Can people with AIDS/HIV be vaccinated?


If there is no immune system,it seems like vaccines wouldn't do much since there is no adaptive immune system to develop antibodies and memory cells. But can people with AIDS/HIV still be vaccinated? It is expected that a normal person will have antibodies to attack the minimal infection produced by the vaccine and generate memory cells, but without an immune system I expect vaccines to be deadly.

Is that right?


Can people with AIDS/HIV be vaccinated?

Yes. Immunization is an important part of the overall treatment strategy for HIV positive individuals. HIV infection is a risk factor for a number of vaccine preventable infectious diseases. Immunization in these patients is particularly important because of their increased risk of developing disease. (See Cecil Medicine Ch 396)

Can the immune system still mount a response to the vaccine?

Yes. HIV infection does lead to a decreased immune response. Though the primary deficiency is a decrease in both CD4+ (helper) T-cell count and function, there is, perhaps consequently, B-cell dysfunction as well. This would suggest that vaccines are less immunogenic. When this is studied directly, as would be expected, we see that vaccines are less immunogenic, but they are still effective.

Which vaccines are given?

Specific recommendations are based on both the age of the individual and their immune status. As a rule, vaccines are more effective when given early in the natural history of an HIV infection or after immune reconstitution with HAART, but there is some effectiveness and little risk of heat killed or subunit only vaccines even in highly immunosuppressed individuals. While live attenuated vaccines are contraindicated in individuals with a CD4+ cell count below 200, these vaccines are given routinely to other HIV positive patients. Current guidelines are found here. Here is the main figure from those guidelines:


Can people with HIV still be vaccinated?

  • No (most of the time) if the vaccine is an attenuated vaccine, this means it contains living organisms that have been modified in order to reduce their virulence. The reduction would keep a healthy individual unharmed while still inducing an immune response to form antibodies, however it is considered dangerous to administer these kinds of vaccines to HIV positive people. Some physicians will decide to administer these kinds of vaccines if the patient has had excellent control of his/her disease and is strong enough to take for example, the influenza virus vaccine without any major complications.

  • Yes if the vaccine is not an attenuated vaccine. Being HIV positive doesn't mean "no immune system" right away. The damage to the immune system goes in function with the viral load and the CD4 count; if the viral load is low the HIV positive individual can still benefit from vaccination, moreover he should be vaccinated because he is more exposed to infections than an average person.

source: HIV InSite, University of California San Francisco.

I would suggest also reading more about CD4 count in HIV patients and viral HIV load.


A person with AIDS cannot be vaccinated. The immune system is no longer functional and is unable to mount an immune response to your vaccine.

If the vaccine is a "live vaccine", the person will get a dose of viruses that body can no longer fight against. And the live vaccine would probably give the AIDS patient an infection of what the vaccine was suppose to protect against

However if the vaccine is an attenuated vaccine (which is the case for most vaccines made today), then all your be introducing into the body is parts and pieces of a virus or bacteria. These piece can trigger an immune response in a healthy person but as they just pieces, are not a live cell or a functional virus. So in a person with AIDS, the attenuated vaccine will be harmless.

A person with HIV can be vaccinated. The HIV virus is in the body multiplying. However the immune system while damaged is still functional.


When To Immunize Your HIV-Infected Child?

The information on this page is the recommended immunization schedule for HIV-infected children, adapted from the 1999 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected with HIV (updated May 14, 1999). This schedule also applies to children born to HIV-infected mothers, in which the child's HIV infection status has not been determined.

Vaccine recommendations for immunosuppressed children

Vaccine recommendations for all children

(those immunocompetent and immunocompromised)

HB vaccination consists of three doses. The second dose should be administered at least one month after the first dose, and the third dose should be administered at least four months after the first dose and at least two months after the second dose (Dose 1 at birth Dose 2 at one month and Dose 3 at six months).

Infants born to HB-positive mothers should receive HB immune globulin and be vaccinated within 12 hours after birth. Infants born to mothers whose HB status is unknown should also be vaccinated within 12 hours after birth. If the mother is found to be HB-positive, the infant should receive HB immune globulin no later than one week of age. Infants born to HB-negative mothers should be vaccinated after birth. Children and adolescents who have not been vaccinated against HB in infancy may begin the series during any childhood visit.


