Human immunodeficiency virus is the causative agent of acquired immunodeficiency syndrome (AIDS) in humans. There are two variants of HIV that causes AIDS in humans viz: HIV-1 and HIV-2. HIV-1 is more pathogenic in nature and globally distributed while HIV-2 is less pathogenic and is restricted to the West African sub region and other parts of the world where it may have spread to. While HIV-1 is mainly transmitted through blood and from mother to child and is thus a neonatal infection acquired congenitally, HIV-2 is transmitted through blood and sexual contact or having unprotected sex with an already infected person. Nonetheless, both HIV-1 and HIV-2 have almost the same route of transmission in human population.
HIV-2 is the less-pathogenic strain of HIV. HIV-2 is mainly concentrated in West Africa and it may also be found in some other parts of the world including United States of America, India and Europe. Unlike in HIV-1 infection where disease state is usually characterized by a drastic depletion of the CD4+ T cell population in HIV-1 infected individuals; HIV-2 infection is notable for a protracted asymptomatic stage of infection and slower progression to AIDS. HIV-2 is usually characterized clinically by higher CD4+ T cell count and lower viral RNA levels. This is a clear-cut difference between the clinical presentations and pathologies of HIV-1 and HIV-2. However, HIV-2 can cause AIDS even though they are less-virulent than HIV-1. HIV-2 is naturally found in the endangered African sooty mangabey (SM) monkey. HIV-2 is less- transmissible and less virulent than HIV-1. HIV-2 is also a close relative of the SIV found in SM.
HIV was first discovered as a human viral pathogen in the early 1980’s; and the disease (i.e., AIDS) caused by the virus has since caused innumerable number of morbidity and mortality in the human population. Even till date, there is still no cure or vaccine for HIV infection in humans. The actual origin of AIDS in the human population is as a result of cross-species infection of humans by a chimpanzee Lentivirus particularly the simian immunodeficiency virus (SIV), which infects only monkeys, chimpanzees and other like-primates in the West Central African region. The scourge of the AIDS disease has impacted negatively on the economies of the world due to its ability to deteriorate the immune system of HIV-infected individuals. And yet, there is still no functional cure or vaccine for the dreaded disease.
PATHOGENESIS OF HIV INFECTION
HIV is mainly transmitted through sexual intercourse especially unprotected sexual intercourse with an infected person. Transmission through contact with body fluids and blood and other sharp objects contaminated with blood of an HIV-positive individual is also possible. HIV can also be transmitted congenitally from an infected mother to an unborn child. Intravenous drug users, heterosexuals and homosexuals are also at high risk of infection with HIV. People with other sexually transmitted disease (STD) such as gonorrhea are also more prone to becoming infected with HIV especially if they engage in unprotected sex with an infected individual or live promiscuously. HIV is entirely an infection of the immune system of humans, and the CD4+ T helper cells (TH) of the cellular immune system are the main receptor of the virus. HIV binds to the CD4 cells and also on other cellular cells of the human host that bears the CD4 marker or receptor on their cell surfaces.
This binding leads to the suppression of the individual’s cellular immune response due to the loss of CD4+ T helper cells. The CD4+ T helper cells are unique in the cellular immune response of humans because they play a central role in both cellular and humoural immune response when foreign bodies (i.e., antigens inclusive of pathogenic viruses like HIV) invade the body. CD4 cells secrete numerous cytokines that activates other specific components of the immune system such as the macrophages; delayed-type hypersensitivity T cells (TDTH) and the cytotoxic T cells (CD8) which carries out the killing of antigens in the body. HIV infects and kills immune system cells (especially the CD4 lymphocytes) that are vital for effective immune response against pathogens that invades the body.
Once the HIV has attached to the CD4 cells, it facilitates its entry into the cell through several cell-entry techniques. And once inside the cell, the virus uncoats and its RNA genome is transcribed with the help of its reverse transcriptase (RT) enzyme to a viral DNA or provirus that is integrated into the chromosomal DNA of the infected host cell. Since the CD4 cells are primarily responsible for the mediation or activation of T cell immunity during antigen invasion of the body, acquired immunodeficiency syndrome (AIDS) finally results following a marked decrease or depletion of the CD4 cells of the affected individual by HIV over time. HIV infection can be acute (during which the infection is rapid in progression) or chronic (during which the infection is slow in progression) in occurrence but the actual clinical outcome of the disease is dependent on several factors which include the genetics of the infecting virus, the genetics of the affected host, the virulence of the infected virus strain and the immune status of the infected host.
HIV-infected people remain infectious throughout the period of their lifetime especially in the acute stage of the disease, and such individuals are potential routes through which the disease can be transmitted to susceptible human populations. At the acute stage of HIV infection, the viral load in infected individual is very high and such patients show a high level of viraemia at this phase when viral count of their blood is taken. During the chronic stage of the disease, some of the dead CD4 cells are rapidly replaced and the patients usually show low viral load count and normal CD4 cell count too. But AIDS definitely sets in; and it is generally characterized by the emergence of several opportunistic infections caused by bacterial, fungal and protozoan pathogens and even some viruses such as cytomegalovirus (CMV). Development of tumours (especially cancers of the skin) and some neurological disorders such as wasting and aseptic meningitis are other accompanying (opportunistic) infections that characterize AIDS in HIV-infected individuals.
