Sunday, April 22, 2012

HIV Introduction

Acquired immunodeficiency syndrome or acquired immunodeficiency syndrome (AIDS) is an immune system disease caused by human immunodeficiency virus (HIV). The disease interferes with the immune system, making people with AIDS much more likely to get infections, including opportunistic infections and tumors that do not affect people who work with the immune system. This susceptibility worsens as the disease continues.
HIV is transmitted in many ways, such as sex (including oral sex and anal sex), transfusions of contaminated blood and needles, and the exchange between mother and baby during pregnancy, childbirth and breastfeeding. It can be spread by any contact of a mucous membrane or the bloodstream with a bodily fluid that has the virus on it, such as blood, semen, vaginal fluid, pre-ejaculate, or breast milk from an infected person.
The virus of the disease and are often referred to together as HIV / AIDS. The disease is a major health problem in many parts of the world, and is considered a pandemic, an outbreak of disease that is not only present in a large area but is spreading actively. In 2009, the World Health Organization (WHO) estimates there are 33.4 million people living with HIV / AIDS, with 2.7 million new HIV infections per year and 2.0 million deaths due to AIDS. In 2007, UNAIDS estimated: 33.2 million people worldwide were HIV positive, AIDS killed 2.1 million people in the course of the year, including 330,000 children, and 76% of these deaths occurred Sub-Saharan Africa. According to UNAIDS 2009 report, worldwide about 60 million people have been infected since the beginning of the pandemic, with about 25 million deaths and 14 million orphans in southern Africa.
Genetic research indicates that HIV originated in west-central Africa in the late nineteenth and early twentieth. AIDS was first identified by the Centers for Disease Control and Prevention (CDC) in 1981 and its cause, HIV, identified in the 1980's.
Although treatments for HIV / AIDS can slow the course of the disease, no cure or vaccine against HIV. Antiretroviral treatment reduces both deaths and new HIV infections / AIDS, but these are expensive drugs and medicines are not available in all countries. Because of the difficulty in treating HIV infection, preventing infection is a key aim in controlling the AIDS pandemic, with organizations of health promotion and safe sex needle exchange programs in attempts to reduce the spread of the virus.
Signs and symptoms
 
The main symptoms of AIDS.
 
X-ray of Pneumocystis pneumonia (PCP). There is increased white (opacity) of the lower lungs on both sides, characteristic of PCP.
The symptoms of AIDS are primarily the result of conditions not normally develop in individuals with healthy immune systems. Most of these conditions are opportunistic infections caused by bacteria, viruses, fungi and parasites that are normally controlled by the elements of the immune system that HIV damages. These infections affect nearly every organ system.
People with AIDS also have an increased risk of developing various cancers such as Kaposi's sarcoma, cervical cancer and cancers of the immune system known as lymphomas. In addition, people with AIDS often have systemic symptoms of infection like fevers, sweats (particularly at night), swollen glands, chills, weakness and weight loss. The specific opportunistic infections that AIDS patients develop depend in part on the prevalence of these infections in the geographic area in which the patient lives.
Pulmonary
Pneumocystis pneumonia (originally known as Pneumocystis carinii pneumonia, and still abbreviated as PCP, which now stands for Pneumocystis carinii pneumonia) is relatively rare in healthy, immunocompetent, but common among HIV-infected individuals. It is caused by Pneumocystis jirovecii.
Before the advent of effective diagnosis, treatment and routine prophylaxis in Western countries, it was a common cause of immediate death. In developing countries, remains one of the first indications of AIDS in untested individuals, although it usually does not occur unless the CD4 count falls below 200 cells per microliter of blood.
Tuberculosis (TB) is unique among infections associated with HIV because it is transmissible to immunocompetent people, through the airway, and it is easily treatable once identified. Multidrug resistance is a serious problem. TB co-infected with HIV (TB / HIV) is a global health problem, according to World Health Organization, in 2007, 456,000 deaths among TB cases were HIV-positive, one third of deaths from TB and about a quarter of the estimated 2 million deaths from HIV in that year. Although its incidence has decreased due to the use of directly observed therapy and other best practices in Western countries, this is not the case in developing countries where HIV is most prevalent. In early HIV infection (CD4 count> 300 cells per microliter), TB typically presents as a pulmonary disease. In advanced HIV infection, TB often presents atypically with extrapulmonary (systemic) disease a common feature. Symptoms are usually constitutional and are not located in a particular site, often affecting bone marrow, bone, urinary and gastrointestinal tract, liver, lymph nodes, and central nervous system.