How HIV Hampers Vaccine Development

From the most fundamental standpoint, efforts to develop an HIV vaccine have been hampered by the genetic diversity of the virus itself. The replication cycle of HIV is not only fast (a little more than 24 hours) but is prone to frequent errors, churning out mutated copies of itself which recombine into new strains as the virus is passed from person to person. Developing a single vaccine able to eradicate over 60 dominants strains as well as the multitude of recombinant strains—and on a global level—becomes all the more challenging when conventional vaccines can only protect against a limited number of viral strains.

Secondly, fighting HIV demands a robust response from the immune system, and this again where systems fail. Traditionally, specialized white blood cells called CD4 T-cells initiate the response by signaling killer cells to the site of the infection. Ironically, these are the very cells that HIV targets for infection. By doing so, HIV hobbles the body’s ability to defend itself as the CD4 population is systematically depleted, resulting in the eventual breakdown of defenses called immune exhaustion.

Finally, the eradication of HIV is thwarted by the virus’ ability to hide from the body’s immune defenses. Soon after infection, while other HIV is circulating freely in the bloodstream, a subset of virus (called provirus) embeds itself in hidden cellular sanctuaries (called latent reservoirs). Once inside these cells, HIV is shielded from detection.

Instead of infecting and killing the host cell, latent HIV divides alongside the host with its genetic material intact. This means that even if free circulating HIV is killed, the "hidden" HIV has the potential to reactive and start infection anew.


Transmission of HIV

HIV is considered to be a sexually transmitted infection (STI) because that is its most common mode of transmission. However, unlike some other pathogens that cause STIs, HIV is also commonly transmitted through nonsexual contact with HIV-contaminated blood and from HIV-infected mothers to their children.

Sexual Transmission

The majority of all HIV transmissions worldwide occur through sexual contact. Of these cases, most are the result of heterosexual contact. However, the pattern of transmission varies geographically. In the United States, HIV is transmitted more often in men who have sex with men. The risk of transmission from anal intercourse is especially high, whereas the risk of transmission from oral sex is relatively low.

The risk of HIV transmission increases when people are already infected with other sexually transmitted infections, and especially when they have open sores on their genitals. In fact, the presence of genital sores increases the risk of transmission by about fivefold. The risk of transmission is also greater during the early months of infection when infected people usually have the greatest viral load. Viral load refers to the amount of virus in a sample of an infected individual&rsquos blood.

Transmission Through Contaminated Blood

The second most frequent mode of HIV transmission is via contaminated blood and blood products. Blood-borne transmission can occur through needle sharing during intravenous drug use, needle-stick injury in health professionals, transfusion of contaminated blood or blood products, or medical injections with unsterilized equipment. Theoretically, giving or receiving tattoos or piercings can also transmit HIV, but no confirmed cases have been documented. It is not possible for mosquitoes or other blood-sucking insects to transmit HIV.

In 2009 in the United States, intravenous drug users made up 12 percent of all new cases of HIV, and in some areas, more than 80 percent of people who injected drugs were infected with HIV. In rich nations, the risk of acquiring HIV from a blood transfusion is now virtually nil because of careful screening of blood donors and blood products. In poor nations, on the other hand, screening is less rigorous therefore, rates of transmission through contaminated blood are higher. Unsafe medical injections and invasive medical procedures are also a significant mode of transmission in poor nations, particularly in sub-Saharan Africa. While it is possible to acquire HIV from the infected organ or tissue transplantation, this is rare because of screening.

Figure (PageIndex<2>): A young individual on a poster. The writing on the poster says, "If you're dabbling in drugs you could be dabbling with your life."This 1989 poster from the CDC highlighted the association between injected drug use and the threat of HIV infection and AIDS

Mother-to-Child Transmission

The third most common way HIV is transmitted worldwide is from an untreated mother to her child during pregnancy, childbirth, or breastfeeding. If the mother is infected with HIV, there is about a 15% chance that the virus will be transmitted to her infant through her breast milk. The transmission of pathogens from one generation to the next in these ways is called vertical transmission. This mode of transmission accounts for most cases of HIV infection in children.


