Introduction
Acquired immunodeficiency syndrome was first reported in 1981 by the Centers for Disease Control, with the identification of the human immunodeficiency virus 1 (HIV-1) as the causative agent (CDC, 1981). To date, approximately 60 million individuals around the world are infected with the HIV-1 virus and this infection has caused the death of 25 million people (UNAIDS, 2005). The analysis of HIV in several continents around the world has shown that there are certain evolutionary trends that would lead us to a better understanding of the pathogenesis, transmission and ultimately, treatment of AIDS around the world. The greatest number of AIDS cases has already reached its highest number in the last decade, hence access to effective anti-HIV agents is of utmost concern.
Global epidemiological analysis of HIV infections has shown that the HIV is distributed around the world through two major patterns. One distribution pattern has been observed among several countries around the world, wherein there are specific times when an epidemic erupts and the virus infects a significant number of individuals in a particular country. In addition, these epidemics involve infection of a specific population, which is often considered to be at risk, including homosexuals, drug addicts and those individuals who employ sex as a way of living. The other distribution pattern of HIV is inherently observed in countries situated next to the Sahara desert, of which residents of these countries are not involved in any of the peculiar activities of HIV patients in the rest of the world. For the HIV-infected African individuals, they are considered to be self-sustaining and are not involved in any drug addiction or sex activities as a way of living.
Classification and Epidemiology of HIV Viruses
It is now clear that two types of HIV viruses are involved in the pathogenesis of AIDS among humans. The first HIV type, HIV-1, has been suggested to be transmitted from one species to another. Thus, the HIV-1 virus is hypothesized to originate from the chimpanzee species and somehow was inserted into the genome of the human species (Sharp et al., 2005). On the other hand, the HIV-2 virus has been suggested to originate from the Sooty mangabey (Lemey, 2003). There are currently 3 subtypes of HIV-1 identified (M, N and O) and each subtype is distinguished from the others through straightforward genetic differences. It has been estimated that the M HIV-1 subtype is a most common pathogenic HIV-1 and this subtype has been further subdivided into 9 clades for better classification and treatment. Sequence analysis of virus from each clade show that there is approximately 15 to 20% variation in their nucleic acid sequences.
Comparative analysis of the HIV-1 virus at the global level has shown that HIV patients around the world are infected with different HIV-1 subtypes. For example, HIV patients from North America and Europe are generally infected with the clade B HIV-1 subtype, while HIV-1 patients in South Africa are infected with the clade C HIV-1 subtype. Interestingly, there are now certain strains of HIV-1 that show a combination of two HIV-1 subtypes. This has been observed in China, where HIV-1 patients are infected with the B/C strain of HIV-1. Such observation suggests that HIV infection may be more complex than previously envisioned and each subtype could have been transmitted uniquely. More importantly, the existence of several subtypes also depicts that the HIV virus may not be treated with a single regimen because the issue of evolution must play a major role in its constant genetic modification.
Aside from the basics genetic and endemic site differences between HIV-1 and HIV-2, specific pathological features have also been observed in these viral agents. Research reports have described that the progression of the condition of immune deficiency is significantly slower among patients infected with HIV-2. In addition, the efficiency is transmission of the HIV-2 virus from one individual to another is lower than what has been observed with HIV-1. The HIV-2 has only evolved into 5 subtypes, of which only 2 are prevalent in specific countries.
An interesting observation with regards to the AIDS pandemic is that the HIV-1 virus is not distributed equally around the world. Although all of the countries around the globe have reported HIV cases, there are still certain regions of the world, as well as particular populations that show a markedly high number of infections as compared to the rest of the countries or the rest of the human population. Researchers have thus tried to determine the factors that influence the increase in infection rates so that measures can be adapted to prevent future spread of the virus. Scientific analysts have suggested that the unequal distribution of HIV-1 infections around the world indicates that the transmission of HIV-1 involves at least two major factors, one of which may be biological, and the other factor, social in nature. The biological factors may involve the employment of syringes during the administration of drugs among addicts, as well as engagement in sexual relations with a homosexual partner. The social factors that influence HIV-1 infection include cultural beliefs and activities, as exemplified in particular societies such as African American and the Latino populations.
