HIV – AIDS

Researchers Are Using Viruses to Make Superbugs Commit Suicide

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The gene-editing technology called CRISPR has its origins as a bacterial immune system against viruses, a feature which could be turned against them in the future.

By arming bacteriophage viruses with the tools to force bacteria into falling on their own swords, scientists hope we will be able to develop powerful new ways to defeat antibiotic resistant pathogens and perhaps even shape our body’s microflora.

Research presented at the CRISPR 2017 conference in the US described the progress that has been made in modifying viruses that target specific bacteria with genes that make the host’s enzymes cut into its own DNA.

Clustered regularly interspaced short palindromic repeats – CRISPR for short – are sequences of DNA made of a repeating codes that form a long palindrome.

Bacteria produce them as a kind of immune system against viruses called bacteriophages, slipping bits of the virus’s genes scavenged out of the environment into the repeating codes.

With the viral DNA stored away in CRISPR sequences, any future infections can be detected quickly and a CRISPR-associated system (or cas) enzyme can then use the sequence as a beacon, latching onto the infecting virus genes and either snipping them selectively or tearing them to shreds.

About 25 years ago, researchers realised this cut-and-paste system of CRISPR sequences and cas enzymes could be used in the lab to edit sequences artificially, and a new engineering toolkit was born.

The technology has been in the news quite a bit in recent years as advances have been made in applying it to cancer treatments and even eliminating HIV infections.

While it might not be without certain risks, CRISPR gene editing has sparked a something of a minor revolution.

Bringing it back to its roots and turning it into a weapon against its creators has a sense of serendipity about it.

“I see some irony now in using phages to kill bacteria,” said the chief scientific officer of Locus Biosciences, Rodolphe Barrangou, at the CRISPR 2017 conference.

Using bacteriophages as a form of therapy to treat infection isn’t all that new, with trials dating as far back as the 1920s.

The use of phages is appealing because they are far more specific than antibiotics, targeting only specific types of bacteria and therefore posing no risk to our own health. The viruses can also penetrate the coatings of sticky film bacteria produce for protection and adherence.

Russia experienced a fair degree of success with phage therapy behind its Iron Curtain during the Cold War, but unable to patent the naturally occurring viruses and with the bacteria quickly adapting, red tape and limitations in technology have made it far easier to focus on antibiotics in the west.

With looming epidemics of superbugs on the horizon, attention is returning to bacteriophages as ways to kill bacteria, and CRISPR has put a new spin on the old idea.

A spin-off company from North Carolina State University, Locus Biosciences is testing the limits of CRISPR technology, including giving bacteriophages CRISPR sequences containing codes for antibiotic resistance genes.

Targeting bacteria with the genes, the CRISPR sequence would form a target for the bacteria’s own cas enzymes, effectively blocking resistance or even prompting the bacteria into chewing up its own DNA and self-destructing.

In recent years our eyes have been opened to how complex our relationship is with bacteria in our environment, and how dull our tools are for dealing with them.

Variations in our gut microflora has been linked with everything from Parkinson’s disease to autism to obesity, suggesting the species of bacteria we harbour could have major ramifications on many aspects of our health.

With its razor-honed surgical precision, it’s possible the technology could one day be used to select specific strains of bacteria in our gut, deleting them from the ecosystem and allowing us to edit our microbiomes.

Given we’re practically at the dawn of both CRISPR technology and our grasp on the complexity behind our body’s bacterial ecosystems, we can only speculate for the time being.

As antibiotics slowly lose their shine it’s probably worth paying close attention to radical new solutions such as these.

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Vaginal Bacteria Have Been Found to Neutralise HIV Treatment

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A study on the vaginal bacteria of South African women has revealed that a certain type of bacteria is able to break down a common drug used for the prevention of HIV.

Annually, more than 1 million women are infected with human immunodeficiency virus (HIV). HIV infection rates among women are a major health concern, as HIV can be passed from mothers to their children during pregnancy, childbirth ,and breastfeeding.

“I believe this will change the way we approach HIV prevention studies in women,” lead researcher Nichole Klatt, from the University of Washington, told ScienceAlert.

The microbicide drug, tenofovir, is widely used to combat the spread of HIV, and works by inhibiting the process that allows HIV to replicate. While tenofovir routinely protects men against HIV infection, women using the same drug might not see the same results.

But what exactly does the vagina have to do with drug administration?

In Africa, tenofovir is being applied in a gel directly into the vagina. Taking a tablet isn’t always ideal in Sub-Saharan Africa, and the focus of prevention here is to stop the spread of HIV at the site of infection during sex.

Other studies have revealed that the vagina may contain bacteria that acts as a sort of ‘biological condom’, protecting against the infection of HIV and STIs.

To investigate the potentially negative effects these bacteria are having on tenofovir, Klatt and her team collected vaginal swabs from 688 South African women as they participated in a clinical trial into the efficiency of an intravaginal gel against HIV infection.