Is the COVID-19 Vaccine Safe for People With HIV?

While neither Pfizer nor the CDC has stated that the vaccine is unsafe for people with HIV, neither body has commented with certainty that it is safe, either. That’s because although 120 people with HIV participated in the phase 2 and 3 trials, Pfizer did not present separate data for them, stating that the sample population was too small.

A report from the Vaccines and Related Biological Products Advisory Committee meeting on Dec. 10 notes the challenge of drawing conclusions regarding efficacy, not safety, involving immunocompromised individuals, using PLWH as an example.

The report states: “Although the proportion of participants at high risk of severe COVID-19 is adequate for the overall evaluation of safety in the available follow-up period, the subset of certain groups such as immunocompromised individuals (e.g., those with HIV/AIDS) is too small to evaluate efficacy outcomes.”

And, too, the official emergency use authorization (EUA) indication is fairly general—though importantly, it does not list HIV as one of the contraindications (i.e., a reason to avoid receiving the vaccine). However, immunocompromised people are referenced in a warning: “Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to the Pfizer-BioNTech COVID-19 vaccine.” (The term “immunocompromised” is still often used to describe people living with HIV, though it is often not considered to apply to people with an undetectable viral load or high CD4 count.)

Still, that warning does not exempt immunocompromised people from getting the vaccine, according to both the CDC and Pfizer. In a meeting of ACIP on Dec. 12, CDC medical officer Sarah Mbaeyi, M.D., M.P.H., stated that, unless there is a contraindication, people living with HIV should get the COVID-19 vaccine, especially given that “people with HIV infection, or other immunocompromising conditions, or who take immunocompromising medications or therapies, might be at increased risk for severe COVID-19.”

Both Mbaeyi and Pfizer stated that the EUA warning should not be considered as a contraindication. Although the FDA is requiring relevant post-authorization studies to provide more information about the effect of the COVID-19 vaccine on people with HIV, it does not specify that this additional research is required to ensure safety in people living with HIV.


Clinical trial brings an effective HIV vaccine a step closer

Researchers have taken the first step toward developing a novel type of vaccine regimen that could protect people against HIV.

The virus, which progressively weakens the immune system, affects about 38 million people worldwide.

Highly effective antiviral treatments for HIV are available, but those living with the virus must take them for the rest of their life, and the long-term health effects of infection remain challenging.

In addition, access to prevention and treatment services is limited in some parts of the world.

The World Health Organization (WHO) estimates that, as a result, there were 1.7 million new infections with HIV in 2019, and 690,000 people died from HIV-related causes.

Despite decades of work, scientists have failed to develop an effective vaccine against the virus.

The reason for this is that most of the surface of the virus is densely coated with sugar molecules that do not trigger an immune response, and the parts that are exposed are highly variable.

As with SARS-CoV-2, which is the virus that causes COVID-19, HIV uses spike proteins on its outer surface to gain entry to its host cells.

“The spike protein on HIV viruses is much more devious,” explains William Schief, Ph.D., a professor and immunologist at the Scripps Research Institute in La Jolla, CA, and executive director of the International AIDS Vaccine Initiative (IAVI).

As a result of the rapid mutation of the genes that make the spike, HIV has millions of different strains. Due to this, antibodies against one strain are unlikely to neutralize the others.

“And so HIV is not really one virus,” says Prof. Schief. “It’s really like 50 million different viruses around the world right now.”

However, researchers have known for some time that there are hard-to-access parts of the spike that do not change very much.

Antibodies that bind to these regions are known as broadly neutralizing antibodies (bnAbs) because, in theory, they could target a wide variety of HIV strains.

On rare occasions, people with HIV make these antibodies naturally.

This natural production gives scientists the opportunity to identify where the antibodies bind to the virus. With this knowledge, they can develop “immunogens” to use in vaccines.

