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ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS)AN OVERVIEW

Mohammad Raziuddin Professor of Zoology, Vinoba Bhave Universoty, Hazaribag 825301, Jharkhand. India Email: mrazi.vbu@gmail.com

AIDS (Acquired Immune Deficiency Syndrome) is the most serious infectious disease to have affected humankind with fatality rate close to 100%, making it an infection of devastating ferocity. It is caused by the blood-borne human immunodeficiency virus (HIV). It is a disease of the human immune system in which the in-built defence system of the body gradually becomes too weak to fight off infections and ultimately break down completely due to total depletion of a very important cell component of the immune mechanism. Affected individual is thus much more likely to get infections, including opportunistic infections like TB, pneumonias, diarrhoeas, common cold etc that do not affect people with working immune systems. This susceptibility gets worse as the disease continues and death is the ultimate result. Because of the varied nature these AIDS related diseases; AIDS has been identified as a syndrome (a group of health problems that make up a disease) rather than a single clinical entity. Although medical knowledge and advance technologies have made significant improvements and breakthroughs, HIV/AIDS still continue to ravage and claim millions of lives. It continues to be a major health problem worldwide. Since AIDS was first identified in the early 1980s, an unprecedented number (60 million) of people have been affected by the global AIDS epidemic and more than 25 million have died of HIV-related causes (Merson et al., 2008). Today, there are an estimated more than 40 million individuals living with HIV/ AIDS worldwide (Borroso et al., 2011) of which more than 3.4 million are under the age of 15. In 2010, an estimated 2.7 million people were newly infected with HIV and 1.8 million people died from AIDS. Developing countries have experienced the greatest HIV/AIDS morbidity and mortality, with the highest prevalence rates recorded in young adults in sub-Saharan Africa (http://www.unaids.org/). People with HIV/AIDS are not only be unable to work, but will also require significant medical

care thus affecting economic growth of a country by reducing the availability of human capital. HISTORY OF AIDS Where did AIDS come from? This question has puzzled scientists ever since the illness first came to light in the early 1980s and for many years it has been the subject of fierce debate and the cause of countless arguments. All current evidence points to Kinshasa (Leopoldville) in the nearby country of Congo as the cradle of the AIDS pandemic (Sharp and, 2011) because the first human known to be infected with HIV was a man from Kinshasa who had his blood stored in 1959 as part of a medical study, decades before scientists knew the AIDS virus existed (http://www.msnbc.msn.com). AIDS was first recognized in the USA in the early 1981 (CDC, 1981). A number of young homosexual men in New York and California suddenly began to develop rare opportunistic infections and cancers that did not respond any treatment (Hymes et al., 1981; MMWR Weekly, 1981). It quickly became obvious that all of them were suffering from a common syndrome. The discovery of HIV was made soon after and there is now clear evidence to prove that a retrovirus, termed human immunodeficiency virus (HIV), is the causative agent of AIDS, the most devastating infectious diseases to have emerged in recent history (Barre-Sinoussi et al. 1983; Gallo et al. 1984; Popovic et al. 1984). In fact two types of HIV infect humans: HIV-1 and HIV-2. HIV-1 is more virulent, is more easily transmitted and is the cause of the vast majority of HIV infections globally (Reeves, 2002). It is not just one virus, but comprises four distinct lineages, termed groups M, N, O, and P, each of which resulted from an independent cross-species transmission event. Group M was the first to be discovered and represents the pandemic form of HIV-1 and has been found in virtually every country on the globe (Sharp and Hahn, 2011). HIV-2 is a less common strain of HIV than HIV-1 strain. As much as they are alike they have subtle differences. HIV-2 seems to weaken the immune system more slowly than HIV-1. This strain is highly concentrated in West Africa countries such as Senegal, Nigeria, Ghana, and the Ivory Coast. HOW, WHEN AND WHERE HIV FIRST BEGAN TO CAUSE DISEASE IN HUMANS? It is likely that we will never know who the first person was to be infected with HIV, or exactly how it spread from that initial person (Patient 0). Most researchers believe that HIV originated in sub-Saharan Africa during the twentieth century. After the HIV first

