ViiV head of research and development Dr Kimberly Smith. Credit: ViiV. To help overcome stigma and burden associated with HIV, ViiV is committed to developing longer-acting treatments and a cure for this infectious disease. Credit: Shutterstock.
More than a decade after its founding, specialist pharma company ViiV Healthcare remains committed to furthering the excellent achievements in transforming human immunodeficiency virus (HIV) from a death sentence into a disease that is now manageable through medication to such an extent that HIV patients can live a normal lifespan.
Despite these achievements, significant stigma and burden still exists around this infectious disease, meaning further innovation is required to continue to improve the lives of HIV patients. As ViiV head of research and development Dr Kimberly Smith explains, her company is working to combat this by investigating longer-acting anti-retroviral therapies.
After proving once-monthly dosing of cabotegravir and Janssen’s rilpivirine was as safe and effective as daily dosing, ViiV announced in March this year that the same two drugs were as effective when dosed every two months. The study met its primary endpoint of non-inferiority to monthly doses in terms of anti-viral activity and safety.
Smith goes on to note the importance to ViiV of not stopping innovation at treatment, but also focusing research efforts on developing a cure against this devastating disease.
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Allie Nawrat: How much stigma is still related to HIV? Has there been a significant decline in recent years?
Kimberly Smith: Recent surveys show that more than 80% of people living with HIV say they have experienced some sort of stigma in the past year. So, yes, it is still very much prevalent.
A lot of people have made the effort to become more knowledgeable about HIV, [compared to the] early days where there was a huge paranoia and fear about HIV.
But, nonetheless, there’s still stigma where people do not understand that people who are living with HIV can live a normal lifespan if they are on treatment, and if they are on treatment and have their virus suppressed they cannot pass it on to their partner through sexual contact. As the general public gets to know more and more, we hope that that will ultimately lead to less stigma.
AN: Why is there a need to optimise and improve upon anti-retroviral therapeutic approaches?
KS: It’s important to recognise that, even though there’s been tremendous progress in HIV treatment, we don’t have everyone on treatment, and not everyone who’s on treatment is suppressed. That is an indicator that obviously there’s a number of systemic problems that mean individuals aren’t consistently on therapy.
This suggests we need to have more options for people.
While we were extremely excited to progress to the point where we had one pill a day in comparison to the bad old days when people took 20 pills, for some people, that’s still tough.
It’s a daily reminder of living with a very stigmatised disease. Also, having consistent access to healthcare and insurance is still a challenge [for many].
- We need to have more options that meet the needs of all patients who are living with HIV.
- AN: How could long-acting and fewer doses of ART reduce the burden of the disease, and related stigma, for patients?
- KS: A year ago, we proved that once a month dosing with cabotegravir and rilpivirine was as effective as staying on daily therapy, but was highly preferred over daily therapy.
A couple of weeks ago, we presented [data from a] brand new study ATLAS-2M, which showed that twice monthly dosing [with cabotegravir and rilpivirine] was as effective as once a month, and it was highly preferred over once monthly and daily – 98% of individuals preferred changing their dose to every two months compared to daily and then 94% preferred every two months over monthly. People love the idea of going from dosing 365 days a year to dosing six days a year.
There is this terrible fear, for example, when people travel and they have to take their HIV meds with them.
They are worried someone from TSA [Transportation Security Administration] will pull the bottle out and ask them, what it’s for, and they will have to explain in a public setting.
In some countries in the world, sadly, they will try to exclude people from entering the country who are living with HIV. Some of the individuals in our trials who travel a lot for work talked about how wonderful it felt to not have to take that pill with them anymore.
People who are living with HIV don’t only experience external stigma, but self-stigma. As much as they’ve fought it, many people with HIV judge and blame themselves.
But it’s not something they did wrong, they just happened to be unlucky.
We hear from individuals who’ve been a part of our trials that they were actually surprised at how much better and more liberated they felt from not having to have that daily reminder [from a daily pill].
- AN: Why does pharma have a responsibility to reduce and control stigma related to HIV?
- KS: For us, we feel an added responsibility to address issues that are not just about treatment, but really about the lives of people who are living with HIV.
- It’s important to recognise that stigma can be a big deterrent for some individuals seeking care and treatment, especially if you’re fearful that you’re going to be somehow outed as living with HIV, because you go to a clinic where HIV is being treated or you’re seen to have a medicine.
