HIV and AIDS were completely unheard of in the medical community up until the early 1980s, the emergence of these and related illnesses were initially isolated to specific communities, namely male homosexuals, however, the emergence of newly reported cases, which stemmed from blood transfusion patients and also intravenous drug users, prompted a re-evaluation of the underlying biological causes of the blood borne pathogen.
HIV and AIDS are not regionally discriminatory; they are not endemic to any one country, however, several identifiable factors have been shown to influence prevalence rates and high risk status, such as poverty, access to affordable treatment, sexually promiscuous behaviour and intravenous drug use.
The global report compiled jointly by the World Health Organisation and The United Nations currently estimates that, as of 2009, 33.3 million people are infected with HIV worldwide; with 22.5 million of those living in sub-Saharan Africa alone, which accounts for 67% of the HIV distribution worldwide; comparatively, North America has an estimated infected population of 1.5 million people, with a prevalence percentage of just 4.5%. The prevalence of many South America countries is often sidelined in favour of more apparent HIV and AIDS crises, however, given the level of poverty
The pandemic status of HIV and AIDS has become more and more isolated as Westernised medicine led the way in clinical research and preventative measures, developed countries have, as a result of this, benefited exponentially, whereas developing countries have become heavily reliant on the aid of high-income countries.
Throughout the world the death toll, per year, has been increasing rapidly since the onset of HIV and later stage AIDS and is currently responsible for 1.8 million deaths worldwide per year, which roughly equates to 13 deaths every minute. However, figures show that most developed countries have seen a decline in new infections, but this is not the case for underdeveloped countries and nowhere is more severely affected than sub-Saharan Africa and the African epidemic, borne out of financial inequality and a lack of preventative measures is the leading cause of adult deaths in Africa
The data in the image below presents a grim approximation of the future of sub-Saharan Africans given their HIV and AIDS epidemic, it suggests that within the short space of 30 years the number of deaths will have dramatically increased.
HIV is unable to self-replicate independently, it relies on the enzymes; reverse transcriptase, protease and integrase, these enzymes give it the ability to replicate itself within a human cell. Reverse transcriptase enables the virus to reverse transcribe their RNA into DNA. The new viral DNA is then integrated into the host’s DNA with the aid of the enzyme integrase. Below is a simplistic illustration of the HIV life cycle.
The transmission of HIV can occur in several ways, vertical transmission between a pregnant mother and child, sexual intercourse via bodily fluids, or using needles that have been used by another person. A test which screens the CD4 count is used as a way of diagnosing HIV; normal CD4 levels should be between 500-1500 per cubic millimetre, a value lower than 200 and they will be suffering from the disease. The weakened immunity of individuals affected with HIV means that they are increasingly more susceptible to opportunistic infections, which can reduce their quality of life and leave them at risk of developing AIDS.
There is currently no cure for HIV and AIDS, however, treatment options are at the pinnacle of advancement; combination antiretrovirals are the primary method of managing the disease effectively and with more than 20 ARVs approved for treatment throughout the world, the progression from HIV to AIDS has never been so slow, or preventable.
There are several sub-groups within antiretroviral drugs, each with a specific biological function:
* Nucleoside/Nucleotide Reverse Transcriptase Inhibitors or NRTIs
NRTIs contain faulty nucleotides, used by the enzyme reverse transcriptase; these nucleotides prevent the structure of DNA from forming correctly.
* Non-Nucleoside Reverse Transcriptase Inhibitors or NNRTIs
NNRTIs bind to the enzyme reverse transcriptase and prevent the reverse transcription of HIV RNA into DNA.
* Protease Inhibitors
In the HIV life cycle protease enzymes are responsible for cutting the proteins into smaller sections in order to replicate, the protease inhibitors prevent this process from happening.
* Fusion or Entry Inhibitors
In order to gain entry into a cell the HIV cells must initially bind to the proteins on the surface of a CD4 cell, entry inhibitors work by binding to either proteins on the HIV cell itself, or to the proteins on the CD4 cell; this action prevents the HIV from binding to the CD4 cell.
* Integrase inhibitors
The newly formed viral DNA must insert itself into the DNA of the CD4 host cell; with the aid of integrase inhibitors this integration is halted.
Research into antiretroviral therapy is ongoing and new information is emerging constantly, it is for this reason that at the present time it is thought that the most beneficial approach to treatment is with a triple combination of drugs, known as HAART.
Several clinical studies support the use of triple combination therapy over both mono and double combinations, in reducing the level of HIV RNA plasma and correspondingly increasing CD4 cell count. A randomised, double-blind trial carried out by INCAS, a university affiliated collaboration of clinics, found that the efficacy of a triple combination that included, Zidovudine, Didanosine and the NNRTI Nevirapine showed a more substantial and prolonged decrease in the plasma viral load than the two-drug combinations did. The percentage of detectable HIV-1 RNA in the patient’s plasma was compared between each of the three trial groups, the results of which can be seen in the graph below.
Similar efficacy has been established by other clinical trials since then, another randomised; double blind trial, which utilise 106 antiretroviral-naive patients, found that a combination of Zidovudine, Lamivudine and Lovride produced a prolonged reduction in HIV-1 RNA plasma and increase in CD4 cell counts in comparison with a double combination of Zidovudine and Lamivudine alone.