The catch is that only a rare type of immature immune cell, known as a naive B cell, can develop into circulating B cells capable of making bnAbs against HIV.

Only about 1 in a million naive B cells have this potential, says Prof. Schief.

To overcome this issue, he and his colleagues at Scripps Research and IAVI used a technique called germline targeting to create a vaccine that activates these rare cells.

In a phase 1 clinical trial, the vaccine appeared to be safe, and it had the desired effect in nearly all of the volunteers who received it.

Researchers at George Washington University in Washington, D.C., and the Fred Hutchinson Cancer Research Center in Seattle, WA, recruited 48 healthy adult volunteers for the trial.

They gave the participants two doses of either the vaccine or a placebo.

The scientists report that the vaccine activated naive B cells in 97% of participants who received it.

“A holy grail of the HIV vaccine field is to elicit broadly neutralizing antibodies by vaccination. And here, we’ve shown in humans that we can start that process,” says Prof. Schief.

He presented the results at a virtual conference of the International AIDS Society HIV Research for Prevention on February 3, 2021.

It is worth noting that the trial was small and that the results have yet to be published in a scientific journal.

In addition, it is important to note that further research and several more clinical trials will be necessary to develop and test later stages in the vaccine regimen.


Superstition and science denial

Science has made considerable progress in understanding, treating, and preventing HIV/AIDS. But it has had to fight superstition and science denial every step of the way. There are still those who claim that poverty, not HIV, is the cause of AIDS, that anti-retroviral drugs are poisons, and that HIV tests are flawed. All kinds of untested, ineffective remedies have been proposed the infamous Dana Ullman even recommends homeopathy for AIDS. These people ignore the evidence or try to explain it away, sometimes with fatal results, as in the case of Christine Maggiore, who refused anti-retroviral treatment for herself and her 3-year-old daughter. They both died of AIDS. Herbal remedies have been used in place of effective drugs. Hundreds of thousands of South Africans died unnecessarily because science denial influenced public policy: the health minister, Dr. Manto Tshabalala-Msimang was an AIDS denialist who promoted dietary measures like lemons, garlic, and olive oil and denied effective drugs to patients in South Africa. She was known as Dr. Beetroot for one of her dietary AIDS cures.


I’m living with HIV and have had the COVID vaccine

I’m fully vaccinated against COVID-19. Isn’t that an extraordinary statement? Twelve months ago nobody had heard of COVID-19. Yet here I am with vaccine-induced antibodies that provide a significant level of protection against a virus that has caused so much illness, death, grief, hardship and loneliness, and made 2020 miserable.

I still can’t quite believe that I’ve benefited from a scientific and human achievement that, to my mind at least, ranks alongside the development of the effective HIV treatments which meant that I didn’t die a premature death in mid-1990s in my twenties but am alive and well today.

These medical breakthroughs are thanks to meticulously conducted clinical trials. Indeed, I know I’ve received both doses of the COVID vaccine because in early November I enrolled in a sub-study of the Oxford/AstraZeneca vaccine that was specifically designed to assess the vaccine’s safety and effectiveness in people with HIV. Everybody in the HIV sub-study has or will receive the vaccine. I received my first dose in the second week of November and the second four weeks later.

Clinical trial development

Clinical trials are essential to test the safety and effectiveness of experimental treatments and vaccines such as the one I’ve just received. After a promising therapy is developed in a lab, it goes through three separate studies to ensure that it won’t cause any serious harm and will be of real medical benefit. Only if it passes all three stages will a new therapy be evaluated by a group of independent experts to assess if it’s safe and effective and can receive a licence for use in the general public. The Oxford/AstraZeneca vaccine is on the verge of such approval.

Glossary

In HIV testing, when the person testing collects their own sample and performs the whole test themselves, including reading and interpreting the result.

The third and most definitive stage in the clinical evaluation of a new drug or intervention, typically a randomised control trial with the new intervention compared to an existing therapy or a placebo, in large numbers of participants (typically hundreds or thousands). Trial results are used to evaluate the overall risks and benefits of the drug and provide the information needed for regulatory approval.

