Category: HIV

Categories : Healthcare Politics and Regulations HIVTags :

Health Department Secures Lower Antiretroviral Prices

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Image by Cottonbro on Pexels

By Liezl Human

The national Department of Health (DOH) has managed to secure a significant reduction in prices for antiretroviral medicines that treat HIV, with the price of the regimen that is prescribed to most new patients (tenofovir/lamivudine/dolutegravir – TLD) dropping over 30%, from R99 to R68. By comparison the regimen costs well over R250 in the private sector.

TLD is recommended by the World Health Organisation as the preferred first-line regimen for adults living with HIV.

Currently over 4 million South Africans are using this regimen, according to statistics from the DOH. There are about over 5.5 million people receiving treatment for HIV, and 8 million people living with the virus in this country. 

Prices of ABC/3TC, commonly used to treat children with HIV, also fell with the DOH’s new contract.

Khadija Jamaloodien, director of the Affordable Medicines Directorate in the DOH, told GroundUp that South Africa is the biggest buyer of ARVs in the world. She said because of the sheer number of people needing ARVs, the department was able to bring the price down.

“Our volumes are just so huge that it makes it more efficient for manufacturers to be able to supply at reasonable prices,” said Jamaloodien.

She said another reason the department was able to reduce the price was that the manufacturers were applying for a three-year contract with “a certainty of demand”. She said constant communication with manufacturers about changes in demand also helped. If demand is likely to be reduced, the department would inform manufacturers who then would not “sit with stock that they are going to have to write off”.

The contract, which is already being executed, was awarded from July 2022 and ends in June 2025.

Jamaloodien said lower prices meant that the department could serve more patients and provide more medicines within the same budget envelope. (ARVs are provided free to public sector patients.)

Juliet Houghton, CEO of the Southern African HIV Clinicians Society (SAHCS), praised the DOH’s efforts to secure the ARVs so cheaply. She said a “healthy” degree of competition between manufacturers also helped drive prices down.

Houghton added that the reduction in prices “offers an opportunity to reinvest some of the savings into more expensive, particularly prevention drugs, that are coming”.

See DOH presentation

“As a country, we don’t want to just keep treating more and more people with HIV, we actually want to prevent it,” said Houghton. She said that the remaining budget could also be invested in prevention injectables, which might be more expensive.

Jamaloodien said that the injectable pre-exposure prophylaxis (PrEP) medicines are not yet registered with South African Health Products Regulatory Authority (SAHPRA). These help prevent sexually active people from contracting HIV. She said after the medicines are registered, they will have to look at whether they are affordable.

Francois Venter, executive director of Ezintsha at Wits, also praised the DOH’s “excellent work in securing these price reductions”.

“We also need the department to start using these processes better to secure similar world-class treatments for other common diseases – including diabetes, cancer, obesity, and TB,” he said.

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Source: GroundUp

Categories : HIVTags :

HIV Uses Immune Response as a Way to Hide

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HIV Infecting a T9 Cell. Credit: NIH

An immune response that likely evolved to help fight infections appears to be the mechanism that drives human immunodeficiency virus (HIV) into a latent state, lurking in cells only to erupt anew, according to research published in the journal Nature Microbiology. The findings help explain why HIV particularly stealthy, but could also apply to other viral infections.

“HIV has proven to be incurable because of a small number of latently HIV-infected T-cells that are untouched by both antiviral drugs and the immune response,” said senior author Bryan R. Cullen, PhD, professor at Duke University School of Medicine.

“These cells, which are very long lived, can spontaneously emerge from latency and start producing HIV even years after infection, thus necessitating the life-long use of antiretrovirals,” Cullen said. “The origin of these latently infected cells has remained unknown despite considerable effort.”

The findings offer important insights, pointing to a protein complex called SMC5/6, which is involved in a host cell’s chromosome function and repair.

HIV enters the body, infects the immune system’s CD4+ T-cells, then makes a genome-length DNA molecule that it integrates into a host cell chromosome where it is then copied to generate viral RNAs and proteins.