emerged it spread for some 50 to 70 years before it was recognized. Scientists have confirmed that the HIV virus plaguing humans really did originate in wild chimpanzees, in a corner of Cameroon. HIV is thus a descendant of Simian Immunodeficiency Viruses (SIVs), endemic in wild ape populations of West Central Africa that had at some point crossed species from chimps to humans as a case of zoonosis (transfer of a pathogen from non-human animals to humans) during the late 19th or early 20th century. Transmission most likely would have occurred through cutaneous or mucous membrane exposure to infected ape blood and/or body fluids. Such exposures occur most commonly in the context of bushmeat hunting (Peeters et al. 2002). HIV1 and HIV2 viruses are related to different SIVs and therefore have different evolutionary origins. HIV-1 is most closely related to the SIVs, endemic in wild ape populations of West Central African forests. HIV-1 is either closely related to the SIV that infects the chimpanzee subspecies Pan troglodytes troglodytes (SIVcpz), or to the SIV that infects Western lowland gorillas (Gorilla gorilla gorilla), called SIVgor ( Sharp et al., 2001; Keele et al., 2006; Van Heuverswyn et al., 2006; Plantier et al., 2009). HIV2 originated from a different independent event where virus was transmitted from sooty mangabey monkeys (Cercocebus atys) to humans (Rambaut et al., 2004). It is most closely related to SIVsm (Gao et al., 1992) which is found at high prevalence in sooty mangabey. Sooty mangabeys are most frequent in the regions of West Africa where HIV-2 is likely to have emerged. THE VIRUS HIV belongs to a group of retroviruses called lentiviruses. Lentiviruses are highly specific in nature and are transmissible only to closely related species. They bud from the cell membrane. A retrovirus contains ribonucleic acid (RNA) as genetic material that must reverse to deoxyribonucleic acid (DNA) before replicating. It is the DNA gene that enables the virus to replicate. HIV is fragile outside but can live a long time (years) inside the cells. HIV is spherical with roughly a diameter of 120 nm. It has a very complex genome. It is surrounded by a coat of fatty material known as the viral envelope (membrane). Projecting from this are little spikes, which are formed from the proteins gp120 and gp41. Just below the viral envelope is a layer called the matrix, which is made from the protein p17. The spikes allow the virus to effectively bind and fuse with human immune cells.

The viral core called capsid is usually bullet-shaped and is made from the protein p24. Inside the core is the HIVs genetic material, which consists of two identical strands of RNA. Enzymes required for HIV replication called reverse transcriptase, integrase and protease are also present inside the core (Fig. 1 ).

HIV GENES AND THEIR MAJOR FUNCTIONS HIV has only nine genes (compared to more than 500 genes in a bacterium, and around 20,000-25,000 in a human). These genes are sequences of RNA that encode a particular protein. Three of the HIV genes, called gag, pol and env, contain information needed to make structural proteins for new virus particles. The other six genes, known as tat, rev, nef, vif, vpr and vpu, code for proteins that control the ability of HIV to infect a cell, produce new copies of virus, or cause disease. The regulation of HIV gene expression is accomplished by a combination of both cellular and viral factors.

Fig. 2. The genome of HIV provirus (The integrated form of HIV-1) with major function (Source http://www.gladstone.ucsf.edu)

LIFE CYCLE OF HIV Life cycle of HIV is completed in the following six steps (Fig. 2): 1. Binding and Fusion: HIV begins its life cycle when it binds to the surface molecule (CD4) of T helper cells and macrophages and one of two co-receptors on the surface of T lymphocyte. The viral envelope then fuses with the host cell membrane. After fusion, the virus releases its genetic material (RNA) into the host cell. 2. Reverse Transcription: An HIV enzyme called reverse transcriptase converts the single stranded HIV RNA to double-stranded HIV DNA.
Reverse transcriptase

RNA -------------------------------> DNA

3.