These opportunistic infections exemplify the main clinical features of AIDS in HIV infected individuals and they appear during the progressive loss of CD4 cells in infected persons. Unexplained weight loss, fever, pharyngitis, headache, arthralgia, myalgia, and malaise are some of the main non-specific symptoms or clinical features that characterize the primary stage of HIV infection (i.e., the stage at which the individual is newly infected). The incubation period of the disease is usually 2-6 weeks after exposure but this can also last up to 3 months or 6 months. It is noteworthy that the clinical course of HIV infection in humans varies from one individual to another. While some individuals can show clinical signs of AIDS within 10 years of infections, others can live beyond this limit without showing any clinical signs of AIDS. However, the AIDS stage of HIV infection is usually defined by a marked decrease in the CD4 level of the infected host. A CD4 cell count of less than 200 cells/µL is clinically indicative of AIDS stage. The appearance of some opportunistic infections, cancers or tumours can also define the AIDS-stage of the disease.
AIDS usually appear after about 10 years of infection with HIV; and due to the marked disintegration of the host immune system especially that of the cellular immunity, the individual is exposed to plethora of opportunistic infections caused by other microbes including non-pathogenic bacteria, viruses, protozoa and fungi. The severity of HIV infection according to studies have been linked to co-infection with other non-retroviral agents such as hepatitis B virus (HBV), hepatitis C virus (HCV) and CMV amongst others; and this has affected or increased the rate of progression of the disease in HIV-positive patients who have these co-infections.
LABORATORY DIAGNOSIS OF HIV INFECTION
Clinically, the presence of opportunistic infections such as cryptococcal meningitis and recurrent vulvovaginal candidiasis amongst others mentioned above without a known cause of immunodeficiency in a person should raise suspicion of HIV infection. Nevertheless, the laboratory diagnosis of HIV infection is largely dependent on the detection of HIV-1 or HIV-2 antibodies in the serum or blood samples of patients using serological or molecular techniques that includes enzyme linked immunosorbent assay (ELISA), polymerase chain reaction (PCR) and other rapid diagnostic laboratory techniques.
In addition, specific antigens of the virus especially the capsid proteins of HIV such as p24 can be detected in serum following infection using HIV antigen detection kits. The detection of HIV capsid proteins some days after infection aids in the early diagnosis of infection since these proteins appear in the serum or blood of infected individuals few days after infection and before HIV-1 or 2 antibodies starts to appear. The AIDS defining illness of the disease can also be confirmed in the laboratory by determining the patients CD4 count. And if the CD4 cell count is less than 200 cells/µL, then the individual is likely to be in the AIDS phase of the disease.
TREATMENT AND MANAGEMENT OF HIV INFECTION
One of the major impediments to the effective treatment of HIV infection is the development of resistance to some readily available antiretroviral drugs especially when such drugs are used singly for treatment. In lieu of this, antiretroviral drugs are now administered in combinations of three antivirals i.e., as a triplet; and this has helped to contain the possibility of development of resistance to antiretroviral drugs when they are used singly. To this end, highly active antiretroviral therapy (HAART) which is the type of HIV treatment in which antiviral drugs are used in combination as triple therapy is now being used for HIV treatment.
In HAART, one nucleoside analog and one protease inhibitor are included in the antiretroviral therapy, and the main aim of this triple therapy is to slow the development of resistance to any of the antiviral agent and also to ensure effective treatment. Most antiretroviral drugs target key steps in the replication cycle of retroviruses in order to inhibit or slow their replication. Also, antiretroviral drugs help to reduce the number of viruses in the individual as quickly as possible so that the nefarious activity of the virus (especially in suppressing the cellular immunity) can be contained and assuaged on time.
The major classes of antiretroviral drugs available for the treatment of HIV-infection are nucleoside inhibitors and protease synthesis inhibitors. The nucleoside inhibitors include zidovudine or azidothymidine (AZT), lamivudine (3TC) and didanosine (ddl). These antiretroviral drugs are nucleoside analogs and they basically inhibit the activities of reverse transcriptase (RT) during HIV replication. They bind to the active site of RT enzyme, and thus become incorporated into the growing DNA strands (i.e., the viral cDNA or provirus). By interfering with the synthesis of viral DNA, AZT acts as chain termination to stop the elongation of the DNA strand so that an incomplete genome of the virus will be produced. Protease inhibitorsbasically act by inhibiting the production of protease which is vital for the formation of viral proteins.
Examples of antiretroviral agents that are protease inhibitors include ritonavir (RTV), indinavir (IDV) and saquinavir (SQV). Protease inhibitors generally inhibit viral maturation since proteases play critical roles in the synthesis of viral proteins required for the coupling of new virions. Other antiretroviral drugs used in the treatment of HIV infection include: integrase inhibitors or integrase strand transfer inhibitors (INSTIs) such as raltegravir, dolutegravir and elvitegravir; and non-nucleotide reverse transcriptase inhibitors (NNRTIs) such as efavirenz, nevirapine, etravirine and rilpivirine. No effective vaccine currently exist for the vaccination of susceptible human population against HIV infection but vaccine development for HIV prevention is still underway and promising. The search for a functional drug that will be used for the cure and eradication of HIV is also on course.
The AIDS virus (HIV) has a rapid rate of maturation or replication, and its genetics is inconsistent due to the ease with which the virus mutates into different and new viral forms. And the human body can still not produce protective immunoglobulins against HIV. These factors have greatly affected the development of novel and potent vaccine for the effective vaccination of the human race against the scourge.Having safe sex and sticking to only one partner when married, screening of blood and organs before transfusion or transplantation and avoiding the sharing of sharp objects such as needles are some of the measures that can be taken for the prevention of HIV infection.
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