Gastrointestinal
Esophagitis is an inflammation of the lining of the lower end of the esophagus (throat or swallowing tube leading to the stomach). In people with HIV, this is normally due to fungal (candidiasis) or viral (herpes simplex-1 or cytomegalovirus) infections. In rare cases, may be due to mycobacteria.
Unexplained chronic diarrhea in HIV infection is due to many possible causes, including common bacterial (Salmonella, Shigella, Campylobacter and Listeria) and parasitic infections, and uncommon opportunistic infections such as cryptosporidiosis, microsporidiosis, Mycobacterium avium complex ( MAC) and viruses, astrovirus adenovirus, rotavirus and cytomegalovirus, (the latter as a course of colitis).
In some cases, diarrhea can be a side effect of several medications used to treat HIV, or simply accompany HIV infection, especially during primary HIV infection. It can also be a side effect of antibiotics used to treat bacterial causes of diarrhea (common for Clostridium difficile). In the late stages of HIV infection, diarrhea is thought to be a reflection of changes in the way that nutrients absorbed intestinal tract, and may be an important component of HIV-related wasting.
Neurological and psychiatric
HIV infection can lead to a variety of neuropsychiatric sequelae, either by infection of the nervous system now by susceptible organisms, or as a direct consequence of the disease itself.
Toxoplasmosis is a disease caused by single-celled parasite called Toxoplasma gondii, which usually infects the brain, causing toxoplasma encephalitis, but can also infect and cause disease in the eyes and lungs. Cryptococcal meningitis is an infection of the meninges (the membranes covering the brain and spinal cord) by the fungus Cryptococcus neoformans. It can cause fever, headache, fatigue, nausea and vomiting. Patients may also develop seizures and confusion, left untreated, can be lethal.
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease, in which the gradual destruction of the myelin sheath covering the axons of nerve cells affects the transmission of nerve impulses. It is caused by a virus called JC virus which occurs in 70% of the population in latent form, causing disease only when the immune system has been severely weakened, such as AIDS patients. It progresses rapidly, causing death within months of diagnosis.
AIDS dementia complex (ADC) is a metabolic encephalopathy induced by HIV infection and fueled by immune activation of HIV-infected macrophages and brain microglia. These cells are productively infected by HIV and secrete neurotoxins of both host and viral origin. Specific neurological disorders are manifested by cognitive, behavioral and motor abnormalities that occur after years of HIV infection and is associated with low CD4 T cell levels and high plasma viral loads.
The prevalence is 10-20% in Western countries, but only 1-2% of HIV infections in India. This difference is possibly due to the HIV subtype in India. The AIDS related mania is sometimes seen in patients with advanced HIV disease, but occurs more irritability and cognitive impairment and less euphoria than one episode of mania associated with bipolar disorder true. Unlike the latter condition can have a more chronic course. This syndrome is less frequent with the advent of multi-drug therapy.
Tumors
 
Kaposi Sarcoma
Patients with HIV infection have substantially increased the incidence of various cancers. This is mainly due to the co-infection with oncogenic DNA viruses, especially Epstein-Barr virus (EBV), Kaposi's sarcoma associated herpes virus (KSHV) (also known as human herpesvirus 8 [HHV- 8]), and human papillomavirus (HPV).
Kaposi's sarcoma (KS) is the most common tumor in HIV infected patients. The appearance of this tumor in young homosexual men in 1981 was one of the first signs of the AIDS epidemic. Caused by a virus called gammaherpes Kaposi sarcoma-associated herpes virus (KSHV), which often appears as purplish nodules on the skin, but can affect other organs, especially the mouth, gastrointestinal tract and lungs. High grade B cell lymphomas such as Burkitt lymphoma, Burkitt-like lymphoma, diffuse large B-cell (DLBCL) and primary lymphoma of the central nervous system occur more frequently in HIV-infected patients. These particular cancers often foreshadow a poor prognosis. Epstein-Barr virus (EBV) or KSHV cause many of these lymphomas. In HIV-infected patients, lymphoma often occurs in extranodal sites such as the gastrointestinal tract. When produced in an HIV infected patient, KS and aggressive B-cell lymphomas confer an AIDS diagnosis.