If this so-called DNA provirus is prevented from integrating into the host cell DNA, for example by a drug that blocks this process, then it fails to make any viral RNAs and proteins and becomes inert. In contrast, DNA proviruses that are able to integrate are normally able to drive a productive HIV infection.

Cullen and his team found that, in a small number of infected cells, the SMC5/6 protein complex initiates a process that silences the DNA provirus before it integrates into a host cell chromosome. These proviruses remain inert even after integration and result in latent infections, lying low until prompted to erupt into an active infection.

“Our research suggests that latency results not from any intrinsic properties of the infecting HIV but rather from an unfortunate side effect of a cellular innate immune response that probably evolved to silence invasive foreign DNA,” Cullen said.

The researchers found that a molecule that shuts down SMC5/6’s silencing action showed promising results as a potential therapeutic strategy as it inhibited the establishment of latent HIV infections. Reactivated proviruses are vulnerable to natural immune system responses and anti-retroviral drugs.

“Although antiretroviral therapies can reduce the viral load in AIDS patients to below the level of detection, these drugs fail to eradicate HIV-1,” Cullen said. “While there has been considerable effort expended on trying to develop therapies that can activate latent HIV-1 and help antiretroviral therapies clear the body of infectious virus, this effort has so far failed to identify drugs that are both effective and non-toxic. Our study represents a potentially important step toward achieving this goal.”

“Clearly, understanding the mechanism that results in HIV-1 latency may provide insights into how latent HIV-1 proviruses can be reactivated and then destroyed,” Cullen said.

Source: Duke University Medical Center

Categories : HIVTags :

HIV Infection Creates Chronic ‘Jet Lag’ in Patients

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Photo by Malvestida on Unsplash

Research from South Africa and the UK has found that people living with HIV have a significantly delayed internal body clock, consistent with the symptoms of jet lag. The findings, which appear in the Journal of Pineal Research, may explain some of the health problems experienced by people with HIV, and guide research towards improving their quality of life.

Researchers from the University of the Witwatersrand and University of Cape Town along with Northumbria and Surrey universities in the UK and studied people aged 45 years and above living in Mpumalanga province, where nearly one in four people is living with HIV. As such, the infection is endemic and does not associate with any difference in lifestyle.

They found that physiological daily rhythms, as measured by the hormone melatonin, were delayed by more than an hour on average in HIV positive participants. Their sleep cycle was also shorter, with researchers noting that their sleep started later and finished earlier.

This suggests the possibility that HIV infection may cause a circadian rhythm disorder similar to the disruption experienced in shift work or jet lag.

The authors believe that this body clock disruption may contribute significantly to the increased burden of health problems that people living with HIV are experiencing despite successful treatment, such as an increased risk of cardiovascular, metabolic, and psychiatric disorders.

Researchers believe there is a strong need for further funding to identify whether similar disruption to the body clock is experienced by younger people living with HIV in other countries.

“The participants living with HIV essentially experience the one-hour disruption associated with switching to daylight savings time, but every single morning,” says corresponding author Malcolm von Schantz, Professor of Chronobiology at Northumbria University.

“This happens in spite of the fact that essentially everybody is exposed to the same light-dark cycle. Our findings have important potential implications for the health and wellbeing of people living with HIV, especially given the well-established relationships between disrupted circadian rhythms and sleep deprivation.”

Senior author Dr Karine Scheuermaier of Wits University added: “This is very similar to the risk profile observed in shift workers. Understanding and mitigating this disruption may be an important step towards helping people living with HIV live healthier lives.”

“Our findings identify an urgent research topic,” says Xavier Gómez-Olivé, also from the University of the Witwatersrand, whose research grant funded the study. “The next step must be to establish if the same body clock disruption exists in people living with HIV who are younger and who live in other countries.”

Co-author Dale Rae, of the University of Cape Town, added “This is a great example of the importance of studying sleep in people living in Africa, and demonstrates how findings from this research can also be relevant to people anywhere in the world.”