Integration: The newly formed HIV DNA enters the host cell's nucleus, where an HIV unique enzyme called integrase inserts viral DNA into host cell chromosome and "hides" the HIV DNA within the host cell's own DNA. The integrated HIV DNA is called provirus. The provirus may remain inactive for several years, producing few or no new copies of HIV (Fig. 3).

4.

5.

6.

Transcription: When the host cell receives a signal to become active, the provirus uses a host enzyme called RNA polymerase to form copies of the HIV genomic material, as well as shorter strands of RNA called messenger RNA (mRNA). The mRNA is used as a blueprint to make long chains of HIV proteins.

7.

Assembly: An HIV enzyme called protease cuts the long chains of HIV proteins into smaller individual proteins. As the smaller HIV proteins come together with copies of HIV RNA, a new HIV particle is assembled.

8.

Budding: The newly assembled virus pushes out ("buds") from the host cell. During budding, the new virus steals part of the cell's outer envelope. This envelope, which acts as a covering, is studded with protein/sugar combinations called HIV glycoproteins. These HIV glycoproteins are necessary for the virus to bind CD4 and coreceptors. The new copies of HIV can now move on to infect other cells.

HIV-1 can persist in a latent form in resting CD4 T cells (Fig. 4a). Latent infection of resting CD4 T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective anti-retroviral therapy.

MODES OF HIV TRANSMISSION Human immunodeficiency virus is passed from one person to another mainly through blood-to-blood and sexual contact. In addition, an infected pregnant woman can pass HIV to her baby during pregnancy or delivery, as well as through breast-feeding. HIV can be transmitted through the body fluids: blood (and any body fluid containing blood), semen, vaginal fluid, breast milk, cerebrospinal fluid (which surrounds the brain and the spinal cord), synovial fluid (which surrounds bone joints) and amniotic fluid (which surrounds a foetus). Though HIV is also present in other body fluids such as saliva and sweat, it is present in such low quantities that transmission through these routes is almost impossible. Transmission of the virus from the hosts saliva is possible when saliva is mixed with blood. Therefore, deep or open-mouthed kissing specially with a partner with bleeding mouth is a risky activity in terms of HIV transmission. Similarly HIV is not transmitted through ordinary social contact such as kissing, shaking hands, coughing and sharing cutlery because the virus is not airborne, water-borne or foodborne , and does not survive for very long outside the human body. It is also not possible to get HIV from mosquitoes or bed bugs. The main modes of HIV transmission are thus: 1. 2. 3. Having vaginal or anal sex without a condom with someone who is infected. Having contact with the blood of someone who has HIV. This could be having a blood transfusion from someone who is infected with HIV From a mother who has HIV to her baby: HIV can pass to the baby during pregnancy, during the birth of the baby, or through breast-feeding. Only about one in three babies born to HIV-positive mothers get HIV. 4. 5. Receiving an injection from an unsterilized needle that was previously used by someone with HIV. Heterosexual transmission is the route by which most people with AIDS have become infected with HIV worldwide. This category of AIDS cases is also among the most rapidly increasing. A significant portion of HIV infection among women in the world is acquired through heterosexual contact. HIV can be found in the blood, semen, pre-seminal fluid, or vaginal fluid of a person infected with the virus. The lining of the vagina can tear and allow HIV to enter the body. Direct absorption of HIV through the mucous membranes

