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PrEP is safe and effective for widespread use, research shows

Worldwide, there are only 300,000 people estimated to be taking PrEP. This is far too small a number to prevent 1.8 million new HIV infections.

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New research shows that pre-exposure prophylaxis (PrEP) could be given to millions of people worldwide with no increased risk of safety issues during treatment. 

PrEP is a combination of two drugs that people can take before sex to prevent HIV infection. Existing evidence shows that people who take tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) as PrEP have a 90% lower chance of being infected with HIV than people not taking it.

However, widespread use of TDF/FTC can be justified only if its preventative benefits outweigh potential risks of safety issues. These new results, presented today, show that PrEP is safe to use.

The researchers undertook a meta-analysis of 13 randomized trials with 15,678 participants. People at risk of HIV infection were given either TDF/FTC as PrEP or no treatment (the control, or placebo). There was no significant difference in risk of high grade or serious adverse events comparing PrEP with control. The risk of serious adverse events was almost the same for both groups: 9.4% for those on PrEP and 10.1% for those on placebo. There was also no significant difference in risk of renal or bone adverse outcomes. The risk of bone fractures was 3.7% on PrEP versus 3.3% on no treatment. The risk of significant renal dysfunction was 0.1% on PrEP and 0.1% for no treatment.

“In 2016, there were 1.8 million new HIV infections worldwide and the same number again in 2017,” International AIDS Society President Anton Pozniak said. “Across a range of studies, men who have sex with men have one in 30 chance of contracting HIV in a year. Other particularly vulnerable populations’, such as people who inject drugs or sex workers, have a one in 50 chance of being infected with HIV.

READ:  871 new HIV cases reported in Phl in Feb. 2018

“Worldwide, there are only 300,000 people estimated to be taking PrEP. This is far too small a number to prevent 1.8 million new HIV infections. Clearly, to have a significant effect on the HIV epidemic, we need to scale up PrEP to reach tens of millions of people worldwide.”

Other PrEP modalities, such as long-acting injectable drugs and antibodies, are being tested in order to offer more choices of how PrEP could be taken.

“Globally, there is a new HIV infection every 18 seconds,” study co-author Dr Andrew Hill, from Liverpool University, said. “Every person newly infected will then need to be treated for life, and could transmit HIV to others. We need radical changes in our prevention strategy to cut new HIV infections down to zero.”

The most widely used PrEP, a combination of TDF and FTC, costs only £40 per year to make. A generic TDF/FTC course is available in the UK for £300 per year and £50 in sub-Saharan Africa. With recent legal rulings, low-cost, generic PrEP is becoming more available. This provides an opportunity, with the decreasing costs making it increasingly feasible to provide PrEP to millions of people at risk of HIV worldwide.

“The World Health Organization updated its official guidelines in 2015 to include the use of PrEP as a prevention method,” Dr. Pozniak commented. “The data is clear and it’s time to globally implement this recommendation.”

These results are supported by another recent analysis, which showed no difference in adverse events between TDF/FTC and a combination of tenofovir alafenamide (TAF) and FTC when taken for treatment with an additional antiviral drug.

READ:  @health_worker5: Taking the challenge to make life better

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Severe anti-LGBT legislations associated with lower testing and awareness of HIV

A meta-analysis involving 44,993 men who have sex with men finds that anti-LGBT legislation is associated with lower HIV testing and awareness.

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A meta-analysis involving 44,993 men who have sex with men finds that anti-LGBT legislation is associated with lower HIV testing and awareness.

This first systematic review to investigate HIV testing, treatment and viral suppression in men who have sex with men in Africa finds that among the most recent studies (conducted after 2011) only half of men have been tested for HIV in the past 12 months. In addition, only a quarter of men living with HIV were on antiretroviral therapy or virally suppressed.

The analysis, published in The Lancet HIV journal, found that testing for HIV was higher where there was more protective and progressive legislation and fewer or no LGBT-related arrests.

Although rates of testing are substantially higher than before 2011, they are not sufficient to achieve the targets set by the UN (to have 90% of people living with HIV aware of their status, 90% of those aware also on antiretroviral therapy, and 90% of these achieving viral suppression by 2020). The findings support previous country-level studies suggesting an association between anti-LGBT legislation and access to testing and treatment.

Globally, men who have sex with men are about 28 times more likely to be living with HIV than are men in the general population, and this is particularly apparent in sub-Saharan Africa where human rights of these men are often violated. Anti-LGBT discrimination creates barriers to implementing effective HIV research, policy and health programs along with disruption of services provided by community and non-governmental organizations.