The immune response is how your body recognises and defends itself against bacteria, viruses and substances that appear foreign and harmful, and even dysfunctional cells.

A patient’s agreement to take a test or a treatment. In medical ethics, an adult who has mental capacity always has the right to refuse.

A research study involving participants, usually to find out how well a new drug or treatment works in people and how safe it is.

By the time I joined the trial, the Oxford study was already in its final 'phase 3' research involving over 20,000 adults in Brazil, South Africa and the UK. The participants were divided at random into two equal groups. Researchers made sure the composition of the groups was comparable in terms of age, gender, race and underlying health conditions. One group received the experimental vaccine and the other a placebo (a dummy therapy, in this case a vaccine against meningitis that it known to be very safe). Rates of side effects and COVID were then compared between the two groups. At the outset, the researchers set strict criteria to ensure that the new treatment really if safe and works and that they couldn’t be accused of moving the goal posts if their study flung up some unexpected or unwelcome findings.

COVID vaccine HIV sub-study

The same rigorous procedures applied to the HIV sub-study I’m taking part in. I noticed a news item about it on aidsmap.com and immediately phoned the clinic conducting the trial. The process, although very friendly and relaxed, was rigorous from the outset and provided reassurance about the integrity and high ethical standards of the study I was about to sign up to.

Basic information on have COVID-19 vaccines been tested in people with HIV?

A nurse asked me some questions to see if I was eligible to take part (confirmed HIV infection, CD4 cell count above 350, undetectable viral load, taking HIV treatment). An appointment was then arranged for a 'screening visit' at the study clinic with one of the research doctors.

This lasted about an hour and a half. I had a physical examination and answered a seemingly endless set of questions about my health and medical history to make sure I really was eligible to take part in the study. The doctor then explained how the vaccine worked using a deactivated, harmless portion of the coronavirus to stimulate an immune response. The potential side effects were also explained: the main ones are pain at the injection site and feeling fluey for a day or two after being jabbed.

The doctor also provided detailed information about the reason the study was temporarily paused in the summer after a man receiving the experimental vaccine developed a rare nerve condition. However, an independent panel of experts concluded this wasn’t due to the vaccine and gave the green light for the trial to continue.

Importantly, the doctor also emphasised that although the global health emergency caused by COVID meant that vaccines against it were being developed by breakneck speed, corners were most definitely not being cut and the study included all the checks and safeguards that are standard when undertaking research into a new medical treatment.

I was then asked if I understood what I’d been told and had any questions and if I gave my consent to take part in the study.

After saying yes, I had blood tests to check my health. The results came back a week later and were satisfactory, thus enabling me to receive the first dose of the vaccine.

Other than very slight soreness where I was injected, I didn’t experience any side effects. I returned three and seven days after the jab for blood tests to make sure that the vaccine wasn’t having an impact on the health of my kidneys or liver. Everyday, I was emailed a link to an electronic diary and asked to record any side effects or symptoms, no matter how mild or unusual. I’ve had nothing to report.

Study results

Find out more: COVID-19 and coronavirus in people living with HIV

In the interval between my first and second doses, interim results from the main study were published showing that the vaccine was very safe and that it reduced the risk of serious COVID-related disease by 70% overall, including a 62% reduction in risk among people receiving the two full doses, increasing to 90% if an initial half dose was followed by a full dose. I was emailed a summary of these findings as soon as they were announced and given the opportunity to ask more questions at my next visit to the clinic.

Around the same time, results from studies of other vaccines were published showing 95% effectiveness. Was I disappointed that the vaccine I received had a seemingly lower rate of effectiveness? Not for one second! To be honest, its effectiveness surpassed my initial expectations and I’d have eagerly have signed up to the trial had I known this information at the outset. Moreover, the fact that not one single person receiving the Oxford/AstraZeneca vaccine who became infected with COVID needed to go into hospital was also massively encouraging.

A number of vaccines will, I’m sure, be needed to bring COVID under control and the one I’ve received will surely have its place.

Further checks to come

I’ll remain enrolled in the trial for months to come and will be regularly checked to see if I’m experiencing any side effects and every week I do a self-test to see if I’ve picked up the coronavirus.