that line the vagina is also a possibility. The male may be at less risk for HIV transmission than the female through vaginal intercourse. However, HIV can enter the body of the male through his urethral opening at the tip of the penis or through small cuts or open sores on the penis. HIV can also be transmitted to a man or a woman through anal sex. SYMPTOMS Many people do not develop any symptoms when they first become infected with HIV. Some people, however, develop flu-like illness within three to six weeks after exposure to the virus. Severe symptoms may not surface for several years, even a decade or more, after HIV first enters the body in adults, or within two years in children born with the virus. This period of "asymptomatic" infection varies from individual to individual. Opportunistic infections are common in people with AIDS (Holmes et al., 2003). These infections affect nearly every organ system. People with AIDS are also particularly prone to developing various cancers, especially those caused by viruses, such as Kaposi's sarcoma and cervical cancer, or cancers of the immune system, known as lymphomas. Main symptoms of AIDS are: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. Rapid weight loss Dry cough and shortness of breath Severe headaches Recurring fever or profuse night sweats Difficult or painful swallowing Profound and unexplained fatigue Swollen lymph glands in the armpits, groin, or neck (Fig. 6) Nausea, abdominal (stomach) cramps, and vomiting Persistent diaorrhea that lasts for more than a week White spots or unusual blemishes on the tongue, in the mouth, or in the throat Pneumonia Red, brown, pink, or purplish blotches on or under the skin or inside the mouth, nose, or eyelids Mental symptoms, such as confusion and forgetfulness, depression, and other neurological disorders 14. 15. Vision loss Coma.

TREATMENT Earlier when AIDS patient was identified in the US, there were no medicines to combat the underlying immune deficiency, and few treatments existed only for the opportunistic Infections due to HIV. Researchers have however, now developed a number of approved medications to treat HIV infections. 1. Nucleoside Reverse Transcriptase (RT) Inhibitors that interrupt an early stage of the virus making copies of itself. These medications may slow the spread of HIV in the body and delay the start of opportunistic infections. This class of medications, called nucleoside analogs, includes: AZT (azidothymidine), ddC (zalcitabine), 2. ddI (dideoxyinosine), reverse d4T (stavudine), inhibitors 3TC (lamivudine), such as: (in Abacavir (Ziagen), Tenofovir (Viread), Emtricitabine (Emtriva). Non-nucleoside Delavridine transcriptase (NNRTIs), (Rescriptor), Nevirapine (Viramune),Efravirenz (Sustiva)

combination with other antiretroviral medications), Etravirine (Intelence) (in combination with other antiretroviral medications). 3. Protease Inhibitors, interrupt the virus from making copies of itself at a later step in its lifecycle. They include: Ritonavir (Norvir), Saquinivir (Invirase), Indinavir (Crixivan), Amprenivir (Agenerase), Nelfinavir (Viracept), Lopinavir (Kaletra), Atazanavir (Reyataz), Fosamprenavir (Lexiva). 4. Fusion Inhibitors are new HIV medications approved recently for the treatment of HIV. These interfere with the virus' ability to enter into cells by blocking the merging of the virus with the cell membranes. Fuzeon (enfuvirtideor T-20) is the first approved fusion inhibitor It reduces the level of HIV infection in the blood,

and may be active against HIV that has become resistant to current antiviral treatment schedules. HIV and AIDS in India India, with 1.22 billion people is the second most populous country in the world after China. India being the world's second most populous country has the second

largest burden of HIV -infected persons. According to an estimate, one of every six new HIV infections occurs in India and two Indians become HIV -infected every minute.
Around half of Indias population is adults in the sexually active age group. It is estimated that around 2.4 million people are currently living with HIV. (UNAIDS, 2010) around half of whom are adults in the sexually active age group. Further, HIV positives 39% are female and 3.5% are children.The first AIDS case in India was detected in April1986 when 10 prostitutes in Chennai were found HIV seropositive (Simoes, 1987). Since then HIV infection has been reported in all states and union territories involving almost all segments of the society. The vast majority of infections however occur through heterosexual sex (80%), and is concentrated among high risk groups including prostitutes, homosexual men , and injecting drug users as well as truck drivers and migrant workers (UNGASS, 2008). A significant trend is that most of the people becoming infected are in the sexually active and economically productive 15 to 44 age group.

