From Wikipedia, the free encyclopedia
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome (AIDS) is a disease of the human immune system caused by the human immunodeficiency virus (HIV).[1][2][3] This condition progressively reduces the effectiveness of the immune system and leaves individuals susceptible to opportunistic infections and tumors. HIV is transmitted through direct contact of a mucous membrane or the bloodstream with a bodily fluid containing HIV, such as blood, semen, vaginal fluid, preseminal fluid, and breast milk.[4][5] This transmission can involve anal, vaginal or oral sex, blood transfusion, contaminated hypodermic needles, exchange between mother and baby during pregnancy, childbirth, breastfeeding or other exposure to one of the above bodily fluids.
AIDS is now a pandemic.[6] As of 2009, AVERT estimated that there are 33.3 million people worldwide living with HIV/AIDS, with 2.6 million new HIV infections per year and 1.8 million annual deaths due to AIDS.[7] In 2007, UNAIDS estimated: 33.2 million people worldwide had AIDS that year; AIDS killed 2.1 million people in the course of that year, including 330,000 children, and 76% of those deaths occurred in sub-Saharan Africa.[8] According to UNAIDS 2009 report, worldwide some 60 million people have been infected, with some 25 million deaths, and 14 million orphaned children in southern Africa alone since the epidemic began.[9]
Genetic research indicates that HIV originated in west-central Africa during the late nineteenth or early twentieth century.[10][11] AIDS was first recognized by the U.S. Centers for Disease Control and Prevention in 1981 and its cause, HIV, identified in the early 1980s.[12]
Although treatments for AIDS and HIV can slow the course of the disease, there is no known cure or vaccine. Antiretroviral treatment reduces both the mortality and the morbidity of HIV infection, but these drugs are expensive and routine access to antiretroviral medication is not available in all countries.[13] Due to the difficulty in treating HIV infection, preventing infection is a key aim in controlling the AIDS pandemic, with health organizations promoting safe sex and needle-exchange programmes in attempts to slow the spread of the virus.
History and origin
Main article:
Origin of AIDSAIDS was first reported June 5, 1981, when the U.S. Centers for Disease Control (CDC) recorded a cluster of Pneumocystis carinii pneumonia (now still classified as PCP but known to be caused by Pneumocystis jirovecii) in five homosexual men in Los Angeles.[14] In the beginning, the CDC did not have an official name for the disease, often referring to it by way of the diseases that were associated with it, for example, lymphadenopathy, the disease after which the discoverers of HIV originally named the virus.[15][16] They also used Kaposi’s Sarcoma and Opportunistic Infections, the name by which a task force had been set up in 1981.[17]
In the general press, the term GRID, which stood for gay-related immune deficiency, had been coined.[18] The CDC, in search of a name, and looking at the infected communities coined “the 4H disease,” as it seemed to single out Haitians, homosexuals, hemophiliacs, and heroin users.[19] However, after determining that AIDS was not isolated to the homosexual community,[17] the term GRID became misleading and AIDS was introduced at a meeting in July 1982.[20] By September 1982 the CDC started using the name AIDS, and properly defined the illness.[21]
The earliest known positive identification of the HIV-1 virus comes from the Congo in 1959 and 1960 though genetic studies indicate that it passed into the human population from chimpanzees around fifty years earlier.[11] A recent study states that a strain of HIV-1 probably moved from Africa to Haiti and then entered the United States around 1969.[22]
The HIV virus descends from the related simian immunodeficiency virus (SIV), which infects apes and monkeys in Africa. There is evidence that humans who participate in bushmeat activities, either as hunters or as bushmeat vendors, commonly acquire SIV.[23] However, only a few of these infections were able to cause epidemics in humans, and all did so in the late 19th—early 20th century. To explain why HIV became epidemic only by that time, there are several theories, each invoking specific driving factors that may have promoted SIV adaptation to humans, or initial spread: social changes following colonialism,[24] rapid transmission of SIV through unsafe or unsterile injections (that is, injections in which the needle is reused without being sterilised),[25] colonial abuses and unsafe smallpox vaccinations or injections,[26] or prostitution and the concomitant high frequency of genital ulcer diseases (such as syphilis) in nascent colonial cities.[27][28] See the main article Origin of AIDS.