At every stage of the study, I’ve been more than satisfied that the research has been conducted to the very highest standards, that nothing has been hidden about the vaccine’s side effects and protection, and that no corners have been cut in its development.

I get very emotional when I think about my participation in the trial and how lucky I am to be among the very first to know I’m fully vaccinated. Like so many others, I have had my world turned on its head because of COVID and have had many a sleepless night worrying about my job. A few weeks ago, I also experienced first hand the devastating human cost of this horrible virus, my dad dying after contracting the disease. It adds poignancy to my participation in the vaccine study and I’d like to thank the scientists, medics and all my fellow study volunteers for helping to develop vaccines that we can be confident are safe and work.

Much as I’m grief-stricken by the loss of my dad, the development and gradual rollout of the vaccines mean that we can all genuinely hope that 2021 will be both happier and healthier than the year we’ve just endured.


What the Recent HIV Vaccine Research Findings Really Mean

Several months into the rollout, vaccines are still very much on our radar. While that truly is a win for public health, last week there was widespread confusion over clinical trial findings first made public in February. According to several dramatic headlines and exuberant, widely shared social media posts, thanks to technology developed by Moderna for their Covid-19 vaccine, a highly effective HIV vaccine is well within reach &mdash like a modern-day public health fairytale.

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Unfortunately, that didn&rsquot happen. But some combination of misinterpreting the study&rsquos findings , and our ongoing thirst for vaccine news, resulted in that feel-good narrative going viral. (Sorry.)

Meanwhile, the actual results of that study do genuinely represent a significant breakthrough, bringing researchers one step closer to the development of vaccines not only for HIV, but other viral infections as well. Here&rsquos what to know about these legitimately exciting findings.

Confusion and vaccine enthusiasm aside, why are we talking about this research?

The short version is that this was the first clinical trial conducted on humans to successfully utilize an approach that primes the immune system to develop a specific type of antibody &mdash a key component of a future HIV vaccine.

Specifically, they found that 97 percent of the participants who received the vaccine had the immune response researchers were hoping for. (And yes, this approach was tested via two doses of a vaccine, which may have added to some of the confusion about the findings.)

How does this vaccine approach work?

Before getting into specifics of this particular clinical trial, it&rsquos important to have some context, says Dr. Mark Feinberg , the president and CEO of IAVI. Though he wasn&rsquot part of the research team that conducted this clinical trial, Feinberg has more than 20 years of experience researching HIV/AIDS, and the biology of other emerging diseases.

&ldquoIt is easier for the immune system to mount a potent effectively neutralizing antibody response to SARS-CoV-2 [than HIV],&rdquo he tells Rolling Stone . &ldquoIt is incredibly difficult to do with HIV, and that’s just due to fundamental differences in the viruses and the kinds of infections that they cause.&rdquo

This helps explain &mdash at least from a scientific perspective &mdash why researchers were able to develop multiple effective Covid-19 vaccines in less than a year, while research into an HIV vaccine has been going for decades. To date, no HIV vaccine study has been able to induce broadly neutralizing antibodies by vaccination &mdash something Feinberg and his colleagues believe is an integral part to developing an effective HIV vaccine. Broadly neutralizing antibodies (bnAbs) are rare but powerful specialized blood proteins that can counteract many different strains of a virus &mdash something especially important with HIV, which mutates far more frequently than other viruses.

&ldquoWe&rsquore worried about Covid [variants], but what Covid does in two months, HIV does in one day,&rdquo says Dr. Larry Corey, a virologist at Fred Hutchinson Cancer Research Center and co-founder of the HIV Vaccine Trials Network (HVTN) . In addition to his contributions to HIV research &mdash including the development of antiretroviral medications &mdash Corey was one of two scientists Dr. Anthony Fauci tapped to oversee the more than 80 clinical trial sites developing Covid-19 vaccine candidates during Operation Warp Speed .

As someone familiar with both viruses but not involved with IAVI G001, Corey explains that while developing an effective HIV vaccine is &ldquoa much more formidable challenge&rdquo than creating one for Covid-19, &ldquothis breakthrough was a good one.&rdquo

What exactly was that breakthrough?

