Category: HIV

Categories : HIVTags :

Inconsistent PrEP Use for HIV in High-risk Groups

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HIV infecting a human cell. Credit: Seth Pincus, Elizabeth Fischer and Austin Athman, National Institute of Allergy and Infectious Diseases/NIH

A large, in-depth look at US patients taking HIV-prevention drug therapy found strong adherence soon after patients get the prescription, but less consistent use thereafter, particularly among groups considered to be high-priority.

The study, published in JAMA Network Open, examined data from 13 906 members of Kaiser Permanente referred for pre-exposure prophylaxis, or PrEP, therapy between 2012 and 2019. The study found certain groups were more likely to stop taking PrEP: young people, Black and Latino individuals, women, and people with substance use disorders.

The findings suggest targeted strategies are needed to support use of this effective prevention in high-risk groups, said lead author Carlo Hojilla, RN, PhD, a research fellow with the Kaiser Permanente Northern California Division of Research.

“The findings have important implications that suggest access to health care is a great way to get people in the door, but we need more effective strategies for making sure people who have an ongoing need for PrEP stay on the medication,” said Dr Hojilla. “These are groups we want to reach, and we need innovative approaches to keep them engaged in PrEP care.”

Some 88% of patients referred for HIV prevention care received a PrEP prescription, and most (98%) of them filled their initial prescriptions. “These findings were encouraging,” Dr Hojilla said. “Kaiser Permanente has managed to do really well increasing uptake of PrEP therapy.”
However, significant inconsistency in use was seen with about half of users discontinuing PrEP at least once; 60% of those filled a prescription again though the study did not explore the reasons for this. Some users may have discontinued PrEP because of a decrease in risk for HIV acquisition, the authors speculated. Medical mistrust, stigma, homophobia, and transphobia as barriers to PrEP uptake and persistence in some communities have been documented in prior studies. Cost was known to be a concern for some, and the study was done before PrEP was provided at no cost, Dr Hojilla said.

The study was also done before the introduction of a new dosing scheme known as 2-1-1, or on-demand, which allows the user to take PrEP only around the time of a potential exposure to HIV, with a similar level of effectiveness as daily dosing. It’s possible that some of the discontinuation reflected in the study was from patients who opted to not take the drug daily because they had only occasional risk exposure, even prior to 2-1-1 dosing being formally recommended, said senior author Jonathan Volk, MD, an infectious disease specialist with The Permanente Medical Group.

No new HIV infections were seen in those remaining on PrEP, the study found. “This shows how incredibly well PrEP works when taken,” Dr Volk said. “But there are important opportunities for us to maximise the population level impact of this vital therapy. To do this, we need to avoid attrition along the care continuum, especially by assisting patients to stay on PrEP throughout periods of risk for HIV acquisition.”

Source: Kaiser Permanente

Categories : Diseases, Syndromes and Conditions HIV UncategorizedTags :

High Burden of Uncontrolled Disease in KwaZulu-Natal

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Photo by Hush Naidoo on Unsplash

A comprehensive health-screening program has found a high burden of poorly controlled or uncontrolled disease KwaZulu-Natal, along with a high incidence of undiagnosed diseases.

The study, published in The Lancet Global Health, found that four out of five women over 30 had a chronic health condition, and that the HIV-negative population and older people had the highest burden of undiagnosed or poorly controlled non-communicable diseases such as diabetes and hypertension. The study was conducted at the Africa Health Research Institute (AHRI).

Study co-leader Emily Wong, MD, at AHRI in Durban, said: “The data will give AHRI researchers and the Department of Health critical indicators for where the most urgent interventions are needed,” Dr Wong said. “The research was done before COVID, but it has highlighted the urgency of diagnosing and treating people with non-communicable diseases — given that people with uncontrolled diabetes and hypertension are at higher risk of getting very ill with COVID.” 

HIV-associated tuberculosis infections are particularly prevalent in Durban. Dr Wong of the University of Alabama works there to understand the impact of HIV infection on tuberculosis pathogenesis, immunity and epidemiology. In sub-Saharan Africa, 15 years of intense public health efforts that increased access to antiretroviral therapy has resulted in decreased AIDS mortality and raised life expectancy. As a result, there is an increasing priority to address other causes of disease, including tuberculosis and non-communicable diseases.

Over 18 months, health workers screened 17 118 people aged 15 years and older via mobile camps within 1 kilometre of each participant’s home in the uMkhanyakude district. They found high and overlapping burdens of HIV, tuberculosis, diabetes and hypertension among men and women.