READ:  Interventions needed to reach older adults and ethnic minorities to address HIV testing, beliefs

Professor Marie-Claude Boily of Imperial College London, UK says: “Nearly one million people living with HIV still die annually because they cannot or do not get tested and engage in treatment. Our results suggest that despite improvements in recent years in Africa, engagement in HIV testing and treatment among men who have sex with men is still low, and additional efforts are urgently needed. With an estimated 67% of men who have sex with men in Africa surveyed after 2011 having ever tested for HIV, we are still a long way off achieving the UNAIDS 90-90-90 targets.”

The review used 75 independent studies conducted between 2004 and 2017 from 28 African countries to estimate HIV testing, status awareness, engagement in care, antiretroviral therapy use, and viral suppression in the men.

Over all studies conducted after 2011, the estimated proportion of participants ever tested for HIV was 67%, which was 1.3 times higher than before 2011, and was highest in southern Africa (80%) and lowest in northern Africa (34 %). In comparison, the proportion of men tested in the last 12 months was 50% in studies after 2011, which was 1.6 times higher than before 2011, and again was highest in southern but lowest in eastern Africa (67% vs 40%).

The proportion of men who have sex with men who are HIV positive and aware of their status was much lower at just 19%, and was particularly low in eastern Africa even after 2011 (9%). Overall, less than 24% of men living with HIV were currently on antiretroviral therapy, and an estimated 25% of men living with HIV were currently virally suppressed. It was not possible to look at changes over time as there was not enough data in the studies on these outcomes.

READ:  When hookup apps can save lives

Levels of HIV testing ever, in the past 12 months, and HIV status awareness were lower in countries with the most severe anti-LGBT legislation, compared with countries with the least severe legislation. Men were more likely to have ever been tested for HIV in countries with more protective and progressive legislation and no LGBT-related arrests from 2014-17.

The authors note some limitations, including that there were no studies in 26 African countries, including 13 countries where same-sex relations are illegal, so the new findings may not apply to the entire African continent and results may be worse in countries with more severe anti-LGBT legislation. Despite a substantial increase in the number of studies on testing for HIV, treatment and viral suppression, data remains scarce for all outcomes except HIV testing, especially from central and northern Africa. This means the study may underestimate or overestimate engagement, especially for antiretroviral therapy use and viral suppression. The authors note that this reflects the challenges of doing research among key populations that face substantial stigma.

The anti-LGBT legislation index used in the study only includes information about legislation, not how it is implemented so may not have captured the full picture. Because most of the studies included were self-reported and used non-confidential interview methods, underreporting and reporting biases are possible.

In a linked Comment article, Dr Jean Joel Bigna of the Centre Pasteur of Cameroon, Yaoundé, Cameroon, says: “Stannah and colleagues have provided important updates on the current situation regarding the HIV care cascade among men who have sex with men in Africa, and highlight areas where urgent action is needed. Governments in Africa should develop comprehensive programs and holistic interventions to provide care, support, and preventive services for this hard-to-reach stigmatized and discriminated vulnerable population. Community mobilization, health-care worker education to decrease stigma and discrimination and engagement remain crucial to end the HIV/AIDS pandemic both globally and at its epicenter in Africa. Human rights are universal and sexual orientation is no grounds for exclusion.”

READ:  @health_worker5: Taking the challenge to make life better

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HIV-negative babies of women with HIV may have compromised health

A study found that maternal HIV infection leaves “profound and lasting impacts” on the HIV-exposed uninfected (HEU) infant. These impacts include: increased mortality and morbidity, immunological changes, and developmental delays compared to their HIV-unexposed (HU) counterparts.

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A study found a link between prenatal HIV exposure and decreased infant immunity despite HIV-negative status at birth.

Analysis of the TCR Repertoire in HIV-Exposed but Uninfected Infants” was written by Benjamin Gabriel, Carey Medin, Jeremiah Alves, Ruth Nduati, Rose Kerubo Bosire, Dalton Wamalwa, Carey Farquhar, Grace John-Stewart and Barbara L. Lohman-Payne, and appeared in Scientific Reports.

The study found that maternal HIV infection leaves “profound and lasting impacts” on the HIV-exposed uninfected (HEU) infant. These impacts include: increased mortality and morbidity, immunological changes, and developmental delays compared to their HIV-unexposed (HU) counterparts.