- Overcoming stigma contributes to maximising people’s outcomes; we still see individuals who don’t get treatment ultimately succumb to this disease.
- AN: Despite all the significant advances in treatment, why is it essential that the industry focuses on finding a cure?
KS: It’s tremendous that we’ve been able to transform HIV from a disease that was almost uniformly fatal, with the exception of few fortunate individuals, to a disease where individuals can live a normal lifespan as long as they take medication. That transformation is a medical miracle, but we are not in a utopia.
The lives of people who are living with HIV are still challenged by the need to take medicines every day. All medicines have side effects and there’s always the risk of individuals developing resistance to medications.
Also, even though we keep the virus at bay, there may be underlying chronic inflammation and other challenges that exist in individuals with HIV, which may make them more prone to certain types of malignancies and frailties, [ranging from] weaker bones, kidney disease to central nervous system diseases.
5 Strategies to Cure HIV
Whilst a person living with HIV can suppress the virus with antiretrovirals, there is no cure. A cure for HIV would be the total eradication of the virus from the body. However, this is not the only option that scientists are looking into. Here are some of the strategies scientists are looking into for an HIV cure.
Light Painting | JonathanCohen via Photopin
Shock and kill technique
HIV hides in reservoir cells in the body and can remain silent as long as a patient takes antiretroviral therapy. As soon as a patient stops taking ARTs, the reservoir virus wakes up and starts replicating all around the body again.
Shock and Kill would ‘wake up’ these reservoirs to activate the silent virus.
Whilst counter-intuitive, the idea is to wake up every single virus and kill all the activated cells, destroying the reservoir in one go. If one virus survives then there is always a risk that it will be able to duplicate and the virus will return.
Currently, scientists have identified drugs that will ‘shock’ or ‘wake up’ the silent reservoir cells. The next challenge is to identify a drug or method that can subsequently destroy these infected cells and avoid healthy cells.
When destroying cells in the body, there is always a risk that drugs will target healthy cells, so this research moves carefully to avoid unnecessary damage.
Pharmacological reactivation of virus as a cure strategy – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4031321/
Locks and Lockers | Eyad Elbayoumi via Photopin
Lock and Block Technique
The ‘Lock and Block’ technique takes the opposite approach to ‘Shock and Kill’. This method aims to trap HIV in its reservoir cell so that it can never be reactivated. Whilst the virus is still present in the body, it is trapped away so that it cannot escape its host cell and cannot replicated.
This technique is being looked into as an alternative to ‘Shock and Kill’. Scientists are currently testing drugs’ abilities to effectively trap HIV in a host cell without disrupting the genetic material of uninfected cells. Ideally, a drug would lock HIV away then deplete the reservoir so there was no possibility of the virus returning.
Current issues that are being researched are drugs not locking away HIV tightly enough.
…new strategy (‘block and lock’), designed to silence the HIV reservoir, rather than eradicate it. The goal of this strategy would be to increase treatment intervals and maybe even obtain a state of ‘HIV remission’.
A cure for HIV the end goal
Incredible advances have been made in the development of effective HIV treatments that allow people living with HIV to suppress their virus to undetectable levels and avoid transmitting it to others. This era of effective treatment with antiretrovirals (ARV) is undoubtedly a gigantic leap forward from the early beginnings of the HIV crisis, but the fact remains that there are almost 38 million people living with HIV worldwide.1
These individuals still have to take a lifetime of treatments, which can take a significant emotional and physical toll. To lift the substantial burdens of daily treatment and social stigma associated with HIV, a cure is essential towards accomplishing our goal of ending the HIV epidemic.
With this goal in mind, we are in pursuit of a cure for HIV:
Because of the unique nature of HIV, discovering a cure comes with some specific challenges.
The most significant of these challenges is the virus’s ability to hide itself and lay dormant in pockets of healthy immune system cells (CD4+ T cells) that are unrecognised by the immune system.
Even if an individual has successfully suppressed their HIV through ARV treatment, the hidden HIV, called the “latent reservoir,” can re-emerge if ARV treatment is stopped.2
Because of this underlying barrier, examples of HIV cure have been few and far between throughout the entire history of the HIV epidemic. In fact, there have been only two instances of confirmed HIV cure, in which two patients (known as the Berlin and London patients), have successfully stopped daily ARV treatment and not experienced a rebound in their HIV.