The team found that there were two major types of vaginal bacteria present in the sample group – one contained Lactobacillus, and the other contained Gardnerella vaginalis.

Of the two major types of vaginal bacteria, the women with non-lactobacillus bacteria had a reduction of HIV infection of only 18 percent, while those with Lactobacillus had a reduction in HIV infection rate of 61 percent when using the gel – a threefold increase in protection.

The scientists investigated further, and discovered that G. vaginalis could metabolise and breakdown the active form of the drug, rendering it useless in the fight against the spread of HIV.

“These data demonstrate that vaginal microbiota must be accounted for and to improve efficacy of HIV prevention, novel interventions to enhance Lactobacillus and decrease Gardnerella and other BV-associated bacteria are needed,” Klatt told ScienceAlert.

The scientists hope that the results will inform the ways in which the drug is administered based on the bacteria present in a patient’s vagina.

“We are now excited to be forging the way ahead in pharmacomicrobiomics studies in HIV and other diseases. Specifically, we are assessing other drugs that bacteria may interact with in the vagina, and the specific mechanisms underlying this,” says Klatt.

“We are also developing systems to assess drug-microbiota interactions in other diseases such as IBD and cancer, where mechanisms underlying variable drug efficacy are unknown.”

The research is published in Science.

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Union Cabinet approves amendments to HIV and AIDS (Prevention and Control) Bill, 2014

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The Union Cabinet under the chairmanship of Prime Minister Narendra Modi has given its approval to introduce official amendments to the HIV and AIDS (Prevention and Control) Bill, 2014 which has been drafted to safeguard the rights of people living with HIV and affected by HIV.

The Bill seeks to address HIV-related discrimination, strengthen the existing programme by bringing in legal accountability and establish formal mechanisms for inquiring into complaints and redressing grievances. The Bill seeks to prevent and control the spread of HIV and AIDS, prohibits discrimination against persons with HIV and AIDS, provides for informed consent and confidentiality with regard to their treatment, places obligations on establishments to safeguard rights of persons living with HIV and create mechanisms for redressing complaints. The Bill also aims to enhance access to health care services by ensuring informed consent and confidentiality for HIV-related testing, treatment and clinical research.

The Bill lists various grounds on which discrimination against HIV positive persons and those living with them is prohibited. These include the denial, termination, discontinuation or unfair treatment with regard to employment, educational establishments, health care services, residing or renting property, standing for public or private office, and provision of insurance (unless based on actuarial studies).  The requirement for HIV testing as a pre-requisite for obtaining employment or accessing health care or education is also prohibited.

Every HIV infected or affected person below the age of 18 years has the right to reside in a shared household and enjoy the facilities of the household. The Bill also prohibits any individual from publishing information or advocating feelings of hatred against HIV positive persons and those living with them. The Bill also provides for Guardianship for minors. A person between the age of 12 to 18 years who has sufficient maturity in understanding and managing the affairs of his HIV or AIDS affected family shall be competent to act as a guardian of another sibling below 18 years of age to be applicable in the matters relating to admission to educational establishments, operating bank accounts, managing property, care and treatment, amongst others.

The Bill requires that “No person shall be compelled to disclose his HIV status except with his informed consent, and if required by a court order”. Establishments keeping records of information of HIV positive persons shall adopt data protection measures. According to the Bill, the central and state governments shall take measures to prevent the spread of HIV or AIDS; provide anti-retroviral therapy and infection management for persons with HIV or AIDS; facilitate their access to welfare schemes especially for women and children; formulate HIV or AIDS education communication programmes that are age appropriate, gender sensitive, and non-stigmatizing; and lay guidelines for the care and treatment of children with HIV or AIDS. Every person in the care and custody of the state shall have right to HIV prevention, testing, treatment and counseling services. The Bill suggest that cases relating to HIV positive persons shall be disposed’ off by the court on a priority basis and duly ensuring the confidentiality.

There are no financial implications of the Bill. Most of the activities are being already undertaken or can be integrated within the existing systems of various Ministries under training, communication and data management, etc. The Bill makes provision for appointment of an ombudsman by state governments to inquire into complaints related to the violation of the Act and penal actions in case of non-compliance. The ombudsman need not be a separate entity, but any existing state government functionary can be deputed or given additional charge.

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A new treatment appears to have erased HIV from a patient’s blood

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The first of 50 patients to complete a trial for a new HIV treatment in the UK is showing no signs of the virus in his blood.

The initial signs are very promising, but it’s too soon to say it’s a cure just yet: the HIV may return, doctors warn, and the presence of anti-HIV drugs in the man’s body mean it’s difficult to tell whether traces of the virus are actually gone for good.

That said, the team behind the trial – run by five British universities and the UK’s National Health Service – says we could be on the brink of defeating HIV (human immunodeficiency virus) for real.

