This paper reviews how and what are the factors leading to the rapid transmission and spreading of HIV throughout the global until become the monumental challenge to global public health where the access to treatment is extremely limited and under research. The challenges faced in producing the effective vaccines are also being highlighted in this paper.
Acquired Immunodeficiency Syndrome (AIDS) started to emerge in the human population on 1981. To date, there is concrete evidence proving that AIDS has characteristic and2 its etiological agent, the human immunodeficiency virus (HIV) able to cross the simian-human species barrier (Korber et al. 2000). The spread of HIV among the human population is due to unsafe injection, heterosexual and homosexual intercourse, and transfusion practices in worldwide, enabling the virus to adapt to humans through mutation and serial passages.
Today, HIV/AIDS is the leading cause of death in sub-Saharan Africa and the fourth biggest killer in the world. An estimated of 14,000 people/day become infected with HIV, with more than 95% of them living in under-development regions of the world (UNAIDS 2008). As deadly AIDS remain incurable and HIV causes the disease to spread non-stop, health authorities, government, non-governmental or organisations, sociologists, health educators and various health-related researchers are reappraising the existing methods of curing the killer disease. In the country-country analyses of AIDS spread carried out by joint venture of United Nations and World Health Organisation (WHO), it had proven that the rate of deadly infection spreading is serious. As a result of that, the development of a safe, effective and affordable vaccine is urgently needed. The first phase trial on HIV vaccine was conducted in USA in 1987. Next, more than 35 vaccines were being tested in over 65 Phase two/three clinical trials which involved more than 10,000 healthy volunteers from more than 10 countries (Girard et al. 2004: 1221). Two phase trials have been done to completion (Cohen 2003) and third one is still under progress (McNeil et al. 2004). However, the most effective HIV vaccine is still uncovered due to multiple challenges. The failure of developing an effective vaccine is due to the high genetic variability of the viral (Korber et al. 2001: 41), lack of knowledge of the virus (Lifson et al. 2000: 2584), the difficulty of generating broadly neutralising antibodies (Burton et al. 2004: 223) and the complexities of the developing a large-scale clinical test trials in developing countries (Excler et al. 2000: 210).
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The scientific questions regarding HIV vaccines trials are complex. HIV vaccine research faces more and larger challenges compared to other vaccines such as Polio virus, H1N1 pandemic flu virus and so forth. Unlike other viruses with successful vaccines, HIV can exist in the host as free virus as well as infected cells (Savla 2004: 146). This is the most difficult part of finding the solution. The HIV targets the immune system itself by incorporating its genetic material into the host cell and reproduce new cells containing the HIV genes itself, thus the HIV reservoirs in other cells harbour intact viruses that can remain undetected by the immune system (Moodie et al. 2006: 148).
The paper begins by briefly highlighting the history of the HIV and how it spreads to worldwide until become a global serious issue. Review of the current progress of HIV/AIDS vaccine research and development, and the challenges will also be discussed.
How big is the problem?
To date, there are approximately 33.2 million persons are currently living with HIV infection worldwide including 15.4 million women and 2.5 million children under 15 years old (UNAIDS/WHO 2007). In the year 2007, there were 2.1 million adults and 0.4 million of children newly infected, and 2.1 million died from HIV infection. Sub-Saharan African countries is accounted with the highest HIV/AIDS case, whereby 67% of all people living with HIV. Other important regions affected by HIV include the Caribbean, Latin America and South and Southeast Asia (Moodie et al. 2006: 148). In many African countries, the overall HIV prevalence in the adult population can be greater than 10%. Among the most severely hit countries are South Africa, with more than 5.6 million people got infected (Bure et al. 2002; 2011). As in many other areas, Asia shows extremely diversity in its HIV epidermises, both geography and temporally. Cambodia, Burma, Thailand and some states like India are those where HIV hit early and hard, where the adult HIV prevalence now exceeds 1% while Bangladesh, Laos, Philippine and South Korea are those having very low levels of infection (Ruxrungthan et al. 2004: 369). Based on projections of economic and social development and increased prevention activities, HIV/AIDS deaths are projected to increase to 3.7 million in 2030 (Mathers and Loncar 2006: 442). Besides that, Mathers and Loncar (2006: 442) also stated that HIV/AIDS transmission will stabilise in higher income countries or to decrease in the next decades, but will still remains as a serious problem in low income countries.
