Tag: HIV

Categories : HIVTags :

HIV Cure A Step Closer With Rare Immune System Discovery

On By ModernMedia
Photo by CDC on Unsplash

Scientists have taken a step closer to understanding how some rare people’s immune systems can suppress HIV.

The innate immune response mounts a fast-acting, general response against pathogens or supports the adaptive immune response, made up of antibodies and T cells that learn to fight specific pathogens after infection or vaccination

In recent years, researchers discovered that some components of the innate immune response can, under certain conditions, also be trained in response to infectious pathogens, such as HIV. 

In a study recently published in the Journal of Clinical Investigation, it was shown that elite controllers, a rare subset of people whose immune system can control HIV without the use of drugs, have myeloid dendritic cells, part of the innate immune response, that display traits of a trained innate immune cell.

“Using RNA-sequencing technology, we were able to identify one long-noncoding RNA called MIR4435-2HG that was present at a higher level in elite controllers’ myeloid dendritic cells, which have enhanced immune and metabolic states,” explained Xu Yu, MD, a Core Member of the Ragon Institute of MGH, MIT and Harvard. “Our research shows that MIR4435-2HG might be an important driver of this enhanced state, indicating a trained response.”

Myeloid dendritic cells’ main role is the support of T cells, which are key to the elite controllers’ ability to control HIV infection. Since MIR4435-2HG was found to be higher only in the cells of elite controllers, Dr Yu explained, it may be part of a learned immune response to infection with HIV. Myeloid dendritic cells with elevated MIR4435-2HG also had greater levels of a protein known as RPTOR, which drives metabolism. Because of this boosted metabolism, the myeloid dendritic cells may better support the T cells controlling the HIV infection.

“We used a novel sequencing technology, called CUT&RUN, to study the DNA of these cells,” says postdoctoral fellow Ciputra Hartana, MD, Ph.D., the paper’s first author. “It allowed us to study epigenetic modifications like MIR4435-2HG, which are molecules that bind to the DNA and change how, or if, the DNA is read by the cell’s machinery.”

The team found that MIR4435-2HG’s mechanism could function by attaching to the DNA near the location of the RPTOR gene. The bound MIR4435-2HG would then prompt cellular machinery to synthesise more RPTOR protein, from the instructions in the RPTOR gene. This kind of epigenetic modification, a ‘trained’ response to HIV infection, would keep the myeloid dendritic cells in a state of heightened metabolism, providing long-term support to the T cells battling the virus.

“Myeloid dendritic cells are very rare immune cells, accounting for only 0.1-0.3% of cells found in human blood,” said Dr Yu. “We were fortunate and thankful to have access to hundreds of millions of blood cells from the many study participants who have donated their blood to support our HIV research. These donations were key to making this discovery.”

A core component of HIV cure research is to figure out exactly how elite controllers’ immune systems can keep HIV under control. By understanding how elite controllers keep the deadly virus in check, scientists could develop treatments to enable other people living with HIV to replicate the same immune response. This would take away the need for daily medication to control the virus, achieving what is known as a ‘functional cure’.

Source: Medical Xpress

Journal information: Ciputra Adijaya Hartana et al, Long noncoding RNA MIR4435-2HG enhances metabolic function of myeloid dendritic cells from HIV-1 elite controllers, Journal of Clinical Investigation (2021). DOI: 10.1172/JCI146136

Categories : HIVTags :

People Most in Need of PrEP Don’t Use It

On By ModernMedia

Though sexual minority men and transgender women are aware of pre-exposure prophylaxis (PrEP), a daily pill to prevent HIV infection, few are currently taking it, a New York-based study has found.

The study, published in the journal AIDS and Behavior, surveyed 202 young sexual minority men and transgender women, who are two high-priority populations for HIV prevention, to better understand the factors in their taking PrEP or not.

According to the Centers for Disease Control and Prevention, sexual minority men are the community most impacted by HIV, making up 69% of all new diagnoses in 2018, and transgender populations are disproportionately affected by HIV and prevention challenges. While Black and Hispanic populations are mostly likely to be newly diagnosed with HIV, PrEP users are more likely to be white.

The research team, who is from the Rutgers School of Public Health’s Center for Health, Identity, Behavior and Prevention Studies (CHIBPS), found that while 98 percent of the study’s participants were aware of PrEP, less than 25 percent were currently taking it.

“It was surprising that so few participants were using PrEP, but we were happy to see that there were no racial or ethnic disparities in who was using it,” Caleb LoSchiavo, Study Co-Author and Doctoral Candidate, School of Public Health, Rutgers University. “I think the study results point to the effectiveness of local efforts to increase the use of PrEP for those who need it most.”