Exposure to HIV or antiretroviral therapy may influence immune development, which could increase morbidity and mortality. But a direct link between the increased mortality and morbidity and the infant’s immune system has not been identified.

And so to arrive at their conclusions, the researchers compared the T-cell receptor beta-chain repertoire of cord blood samples of HEU yet uninfected infants to samples collected from mother-child pairs unaffected by HIV, but who were living in the same communities.

The researchers found that while the TRB repertoire of HU infants was broadly diverse, in line with the expected idea of a naïve T cell repertoire, samples of HEU infants showed a significantly reduced TRB diversity.

Simply put, “despite the success of antiretroviral therapies in helping to suppress the risk of HIV being passed from mother to child, globally, HIV-exposed uninfected infants are a vulnerable population characterized by increased morbidity and mortality, higher rates of hospitalizations and childhood infections with more severe outcomes.”

READ:  This is not 'Hide and Seek'

More than anything, the findings of the study emphasizes the need for special care and attention to this group.

Support for this work came from the National Institute of General Medical Sciences of the National Institutes of Health (NIH).

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1,006 Filipinos infected with HIV in June; 54 from 10-19 age group

In June 2019, the HIV/AIDS & ART Registry of the Philippines reported 1,006 newly confirmed HIV-positive individuals. Notably, 29% were among youth 15-24 years old; 95% were male. Almost all (99%) were infected through sex.

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No, things are not getting better.

The HIV situation of the country continues to worsen; this even as the government continues to falter in providing life-saving antiretroviral medicines to those already living with HIV in the country.

In June 2019, the HIV/AIDS & ART Registry of the Philippines (HARP) reported 1,006 newly confirmed HIV-positive individuals. Nineteen percent (194) had clinical manifestations of advanced HIV infection (WHO clinical stage 3 or 4) at the time of diagnosis.

More than a third (34%, 346) were from the National Capital Region (NCR). Region 4A (15%, 155), Region 3 (11%, 114), Region 7 (8%, 78), and Region 6 (6%, 56) comprised the top five regions with the most number of newly diagnosed cases for the month, accounting for 74% of the total.

YOUNG STILL MOST AFFECTED

Notably, 296 (29%) cases were among youth 15-24 years old; 95% were male. Almost all (99%, 295) were infected through sexual contact (25 male-female sex, 193 male-male sex, 77 sex with both males and females).

Further broken down, there were 54 newly-diagnosed adolescents (10-19 years old at the time of diagnosis). Further, nine cases were 15-17 years old, and 45 cases were 18-19 years old. Almost all (98%) were infected through sexual contact (four male-female sex, 37 male-male sex, and 12 had sex with both males and females).

In addition, there were three diagnosed cases less than 10 years old; all were infected through vertical transmission (formerly, mother-to-child transmission).

FOCUS ON MSM

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Ninety-five percent (951) of the new cases reported in June were male. The median age was 28 years old (age range: 2-77 years old). More than half of the cases (52%, 522) were 25-34 years old and 29% (296) were 15-24 years old at the time of testing.

Sexual contact remained as the main mode of HIV transmission (98%, 983). Among the newly diagnosed, 59% (589) reported transmission through male to male sex, 26% (260) through sex with both males and females, and 13% (134) were through male to female sex.

Other modes of transmission were sharing of infected needles (1%, 9) and vertical transmission (<1%, 3).

Among the newly diagnosed females for this month, five were pregnant at the time of diagnosis. Two cases each were from NCR and Region 7, and one case was from Region 6.

ACCESS TO MEDS STILL PROBLEMATIC

Perhaps continuing to highlight the ongoing issue with accessing life-saving antiretroviral medicines (ARVs) in the Philippines, only 702 of the new PLHIVs were initiated on antiretroviral treatment/therapy (ART).

To date, even if there are 68,401 confirmed HIV cases reported to the HARP, only 38,903 PLHIVs are presently on ART as of June 2019. The Department of Health continues to have issues in procuring medicines that could save people’s lives; even if it was able to allocate resources to hold a beauty pageant.

DOH’s efforts have long been criticized to be lacking – e.g. aside from finally-admitted procurement issues that cause havoc in ARV distribution and therefore access to them, even the June 2019 report from HARP noted delays in submission of reports (sans reported sanctions) of institutions it accredited to provide services to PLHIVs, particularly naming Imus Social Hygiene Clinic and Davao Doctors Hospital.