The invasive cervical cancer in HIV-infected women also considered AIDS-defining, which is caused by human papillomavirus (HPV).
In addition to AIDS-defining tumors listed above, patients with HIV are at increased risk of certain tumors, particularly cancer Hodgkin's disease, anal and rectal carcinoma, hepatocellular carcinoma, head and neck and lung cancer. Some of these are the causes of viruses, such as Hodgkin's disease (EBV), cancer anal / rectal (HPV) in head and neck cancer (HPV) and hepatocellular carcinoma (hepatitis B or C). Other contributing factors include exposure to carcinogens (cigarette smoke to lung cancer), or live for years with minor immune defects.
Interestingly, the incidence of many common tumors such as breast or colon cancer does not increase in patients infected with HIV. In areas where HAART is widely used to treat AIDS, the incidence of many diseases, AIDS-related malignancies has decreased, but at the same time malignant cancers overall have become the most common cause of death in HIV-infected patients . In recent years, an increasing proportion of these deaths have been non-AIDS-defining cancers.
Other infections
AIDS patients often develop opportunistic infections that present with nonspecific symptoms, especially low-grade fever and weight loss. These include opportunistic infections by Mycobacterium avium-intracellulare and cytomegalovirus (CMV). CMV can cause colitis, as described above, and CMV retinitis can cause blindness.
Penicillium marneffei penicilliosis is by now the third most common opportunistic infection (after extrapulmonary tuberculosis and cryptococcosis) in HIV-endemic area of ​​Southeast Asia.
An infection that often goes unrecognized in patients with AIDS is parvovirus B19. Their main result is anemia, which is difficult to distinguish from the effects of antiretroviral drugs used to treat AIDS itself.
Cause
 
A generalized graph of the relationship between HIV copies (viral load) and CD4 counts over the average of untreated HIV infection, of course, any particular individual of the disease can vary considerably. CD4 T lymphocytes (cells / mm ³) HIV RNA copies per ml of plasma
AIDS is the ultimate clinical consequence of infection with HIV. HIV is a retrovirus that primarily infects vital organs of the human immune system such as CD4 T cells (a subset of T cells), macrophages and dendritic cells. It directly and indirectly destroys CD4 T cells.
Once the number of CD4 T cells per microliter (l) of blood falls below 200, cellular immunity is lost. Acute HIV infection usually progresses over time to clinical latent HIV infection and then to early symptomatic HIV infection and later to AIDS, which is identified either on the basis of the number of CD4 T cells remaining in blood, and / or the presence of certain infections, as noted above.
In the absence of antiretroviral therapy, the median time to progression of HIV infection to AIDS is nine to ten years, and median survival after developing AIDS is only 9.2 months. However, the rate of clinical disease progression varies widely between individuals, from two weeks to 20 years.
Many factors affect the rate of progression. Among them, factors that influence the body's ability to defend against HIV such as general immune function of the infected person. Older people have weaker immune systems and therefore have an increased risk of rapid disease progression than younger people.
Lack of access to health care and the existence of coexisting infections such as tuberculosis also may predispose people to disease progression faster. The genetic heritage of the infected person has an important role and some people are resistant to certain strains of HIV. An example of this is people with the homozygous CCR5-Δ32 variation are resistant to infection with certain strains of HIV. HIV is genetically variable and exists as different strains, which cause different rates of progression of clinical disease.
Sexual transmission
Main article: STD
Sexual transmission occurs with the contact between sexual secretions of a person with the rectal mucous membranes, genital or oral to the other. Unprotected sex are riskier for the receptive partner than for the insertive partner and the risk of transmitting HIV through unprotected anal intercourse is greater than the risk from vaginal intercourse or oral sex.
However, oral sex is not entirely safe, as HIV can be transmitted through oral sex insertive and receptive. Sexual assault greatly increases the risk of transmission of HIV that condoms are rarely employed and physical trauma to the vagina or rectum occurs frequently, facilitating the transmission of HIV.