Source: Northumbria University

Categories : HIVTags :

Earlier HIV Diagnosis and Treatment Improves Outcomes

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HIV themed candle
Image by Sergey Mikheev on Unsplash

Compared to delaying antiretroviral treatment (ART) early in the course of HIV infection, an earlier start to ART when the immune system is stronger results in better long-term health outcomes, according to findings presented at the IDWeek Conference.

The findings are based on an extended follow-up of participants in the National Institutes of Health-funded Strategic Timing of Antiretroviral Treatment (START) study. In 2015, START demonstrated a 57% reduced risk of AIDS and serious non-AIDS health outcomes among participants who began ART when their CD4+ T-cell counts were greater than 500 cells/mm³ compared with those who did not begin ART until either their CD4+ counts fell below 350 cells/mm³ or they developed AIDS. Following the 2015 report of these findings, the participants in the deferred treatment arm were advised to begin ART.

The international START study proved the benefit of early ART initiation, but longer-term follow-up of 4446 participants was undertaken to determine whether the health benefits of early ART compared with deferred ART increased, remained constant, or declined after the participants in the deferred arm were advised to begin ART. The primary study endpoints included the number of participants who developed AIDS; those who developed serious non-AIDS health conditions, such as major cardiovascular disease, kidney failure, liver disease and cancer; and those who died.

For participants who began ART before the end of 2015, the median CD4+ cell count at the time of ART initiation was 648 cells/mm³ for the immediate arm and 460 cells/mm³ for the deferred arm. The analysis presented today compared the primary study endpoints before the end of 2015, with those in the extended follow-up period, from 2016–2021. In the latter period, most deferred-arm participants were taking ART. During the second period, people initiating ART in the deferred group had rapid and sustained declines in HIV viral load (less than or equal to 200 copies/mL); however, CD4+ cell counts remained, on average, 155 cells lower compared with that of individuals in the immediate ART group.

While the risk of serious health outcomes was substantially diminished soon after ART was initiated in the deferred treatment group, some excess risk remained compared with the immediate treatment group. The deferred ART group continued to have a somewhat greater risk (21%) of serious health consequences or death in comparison to the immediate treatment group. Over the five-year follow-up, there were 27 cases of AIDS in the deferred group compared with 15 cases in the early group. Similarly, 88 cases of serious non-AIDS health issues occurred in the deferred treatment arm compared with 76 cases in the immediate treatment arm. Lastly, there were 57 deaths in the deferred treatment group compared to 47 in the immediate treatment arm.

These findings confirm that ART significantly improves the health of an individual with HIV and reduce the person’s risk of developing AIDS and serious health issues, and that early diagnosis and treatment are key to maximising these benefits and reducing risk, according to the presenters.

Source: NIH/National Institute of Allergy and Infectious Diseases

Categories : Healthcare Politics and Regulations HIVTags :

TAC Slams Mbeki over His Views on HIV

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Photo: Mohamed Nanabhay (via Flickr, CC BY 2.0)

By Mary-Anne Gontsana for GroundUp

The Treatment Action Campaign (TAC) has called on former president Thabo Mbeki to offer an apology to the public for the “dissident” views he expressed about HIV/AIDS while delivering a speech at the University of South Africa (UNISA) last week Wednesday.

In a scathing statement published by the TAC on Tuesday, the organisation said the “repetition of his scientifically erroneous views with such insensitive arrogance is an insult to the 8 million people living with HIV in SA and the families of 4 million South Africans who have died from HIV over the last three decades”.

Mbeki, who is also the Chancellor at UNISA, was speaking to students, diplomats and members of the media at an event which takes place twice each year and allows students to interact with him on pertinent issues that affect Africans.

The TAC accuses Mbeki of misleading the public when he questions the cause of AIDS. The organisation also goes on to say that they were stunned again by Mbeki’s support of the views of the late former Minister of Health, Manto Tshabalala-Msimang “who was ridiculed for promoting garlic and beetroot as the essential ingredient to manage AIDS, giving it a higher premium than antiretroviral (ARV) treatment”.