The vaccine tested in the IAVI G001 clinical trial was specifically designed to activate certain cells that have the potential to produce bnAbs. &ldquoWe have to walk the immune system down this path to make broadly neutralizing antibodies,&rdquo Feinberg explains, noting that in 97 percent of the participants who received the vaccine, this approach &ldquoworked pretty much exactly the way we wanted it to work.&rdquo

Now, Feinberg says that researchers can shift their efforts towards achieving the next steps necessary to create an HIV vaccine.

Plus, researchers believe that this method of priming the immune system to produce bnAbs may also be applied to creating vaccines for other challenging pathogens like malaria, and the Zika and hepatitis C viruses. Similarly, Feinberg says that this approach also has the potential to play a role in developing a universal influenza vaccine &mdash as in, one that will work on most strains, making our annual flu shot significantly more effective.

How does Moderna and the Covid-19 vaccine fit into the picture?

The reports that this HIV vaccine breakthrough was only possible thanks to the mRNA technology Moderna invented when developing their Covid-19 vaccine is inaccurate for several reasons. First, the research into whether RNA-based vaccines could work for HIV began long before anyone had heard of SARS-CoV-2. &ldquoHIV [vaccine research] created the backbone and the wherewithal that allowed us to do such an incredibly terrific lift on Covid,&rdquo Corey explains. Additionally, while Moderna has partnered with the research team to develop and test an mRNA-based vaccine that uses this approach to produce bnAbs, that is for the next step in the process &mdash in other words, research that hasn&rsquot happened yet.

Having said that, moving forward into the next phases of the research into an effective HIV vaccine, the lessons learned and techniques perfected during the development of a Covid-19 vaccine will certainly be an asset. &ldquoHope springs that Covid teaching us how we do things will help us in HIV vaccines,&rdquo Corey says.

For one, utilizing RNA technology &mdash which uses a messenger (mRNA) that acts as a piece of genetic code, prompting the body to make a decoy protein that resembles the virus, in the hopes that the immune system will be tricked into attacking it, ultimately ending in the development of antibodies to fight off the virus &mdash is expected to speed up the pace of discovery and development efforts towards an HIV vaccine. &ldquoRNA technology is not going to, in and of itself, overcome the fundamental challenges to making an HIV vaccine &mdash those are going to be the same,&rdquo Feinberg explains. &ldquoIt’s just the tool that’s provided by the RNA technology that will allow us to move much more quickly and take our best ideas into human studies faster than we would have been able to do previously.&rdquo

How much faster are we talking? According to Feinberg, it&rsquos still too early to have any type of timeline for the development of an effective HIV vaccine, but he does note that unlike the Covid-19 vaccines, this process will take more than a year.

What else could this mean for HIV vaccine research?

While some of the recent reporting on this clinical trial included what Feinberg refers to as &ldquoirrational exuberance around interpreting some of the data,&rdquo it&rsquos promising to see that a year into our careers as armchair virologists, we&rsquore still really excited about vaccines. &ldquoI think that there’s optimism here,&rdquo Corey says. &ldquoFirst of all, understanding about vaccines has markedly increased in the country, so the interest in developing vaccines is there.&rdquo

Throughout the pandemic, Corey says that he&rsquos been worried that &mdash like so many other things &mdash HIV vaccine research would be &ldquoburied under Covid.&rdquo But now he&rsquos hopeful that moving forward, the increased public awareness of vaccines and their development, thanks to Covid, will ultimately be a boon for HIV vaccine research.

&ldquoAs we emerge from the Covid epidemic, I hope that there will be momentum,&rdquo he says. &ldquoAnd that the citizenry will participate in HIV vaccines like they did in Covid. I mean, how they helped us in Covid is miraculous &mdash all these people stepped up, rolled up their sleeves, and got the critical shots.&rdquo

Editor’s note: This story has been updated to clarify that no HIV vaccine has yet been able to produce bnAbs.