READ:  Interventions needed to reach older adults and ethnic minorities to address HIV testing, beliefs

SPECIAL POPULATIONS

Sixty-one Filipinos who worked overseas within the past five years, whether on land or at sea, were diagnosed to be HIV-positive in June. They comprised 6% of the total newly diagnosed cases for the month. Of these, eighty-five percent (52) were male. Ninety-seven percent were infected through sexual contact (18 male-female sex, 29 male-male sex, and 12 sex with both males and females). The ages of male OFWs ranged from 22 to 57 years (median: 32 years); six were aged 35-49 years old; and one case each were from age groups 15-24, 25-34, and 50 and older.

Among the nine female OFWs diagnosed in June, one was 15-24 years old, one was 25-34, six were aged 35-49 years old, and one was 50 years old and older at the time of testing. The age range among diagnosed female OFWs were 24 to 50 years (median: 38 years).

Still in June, 12% (123) of the newly diagnosed engaged in transactional sex.

People who engage in transactional sex are those who reported that they either pay for sex, regularly accept payment for sex, or do both. Reporting of transactional sex was started in December 2012.

Ninety-eight percent (121) of those who engaged in transactional sex were male and aged from 16 to 77 years old (median: 30 years). Sixty percent (73) of the males reported paying for sex only, 31% (37) reported accepting payment for sex only, and 9% (11) engaged in both.

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Among the two female cases who engaged in transactional sex, both were reported to have accepted payment for sex.

Meanwhile, five pregnant women were newly diagnosed with HIV. Two cases were from NCR and Region 7 and one case was from Region 6. The age of diagnosis ranged from 26 to 40 (median age: 30).

Reporting of pregnancy status at the time of testing was included in 2011.

DEATHS AMONG PLHIVs

In June, there were 102 reported deaths due to any cause among PLHIVs.

The figure may not show the real picture, however, because of under-reporting.

In any case, of the 102 deaths, 92% (94) were males. Eleven (11%) cases were 15-24 years old at the time of death, 55 (54%) were 25-34 years old, 33 (32%) were 35-49 years old, and three (3%) were 50 years and older.

Ninety-six percent of the cases were reported to have acquired the infection through sexual contact: 18 through male-female sex, 51 through male-male sex, and 29 through males who have sex with both males and females. Three (3%) were infected through sharing of needles. One (1%) had no data on mode transmission.

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HIV vaccine nears clinical trial following new findings

A vaccine that clears an HIV-like virus from monkeys is closer to human testing after a new, weakened version of the vaccine has been shown to provide similar protection as its original version.

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A promising vaccine that clears an HIV-like virus from monkeys is closer to human testing after a new, weakened version of the vaccine has been shown to provide similar protection as its original version.

A pair of papers published in Science Translational Medicine describe how the vaccine – which uses a form of the common herpes virus cytomegalovirus, or CMV – was live-attenuated, or weakened so CMV couldn’t spread as easily. The new version still managed to eliminate SIV, the monkey version of HIV, in 59% of vaccinated rhesus macaques. That result is similar to earlier findings involving the vaccine’s original, non-attenuated version. The immunity generated by the attenuated vaccine was also long-lasting, as nine of 12 vaccinated monkeys could still fight off SIV infection three years later.

Having an attenuated version of the vaccine is key to being potentially able to use it in humans. No vaccines use non-attenuated live viruses due to safety concerns. Though humans are often infected with CMV without any trouble, the virus can wreak havoc on those with weakened immune systems such as people with organ transplants. It’s also dangerous for pregnant women, as it can cause congenital defects such as hearing loss and microcephaly in babies.

“This research, using rhesus CMV, provides potentially important insights into the design of a human CMV-based HIV vaccine,” said Klaus Früh, Ph.D., a corresponding author on one of the papers. “We significantly attenuated CMV and still got the same type of immune responses as with the wild version of this vaccine.”

READ:  871 new HIV cases reported in Phl in Feb. 2018

“These papers are important because they recapitulate the previously reported unique CMV vector efficacy with a genetically modified vector that is highly attenuated and therefore potentially safer for clinical use,” said Louis Picker, M.D., a corresponding author on both papers. “In addition, this new work demonstrates most vaccinated rhesus macaques that are protected against SIV can also be protected against a second challenge years after initial vaccination. This is a level of durability that would be very important for a human HIV vaccine”.

Picker and Früh are professors at OHSU’s Vaccine & Gene Therapy Institute and affiliated faculty in the OHSU School of Medicine’s department for molecular microbiology and immunology.