While the study PrEP found no differences in use use, it also found racial and ethnic differences in factors associated with taking it. White participants were more likely to use PrEP with increased age, and were less likely to use it if they held concerns about daily medication use. Participants of colour, however, were more likely to use PrEP if they received information about it from a health care provider and if they had more positive beliefs about its use.

“Our study highlights the importance of clinicians in expanding the use of HIV prevention methods like PrEP among those who need it most, both through informing their patients about PrEP and through combating stigmatizing beliefs about PrEP use,” said senior study author Perry N Halkitis, dean of the Rutgers School of Public Health and director of CHIBPS.

The researchers said that the study emphasised the importance of PrEP education in clinical settings.

“Positive public health messaging about PrEP must reframe risk, combat stigma and normalize preventive healthcare,” LoSchiavo said.

Source: News-Medical.Net

Journal information: Jaiswal, J., et al. (2021) Correlates of PrEP Uptake Among Young Sexual Minority Men and Transgender Women in New York City: The Need to Reframe “Risk” Messaging and Normalize Preventative Health. AIDS and Behavior. doi.org/10.1007/s10461-021-03254-4.

Categories : HIVTags :

Home Deliveries of Antiretrovirals Worked Better for SA HIV Patients

On By ModernMedia

A study investigating the feasibility of home delivery of antiretroviral therapy (ART) was well received and had significantly more participants achieving viral suppression.

In South Africa, 27% of the population is HIV positive, with viral suppression achieved only in 64% of the population. Post-apartheid healthcare reforms have done little to improve access to healthcare for most South Africans. HIV positive pregnant women, for example, have difficulty achieving viral suppression for a number of reasons including crowded clinics that are often at a great distance.

To investigate the feasibility of home delivery of ART recruited 162 people living with HIV, 88% of those randomised to home delivery experienced viral suppression (defined as viral loads less than 100 copies/ml) compared to 74% of those randomised to clinic visits, reported Ruanne Barnabas, MBChB, DPhil, of the University of Washington. The participants were followed for a median of 47 weeks, even during COVID restrictions.

Dr Barnabas reported that the difference was even more pronounced in men (64% in clinic group vs 84% in delivery group). This is important as there are gaps in viral suppression with standard, clinic-based ART, especially among men and priority populations. Home ART delivery and monitoring can increase access and the intention to treat.

“If a client pays for the service, and the benefits are sufficient, this could become a scalable strategy,” Dr Barnabas said. This could help achieve UNAIDS viral suppression targets for South Africa of 86%, she added.

Dr Barnabas described the home delivery as an Amazon Prime-type service, where clients paid an income-scaled one-time fee, for ART delivery and monitoring.

Viral load testing was a secondary objective while testing of the ability to pay the fee and the acceptability of the service was the primary objective. The participants were from a lower income group, with 19% being labourers or semi-skilled workers, and 60% unemployed.

The participants responded well to the home delivery, with 98% of participants paying the fee, and 100% saying they thought the fee was reasonable, that it reminded them to take their medications, and that they would continue to pay it if delivery was available. The next step would be to see if the service could be financially viable if scaled up. 

Source: MedPage Today

Presentation information: Barnabas R, et al “Fee for home delivery and monitoring of ART raises viral suppression in South Africa” CROI 2021; Abstract 111LB.

Categories : HIVTags :

Revolutionary HIV Prophylaxis Pill Rollout in SA

On By ModernMedia

Amidst the COVID pandemic and concerns about vaccines, the South African government is rolling out a gaming-changing pill that protects against contracting HIV.

Due to delays including COVID-19, the revolutionary HIV pre-exposure prophylaxis (PrEP) pill is currently only available at 36% of public healthcare facilities – but the impact as it is rolled it will be significant.

Yogan Pillay, Deputy Director for Communicable and Non-Communicable  Diseases, Prevention, Treatment and Rehabilitation at the National Department of Health, says the PrEP pill will be available at all public healthcare providers by the end of September this year.

The pill combines two antiretrovirals, tenofovir disoproxil fumarate and emtricitabine (TDF/FTC), and gives nearly complete protection against contracting HIV. Over the past 4 years, over 50 000 people received the pill during trials. Young women and adolescent girls aged 15 to 24 are at four times higher risk of contracting HIV than males the same age, and since they may not be in a position to negotiate condom use, PrEP allows them to reduce the risk of contracting HIV through sexual activity. The TDF/FTC pill takes seven days to achieve full protection, and should be continued to be taken 28 days after the last HIV exposure. Periodic HIV and kidney function tests will be administered after the first month.

“The PrEP targets in the National Strategic Plan (NSP) for HIV, TB and STIs 2017-2022 is 85 000,” said Pillay. “We do however estimate based on the uptake trend at the current PrEP sites that approximately 10.5% of HIV negative persons offered PrEP will take up PrEP.”