“This is one of the first serious attempts at a full cure for HIV,” Mark Samuels, Managing Director of the National Institute for Health Research Office for Clinical Research Infrastructure, told Jonathan Leake at The Sunday Times.

“We are exploring the real possibility of curing HIV. This is a huge challenge and it’s still early days but the progress has been remarkable.”

HIV has long proved very difficult to treat because the disease can hide in dormant cells where the immune system can’t get to it.

This new therapy is the first aimed at destroying HIV in every part of the body, and it works by combining a drug that reactivates these dormant HIV cells with a vaccine designed to help the immune system find and kill them.

The vaccine is given to patients first, boosting the immune system’s ability to detect and combat HIV-infected cells. Then, a drug called Vorinostat is used, activating the dormant HIV cells left over, so the immune system can fight them too.

It’s as though the infected cells suddenly step out from their hiding place, and the newly boosted immune system can then pick them off.

Standard antiretroviral drugs in use today are effective at stopping HIV from reproducing and can keep the virus at bay, but are unable to kill it off altogether.

But the drug combination being used in this trial – which is being tested on 50 HIV patients – could mean we have a more effective treatment on our hands.

The unnamed 44-year-old man who is currently showing no sign of the virus in his blood is the first to finish the trial. In a few months, when the antiretroviral drugs wear off from him and the other participants in the study, we should have a better idea of whether the HIV has truly disappeared.

If the 44-year-old indeed has no traces left of HIV, it would mean he is only the second person to ever be cured of the disease, which affects some 37 million people around the world.

To date the only person considered to have been cured of HIV is American Timothy Ray Brown, who was given a bone marrow transplant from a donor known to be resistant to HIV. The stem cells he was given rebuilt his immune system, eradicating both the HIV and his acute myeloid leukaemia at the same time.

But that kind of treatment is too specific, too costly, and too dangerous to be used widely, which is why this new trial is causing a lot of excitement.

However, nobody’s taking anything for granted yet, including the male patient.

“I took part in the trial to help others as well as myself,” he told The Sunday Times.

“It would be a massive achievement if, after all these years, something is found to cure people of this disease. The fact that I was a part of that would be incredible.”

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India, South Africa to begin collaborative research on HIV/AIDS and TB

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The Department of Biotechnology (DBT) in collaboration with Department of Science & Technology, and the Department of Science & Technology, Government of South Africa, and South African Medical Research Council will soon embark on a collaborative research programme on HIV, TB and TB/HIV. The programme would be under the framework of bilateral Science and Technology Cooperation Agreement between the Department of Science and Technology, Ministry of Science and Technology, Governments of India and South Africa.

The thrust areas of the programme would be on development of preventive HIV vaccine by designing immunogens that can elicit potent and broadly neutralizing antibodies; isolation and characterization of neutralizing MAbs effective against clade C HIV-1 viruses for use in combination therapies, passive immunization, and/or for designing preventive vaccines; Creation of cohorts of TB patients with HIV-1 co-infection and formation of national biorepositories (for breath condensates, blood, tissue etc.)to facilitate immunological studies on HIV and TB; and identification of biomarkers and development of novel assays for diagnosis and management of tuberculosis and tuberculosis with HIV co-infection.

The DBT’s initiative in this regard is significant as the human immunodeficiency virus (HIV) and tuberculosis (TB) are the leading causes of death in adults and children in both India and South Africa, and the impact of the converging dual epidemics is one of the major public health challenges of our time. Development of effective biomedical tools and solutions for diagnosis, prevention and treatment of AIDS and tuberculosis is required to address challenges in disease management and control.

Interdisciplinary research in these areas will not only accelerate development of transformational technologies but also help to develop capabilities and solutions for these unconquered diseases. The proposal should be geared towards product development or have clinically useful applications. It should have intra country linkages and a strong collaborative component utilizing complementary expertise of both countries, and addressing regional needs.

Scientists in either country could also submit proposals in case they have an existing product or a proof of concept and they would like to access facilities in either country for a collaborative framework to help facilitate product development in an accelerated manner (e.g. manufacturing, preclinical testing etc.). The programme is aimed to facilitate partnerships between research institutions in India and South Africa. This programme will leverage upon existing scientific capacities, enable technology transfer and catalyze mentorship/training. Thus, this collaboration will synergistically advance discovery efforts towards development of new technologies and products for prevention and management of HIV/AIDS and TB by building scientific leadership capacity, fostering a sustainable environment for translational research and enhancing clinical capability/capacity. In South Africa, this call for proposal is open to researchers residing in South Africa and who are affiliated with a recognized higher educational or research institution such as a university, university of technology or science council. The South African applicant must be in possession of a PhD. Private sector companies are not eligible for this call. In India, the lead Indian applicants should be scientists/faculty members working in regular capacity in universities, academic institutes or national research and development laboratories/institutes. Private sector companies are not eligible for this call.

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