“Whilst there may be benefits in all healthy foods, the idea that these vegetables are what are most required in the management of AIDS has no basis in fact and is misleading to the public,” said the statement.

Speaking about HIV/AIDS after a question was raised in the event, Mbeki said the questions that he raised then, he would still raise today. He emphasized that AIDS was a syndrome and not a disease.

“Now this syndrome in medical terms is a group of diseases. So all of these diseases which fall under this syndrome, meningitis, TB, they’re in the syndrome.”

“Causes of Tuberculosis are known and historical, but it’s part of the syndrome. So you can’t say one virus causes all of these illnesses, what you can say is this virus impacts negatively on the immune system, it’s that weakened immune system which results in a syndrome.”

“But there’s a consequence to that kind of thinking which is when you go to test and that test says HIV positive… it does not necessarily mean you’ve got the virus. What it means is that the immune system is responding to something that is threatening the body, and therefore you need a clinical analysis in order to determine what is this thing that the immune system is rejecting. It’s in all the medical documents that go about it, and it’s correct, because then you have to go and do this clinical examination in order to determine which of these illnesses in the syndrome is the one that’s affecting this person. And then you treat the person for that particular disease,” said Mbeki.

Mentioning the views of Tshabalala-Msimang, Mbeki started off by saying as government they had to respond in an effective manner to the HIV/AIDS pandemic and various interventions were needed to do this.

“Which is why the question was raised by the then Minister of Health in a very dramatic fashion. Nutrition. Nutrition is very very critical to solving this problem and that’s why she was saying that we must take garlic and beetroot and so on. She was not saying that with those things you’re going to be cured.”

“She was raising the matter about the importance of nutrition. And those particular types of foods even today have been raised in the context of this Covid-19,” said Mbeki.

The TAC, which successfully campaigned in the 2000s for Mbeki’s government to roll out life-saving medicines, was not impressed.

“There is much ongoing stigma and denial when it comes to HIV and we call on Mr Mbeki to desist from statements about HIV that have no basis in fact,” said the TAC statement.

It said: “The former president’s statements remind us that his unscientific views led to a delay in the rollout of the ARV programme during his presidency.”

The TAC’s General Secretary, Anele Yawa, said that if Mbeki was not prepared to apologise, the organisation would make sure that his HIV denialism and the thousands of deaths that resulted, would be the only thing that he would be remembered for.

These are the facts when it comes to HIV/AIDS under Thabo Mbeki’s presidency

By Nathan Geffen, GroundUp Editor

It’s seldom clear what Thabo Mbeki means when it comes to HIV/AIDS. There is much obfuscation. But the key facts are this:

  1. HIV destroys immune system cells in infected people.
  2. Usually over a period of several years, if left untreated, the immune system collapses, causing the person to become ill with life-threatening infections. This is known as AIDS.
  3. Only antiretroviral medicines can halt this process. They have been so effective that the life-expectancy for people with HIV who take them is brought back to almost normal.
  4. HIV tests are reliable. If proper protocols are followed the odds of an incorrect result are extremely small.
  5. Mbeki’s government delayed the rollout of antiretroviral treatment in the public sector until 2004, even though an effective combination of antiretroviral medicines was available from the mid to late 1990s.
  6. It was only due to pressure from the TAC and its allies that Mbeki’s government made antiretrovirals available in the public sector.
  7. The prices of these medicines also became affordable because of the TAC’s (and its allies) campaigning against pharmaceutical companies. Mbeki’s government was largely AWOL in these efforts, despite Mbeki’s rhetoric about these companies.
  8. Two different studies have estimated that the delayed rollout of antiretrovirals resulted in well over 300 000 avoidable deaths. These estimates are conservative.
  9. These estimates also exclude those who died because they were convinced by Mbeki, Tshabalala-Msimang and their acolytes to try treatments promoted by as alternatives to antiretroviral medicines. The promotion of these nonsense remedies by Mbeki and his health minister continued long after the antiretroviral treatment rollout began.