These individuals were cured of their HIV after treatment for their separate cancer diagnosis, which required a series of difficult and intensive treatments to eradicate their immune and bloodforming cells and replace them with an HIV-resistant bone marrow transplant. While their treatments were extremely high risk and not amenable to wide scale implementation, these instances of cure bring hope of what is possible in our efforts to end the HIV epidemic.
Induce and reduce: our approach to HIV cure
HIV is a sneaky virus that can stay hidden in a small population of cells even while its being suppressed by ARVs. Unless we can find a way to selectively target the hidden HIV, we’ll continue to require chronic treatments to keep the virus at bay. That’s why cure research currently underway by ViiV Healthcare targets these pockets of virus through the novel concept of “induce and reduce.”
Searching for a cure for HIV and AIDS
There is still no known cure for HIV. However, scientific efforts to improve treatment, prevention and awareness tools are continuing to have a positive impact on the lives of many until a cure is discovered.
There are many logistical limitations and cost challenges that come with providing life-long care to those living with HIV. So continuing research to find a cure that controls the virus in the absence of antiretroviral treatment (ART) remains an important step to ending the epidemic.1
Cure research is still at an early but promising stage, and scientists are working on two broad types of HIV cure research – a ‘functional cure’ and a classic, ‘sterilising cure’ (see below).
How HIV has evaded a cure
Due to the complex nature and structure of HIV, locating and quantifying the amount of virus in the body is proving to be a daunting task.
HIV evades the immune system by staying dormant in infected T- lymphocyte cells (T-cells) until they are activated to respond to infections. This state is called latent infection.
Some of these cells may live for decades without becoming activated. Cells that are latently infected are described by scientists as the `HIV reservoir`.
Detecting and eliminating these cells are the biggest challenges facing cure research.
A reservoir of HIV-infected T-cells can be found in the lymphoid tissue of people living with HIV, even if HIV is undetectable on viral load tests in the blood.
It is here that lymphocytes are produced and primed to fight infections in the body. The main concentrations of lymphoid tissue in the body are found in the thymus, spleen and lymph nodes in the gut, neck, under the arms and in the groin.
HIV-infected T-cells can also be found in the bone marrow and the brain.
Studies have also shown that HIV does not only infect T-cells – the virus can also persist in macrophages, cells which are found in virtually every tissue in the body.2 As a result, other sites in the body, such as the lungs, brain and genital tract, are also important reservoirs of latently-infected cells.
Is There A Cure For HIV/AIDS? — (RED)
A few weeks after word was out on the success of the London Patient, the world received more hopeful news.
Nina Martinez became the world’s first living HIV-positive person to donate an organ to an HIV-positive recipient, giving the anonymous patient one of her kidneys. Until recently, the medical world considered it unsafe for someone with HIV to live with only one kidney, but thanks to antiretroviral treatment, those with HIV can be organ donors without the past fear of complications.
The CRISPR Method
Flash forward a few months to July 2019, when researchers announced another major breakthrough. Scientists from Temple University and the University of Nebraska Medical Center were able to successfully eliminate HIV in living mice for the first time.
Using a super form of antiretroviral therapy, called LASER, and a gene-editing technology known as CRISPR, these scientists were able to eliminate HIV from the DNA of 9 mice. After treating the mice with LASER, researchers used CRISPR to erase any remaining HIV DNA from their bodies.
These results are the first to prove that removing HIV in living animals is in fact possible. Next up, researchers are looking to replicate this success in primates.
What It All Means
All of these results are incredibly hopeful. They show that new approaches to HIV treatment are becoming increasingly effective and that researchers are slowly getting closer to finding a true cure.
That being said, it’s important to remember that the successes of the Berlin patient and the London patient occurred under very special circumstances.
The procedures were intended to treat cancer, and they came with a large price tag and an even larger risk.
After the Berlin Patient, many of the attempts to replicate his treatment ended with the virus coming back, or with HIV+ patients dying from their cancer. Brown himself almost died because of the toll the procedure took on his immune system.
In terms of the major developments using the CRISPR method, it’s important to remember that gene editing is still a very new technology. While eliminating HIV in mice was certainly a major feat, we’re still a while away from being able to safely test the CRISPR method on humans.
These discoveries also do not change the current situation for most of the 38 million people currently living with HIV, nearly two-thirds of whom are in sub-Saharan Africa. Given nearly half of all people living with HIV still need access to HIV medication, a rare, dangerous and costly procedure isn’t a realistic solution to the AIDS fight.