The drug has been studied as a possible predictor of HIV transmission. Perry N. Halkitis found that methamphetamine use significantly related to unprotected sexual behavior. The study found that methamphetamine users to be at greater risk of contracting HIV.
Other sexually transmitted infections (STIs) increase the risk of HIV transmission and infection because they cause disruption of normal epithelial barrier by genital ulceration and / or microulceration, and the accumulation of clusters of cells susceptible to HIV or infected by HIV (lymphocytes and macrophages) in semen and vaginal secretions. Epidemiological studies of Africa, Europe and North America suggest that genital ulcers, such as those caused by syphilis and / or chancroid, increase the risk of becoming infected with HIV about four times. There is also a significant but smaller increase in the risk of sexually transmitted infections like gonorrhea, chlamydia and trichomoniasis, which all cause local accumulation of lymphocytes and macrophages.
HIV transmission depends on the infectiousness of the index case and susceptibility of the uninfected partner. Infectivity seems to vary during the course of the disease and is not constant among individuals. An undetectable viral load does not necessarily mean a low viral load in genital secretions or seminal fluid.
However, each 10-fold increase in the level of HIV in blood is associated with a 81% rate of increase in transmission. Women are more susceptible to HIV-1 infection due to hormonal changes, vaginal microbial ecology and physiology, and a higher prevalence of sexually transmitted diseases.
People who have been infected with a strain of HIV may become infected later in their lives by other more virulent strains.
Infection is unlikely in a single encounter. High rates of infection have been linked to a pattern of long-term accumulation sex. This allows the virus to spread rapidly to several couples who in turn infect their partners. A pattern of serial monogamy or occasional casual encounters is associated with lower infection rates.
HIV is easily transmitted through heterosexual sex in Africa, but less so elsewhere. One possibility is being investigated for schistosomiasis, which affects up to 50% of women in parts of Africa, damages the lining of the vagina.
Blood products
 
 
CDC poster of 1989, highlighting the threat of AIDS associated with drug use
This route of transmission is particularly relevant to intravenous drug users, hemophiliacs and transfusion recipients of blood and blood products. Sharing and reusing syringes contaminated with HIV infected blood represents a major risk for infection with HIV.
Sharing needles is the cause of one third of all new HIV infections in North America, China and Eastern Europe. The risk of getting HIV from a single prick with a needle that has been used by a person infected with HIV is thought to be about 1 in 150 (see table above). Post-exposure prophylaxis with anti-HIV drugs can further reduce this risk.
This route can also affect people who give and receive tattoos and piercings. Universal precautions are often not followed in both sub-Saharan Africa and much of Asia, both because of a shortage of supplies and inadequate training.
WHO estimates that approximately 2.5% of all HIV infections in sub-Saharan Africa are transmitted through unsafe healthcare injections. Because of this, the UN General Assembly has urged the nations of the world to implement precautions to prevent HIV transmission by health workers.
The risk of HIV transmission to recipients of blood transfusions is extremely low in developed countries, where they performed the selection of donors and HIV. However, according to WHO, the vast majority of the world's population lacks access to safe blood and between 5% and 10% of HIV infections in the world come from the transfusion of infected blood and blood products.
Perinatal transmission
HIV transmission from mother to child can occur in utero during the last weeks of pregnancy and childbirth. Untreated, the rate of transmission between mother and child during pregnancy, childbirth is 25%.
However, when the mother takes antiretroviral therapy and gives birth by caesarean section, the transmission rate is only 1%. The risk of infection is influenced by the mother's viral load at birth, with the highest viral load, the greater the risk. Breastfeeding also increases the risk of transmission by about 4%.
Misconceptions
Main article: Misconceptions about HIV and AIDS
There are many misconceptions about HIV and AIDS. Three of the most common are that AIDS can be transmitted by casual contact (like shaking hands, hugging, or a casual kiss), that sex with a virgin cures AIDS and that HIV can infect only men homosexuals and drug users. Other misconceptions are that any act of anal sex among gay men can lead to HIV infection, and that open discussion of homosexuality and HIV in schools increased rates of homosexuality and AIDS.
Pathophysiology
The pathophysiology of AIDS is complex. Ultimately, HIV causes AIDS by depleting CD4 T helper lymphocytes. This weakens the immune system and allows opportunistic infections. T lymphocytes are essential for immune response and without them the body can not fight infections or kill cancer cells. The mechanism of depletion of CD4 T cells differ in acute and chronic phases.
