STRIDES IN HIV RESEARCH
By Vithusan Kuganathan
HIV is a sexually transmitted disease. It can be passed through sexual contact and through the sharing of hypodermic needles, but there was essentially no treatment. HIV stands for human immuno-deficiency virus and is a disease which essentially attacks your immune system – it attacks CD4 cells/T-cells. Whilst HIV isn’t necessarily detrimental to your health in and of itself, the potency of the disease is due to the development of HIV into AIDS; HIV develops into AIDS once your CD4 count reaches a certain threshold – 200 cells/mm3. The loss of your CD4 cells means launching an effective immune response to an infection is almost impossible. As such, a relatively simple infection to fight off – the common cold – becomes fatal. It’s this exacerbation of other illnesses that makes HIV so detrimental.
Naïve Helper T-cells and APC
When macrophages engulf a microbe by phagocytosis, they process the antigens on the surface of the phagocyte, and they present it on their own surface and become an antigen presenting cell (APC). This then sends signals to the naïve helper T cells, which subsequently activates them. One of which could be the costimulatory protein B7; Co-stimulation refers to repeated signals being exchanged between the two molecules. This binds to a co-receptor molecule, CD28, which is also on the surface of the helper T cell (Th cell). This binding of the receptors leads to the differentiation and proliferation of the naïve Th cell into effector cells. Another example would be the peptide-MHC protein to another T cell receptor.
To clarify, CD4 cells are really important in your immune system, as they are vital for adaptive immunity. This is, when your body may not be familiar with a pathogen and initiates a response upon encounter with the it. They do several things; between activating B-cells and activating cytotoxic T cells, which help with the infection. This kills off the infected cells and as a result, HIV, which limits this ability of your immune system. As such, these HIV viruses continue to multiply in the body using the cell’s ‘machinery’. HIV clearly has very detrimental physiological impacts, however, it had a profound sociological impact as well.
the hiv epidemic
HIV grew in profile during the mid-20th century. It was believed to have crossed the species barrier from chimpanzees to humans in the 1920s in the democratic republic of Congo, Kinshasa (reasons for which I’m sure you’d rather not look up). In the 1970’s there was a rise in the number of cases of HIV, with sporadic cases around the world. However, by 1980, there were 100,000 to 300,000 people infected. In 1981, the emergence of PCV (Pneumocystis carinii pneumonia) amongst 5 previously healthy gay men was recorded, as well as some cases with those who had injected themselves with drugs. By the end of this year, 270 cases of stunted immune responses had been recorded amongst gay men – 121 of them had died. This led to outlandish claims from newspapers with headlines such as, “the gay cancer” and “the gay pneumonia” from the Bay area reporter and the New York Times. As a result, these terms became commonly used. By August, Larry Kramer held a meeting in New York City to raise funding for HIV research – as there was no funding from the public or private sector to fight this epidemic – a scathing indictment of homophobic attitudes in this time. In 1983, international institutes – the Pasteur institute, the Centre for Disease Control, the World Health Organisation are all fighting against the epidemic as in January of the same year, it was determined that heterosexual sex could lead to the transmission of the disease. By September, the CDC identified that major paths of transmission were not at fault and by November WHO set their first meeting to analyse the global AIDS situation. This once again emphasises the unjust marginalisation that gay people experienced during this time, which was further exacerbated by this epidemic. By the end of 1984, there were 7,699 cases of AIDS and 3,665 deaths.
1985 – the FDA approved the ELISA test; a blood test available to the public to test for the antibodies that are complementary to the virus and are therefore effective against the virus. Blood banks were now obliged to screen for HIV in the US blood supply. Ryan White, a teenager, contracted AIDS from contaminated blood products for his haemophilia. He was banned from attending school. Rock Hudson died from AIDS in October. As a celebrity, AIDS was becoming more and more exposed in the public eye.
1987 was a pivotal year for the treatment for AIDS. The WHO launched a global program on AIDS to raise awareness. They generated policies from scientific research and provided technical and financial support to countries. They promoted the role of non-governmental organisations in a bottom-up approach in educating isolated communities in the fight against AIDS. The first anti-retroviral drug – zidovudine was approved by the FDA and a more sensitive HIV blood test was made available to the public. The epidemic had become so widespread that the UN general assembly debated the best course of action in the fights against AIDS. The care system in the US was reformed to financially support people suffering from AIDS – the Ryan White CARE Act and was later ratified in 1990. The same year, the Americans with Disabilities Act was ratified which made it illegal to discriminate against those who suffered from AIDS. In 1990, there 307,000 reported cases of AIDS globally, with estimations reaching a million. 2002 was when the first rapid HIV test entered the public scope, this was 99.6% accurate. Over the most recent decades, within our lifetimes, a series of antiretroviral drugs have been passing their trials in order to tackle the antigenic variability expressed by HIV.
Whilst significant strides have been made in the treatment of HIV, there’s still much to do, especially in some regions of sub-Saharan Africa, where HIV prevalence rates can reach 30%. In spite of this improvement, the HIV epidemic truly emphasised the reluctance to act when a marginalised group was affected – concrete action was only taken once heterosexual partners were being infected. However, it also exemplifies the international collaboration undertaken to fight this epidemic – an issue that crossed political boundaries. But most of all, it showed a willingness for social adaptation. WHO declared 1st December as World AIDS day to emphasise the importance of acceptance and support for those who have been infected in society.
Researchers at UCL and Imperial have managed to sustain remission in a second person suffering from HIV-1 after stopping treatment. Stem cell transplants were used to treat these patients and they prevented the expression of the HIV receptor – CCR5. Since this receptor can’t be expressed, the ‘hostile takeover’ of the cell can’t take place and a typical immune response can instead. The receptor enables the HIV virus to bind to the host cell and then invade the CD4 cell.
At the moment, the only way in which HIV is treated is through the use of antiretroviral drugs. These don’t completely cure the patient, but they suppress the virus and can prolong the patient’s life for more than 30 years. The patient still has to take the drug for the rest of their life, which can be a minor inconvenience and somewhat infeasible in developing countries, where they may not have access to a pharmacy nearby. However, the elimination of the virus from the host would be a monumental step in eradicating the disease.
A patient in the UK was diagnosed with Lymphoma – a blood related cancer and he later was the recipient of haematopoietic stem cells in a transplant. A haematopoietic stem cell is a stem cell which is multipotent and can differentiate into a blood cell. This was from a donor who had two copies of the CCR5 ∆32 allele. This means that the allele is recessive as both pairs must be present to be expressed. This CCR5 allele is resistant to the HIV-1 virus as it uses this receptor and as such they cannot bind to cells. There were minor complications in the procedure, the patient did suffer from graft-versus-host disease. This is essentially when the antigens on these haematopoietic stem cells are recognised as “non-self” and as such are attacked as foreign microbes. This was somewhat minor however.
These observations were noted in the ‘Berlin patient’, who had undergone full-body irradiation (radiotherapy for the whole body), compared to the relatively less intensive chemotherapy of the British patient. However, the use of this CCR5 gene proves that this patient wasn’t anomalous and there is scope for identifying a treatment against HIV through the manipulation of this CCR5 allele.
This research proves to be the fundamental basis for further HIV research and acts as a beacon of hope for those suffering from HIV. But questions still remain about how this treatment will reach everyone and whether or not this remission will be sustained. One thing I hope you got from this article at the least, is the idea that HIV is a prevalent disease and as such it’s important to appreciate the level of medical development that has gone into ensuring that future generations don’t suffer from this disease.
For a more in depth understanding of the life-cycle of HIV:- https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/19/73/the-hiv-life-cycle