The TDF/FTC pill can be taken at any point of the day, with alcohol, and is compatible with the use of birth control pills and other contraceptives. The pill will be made available through the public sector to any HIV negative person with healthy kidneys willing to take it daily. The TDF/FTC pill can only be prescribed by NIMART (Nurse Initiated Management of Antiretroviral Therapy) trained nurses, not other nurses or clinical associates at this time.

Source: Spotlight

Categories : COVID HIVTags :

Novavax COVID Vaccine only 49.4% Effective in SA

On By ModernMedia

On Thursday, Novavax announced that its vaccine was 89% effective, according to its UK trials which had 15 000 participants. However, its SA trials showed a much lower effectiveness of 49.4%, believed to be caused by the SA COVID variant B.1.351 (aka 501.V2). 

The company conveyed the information in a press release, with a detailed journal publication still to come. The SA trial had 4400 participants, and the observed protection varied depending on HIV status. In people who were HIV negative, the vaccine conferred 60% protection. If the vaccination trial included a representative proportion of HIV positive adult South Africans, it may mean that its effectiveness for this vulnerable segment is very low.

“The higher efficacy of the vaccine in the UK than in South Africa is because the variants circulating in SA are less sensitive to vaccine induced immune responses,” said Professor Shabir Madhi, Executive Director of the Vaccines and Infectious Diseases Analytics Research Unit (VIDA) at Wits, and principal investigator in the Novavax COVID vaccine trial in SA.

“Nevertheless, the 60% reduced risk against Covid-19 illness in vaccinated individuals in South Africans underscores the value of this vaccine to prevent illness from the highly worrisome variant currently circulating in South Africa, and which is spreading globally. This is the only Covid-19 vaccine for which we now have objective evidence that it protects against the variant dominating in South Africa.”

Novavax is pressing ahead with a trial involving 30 000 participants in the United States and Mexico, and has shared data with the UK’s pharmaceutical regulator. It is not clear whether the data from the US and Mexico trial will be required before the vaccine receives approval there. Meanwhile on Friday, the Johnson & Johnson vaccine developed by its subsidiary Janssen has been shown to be 66% effective. It is a single dose vaccine with minimal refrigeration requirements, making it very important for the logistical challenge of vaccinations in developing countries. Since Aspen would be producing some of the doses locally, the SA government had been in talks with Johnson & Johnson to secure some of those vaccines for SA use. However, there are signs that it too is less effective against the B.1.351 variant.

Source: Business Insider

Categories : UncategorizedTags :

HIV Prophylactic Injection 9 Times More Effective than Oral Administration

On By ModernMedia

According to The Citizen, researchers have reported that pre-exposure prophylaxis (PrEP) in the form of an injection once every eight weeks was 9 times more effective than a daily oral pill in preventing HIV contraction. The daily pill is currently the standard PrEP available to the public.

Dr Sinead Delany-Moretlwe, director of research at the Wits Reproductive Health and HIV Institute (Wits RHI), said, “We know that adherence to a daily pill continues to be challenging, and an effective injectable product such as a long-acting CAB [cabotegravir injection] is a very important additional HIV prevention option for them. We are grateful to the women who volunteered for this study and the research staff, as this study would not have been possible without their commitment to HIV prevention.”

The HIV Prevention Trials Network (HPTN) took place over several years, measuring the effectiveness of PrEP in preventing the contraction of HIV.  3223 cisgendered women with an average age of 26 were enrolled in the study in South Africa, Botswana, Eswatini, Kenya, Malawi, Uganda and Zimbabwe. The trial found that of 38 women who contracted HIV, four were receiving the injection while the remainder were using the oral pill.

Executive director of Wits RHI, Professor Helen Rees, said, “These results are a milestone for prevention of HIV among women at risk worldwide and especially for women in sub-Saharan Africa. If we are to turn the tide on the HIV epidemic, we will need prevention options that work for women in sub-Saharan Africa. These findings provide great hope and motivation for additional studies to show safety and acceptability in adolescents, pregnant and breastfeeding women.”

The game-changing medication will not be available to the public until further testing is completed. 

Categories : HIV PoliticsTags :

UNAIDS Calls for Renewed Action and Sets 2025 Targets

On By ModernMedia

In a press release, UNAIDS reflects on the current state of the fight against HIV and AIDS, and notes that while there are numerous setbacks, it is possible to renew the fight.

It notes that the global response to HIV was already flagging before the advent of the COVID pandemic, and this has only pushed back the effort further. According to the agency, projections show 123 000 to 293 000 additional new HIV infections, along with 69 000 to 148 000 additional AIDS-related deaths between 2020 and 2022.

