Category: HIV

Home Deliveries of Antiretrovirals Worked Better for SA HIV Patients

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.

Revolutionary HIV Prophylaxis Pill Rollout in SA

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

Anti-HIV Drugs may Combat Macular Degeneration

New research has shown that anti-HIV drugs may fight macular degeneration – overturning a preconception about DNA in the process.

Macular degeneration is the leading cause of blindness in developed countries. Even though HIV does not cause dry macular degeneration, the drugs prevented the loss of vision.

“We are extremely excited that the reduced risk was reproduced in all the databases, each with millions of patients,” said Jayakrishna Ambati, MD, a leading macular degeneration researcher at the University of Virginia School of Medicine. “This finding provides real hope in developing the first treatment for this blinding disease.”

A Big Data Archeology review of four health insurance databases showed that Nucleoside Reverse Transcriptase Inhibitors (NRTIs), a commonly used HIV treatment, reduced the incidence of dry macular degeneration by 40%. The records spanned two decades and covered over 100 million patients. The drugs had also previously been shown to possibly prevent diabetes.

The finding also comes with the discovery that DNA can be produced inside the cytoplasm. Alu DNA (found exclusively in primates), which makes up 10% of the human genome, is transposable and can insert itself into other places on the genome. It was long considered “junk” DNA, but are now believed to have important functions, such as allowing for multiple expressions of proteins from a single Alu element. Since it cannot replicate itself, Alu DNA requires a transposon called L1 to accomplish this, which was now reported to allow the production of Alu DNA outside the chromosome. The buildup of Alu DNA in cells contributes to macular degeneration, by killing off cells that support the retina.
The researchers are urging further investigation into NRTIs or safer derivatives known as Kamuvudines, both of which block a key inflammatory pathway, can be useful in preventing vision loss from dry macular degeneration.

“A clinical trial of these inflammasome-inhibiting drugs is now warranted,” said Ambati. “It’s also fascinating how uncovering the intricate biology of genetics and combining it with big data archeology can propel insights into new medicines.”

Source: Medical Xpress

Journal Information: Shinichi Fukuda el al., “Cytoplasmic synthesis of endogenous Alu complementary DNA via reverse transcription and implications in age-related macular degeneration,” PNAS (2021). www.pnas.org/cgi/doi/10.1073/pnas.202275111

Novavax COVID Vaccine only 49.4% Effective in SA

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

UNAIDS Calls for Renewed Action and Sets 2025 Targets

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

HIV Vaccine Search is a Marathon

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

Long-term HIV Immunisation in Mice with Gene Technology

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

T-cells can detect HIV-1

A new study reported by News 24 shows that T-cells can detect HIV-1 in patients years after commencing antiretroviral therapy (ART): 

In the HIV-1 proteome (the entire set of proteins expressed by the virus) for each participant, the team identified T-cell epitopes (regions of proteins that trigger an immune response). They sequenced HIV-1 ‘outgrowth’ viruses from resting CD4+ T cells and tested mutations in T-cell epitopes for their effect on the size of the T-cell response.

These strategies revealed that the majority (68%) of T-cell epitopes did not harbour any detectable escape mutations, meaning they could be recognised by circulating T cells.

“Our findings show that the majority of HIV-1-specific T cells in people on ART can detect HIV viruses that have the capacity to rebound following treatment interruption,” concludes senior author Nilu Goonetilleke, a faculty member at the Department of Microbiology and Immunology, University of North Carolina at Chapel Hill.

HIV Death Rates in Men Far Exceed Women in SA

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

Many HIV Deaths in Africa Due to Interrupted Care

An article written for The Conversation explores the reasons why, in an era of antiretroviral therapy (ART), so many people around the world are still dying of HIV.

Despite fierce resistance under Thabo Mbeku’s leadership, ART became widely available in South Africa. Yet in 2019, despite the world’s largest ART programme with 71% coverage, there were still 72 000 HIV-related deaths in South Africa. 

Medecins Sans Frontieres (MSF) supports hospitals across Africa in treating people with HIV, but because patients present with advanced HIV up to a third die during their hospital stay.

HIV is a lifelong disease, and requires lifelong treatment. Some struggle to take tablets on a daily basis, risking drug resistance.

People with advanced HIV now typically have interrupted or failing treatment. MSF-funded studies in Kenya and the DRC showed that only 20-35% of patients with advanced HIV had never received ART.

The “Welcome Back Services” provided by Medecins Sans Frontieres in Khayelitsha, Cape Town are an example of getting patients who have lapsed back into care.

In deprived settings, TB is the leading cause of death for people with HIV, along with cryptococcal meningitis and bacterial infection. These are all treatable if caught in time; cryptococcal meningitis effectively has a zero survival rate but mortality can be reduced by 40% when treated with flucytosine and amphotericin B. By testing patients before they reach the stage where hospitalisation is necessary, survival rates can be greatly improved.