The CMV vaccine platform has been licensed by Vir Biotechnology, Inc., of San Francisco, which plans to lead a clinical trial with a human version of the CMV-based HIV vaccine. The same platform is also expected to be used for vaccines being developed to fight tuberculosis.

REFERENCES:

Emily E. Marshall, Daniel Malouli, Scott G. Hansen, Roxanne M. Gilbride, Colette M. Hughes, Abigail B. Ventura, Emily Ainslie, Andrea N. Selseth, Julia C. Ford, David Burke, Caraig N. Kreklywich, Jennie Womack, Alfred W. Legasse, Michael K. Axthelm, Chrisoph Kahl, Daniel Streblow, Paul T. Edlefsen, Louis J. Picker and Klaus Früh, “Enhancing safety of cytomegalovirus-based vaccine vectors by engaging host intrinsic immunity,” Science Translational Medicine, July 17, 2019, DOI: 10.1126/scitranslmed.aaw2603

Scott G. Hansen, Emily E. Marshall, Daniel Malouli, Abigail B. Ventura, Colette M. Hughes, Emily Ainslie, Julia C. Ford, David Morrow, Roxanne M. Gilbride, Jin Y. Bae, Alfred W. Legasse, Kelli Oswald, Rebecca Shoemaker, Brian Berkemeier, William J. Bosche, Michael Hull, Jennie Womack, Jason Shao, Paul T. Edlefsen, Jason S. Reed, Ben J. Burwitz, Jonah B. Sacha, Michael K. Axthelm, Klaus Früh, Jeffery D. Lifson, Louis J. Picker, “A live-attenuated RhCMV/SIV vaccine shows long-term efficacy against heterologous SIV challenge,” Science Translational Medicine, July 17, 2019, DOI: 10.1126/scitranslmed.aaw2607

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OTHER LINKS:

Louis Picker, M.D.: https://www.ohsu.edu/vaccine-gene-therapy-institute/louis-picker-md

Klaus Früh, Ph.D.: https://www.ohsu.edu/vaccine-gene-therapy-institute/klaus-fruh-phd

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Repeated semen exposure may help prevent HIV infection in women, says study

But semen-treated animals that remained uninfected after exposure to low viral amount became infected when subsequently challenged with high doses of virus, confirming that they were still susceptible to infection and that repeated semen exposure provides only partial protection and does not block HIV infection.

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Semen exposure CAN promote host resistance but DOES NOT protect against infection.

This is according to scientists at The Wistar Institute and the University of Puerto Rico, who found that frequent and sustained semen exposure can change the characteristics of the circulating and vaginal tissue immune cells that are targets for infection, reducing the susceptibility to a future infection. This goes contrary to the long-held view that semen can only act as a way to transmit HIV-1 from men to women.

This finding, published in the journal Nature Communications, also provides a potential explanation as to why a small number of female sex workers worldwide continue to test negative for infection despite continuous high-risk sexual activity.

Research previously reported by the laboratory of Luis J. Montaner, D.V.M., D.Phil., the Herbert Kean, M.D., Family Professor and director of the HIV-1 Immunopathogenesis Laboratory at Wistar’s Vaccine & Immunotherapy Center, together with investigators at the University of Puerto Rico, showed in a 2015 paper how continued semen exposure in female sex workers resulted in changes in the cervicovaginal tissue that predicted an increased resistance to HIV infection. The current study directly addressed if semen could be a factor in resistance.

“While HIV infection has been with us for more than 30 years, this is the first study that describes how semen exposure over time could result in local tissue changes that limit HIV infection in humans,” said Montaner, lead author of the new study. “Apart from defining a new factor that may regulate HIV transmission, this unexpected finding could directly impact the design of future HIV vaccine studies that commonly recruit female sex workers. Currently, condomless sex is assumed to only promote the likelihood of infection. Our observation, however, raises the hypothesis that frequent semen exposure may potentially reduce HIV transmission.”

READ:  54% of April's HIV cases from 25-34 age group; and 29% are 15-24 years old at time of testing

According to Edmundo N. Kraiselburd, Ph.D., professor at the University of Puerto Rico (UPR), “this research clearly shows the valuable information the macaque model can provide when used to study what may determine HIV infections in humans.”

Kraiselburd co-directed this research project and supervised the use of non-human primates (NHP) from the Caribbean Primate Research Center. NHPs are a principal pre-clinical research model used to test prophylactic anti-HIV interventions. 

In the study, animals were exposed to semen twice a week over 20 weeks with or without inactivated particles of the simian immunodeficiency virus (SIV is an HIV-like virus that infects primates and causes a disease similar to AIDS). After this conditioning period, the animals received low-dose intravaginal SIV challenges. 