Modes of Transmission of HIV
Elucidation of transmission routes of the HIV generally involves the identification of the index case, which technically pertains to the individual who introduces the HIV-1 virus to another individual. In addition, there are also other factors that are considered to determine the rate of infection and transmission. Firstly, the susceptibility for infection of the next individual also influences whether the transmission will be successful. Secondly, the amount of HIV-infected cells must reach a critical amount in order for the virus to be effectively transmitted to another person. In such cases, a significant amount of blood or body secretions are required in order for the HIV virus to survive in his new host. However, it has also been reported that the amount of cells that are required in order for an effective transmission to occur also depends on the stage of the AIDS of the infecting person (Pilcher, 2007). It has been reported that the amount of HIV virus is highest during the first few weeks after an individual is directly infected. In the case of individuals with full-blown AIDS, these individuals are generally at the advanced stage and are thus highly infective. The exact mechanism for such differences in infectivity is yet to be determined through biomedical research and analysis.
HIV infection is often coupled with another viral infection such as malaria. This co-morbidity is generally due to the decrease in the degree of immune response of the infected individual. It is therefore common to see cases in the African continent that HIV patients are also suffering from malaria. Other viral infections that may co-exist with HIV infection include sexually transmitted diseases (STDs) such as herpes simplex.
Treatment Regimen for HIV
During the 1980’s, treatment for HIV infection was considered difficult due to the limited information that has been uncovered with regards to the causative agent. The only initial information that was gathered then was that patients infected with HIV showed significantly high levels of CD4+ T cells, which in turn triggered more research into the relation of these particular T cells to immune response. Currently, HIV-1 infection is well understood, especially in terms of the replication process of the virus and the specific points of the cell cycle where treatment regimens may be administered. Although it is also known that once the full-blown symptoms of AIDS signifies a definite time point for the death of the patient, another obstacle of HIV treatment involves the delivery of the appropriate antiviral drug to the patient at the right time. It is important though, to understand that anti-viral drugs are suppressive, meaning they do not kill the HIV itself but only inhibit the patient from further expressing the full-blown AIDS features which are strongly associated with the death of the patient.
Significant improvements with regards to anti-HIV therapy have been observed in the last decade and the mortality rates due to HIV have significantly declined (Palella FJ, 1998). The first effective antiviral drug for the treatment of HIV is azidothymidine (AZT), yet the administration of this drug has also resulted in the creation of drug-resistant strains of HIV. In response to this mutation, combinations of anti-viral drugs were then formulated and this is now collectively known as the highly active antiretroviral therapy (HAART) (Larder, 2001). The goal of the HAART was to suppress the rate of generation of drug-resistant strains of the virus as well as allow the control of viral replication. Unfortunately, the employment of HAART therapies has also resulted in the significant potency of the anti-viral drugs to suppress viral replication. In addition, the combination of strong drugs within the body of an HIV patient also results in total body weakening due to the suppressive effect of the active ingredients of the combinatorial therapy. The weakening of the body of the HIV patient thus increases the chances that the patient will allow other opportunistic microbial pathogens to infect the body, even associating intrusion into the cardiovascular system and eventually resulting in death.
Co-Morbidity of HIV and Tuberculosis
It has been reported that most of the HIV patients also suffered from tuberculosis infections. Epidemiological data describes that there are approximately 14 million HIV patients who are also showing positive diagnostic results to the bacterial pathogen Mycobacterium tuberculosis. The presence of the HIV weakens the immune system of the patient thus opportunistic microbial species find its way into the system of the HIV patients within a few months. In addition, the precedent HIV infection increases the rate of progression of tuberculosis in the patient, as well as enhances the chances for tuberculosis re-infection. Active tuberculosis in patients with HIV-1 infection is generally observed to be atypical and these individuals are usually found to lead a short length of survival. Common diagnostic tests for tuberculosis can not be performed on HIV-1 infected patients because their sputum samples do not contain enough bacterial specimens, making these diagnostic tests only 50% efficient in detecting the bacterial pathogen. The presence of pulmonary cavitations also decrease the likelihood that sputum specimens of HIV infected patients will contain antigens that are essential in detection for tuberculosis infection.
Treatment of patients infected with HIV-1 and tuberculosis bacteria are often found to be difficult because of the complexity of drugs that need to be administered to the patient. One complication is that the larger number of drugs needed to be introduced to the patient result in drug toxicities that generally show some overlap in terms of drug effects. In addition, anti-HIV drugs interact with anti-tuberculosis drugs, either deactivating one drug or masking the effect of the other. It is thus important that an optimal setting for the administration of the anti-tuberculosis and anti-HIV drugs be designed in order to treat the patient.
It has been established that anti-HIV therapy be administered to a patient who has been determined to have CD4+ T cell counts of lower than 350 cells per cubic millimeter. The choices of anti-HIV drugs in pediatric patients are more difficult to provide because these children are often born to poor parents who could not afford to purchase such expensive medications. It is thus a common occurrence that pediatric HIV patients die during the first couple of years due to lack of therapeutic treatment for these children.
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