While the HIV cases were largely well diagnosed and treated, some demographic groups  still had high rates of undiagnosed and untreated HIV, such as men in their 20s and 30s. In contrast, the majority of people with tuberculosis, diabetes or hypertension were either undiagnosed or not well controlled. Of particular concern was the high rates of undiagnosed and asymptomatic tuberculosis discovered, as it remains one of the leading causes of death in South Africa.

“Our findings suggest that the massive efforts of the past 15 years to test and treat for HIV have done very well for that one disease,” Dr Wong said. “But in that process, we may have neglected some of the other important diseases that are highly prevalent.”

The mobile camps screened for diabetes, high blood pressure, nutritional status (obesity and malnutrition), and tobacco and alcohol use, as well as HIV and tuberculosis. The tuberculosis screening component included high-quality digital chest X-rays and sputum tests for people who reported symptoms or had abnormal X-rays. Clinical information was combined with 20 years of population data from AHRI’s health and demographic surveillance research. Using a sophisticated data system combined with artificial intelligence to interpret the chest X-rays, AHRI’s clinical team examined the information in real time, referring people to the public health system as needed.

The study found that: 

  • Half of the participants had at least one active disease, and 12 percent had two or more diseases. Diabetes and hypertension incidences were 8.5 percent and 23 percent, respectively.
  • One-third of the people were living with HIV, but this was mostly well diagnosed and treated. A particularly high burden of HIV, high blood pressure and diabetes was seen in women.
  • For tuberculosis, 1.4 percent of the people had active disease, and 22 percent had lifetime disease. About 80 percent of the undiagnosed tuberculosis was asymptomatic, with higher rates of active tuberculosis seen in men.
  • Several disease patterns varied by geographical location — eg, the highest HIV burden was seen near main roads, while higher rates of tuberculosis and non-communicable diseases were seen in more remote areas.

Source: University of Alabama at Birmingham

Journal information: Wong, E. B., et al. (2021) Convergence of infectious and non-communicable disease epidemics in rural South Africa: a cross-sectional, population-based multimorbidity study. The Lancet Global Health. doi.org/10.1016/S2214-109X(21)00176-5.

Categories : COVID HIVTags :

HIV Increases Risk of COVID Infection and Mortality

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Man with red HIV ribbon on shirt. Photo by Anna Shvets from Pexels

New research shows that individuals living with HIV and AIDS have an increased risk of SARS-CoV-2 infection and death from COVID.

An estimated 38 million people around the world are living with HIV/AIDS, according to the World Health Organization, 7.5 million of whom are in South Africa, according to UNAIDS.

In their review, researchers at  Penn State College of Medicine found that people living with HIV had a 24% higher risk of SARS-CoV-2 infection and a 78% higher risk of death from COVID than people without HIV. They analysed data from 22 prior studies with nearly 21 million participants in North America, Africa, Europe and Asia to determine to what extent people living with HIV/AIDS are susceptible to SARS-CoV-2 infection and death from COVID.

Participants were mostly male (66%) and the median age was 56. The most common comorbidities among the HIV-positive population were hypertension, diabetes, chronic obstructive pulmonary disease and chronic kidney disease. Most patients (96%) were on antiretroviral therapy (ART).

“Previous studies were inconclusive on whether or not HIV is a risk factor for susceptibility to SARS-CoV-2 infection and poor outcomes in populations with COVID-19,” said Dr Paddy Ssentongo, lead researcher and assistant professor at the Penn State Center for Neural Engineering. “This is because a vast majority of people living with HIV/AIDS are on ART, some of which have been used experimentally to treat COVID-19.”

Pre-existing conditions common among people living with HIV/AIDS, may contribute to the severity of their COVID infections, noted the investigators. It remains inconclusive as to whether antiviral drugs, such as tenofovir and protease-inhibitors, reduce the risk of SARS-CoV-2 infection and death from COVID in people with living with HIV/AIDS.

“As the pandemic has evolved, we’ve obtained sufficient information to characterize the epidemiology of HIV/SARS-CoV-2 coinfection, which could not be done at the beginning of the pandemic due to scarcity of data,” said Vernon Chinchilli, fellow researcher and chair of the Department of Public Health Sciences. “Our findings support the current Centers for Disease Control and Prevention guidance to prioritize persons living with HIV to receive a COVID-19 vaccine.”

Source: Penn State University

Categories : HIVTags :

HIV Cure A Step Closer With Rare Immune System Discovery

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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

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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

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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

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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 : Ageing HIVTags :

Anti-HIV Drugs may Combat Macular Degeneration

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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

Categories : COVID HIVTags :

Novavax COVID Vaccine only 49.4% Effective in SA

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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 : HIV PoliticsTags :

UNAIDS Calls for Renewed Action and Sets 2025 Targets

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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