Tag: HIV

AstraZeneca Vaccine Confers COVID Protection for People with HIV

Image by Ivan Diaz on Unsplash

Interim results from a phase 1B/2A clinical trial conducted by the Wits Vaccines and Infectious Diseases Analytical (VIDA) research unit showed that the AstraZeneca vaccine conferred COVID protection in people living with HIV.

The findings, published in Lancet HIV, show that the AstraZeneca COIVD vaccine is likely to work as well in people living with HIV compared with people who are HIV negative.

These interim findings are vital for informing the clinical management of people with HIV during the COVID pandemic.

In general, clinical trials which evaluate the safety and immunogenicity of COVID vaccines in people living with HIV are limited, and in Africa they are virtually non-existent. This is despite the overwhelming prevalence of HIV infection in Africa, especially South Africa .

“We searched PubMed for peer-reviewed articles published between 1 January 2019 and 29 June 2021, using the terms ‘safety’ and ‘Covid-19’ and ‘vaccine’, but we did not find any reports that evaluated safety and immunogenicity of COVID vaccines in this population,” said Shabir Madhi, Professor of Vaccinology and Director of Wits VIDA, which led the first South African trial for a COVID vaccine in June 2020.

Compared to the general population, people living with HIV have an increased risk of infectious diseases and have a greater mortality risk when hospitalised with severe COVID.

In addition, compared with HIV-negative individuals, people with HIV are at greater risk for infectious diseases, such as influenza, including during antiretroviral therapy (ART).

Risk factors for severe COVID in people with HIV include more advanced stage of HIV/AIDS, the HIV-1 infection not being virally suppressed, and CD4 counts below 500 cells per microlitre.

The study was an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial. In 2020, the trial enrolled 104 people living with HIV were enrolled in the trial, HIV-negative people. Eligibility criteria for people with HIV included being on ART for at least three months, with a plasma HIV viral load of less than 1000 copies per microlitre.

The HIV study was a unique addition to the AstraZeneca COVID vaccine clinical trial, and aimed to assess safety and immunogenicity of this vaccine in people with HIV and HIV-negative people in South Africa. The primary endpoint in all participants regardless of HIV status was the safety, tolerability, and reactogenicity profile of the AstraZeneca COVID vaccine.

Reactogenicity refers to a subset of reactions that occur soon after vaccination, and are a physical manifestation of the inflammatory response to vaccination. Such symptoms include pain, redness, swelling or induration for injected vaccines, and systemic symptoms, such as fever, myalgia, headache, or rash. In clinical trials, information on expected signs and symptoms after vaccination is actively sought.

The interim findings show that the AstraZeneca COVID vaccine was well tolerated and showed favourable safety and immunogenicity in people with HIV, including heightened immunogenicity in SARS-CoV-2 baseline-seropositive participants.

Source: University of the Witwatersrand

J&J HIV Vaccine Fails in Local Trials

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

Johnson & Johnson and its partners announced preliminary results showing their HIV vaccine trial failed to provide sufficient protection against HIV infection in a population of young women in sub-Saharan Africa.

The vaccine had a favourable safety profile with no serious adverse events.
The Phase 2b HIV vaccine clinical trial was known as the Imbokodo study (also known as HVTN 705/HPX2008), which will now be discontinued. Further analysis of the Imbokodo study is ongoing, and the study has provided enough data to progress with key immunological correlates research.

“The high incidence of HIV among young women in sub-Saharan Africa reminds us that, despite great progress made in treatment and prevention, HIV remains a major health challenge for the region,” said Professor Glenda Gray, President and Chief Executive Officer, South African Medical Research Council (SAMRC) and Imbokodo’s Protocol Chair. “This underscores the need to apply the knowledge that will be gained from this trial to continue to advance the pursuit of a global HIV vaccine.”A parallel, ongoing Phase 3 Mosaico study (HVTN 706/HPX3002) with men who have sex with men and transgender individuals in Europe and Americas will continue due to the different HIV strains that are circulating in the trial areas and the different HIV vaccine regimen.
The HIV regimen consisted of an adenovirus vector containing four mosaic immunogens (Ad26.Mos4.HIV) at four vaccination visits over one year. The Imbokodo regimen contains a soluble protein component (Clade C gp140, adjuvanted with aluminum phosphate) which is administered at vaccination visits three and four. The ongoing Phase 3 Mosaico study is testing a different investigational vaccine regimen that involves the administration of a mosaic-based mixture of soluble proteins (Clade C/Mosaic gp140) at vaccination visits three and four.

Imbokodo participants had four vaccination visits over one year, with the primary endpoint based on new HIV infections through month 24. These data found that 63 of 1109 placebo arm participants compared to 51 of 1079 vaccine arm participants. This analysis demonstrated a vaccine efficacy point estimate of 25.2% (95% confidence interval of -10.5% to 49.3%).

HIV is prevalent in Sub-Saharan Africa, where women and girls accounted for 63 percent of all new HIV infections in 2020. The study enrolled roughly 2600 young women across Malawi, Mozambique, South Africa, Zambia and Zimbabwe. Researchers ensured that any HIV-infected participants in Imbokodo were referred to high-quality HIV treatment and care services. 

Source: PR Newswire

Inconsistent PrEP Use for HIV in High-risk Groups

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

High Burden of Uncontrolled Disease in KwaZulu-Natal

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.

HIV Increases Risk of COVID Infection and Mortality

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

HIV Cure A Step Closer With Rare Immune System Discovery

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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

People Most in Need of PrEP Don’t Use It

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.

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

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