During the acute phase, HIV-induced cell lysis and death of infected cells by cytotoxic T cells accounts for the depletion of CD4 T cells, although apoptosis may also be a factor. During the chronic phase, the consequences of generalized immune activation with gradual loss of the immune system's ability to generate new T cells appear to account for the slow decrease in the number of CD4 T
Although symptoms of immune deficiency characteristic of AIDS do not appear for years after a person is infected, the bulk of the loss of CD4 T cells occurs during the first weeks of infection, especially in the intestinal mucosa, which houses the majority of lymphocytes found in the body. The reason for the preferential loss of CD4 T cells mucosa is that a majority of mucosa cells expressing CD4 coreceptor CCR5, while a small fraction of CD4 T cells in the blood do so.
HIV finds and destroys CD4 cells expressing CCR5 during acute infection. A vigorous immune response eventually controls the infection and clinically latent phase starts. However, CD4 T cells in mucosal tissues remain depleted throughout infection, although sufficient to prevent a principle remain threatening infections.
Continuous HIV replication results in a state of generalized immune activation persisting throughout the chronic phase. Immune activation, as reflected in the increased activation status of immune cells and release of proinflammatory cytokines, the results of the activity of several gene products of HIV and the immune response to the ongoing HIV replication. Another cause is the breakdown of immunological surveillance of the mucosal barrier caused by the depletion of mucosal CD4 T cells during the acute phase of illness.
This results in systemic exposure of the immune system to microbial components of normal gut flora, which in a healthy person is kept in check by the immune system of mucous membranes. Activation and T cell proliferation resulting from immune activation provides new targets for HIV infection. However, the direct killing by HIV alone can not account for the observed decline of CD4 T cells, with only 0.01 to 0.10% of CD4 T cells in the blood are infected.
One of the main causes of loss of CD4 T cells appears to be the result of their increased susceptibility to apoptosis when the immune system remains active. Despite new T cells is continuously produced by the thymus to replace the lost, the regenerative capacity of the thymus is slowly destroyed by direct infection of its thymocytes by HIV. Finally, the minimum number of CD4 T cells needed to maintain a sufficient immune response is lost, which leads to AIDS
The affected cells
The virus entering through which ever route, acts primarily on the following cells:
• lymphoreticular system:
or CD4 + T-lymphocytes
Macrophages or
or monocytes
or B lymphocytes
• Endothelial cells certain
• Central nervous system:
Or microglia of the nervous system
or astrocytes
Oligodendrocytes or
Neurons or - indirectly by the action of cytokines and gp-120
The effect
The virus has cytopathic effects, but how it does, is not yet clear. It can lie dormant in cells for prolonged periods, however. This effect is hypothesized to be due to the CD4-gp120 interaction.
• The most prominent effect of HIV is the T-helper cell suppression and lysis. The cell is simply killed or disturbed to the point of being function-less (that do not respond to foreign antigens). The infected B cells can not produce enough antibodies either. Thus, the immune system collapses leading to the known complications of AIDS, such as infections and neoplasms (vide supra).
• Infection of the central nervous system cells cause acute aseptic meningitis, subacute encephalitis, vacuolar myelopathy and peripheral neuropathy. Later takes dementia complex, including AIDS.
• The interaction of CD4-gp120 (see above) also is permissive with other viruses such as cytomegalovirus, hepatitis, herpes simplex virus, etc. These viruses lead to cell damage i. e. cytopathy.
Molecular basis
For more information, see:
• Structure and genome of HIV
• HIV replication cycle
• HIV tropism
Diagnosis
The diagnosis of AIDS in a person infected with HIV is based on the presence of certain signs or symptoms. From June 5, 1981, the definitions have been developed many of surveillance, such as the Bangui definition and the 1994 World Health Organization expanded the definition of AIDS cases. However, the clinical classification of patients was not an intended use for these systems because they are neither sensitive nor specific. In developing countries, classification system of World Health Organization for HIV infection and disease is used (from clinical and laboratory), and in developed countries, rating system CDC is used.
World Health Organization
Main article: System of Diseases of the WHO test for HIV infection and disease