Theories of the origin of HIV/AIDS
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Since the outbreak of the epidemic, there are many debates around on the theory of the origin of the HIV/AIDS. However, there is a danger in identifying the correct theory of the origin of the HIV/AIDS because some people will use the debate to put blame on a particular group of individuals (Adesoji 2005). In order to explain this matter, Adegbenjo (2001) stated that the first case of HIV/AIDS occurred in the United States in the early 1980s, but there is lack of source regarding the source of the disease. Below are some of the theories of HIV/AIDS epidemic emergence.
The Chimpanzee Theory
HIV is a part of the family of viruses called lent viruses and other than HIV, they have been found in a wide range of human primates (Adesoji 2005; 42). The others viruses are known as simian (monkey) immunodeficiency viruses; a subscript character is used for denoting their species of origins (Fritzen 2000).
According to Kanabus and Allen (2001), the HIV is generally being accepted as the descendant of the SIV virus because some of the SIV bear a very close resemblance to the HIV virus especially the HIV-1 and HIV-2. Although it is believed that the chimpanzees are responsible to transmit the virus to human, it is still assumed that human was affected by an unidentified third party (Adegbenjo, 2001).
Another suggestion by the researchers is that the human must have killed the chimpanzee and eat the meat, thus causing the virus to be transmitted into the human body (Adesoji 2005; 43).
Polio Vaccine Theory
According to this theory, Dennis Hooper postulates that humans in the early testing on polio vaccine in Africa in the 1950s indirectly brought the HIV virus into human (O'Neil 2000; 1051). It suggests that an oral polio vaccine must have been manufactured from contaminated chimpanzee's kidney tissue that was subsequently introduced to the African human population (Fritzen 2000). Although the Hooper's theory is not scientific, but the time and the earliest case of the AIDS and the testing of vaccine coincide with each other, and if Hooper is correct, when the human consumed the vaccine, the virus must have entered into the human blood stream and evolved into HIV-1 (Adesoji 2005; 43).
The Pathogenitical Transfer Theory
Besides the two possible theories mentioned above, another controversial theory is HIV was transmitted iatrogenically or in simple words via medical experiments. One famous theory is the polio vaccine theory which causes the virus to be transferred. However, this theory was objected by Chireshe and Chireshe (2003; 25).
Chireshe and Chireshe (2003; 25) has identified three of the earliest known instances of HIV infection. The first statement is a plasma was taken in 1959 from an adult man in what is now the Democratic Republic of Congo. The second statement is HIV found in the samples from an African American teenager who died in St. Louis in 1969, and the third statement is HIV was found in the tissue sample from a Norwegian sailor who died around 1976.
The proponent of the conspiracy theory is John S. James (O'Neil 2001; 1051). This theory views AIDS as a weapon developed by someone's germ warfare experiments and released accidentally or deliberately (Adesoji 2005; 43).
Factors involved in the spread of the HIV/AIDS
A number of factors are involved in the spread of the virus and below are some of the factors highlighted by some of the researchers (Adesoji 2005; 44).
Because sexual intercourse is the main source of the spread of the HIV/AIDS, a lack of the clear moral standards evidently promotes the spread of the virus. This analysis appears to be confirmed by the conduct of young people. For example, a survey in one country indicated that about a third of youths aged between 12 and 17 had engaged in sexual intercourse (Adegbenjo, 2001).
Sexually Transmitted Disease
The presence of a sexually transmitted disease (STD) increases the risk of HIV infection. Research results had shown that STD are common in the youth and there is a high tendency that people who suffer STD are likely to be prone to HIV/AIDS (Chireshe and Chireshe 2003; 25).
Many poor countries are battling for poverty especially Africa has created a climate favourable to the spread of the HIV/AIDS. Many residents encounter malnutrition problem and the lack of the medical facilities. These factors are contributing to the spread of the viruses (Adesoji 2005; 44).