Geffen was involved with the TAC from 2000 to 2013.

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Views expressed are those of GroundUp and not Quicknews.

Source: GroundUp

Categories : HIVTags :

HIV Antiretroviral Therapy’s Life Expectancy Success

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HIV themed candle
Image by Sergey Mikheev on Unsplash

Since the introduction of the first antiretroviral therapy (ART) drug for HIV/AIDS treatment 35 years ago, life expectancy in Sub-Saharan Africa has steadily increased. ART medications are specifically designed to help an individual’s immune system fight HIV and in turn suppress HIV replication. However, there is a limited understanding of the combined effects of HIV and ART on disability and healthy longevity for individuals with the disease.

In a study published in The Lancet HIV, investigators from the Brigham and Women’s Hospital collaborated alongside international partners in South Africa to compare people with both virally suppressed and unsuppressed HIV, with people who were uninfected with HIV. The team used data they collected in an observational, longitudinal, population-based cohort study that included baseline interviews and blood collection, as well as subsequent follow-up interviews and blood collection about four years later. Their modelling analysis found that those receiving ART medication were predicted to live considerably longer and with less disability than those with unsuppressed HIV.

This research demonstrates the role of ART in healthy aging, as well as the continued importance for international global health organisations to provide HIV treatment to those all over the world, including in Africa.

“It was exciting for us to find that – at the population level – achieving high rates of viral suppression among people with HIV will not only lead to increases in life expectancy but also to healthier aging,” said senior author Jennifer Manne-Goehler, MD of the Division of Infectious Diseases. “This confirms the critical importance of maintaining support for antiretroviral programs as a way to ensure the best long-term health outcomes for people growing older with HIV.”

Source: EurekAlert!

Categories : Cardiovascular Disease HIVTags :

People with HIV and Hepatitis C Have Increased Heart Attack Risk

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Source: Wikimedia Commons CC0

As people with HIV age, their risk of myocardial infarction increases far more if they also have untreated hepatitis C virus, according to new research published today in the Journal of the American Heart Association.

According to the findings, even with antiretroviral therapy (ART), the risk of myocardial infarction (MI) among people with HIV is at least 50% higher than people without HIV. This new study evaluated if people with HIV who also have hepatitis C have a higher risk of MI.

“HIV and hepatitis C coinfection occurs because they share a transmission route – both viruses may be transmitted through blood-to-blood contact,” said Associate Professor Keri N. Althoff, PhD, MPH, senior author of the study. “Due in part to the inflammation from the chronic immune activation of two viral infections, we hypothesised that people with HIV and hepatitis C would have a higher risk of heart attack as they aged compared to those with HIV alone.”

Researchers analysed health information for 23 361 people with HIV in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) between 2000–2017 started on antiretroviral treatment for HIV, median age 45 at enrolment. One in 5 study participants (4677) were also positive for hepatitis C. During a median follow-up of about 4 years, the researchers compared the occurrence of a heart attack between the HIV-only and the HIV-hepatitis C co-infected groups as a whole, and by each decade of age.

The analysis found:

  • With each decade of increasing age, MI incidence increased 30% in people with HIV alone and 85% in those who were also positive for hepatitis C.
  • The risk of heart attack increased in participants who also had traditional heart disease risk factors such as high blood pressure (more than 3 times), smoking (90%) and Type 2 diabetes (46%).
  • The risk of heart attack was also higher (40%) in participants with certain HIV-related factors such as low levels of CD4 immune cells (200 cells/mm3, signalling greater immune dysfunction) and 45% in those who took protease inhibitors (one type of ART linked to metabolic conditions).

“People who are living with HIV or hepatitis C should ask their doctor about treatment options for the viruses and other ways to reduce their cardiovascular disease risk,” said Assistant Professor Raynell Lang, MD, MSc, lead study author.