This is why the Global Fund, the organization that receives 100% of money generated by (RED) partners, is so important.
While the medical community continues to work on finding a safe, cost-effective cure for HIV/AIDS, Global Fund programs in over 100 countries are focused on scaling up access to antiretroviral treatment—the current, closest thing to a cure for people living with HIV.
These programs also provide prevention services, care, treatment and education to the people most affected by HIV, which are crucial to limiting the spread of the virus.
We should applaud these discoveries, but we’re not at the finish line yet. AIDS is still a crisis but it doesn’t have to be. When you shop (RED) products on Amazon.com/RED, you’re helping to change this.
New Research Suggests a Cure for HIV Could be on the Horizon
Modern retroviral therapies have done a good job of turning HIV/AIDS into a treatable chronic illness, but except in a few rare experimental cases using stem cell transplants, there is no cure. Cure, in this case, meaning that the HIV virus is completely eradicated in the patient. Retroviral therapies cause the virus to become inactive, but they still remain in the body and may potentially reactivate if treatment ends.
Researchers at the University of California, San Diego (UCSD) School of Medicine have now identified a key switch that has the potential to eliminate dormant HIV reservoirs. They published their research in the journal mBio.
“This is one of the key switches that the HIV field has been searching for three decades to find,” said Tariq Rana, professor of pediatrics and genetics at UCSF.
“The most exciting part of this discovery has not been seen before.
By genetically modifying a long noncoding RNA, we prevent HIV recurrence in T-cells and microglia upon cessation of antiretroviral treatment, suggesting that we have a potential therapeutic target to eradicate HIV and AIDS.”
Rana and fellow researchers utilized genome-wide expression analysis of long noncoding RNA (lncRNA) in specialized immune cells called macrophages that had been infected with HIV.
Macrophages promote inflammation, stimulate the immune system and remove foreign matter. Usually, lncRNAs don’t behave the way other RNAs do, which is to say, RNAs deliver DNA codes for proteins.
The lncRNAs are involved in controlling which genes are switched on or off in a cell.
The researchers focused on a single lncRNA called HIV-1 Enhanced LncRNA (HEAL) that is found in higher amounts in HIV patients. The researchers believe this is a recently emerged gene that regulates HIV replication in immune cells, including macrophages, microglia and T-cells.
They ran experiments that silenced HEAL or removed it using CRISPR-Cas9 gene editing, which resulted in HIV no longer recurring when antiretroviral treatment was halted. The researchers expect to continue to confirm the data in animal models.
“Our results suggest that HEAL plays a critical role in HIV pathogenesis,” Rana said. “Further studies are needed to explain the mechanism that leads to HEAL expression after an individual is infected by HIV, but this finding could be exploited as a therapeutic target.”
This appears to be a major finding, but there have been others recently as well. In August, researchers from the University of Texas Medical Branch at Galveston discovered that the protein BRD4 has a significant role in regulating the production of new copies of the HIV gene.
The research group, led by Haitao Hu, assistant professor of microbiology and immunology, designed, synthesized and studied several small molecules to selectively program BRD4 to suppress HIV.
They then picked a lead compound, ZL-580, which significantly delayed the reactivation of dormant HIV after antiretroviral therapy was halted.
HIV and AIDS – Treatment
While there's no cure for HIV, there are very effective treatments that enable most people with the virus to live a long and healthy life.
If you think you've been exposed to the virus, post-exposure prophylaxis (PEP) medication may stop you becoming infected.
PEP must be started within 72 hours of coming into contact with the virus for it to be effective. It's only recommended following higher risk exposure, particularly where the sexual partner is known to be positive.
PEP involves taking HIV treatment every day for 1 month. It may cause some side effects.
You should be able to get PEP from:
- sexual health clinics or genitourinary medicine (GUM) clinics
- hospitals – usually accident and emergency (A&E) departments
If you already have HIV, try your HIV clinic if the PEP is for someone you've had sex with.
Want to know more?
- Terrence Higgins Trust: post-exposure prophylaxis (PEP)
If you're diagnosed with HIV, you'll have regular blood tests to monitor the progress of the HIV infection before starting treatment.
Two important blood tests are:
- HIV viral load test – a blood test that monitors the amount of HIV virus in your blood
- CD4 lymphocyte cell count – which measures how the HIV has affected your immune system
Treatment can be started at any point following your diagnosis, depending on your circumstances and in consultation with your HIV doctor.
Want to know more?