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A large number of those infected by the disease are not aware of it. They prefer not to be tested clinically because of afraid of losing friends, family and their job as people will turn away from them once they have been confirmed to contain HIV/AIDS inside them (Chireshe and Chireshe 2003; 25).
Epidemiologic patterns of HIV infection and transmission
Basically, epidemiologic, socio-demographic, behavioural, and biological factors can contribute to the spreading and transmission of HIV. The character of each sub-epidemic remains largely determined by the extent to which people are exposed to HIV by modes such as: (1) sexual intercourse (vaginal, anal and oral); (2) injection (sharing of drug injection equipment), transfusion or transplantation of HIV infected blood or organs like liver transplantation, and (3) maternal-infant, from a woman to her foetus or infant (Opuni and Bertozzi 2004: 1013).
Epidemiology by region
It is well known that Africa is the region with most severely HIV/AIDS epidemic. At the end of 2002, 29.4 million people living with HIV/AIDS in sub-Saharan Africa and the region accounts for three-quarters of the 20 million people that have already died (Opuni and Betozzi 2004: 1015). Heterosexual HIV transmission is the major factor contributing to the spread among adults, with very little transmission recognised from homosexual intercourse or injecting drug use (Chireshe and Chireshe 2003; 25). According to Opuni and Betozzi (2004: 1015), an estimated of 2.6 million children under 15 years old were living with HIV/AIDS in sub-Saharan Africa by the end of 2001.
Asia and Pacific
According to Opuni and Betozzi (2004: 1015), there was approximately 1.2 million people were living with HIV/AIDS in East Asia and Pacific by the end of 2002, in which 6 million of people were found in south and southeast Asia. Factors such as cross-border opiate traffic between countries, drug use involving sharing of injection equipment and the sex trade are factors leading to the spread of HIV in this region.
Studies in China have shown that injecting heroin users in western Yunnan province (Beyrer et al. 2000: 78) and increase of sexual transmitted disease are factors of rapid HIV transmission in China (Chen et al. 2000: 140). Commercial sex is also one of the reasons leading to the rapid spreading of HIV especially in Thailand. The many men, who were infected by sexual contact with prostitutes, transmitted HIV in turn to their other female sex partners resulting in a subsequent increase in maternal-infant HIV transmission (Nopkesorn and Mastro 1993: 1235).
Latin America and Caribbean
By the end of 2002, it was estimated that 1.5 million adults and children living with HIV/AIDS in Latin America and Caribbean (Opuni and Betozzi 2004: 1015). The rapid spread transmission of HIV/AIDS is due to homosexual and bisexual among men especially in Brazil (O'Neil 2000; 1051).
Europe and Central Asia
Study by Opuni and Betozzi (2004: 1015) indicates that there were approximately 570,000 people living with HIV/AIDS in Western Europe by the end of 2002. Groups predominantly affected in Western Europe are homosexual and bisexual men and injecting drug users with very low rates among heterosexuals in the populations.
HIV virus is a lentivirus from the family Retroviridae. It can be seen as biological nanostructure (approximately 100-150 nm), consists of a host-derived membrane, a nucleocapsid and genetic material in the form of RNA containing three structure genes (Levy 2009: 148). These genes code for important group specific antigens, essential viral enzymes and the two glycoproteins present in the outer viral membrane, namely gp120 and gp41, are responsible for recognising the CD4 receptor cell and the CCR5 or CXCR4 co-receptor of the host cell membrane, and for the virus cell fusion (Nevas et al. 2010: 459). As a result of constant transcript errors, these viral structures have high polymorphism which will lead to mutation, thus resulting in antiretroviral-resistance development.