Fig. 8. Estimated adult HIV/AIDS prevalence in the states of India

The spread of HIV in India has been uneven. Although much of India has a low rate of infection, certain places have been more affected than others (Fig.8). HIV epidemics are more severe in the southern half of the country and the far north-east. The highest estimated adult HIV prevalence is found in Manipur (1.40%), followed by Andhra Pradesh, Mizoram, Nagaland, Karnataka and Maharashtra (NACO, 2011). PSYCHOLOGICAL ISSUES AIDS is having an enormous impact on society is undisputed. Not only does AIDS cause physical suffering and death, and economic costs in terms of lost labour and medical costs, it also costs in psychological terms. The psychological and social sequel of HIV and AIDS infection is devastating to children, adolescents, women, and their families. There are complex psychological and social issues that impact a family's ability to cope with HIV infection. HIV/AIDS infected individuals and their families are forced to cope with a multitude of stressors. Patients who are diagnosed with AIDS are especially prone to various psychological problems and indeed a number of behavioral and psychosocial problems have been noted in them. One common problem in HIV/AIDS patient is depression, Depression in men with HIV is further aggravated due to low testosterone level. The feeling that such tragedy could have been avoided, add further to their despair and guilt and may lead to suicidal feelings and/or attempts. The social implications of the disease and the ensuing isolation AIDS intensify to the stress of the patient. It is therefore, group support and home care are essential if these patients are to have a decent quality of life for as long as possible. As HIV/AIDS is a chronic and life-threatening illness and adjusting to the illness is a lifelong process the patient initially suffers from emotional dilemmas, besides shock, anger, denial, guilt and anxiety followed by major anxiety disorders (panic disorder, obsessive compulsive disorder). Changes in personality (a[athy and erratic behavior), psychotic symptoms (i.e. hallucination and suspiciousness), and motor symptoms (i.e. ataxia and weakness) are common problems in HIV-seropositive individuals. Major depression is sometimes accompanied by disturbances of higher cognitive functions, including memory and concentration. HIV can cross the blood-brain barrier and enter the central nervous system through virus-infected macrophages. Hence a

significant proportion of HIV-positive persons will develop this neurologically based cognitive disorder. For some that will entail subtle impairments in cognitive function (attention deficits, slower processing of information.) but some develops more pronounced cognitive deficits (including linguistic disturbances and psychomotor slowing). Some patients with this dementia become severely withdrawn and uncommunicative and occasionally, this dementia progresses to psychosis and delirium. INDIAN WOMEN AND HIV/AIDS Indian society is male dominated where females receive less health care than males. Majority of them are forced to lead a life of indignity, social stigma, debt bondage and a host of ailments including HIV/AIDS. The AIDS epidemic has had a unique impact on Indian women, which has been exacerbated by their role within society and their biological vulnerability to HIV infection. They are at a greater risk of heterosexual transmission of HIV and their low economic and social status continues to be a barrier to preventing new infections. AIDS is spreading among young, monogamous, married women in India who get infected by their husbands. Women are more vulnerable to the risk of contracting HIV/AIDS than men because they have a larger internal surface area in their reproductive tract and are thus more susceptible to HIV. Further, Indian women have few opportunities to demand or request that their partner practice safe sex. Women whose spouses are HIV-positive face the fear of his death, the fear of becoming infected and feeling helpless, mental stress over the physical and psychological burden of care, and a sense of despondency and failure about the future (Bor, Miller and Goldman, 1993). Indian HIV-positive women have a high incidence of mental health problems and report greater levels of psychological distress than their male counterparts. Psychosocial distress not only impedes the quality of one's social and emotional life but also is associated with poor physical functioning leading to chronic depressive symptoms. REFERENCES Rambaut, A., David Posada, Keith A. Crandall and Edward C. Holmes (2004): The causes and consequences of HIV evolution. Nature Reviews/ Genetics. 5, 52-61.

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