- NAM aidsmap: CD4 cell counts
- NAM aidsmap: starting treatment
HIV is treated with antiretroviral medications, which work by stopping the virus replicating in the body. This allows the immune system to repair itself and prevent further damage.
- A combination of HIV drugs is used because HIV can quickly adapt and become resistant.
- Some HIV treatments have been combined into a single pill, known as a fixed dose combination, although these often cost more to prescribe.
- Usually, people who have just been diagnosed with HIV take between 1 and 4 pills a day.
- Different combinations of HIV medicines work for different people, so the medicine you take will be individual to you.
The amount of HIV virus in your blood (viral load) is measured to see how well treatment is working. Once it can no longer be measured it's known as undetectable. Most people taking daily HIV treatment reach an undetectable viral load within 6 months of starting treatment.
Many of the medicines used to treat HIV can interact with other medications prescribed by your GP or bought over-the-counter.
URL of this page: https://medlineplus.gov/hivaidsmedicines.html Also called: Antiretroviral therapy
HIV stands for human immunodeficiency virus. It harms your immune system by destroying CD4 cells. These are a type of white blood cells that fight infection. The loss of these cells makes it hard for your body to fight off infections and certain HIV-related cancers.
Without treatment, HIV can gradually destroy the immune system and advance to AIDS. AIDS stands for acquired immunodeficiency syndrome. It is the final stage of infection with HIV. Not everyone with HIV develops AIDS.
What is antiretroviral therapy (ART)?
The treatment of HIV/AIDS with medicines is called antiretroviral therapy (ART). It is recommended for everyone who has HIV. The medicines do not cure HIV infection, but they do make it a manageable chronic condition. They also reduce the risk of spreading the virus to others.
How do HIV/AIDS medicines work?
HIV/AIDS medicines reduce the amount of HIV (viral load) in your body, which helps by
- Giving your immune system a chance to recover. Even though there is still some HIV in your body, your immune system should be strong enough to fight off infections and certain HIV-related cancers.
- Reducing the risk that you will spread HIV to others
What are the types of HIV/AIDS medicines?
There are several different types of HIV/AIDS medicines. Some work by blocking or changing enzymes that HIV needs to make copies of itself. This prevents HIV from copying itself, which reduces the amount of HIV in the body. Several medicines do this:
- Nucleoside reverse transcriptase inhibitors (NRTIs) block the reverse transcriptase enzyme
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs) bind to and later change the reverse transcriptase enzyme
- Integrase inhibitors block the integrase enzyme
- Protease inhibitors (PIs) block the protease enzyme
Some HIV/AIDS medicines interfere with HIV's ability to infect CD4 immune system cells:
- Fusion inhibitors block HIV from entering the cells
- CCR5 antagonists and post-attachment inhibitors block different molecules on the CD4 cells. To infect a cell, HIV has to bind to two types of molecules on the cell's surface. Blocking either of these molecules prevents HIV from entering the cells.
In some cases, people take more than one medicine:
- Pharmacokinetic enhancers boost the effectiveness of certain HIV/AIDS medicines. A pharmacokinetic enhancer slows the breakdown of the other medicine. This allows that medicine to stay in the body longer at a higher concentration.
- Multidrug combinations include a combination of two or more different HIV/AIDS medicines
When do I need to start taking HIV/AIDS medicines?
It's important to start taking HIV/AIDS medicines as soon as possible after your diagnosis, especially if you
- Are pregnant
- Have AIDS
- Have certain HIV-related illnesses and infections
- Have an early HIV infection (the first 6 months after infection with HIV)
What else do I need to know about taking HIV/AIDS medicines?
It's important to take your medicines every day, according to the instructions from your health care provider. If you miss doses or don't follow a regular schedule, your treatment may not work and the HIV virus may become resistant to the medicines.
HIV medicines can cause side effects. Most of these side effects are manageable, but a few can be serious. Tell your health care provider about any side effects you are having. Don't stop taking your medicine without first talking to your provider. He or she may give you tips on how to deal with the side effects. In some cases, your provider may decide to change your medicines.
What are HIV PrEP and PEP medicines?
HIV medicines are not just used for treatment. Some people take them to prevent HIV. PrEP (pre-exposure prophylaxis) is for people who don't already have HIV but are at very high risk of getting it. PEP (post-exposure prophylaxis) is for people who have possibly been exposed to HIV.
- Pharmacogenetic Tests (National Library of Medicine) Also in Spanish