“Several mechanisms may be involved in the increased heart attack risk among co-infected patients. One contributing factor may be the inflammation associated with having two chronic viral infections,” A/Prof Lang said. “There also may be differences in risk factors for cardiovascular disease and non-medical factors that influence health among people with HIV and hepatitis C that plays a role in the increased risk.”

“Our findings suggest that HIV and hepatitis C co-infections need more research, which may inform future treatment guidelines and standards of care,” Althoff said.

The study is limited by not having information on additional factors associated with heart attack risk such as diet, exercise or family history of chronic health conditions. Results from this study of people with HIV receiving care in North America may not be generalizable to people with HIV elsewhere. In addition, the study period included time prior to the availability of more advanced hepatitis C treatments.

“Because effective and well-tolerated hepatitis C therapy was not available during several years of our study period, we were unable to evaluate the association of treated hepatitis C infection on cardiovascular risk among people with HIV. This will be an important question to answer in future studies,” Lang said.

Source: American Heart Association

Categories : HIV Obstetrics & GynaecologyTags :

Dolutegravir-based ART is Better for Pregnant Individuals with HIV-1

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pregnant woman holding her belly
Source: Anna Hecker on Unsplash

Dolutegravir-based antiretroviral therapies (ART) for HIV-1 are more effective for pregnant individuals than some other ART regimens commonly used in the US and Europe, according to a study available online in NEJM.

The study, led by Harvard T.H. Chan School of Public Health researchers, showed that pregnant individuals who took dolutegravir-based regimens had a high probability of being virally suppressed at delivery. No differences were seen in adverse birth outcome risks (preterm birth, low birth weight, small for gestational age, or neonatal death) between dolutegravir-based regimens and the other contemporary regimens.

“Globally, a dolutegravir-based regimen is currently recommended for treating HIV, and this is the first study to directly compare regimens including dolutegravir to other antiretroviral regimens, such as raltegravir-based regimens, that are also listed as ‘Preferred’ in US perinatal guidelines,” said senior research scientistKunjal Patel, lead author of the study.

Dolutegravir, is a newer antiretroviral part of a once-a-day regimen that has been shown to be more effective, easier to tolerate, and less likely to create new drug resistance in people with HIV-1. However, limited data have been available about its effectiveness and safety in pregnancy compared with regimens that commonly have been used during pregnancy in the US and Europe.

In the current observational study, the researchers compared dolutegravir use in pregnancy with atazanavir/ritonavir, darunavir/ritonavir, and raltegravir antiviral regimens that are currently classified as “Preferred” for use in pregnancy in the US About half of the participants started ART before conception. At delivery, 96.7% of pregnancies of participants who received dolutegravir were virally suppressed, whereas those of participants who took atazanavir/ritonavir or raltegravir had viral suppression of 84.0% and 89.2%, respectively.

“We think the observed differences are due to dolutegravir’s ability to rapidly decrease viral loads and its ease of use as part of a once-daily regimen that’s available as a fixed-dose combination,” said Patel. “Our results highlight the continual need for systematic studies that compare new antiretroviral regimens with those already in clinical practice to help inform the evolution of guidelines and clinical practice over time.”

Source: Harvard T.H. Chan School of Public Health

Categories : HIVTags :

A Step Closer to a Once-off Treatment for HIV

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HIV invading a human cell
HIV invading a human cell: Credit NIH

Researchers from Tel Aviv University have demonstrated success of a novel technology that may be developed into a one-time vaccine to treat people with HIV and AIDS. Using CRISPR technology, the researchers engineered B cells that in turn stimulate the immune system to produce HIV-neutralising antibodies.

Published in Nature, the study was led by Dr Adi Barzel and PhD student Alessio Nehmad and conducted in collaboration with additional researchers from Israel and the US.

“Based on this study,” said Dr Barzel, “we can expect that over the coming years we will be able to produce a medication for AIDS, additional infectious diseases and certain types of cancer caused by a virus, such as cervical cancer, head and neck cancer and more.”