Semen-exposed animals showed a 42% decrease in the risk of infection. Scientists analyzed specific markers of immune activation in the cervicovaginal microenvironment and in the bloodstream. On circulating CD4+ cells, semen conditioning was associated with lower expression of the CCR5 receptor, which acts as a binding site for HIV to enter its host cells, supporting the observation of a lower susceptibility to SIV vaginal challenge. Furthermore, semen-conditioned animals had higher levels of the CCL5 cytokine, a natural HIV-suppressive factor, in the cervicovaginal compartment in response to SIV challenge. 

Repeated semen exposure also resulted in elevated cervicovaginal tissue levels of antiviral factors such as MX1, which also positively correlated with levels of IFN-epsilon. IFN-epsilon, which can be induced by semen and protects human cells from bacterial and viral pathogens, has direct anti-HIV properties and was described to be induced in tissues from sex workers in association with sex without condoms.  

READ:  This is not 'Hide and Seek'

Nonetheless, semen-treated animals that remained uninfected after exposure to low viral amount became infected when subsequently given with high doses of virus. This confirms that they were still susceptible to infection, stressing that repeated semen exposure provides only partial protection and does not block HIV infection.

“Importantly, we show that semen exposure can promote host resistance but does not protect against infection,” said Montaner. “Therefore, our data do not change the fact that prevention methods, such as condom use and PrEP (pre-exposure prophylaxis) remain our best strategies to prevent infection.” 

Co-authors of the study included: first author Shaheed Abdulhaqq, Jocelin Joseph, Livio Azzoni, Xiangfan Yin, Megan Wise, David Weiner, and Qin Liu from Wistar; Melween Martinez, Idia V. Rodriguez, Stephanie M. Nichols, Carlos Sariol, and Edmundo N. Kraiselburd from University of Puerto Rico; Guobin Kang and Qingsheng Li from University of Nebraska; David Beaumont and Georgia D. Tomaras from Duke University; Andrea Foulkes from Mount Holyoke College, South Hadley, MA; Jan Münch and Frank Kirchhoff from Ulm University, Germany; Christos Coutifaris from University of Pennsylvania; and Preston A. Marx from Tulane University.

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Study reveals how HIV infection may contribute to metabolic conditions

Baker Institute scientists showed that the HIV protein, Nef, released from infected cells in specialized vesicles, is taken up by uninfected ‘bystander’ cells, impairing cholesterol metabolism in these cells. This impairment triggers inflammation, contributing to the development of diseases including dementia, heart disease and diabetes.

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A single viral factor released from HIV-infected cells may wreak havoc on the body and lead to the development of chronic and potentially deadly diseases like heart disease, diabetes and dementia, according to a new study by scientists at the Baker Heart and Diabetes Institute in Melbourne.

By explaining the mechanisms, it paves the way for targeted treatment that could help provide a longer and healthier life for the 36 million people globally living with HIV/AIDS.

The treatment of HIV/AIDS is so advanced that today life expectancy of people living with HIV is very similar to that of uninfected persons. However, people with HIV may experience co-morbidities like heart disease, diabetes, dementia or related complications. Studies show that not only are people living with HIV at increased risk of these chronic diseases, they are occurring at an earlier age and progress faster.

These co-morbidities persist even after successful application of antiretroviral therapy, when no virus is found in the blood. Scientists have been intrigued as to what is going on in the small number of infected cells, believing that HIV-infected cells instead of the virus release a toxic substance that kills cells around them.

Most co-morbidities of HIV infection share a common element in their pathogenesis, impairment of cholesterol metabolism but exactly how and what was happening remained a mystery. But in this new study published in PLOS Pathogens, Baker Institute scientists have been able to pinpoint the mechanisms involved.

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Baker Institute scientists showed that the HIV protein, Nef, released from infected cells in specialized vesicles, is taken up by uninfected ‘bystander’ cells, impairing cholesterol metabolism in these cells.

This impairment triggers inflammation, contributing to the development of diseases including dementia, heart disease and diabetes.

Head of Lipoproteins and Atherosclerosis at the Baker Institute, Professor Dmitri Sviridov says the study demonstrates how a single viral molecule released from infected cells into circulation may contribute to a range of pathogenic responses.

“The good news is that there are many drugs on the market and in development to tackle impaired cholesterol metabolism which could be repurposed for this specific population to effectively treat these diseases,” says Professor Sviridov.

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