The efficacy of ART or HAART is not only cumulative to finding the correct combination of drugs, but also in following a consistent medication regime as drug resistance can become a problem, specifically, NNRTIs are predominant in generating resistant strains of HIV-1; the rapidity with which these mutations occur has a detrimental effect on future usage of NNRTIs, as resistance to one of the drugs can result in a resistance to all NNRTIs available for treatment.
The disparity between low-income and high-income countries’ access to antiretroviral treatment is one of the most prominent burdens affecting the developing world and the instability of the global economy has cast uncertainty on the sustainability of ART. The economic viability of funding research, treatment and prevention is an increasing concern given the current financial status, particularly, of countries that make up the largest proportion of investors. The pie chart below highlights the dramatic requirements of the world’s most affected countries, in terms of combating HIV and AIDS.
The progression of an antiretroviral drug, from initial research to approval for use, is a long and financially draining route, current estimates suggest that the figure is close to 55 Million (US$). Prior to this it was even higher and these figures will have had a direct effect on the affordability of ARVs for the individual person.
With adequate and constant access to antiretroviral treatment the lives of affected individuals will be extendable to that of an average healthy person; there will be a significant correlation between the life span of an affected individual and how much they contribute to the society. As a result of antiretroviral treatment sub-Saharan Africans have gained a total of 2 million years worth of life between 2002 and 2008, if this could be sustained then the socioeconomic standing of the country could begin to recover. Decreasing the mortality rates of HIV affected adults in sub-Saharan Africa can only have positive effects on the poverty levels within the country.
Taking antiretrovirals is not without risk however, with many there is the accompaniment of side effects. Determining whether or not these added problems outweigh the benefits of the drug can be a difficult decision to make, especially if the person infected is asymptomatic at that time; they may not feel that antiretrovirals are the most beneficial route for them personally and as a result opt not to take them. Whether or not they are qualified to make such a medical decision is debatable, but ethically there is no law that dictates that they must begin treatment. For many affected with HIV, taking antiretrovirals means admitting that they are suffering from the virus, this could have serious connotations for them socially, as it remains, in several parts of the world highly stigmatised.
An AIDS vaccine has been in development since the late 1980s, however, as of today, none of the 30 possible vaccine candidates created since the initial research began have shown enough efficacy to prove successful in combating the disease.
Thus far, there has been research conducted into three techniques of vaccine application:
* Subunit vaccine
* DNA vaccine
* Recombinant vector vaccine
The results from a three year study were published in 2009, of a phase 3 trial, which took place in Thailand, a total of 16,395 HIV negative people were given either, a combination vaccine of two formerly unsuccessful, recombinant vector vaccines, ALVAC-HIV and AIDSVAX B/E, or a placebo. The HIV-1 infection was found to be present in 132 of the participants, with 56 being from the vaccine group and 76 being from the placebo group, though there was no significant difference between the average viral load count in each group.
The results from this clinical trial, while moderate, appeared to cut the risk of infection by 31% over the three year trial period. However, there was no significant decrease in the viral load of those who became infected with HIV during the course of the study. The promising results of this study have rejuvenated the search for a vaccine and I believe that, in the long term, the only solution to the high prevalence rates will be a vaccine that can cure and potentially eradicate the disease.
Preventative measures are one of the most fundamental aspects of combating HIV and AIDS, specifically in underdeveloped countries, as access to education is not consistent throughout each region. Community led initiatives, which deliver comprehensive information to the most at risk communities are at the forefront of prevention; they advocate the usage of condoms, reducing the number of sexual partners and encouraging abstinence, specifically within the younger generation.
The graph below shows the prevalence of new infections at the current rate of preventative measures and with an expanded program of prevention; comparably the results of the current and proposed rates of prevention are vastly different, with a highly positive outcome by the year 2019 if prevention is extended. HIV testing and counselling is another important factor in prevention, education and awareness of HIV status can greatly reduce the transmission rate and protect others from infection.
Evaluation of sources
The World Health Organisation is a highly respected, initiative that spearheads collaboration within the United Nations; it is funded by donations from member states and so there is unlikely to bias as no one country provides sole funding for the organisation. The WHO employs specialists in an array of professions, who work to combat infectious disease and promote healthcare initiatives; they also present reports of collated data on health from around the world. I made reference to several pieces of data obtained from both the WHO website, from their published health reports and fact sheets. These documents are written by multiple people and numerical values that have been cited have been calculated using data collected over periods of years. The WHO is often cited by medical research articles, which suggests that the data is regarded as highly valid and reliable by the scientific community.
The New England Journal of Medicine is a prominent, peer-reviewed, medical journal, which was established in 1812. In order for an article, or piece of research, to be published in the journal it must be reviewed by independent academics within the same field, if they are in agreement that the information given is scientifically correct at the time then it will be accepted into the journal; the journal publish about 1 in 20 entries, which is suggestive of the stringent criteria that must be met.
Several of my references come from research that was published in the NEJM, the results of an AIDS vaccine clinical trial were published, the information I obtained from this source was therefore both valid and reliable as other members of the scientific community reviewed the methods and outcomes of the study and found no issue with them.