Employing Stem Cell Transplantation and Gene Therapy

In the absence of ART, the vast majority of people living with HIV will eventually develop complications, including AIDS. However, some people living with HIV maintain low levels of virus in the blood—or viral load—even without therapy, indicating that their immune cells are protected from HIV. Other individuals claim to have had significant exposure to HIV but did not acquire the virus.

Beginning in the late 1990s, studies revealed that people with stronger natural protection from HIV tended to have mutations in the gene that codes for a protein called CCR5. CCR5 exists on the surface of human immune cells, and it is one of the proteins that HIV uses to enter and infect cells. When CCR5 is dysfunctional or absent, HIV can no longer infect immune cells. If researchers induce CCR5 dysfunction or absence by mutating the CCR5 gene in the cells of adults who do not naturally have this rare mutation, scientists may be able to help these people better control or eliminate HIV infection. Based on these findings, NIAID funds experimental genetic engineering approaches to an HIV cure.

Some clinicians have attempted to cure HIV in people who needed a bone marrow transplant to treat a life-threatening cancer by selecting a donor whose stem cells had the CCR5 mutation. If the procedure is successful and the patient survives, it can lead to a reconstitution of the immune system with cells that are impervious to HIV. This approach has succeeded only twice in curing people of HIV, although it has been tried many other times.

One of these two successful cases was known as “the Berlin patient” for many years before revealing his identity, Timothy Brown. This American man living with HIV was diagnosed with myeloid leukemia while living in Germany. Brown’s doctors determined he needed a complete bone marrow transplant, the standard treatment for his life-threatening cancer, and selected a donor who had the CCR5 mutation. Brown nearly died from the treatment. However, in the end, not only did the procedure cure his leukemia, but also it eliminated HIV from his body. In 2009, Brown’s physicians reported these findings in the New England Journal of Medicine as a case study funded by the German Research Foundation.

In 2019, researchers reported a similar case in the journal Nature. The anonymous “London patient” received a bone marrow transplant for Hodgkin’s lymphoma using stem cells from a donor with the CCR5 mutation. The patient survived the transplant, and multiple subsequent analyses revealed no evidence of HIV infection. At the time of publication, the patient’s HIV had remained in remission without ART for more than 18 months. Researchers will continue to monitor the “London patient” for the reemergence of HIV, as well as long-term health effects of the transplant. The case study was supported by the United Kingdom’s National Institute for Health Research, the Oxford and Cambridge Biomedical Research Centres and amfAR (The Foundation for AIDS Research).

While these extraordinary cases are “proof of concept” that HIV can be cured, a bone marrow transplant is a highly risky, intensive and expensive procedure performed only to treat life-threatening conditions in the absence of other treatment options. It is not a realistic way to cure HIV in the millions of people around the world who are living with the virus. Moreover, attempts to cure HIV with bone marrow transplants in other individuals have not been successful, primarily because the procedure has only been performed in patients with both HIV and blood cancers, which have a high mortality rate even after bone marrow transplants.

Other recent advancements have opened up the possibility of enhancing the immune system’s ability to fight HIV through gene-editing technologies. Clinicians employing such techniques would remove immune cells from an HIV-positive patient, use gene-editing to directly alter the CCR5 gene, and then transfuse the cells back into the individual. In this case, a donor with an advantageous CCR5 mutation is not required, and the patient does not risk life-threatening rejection of donor tissue. Some preliminary research has been done to assess gene-editing as a strategy for both HIV treatment and cure.

Some clinicians have also proposed using gene-editing technology to directly cut viral genes out of the DNA of latently infected cells. This technique would target what is called the HIV provirus. When HIV infects a cell, the virus inserts its own genome into the cell’s DNA. Advances in biotechnology make it possible for scientists to potentially locate and remove these genes from latent cells using programmed DNA-slicing enzymes. Pre-clinical studies in animals have shown that such a strategy can excise proviral DNA from infected cells. However, scientists still need to understand how to efficiently deliver these gene-editing enzymes to all cells that make up the latent HIV reservoir without causing unintended consequences that may be unhealthy for the patient. Therefore, more research needs to be done to evaluate this approach in living organisms.