The agency strongly criticised the lack of political commitment which has led to this combined blow.  Winnie Byanyima, Executive Director of UNAIDS  said, “The collective failure to invest sufficiently in comprehensive, rights-based, people-centred HIV responses has come at a terrible price. Implementing just the most politically palatable programmes will not turn the tide against COVID-19 or end AIDS. To get the global response back on track will require putting people first and tackling the inequalities on which epidemics thrive.” 

By proposing bold new targets for 2025, UNAIDS believes that the world can successfully meet its goal of ending HIV as a public health threat by 2030. The goals include reducing discrimination against HIV sufferers, removing punitive laws and combating gender inequality and gender-based violence. However, not all is negative: countries such as Botswana and eSwatini have already exceeded their 2020 targets. There are other positive spots, such as the infrastructure used to fight HIV/AIDS being leveraged in the fight against COVID.

Source: UNAIDS

Categories : HIV Immune SystemTags :

HIV Vaccine Search is a Marathon

On By ModernMedia

While COVID vaccines have appeared in a record-breaking short time, an HIV vaccine is still yet to arrive – though not without good reasons, as The Daily Maverick reports.

Mitchell Warren, executive director of AVAC, a US-based HIV advocacy organisation explained: “There is still no conclusive research on what type of immune response an HIV vaccine should be trying to trigger.”

“With HIV, you’re trying to do better than nature,” continued Warren. “With a Covid-19 vaccine, the jab merely has to do what nature is doing already — in the form of an immune response — just faster. But with HIV, you’re trying to do better than nature because your body isn’t able to successfully fight off the virus.”

HIV mutates quite rapidly, to the point where there are now two distinct strains, HIV-1 and HIV-1, complicating the process. SARS-CoV-2 on the other hand uses a process called proofreading when it replicates, ensuring a lower rate of mutations.

There are currently three vaccines in development; HPX2008/HVTN 705: Imbokodo and HPX3002/HVTN 706: Mosaico both use adenoviruses to deliver protein fragments of the HIV virus to train the immune system to respond to it. The “Imbokodo” is being trialled with young women, and “Mosaico” is being trialled with transgender men and men who have sex with men, and expected to end in 2022 and 2024 respectively. 

The PrEPVacc vaccine uses DNA inserted into plasmids, which induce the body to produce the virus’ proteins, but not the virus itself. The two shots contain a cocktail of proteins and the plasmids to train the immune system. The trial is expected to end in 2023

Categories : Genetics HIV T-cellsTags :

Long-term HIV Immunisation in Mice with Gene Technology

On By ModernMedia

While some COVID vaccines are entering the final phases of approval less than a year before the disease was first identified, HIV still has no vaccine after decades of research.

Now, engineered immune cells have elicited a response against HIV in mice, presenting an important first step forward in the quest for a vaccine. These broadly neutralising antibodies (bnabs) are effective against a variety of viruses and neutralise the glycan protecting HIV’s proteins.

Previous research had engineered B cells that produced the same antibodies as seen in rare HIV patients who are able to produce bnabs against HIV after many years. Now, this research has shown that it was possible to mature these into memory and plasma cells, conferring long-lasting protection and even showing improved antibodies can be produced, as in the immunisation process.

Principal investigator James Voss, PhD, of Scripps Research said, “This is the first time it has been shown that modified B cells can create a durable engineered antibody response in a relevant animal model.”

Currently it appears it would be an expensive therapy and a great barrier to many of the 38 million living with HIV around the world. A blood draw would be taken to the lab to engineer a vaccine for the patient, but Voss says that his team is looking to make the procedure inexpensive.

“People think of cell therapies as being very expensive,” Voss said. “We’re doing a lot of work towards trying to make the technology affordable as a preventative HIV vaccine or functional cure that would replace daily antiviral therapy.”

Source: Science Daily

Categories : HIVTags :

HIV Death Rates in Men Far Exceed Women in SA

On By ModernMedia

At a virtual conference on Tuesday, the South African National AIDS Council (Sanac) showcased their updated Thembisa model, which is the definitive model for HIV prevalence and incidence in the country.

Between 2000 and 2019, there was a 57% drop in incidence, or new infections, which falls short of the UN target of 75% reduction.  Antiretroviral therapy (ART) coverage is 71% of those infected with HIV.

About 13% of South Africans are currently living with HIV, which is partly a result of longer life expectancy thanks to ART. Among female sex workers, the prevalence is 55%. Due to biological and social factors, the prevalence rate is higher among women but the death rate from HIV is higher in men, due to less ART coverage than in women.

The new Thembisa model also showed the country’s progress towards UNAIDS 90-90-90 model (90% knowing their HIV status, 90% on ART, 90% viral suppression). Although 94% of women and 91% of men knew their statuses, only 74% of women and 71% of men were on ART. Fortunately, 92% of both sexes achieved viral suppression. 

SA’s National Strategic Plan for HIV, TB and STIs is due to be renewed in 2022.

Source: Daily Maverick