There are basically two types of HIV, namely HIV-1 and HIV-2. HIV-1 is phylogenetically close to SIVcpz which is a commensal virus in chimpanzees, and could be due to the single transmission event from chimpanzees to human, whereas the HIV-2 strain is closely related to SIVmac which is the etiological agent of simian AIDS, a commensal virus in sooty mangabey monkeys (Adegbenjo, 2001). HIV-1 is further subdivided into three major groups, they are M (major), O(outlier) and N(non-M or non-O). The majority of HIV-1 strains causing the global AIDS pandemic belong to type M, which has evolved from human to form at least ten genetic subtypes, also known as clades, indicated by alphabetical letters from A to K (Tatt et al. 2001: 60). HIV-1 subtype B is the one predominates in Latin America and the Caribbean. Subtype A and D are found in Central Africa while subtype C are accounted for the majority of infections in southern Africa, eastern Africa and India (Tatt et al. 2001: 60). Antibodies that are specific for isolates from one patient are not capable to recognise isolates from other patients even though it is within a given subtype. Because of this, HIV strains can recombine and form mosaic viruses called Circulating Recombinant Forms (CRF) which in turn can gain epidemiological dominance (McCutchan 2000). The amino acids sequence of the viral envelope glycoprotein shoes up to 25-35% divergence between different subtypes and up to 20% divergence within any given sub-type causes a challenge to vaccine development (McCutchan 2000).
Challenges and difficulties of developing HIV vaccines
Natural infection with HIV does not result in virus clearance by the host immune system and the development of natural immunity to re-infection. HIV is able to resist eradication and continues depleting CD4+ T cells which eventually leads to clinical progression to AIDS. HIV-1 is able to integrate as a latent proviral DNA into the genome of long-lived memory CD4+ T cells, which in turn provide a persistent reservoir of the virus that escapes immune surveillance. The window of opportunity for an HIV vaccine is therefore narrowly limited to the very early stages of infection, before the virus can seed the lymphoid organs in mucosal tissues (Peterlin and Trono 2003: 103).
Besides that, HIV is also able to develop multiple mechanisms to circumvent the host immune responses including its ability to affect the major histocompatibility complex (MHC) class I molecules and minimise its recognition by CTL, as well as its high genetic evolution rates allows it to evade immune responses through the emergence of viral CTL (Evans and Desrosiers 2001: 150). Another difficulty with the development of an effective HIV vaccine is that the virus is envelope glycoprotein is able to conceal its conserved receptor and co-receptor binding sites in crypts that are masked by the hyper-variable loops of the molecule and by glycan residues (Girard et al. 2004: 1221). Neutralising antibodies induced are primarily targeted to the hyper-variable loops of the molecule and they rarely recognise the receptor binding sites, which makes it difficult to generate broadly cross-reactive neutralising antibodies against primary virus isolates from patients (Yang et al. 2004: 12981).
To date, multiple vaccine concepts and vaccination strategies have been tested, including DNA vaccines, subunit vaccines, live vectored recombinant vaccines and various prime-boost vaccine combinations.
The HIV pandemic is now entering the third decade. Large parts of Africa have already been affected by the epidemic and in future will bring an increased burden of AIDS-related death. Asia, home to half of the world's population, will be an important region in the AIDS epidemic in this next millennium. In many countries, AIDS will likely become the leading cause of death in adults and one of the leading causes of infant and child mortality. Further research data is important in tracking the HIV epidemic, directing prevention activities, and guiding research. What is lacking now is the information on the patterns of risk behaviour. Research in this area has to pay more emphasis on the virus behavioural characteristics and prevention measures. A system that is able to compare biological and behavioural data for maximum explanatory power and adapt to the changing needs of epidemics is important to produce quality data that increase and improve the national responses.
To date, many research progresses have been done to make a better understanding of the complex interaction between HIV and the host immune system. This has led to the development of new, potent antiviral drugs able to control the virus replication. However, there are still many basic questions still remain unanswered, including identification of protective immune mechanisms, addressing the high variability of the virus and its ability to evade immune responses. The current viral research suggests that an effective vaccine need the ability to induce both neutralise antibodies and cell-mediated immunity. One of the challenges for HIV vaccine development is to understand how to design envelope immunogens to effectively elicit the high variability of the virus. Among the challenges in the development of HIV vaccines is the lack of scientific knowledge on the nature and level of the immune responses required to protect against HIV infection and development of the disease. Therefore, the most important aspect of HIV vaccine research is to study the effective response of both arms of the immune system.