He explains that the treatment can become a kind of permanent medication, lingering in the body to fight the virus. “We developed an innovative treatment that may defeat the virus with a one-time injection, with the potential of bringing about tremendous improvement in the patients’ condition. When the engineered B cells encounter the virus, the virus stimulates and encourages them to divide, so we are utilising the very cause of the disease to combat it. Furthermore, if the virus changes, the B cells will also change accordingly in order to combat it, so we have created the first medication ever that can evolve in the body and defeat viruses in the ‘arms race’.”

When they mature, the antibody-generating B cells move into the blood and lymphatic system and from there to the different body parts.

Dr Barzel explained: “Until now, only a few scientists, and we among them, had been able to engineer B cells outside of the body. In this study, we were the first to do this within body and then make those cells generate the desired antibodies. The genetic engineering is conducted with viral carriers derived from viruses that were also engineered. We did this to avoid causing any damage, and solely bring the gene coded for the antibody into the B cells in the body.”

“Additionally, in this case we have been able to accurately introduce the antibodies into a desired site in the B cell genome. All lab models that had been administered the treatment responded, and had high quantities of the desired antibody in their blood. We produced the antibody from the blood and made sure it was actually effective in neutralising the HIV virus in the lab dish.”

Source: Tel Aviv University

Categories : HIVTags :

Antibody Cocktail Could Treat HIV while Minimising Escape Risk

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HIV Infecting a T9 Cell. Credit: NIH

Specifically designed cocktails of broadly neutralising antibodies (bNAbs) could help treat HIV while minimising the risk of the virus escaping treatment, researchers reported in eLife.

The study shows that computational approaches to selecting combinations of bNAbs based on viral genetics could help prevent viral escape, making HIV treatment more effective. It may also offer a strategy for designing effective combinations of bNAbs for treating other rapidly evolving pathogens.

bNAbs offer a promising new tool to treat or potentially cure infections with rapidly evolving viruses such as HIV. Clinical trials using a single bNAb to treat HIV have shown that some viral strains may survive the treatment and lead to a rebound of viruses in the blood. Combinations of bNAbs may therefore be a more effective approach, but finding the best combinations is a challenge. 

“For our study, we proposed using a computational approach to predict the effectiveness of bNAb combinations based on the HIV genetics,” said researcher Colin LaMont.

LaMont and colleagues analysed the genetics of HIV viruses collected over 10 years from 11 untreated patients with HIV, and used this data to predict which viral strains might be able to escape treatment with different bNAbs and whether dodging bNAbs had a survival cost. Next, using computational methods, they applied the knowledge gained to predict viral rebounds in three real-life trials of bNAbs.

Finally, the team used their computational approach to find a combination of bNAbs that is least likely to allow any virus to escape. They also found that some bNAbs, such as 10-1074, are better against diverse populations of viruses because mutations that allow viruses to escape also make the virus less likely to survive. Others, including PGT121, are more effective against less diverse viral populations because mutations that enable escape are rare. Overall, the results suggested that the optimal combination includes three bNAbs: PG9, PGT151 and VRC01. 

“We’ve shown the combination of PG9, PGT151 and VRC01 reduces the chance of viral rebound to less than 1%,” LaMont said. “It does this by targeting three different regions of the virus’ protective outer wrapping, or envelope.” 

“Combining bNAbs, administered via intravenous infusion every few months, with current antiretroviral therapies (ART) that require daily doses could further improve long-term HIV treatment success,” suggested senior author Armita Nourmohammad, Assistant Professor at the University of Washington.

ART hinders HIV multiplication and ability to create new variants, limiting the genetic diversity of the viral population and reducing the odds of bNAb escape variants emerging. The authors say that more studies are needed to confirm the potential benefits of combining ART and bNAbs. 

“Our study shows that leveraging genetic data can help us design more effective HIV therapies,” Asst Prof Nourmohammad concluded. “Our approach may also be useful for designing therapies against other rapidly evolving agents that cause disease, such as the Hepatitis C virus, drug-resistant bacteria, or cancer tumour cells.”  

Source: eLife Sciences