One of the first high profile victims of AIDS was the American actor Rock Hudson, a known homosexual who had been married and divorced earlier in life, who died on 2 October 1985 having announced that he was suffering from the virus on 25 July that year. It had been diagnosed during 1984.[29] A notable British casualty of AIDS that year was Nicholas Eden, a Member of Parliament and son of the late prime minister Anthony Eden.[30] Eden junior, a lifelong batchelor, was also a known homosexual.[31] The virus claimed perhaps its most famous victim yet on 24 November 1991, when British rock star Freddie Mercury, lead singer of the band Queen, died from an AIDS related illness having only announced that he was suffering from the illness the previous day;[32] however he had been diagnosed as HIV positive during 1987.[33] One of the first high profile heterosexual victims of the virus was Arthur Ashe, the American tennis player. He was diagnosed as HIV positive on 31 August 1988, having contracted the virus from blood transfusions during heart surgery earlier in the 1980s. Further tests within 24 hours of the initial diagnosis revealed that Ashe had AIDS, but he did not tell the public about his diagnosis until April 1992.[34] He died, aged 49, as a result of the AIDS virus on 6 February 1993.[35]
A more controversial theory known as the OPV AIDS hypothesis suggests that the AIDS epidemic was inadvertently started in the late 1950s in the Belgian Congo by Hilary Koprowski‘s research into a poliomyelitis vaccine.[36][37] According to scientific consensus, this scenario is not supported by the available evidence.[38][39][40]
Signs and symptoms
Main symptoms of AIDS.
The symptoms of AIDS are primarily the result of conditions that do not normally develop in individuals with healthy immune systems. Most of these conditions are infections caused by bacteria, viruses, fungi and parasites that are normally controlled by the elements of the immune system that HIV damages.
Opportunistic infections are common in people with AIDS.[41] 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. Additionally, people with AIDS often have systemic symptoms of infection like fevers, sweats (particularly at night), swollen glands, chills, weakness, and weight loss.[42][43] 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 pneumonia) is relatively rare in healthy, immunocompetent people, 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 immediate cause of death. In developing countries, it is still one of the first indications of AIDS in untested individuals, although it does not generally occur unless the CD4 count is less than 200 cells per µL of blood.[44]
Tuberculosis (TB) is unique among infections associated with HIV because it is transmissible to immunocompetent people via the respiratory route, and is not easily treatable once identified,[45] Multidrug resistance is a serious problem. Tuberculosis with HIV co-infection (TB/HIV) is a major world health problem according to the World Health Organization: in 2007, 456,000 deaths among incident TB cases were HIV-positive, a third of all TB deaths and nearly a quarter of the estimated 2 million HIV deaths in that year.[46]
Even though its incidence has declined because of the use of directly observed therapy and other improved practices in Western countries, this is not the case in developing countries where HIV is most prevalent. In early-stage HIV infection (CD4 count >300 cells per µL), 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 localized to one particular site, often affecting bone marrow, bone, urinary and gastrointestinal tracts, liver, regional lymph nodes, and the central nervous system.[47]
Gastrointestinal
Esophagitis is an inflammation of the lining of the lower end of the esophagus (gullet or swallowing tube leading to the stomach). In HIV-infected individuals, this is normally due to fungal (candidiasis) or viral (herpes simplex-1 or cytomegalovirus) infections. In rare cases, it could be due to mycobacteria.[48]
Unexplained chronic diarrhea in HIV infection is due to many possible causes, including common bacterial (Salmonella, Shigella, Listeria or Campylobacter) and parasitic infections; and uncommon opportunistic infections such as cryptosporidiosis, microsporidiosis, Mycobacterium avium complex (MAC) and viruses,[49] astrovirus, adenovirus, rotavirus and cytomegalovirus, (the latter as a course of colitis).
In some cases, diarrhea may be a side effect of several drugs used to treat HIV, or it may simply accompany HIV infection, particularly during primary HIV infection. It may also be a side effect of antibiotics used to treat bacterial causes of diarrhea (common for Clostridium difficile). In the later stages of HIV infection, diarrhea is thought to be a reflection of changes in the way the intestinal tract absorbs nutrients, and may be an important component of HIV-related wasting.[50]
Neurological and psychiatric
HIV infection may lead to a variety of neuropsychiatric sequelae, either by infection of the now susceptible nervous system by organisms, or as a direct consequence of the illness itself.[51]
Toxoplasmosis is a disease caused by the single-celled parasite called Toxoplasma gondii; it usually infects the brain, causing toxoplasma encephalitis, but it can also infect and cause disease in the eyes and lungs.[52] Cryptococcal meningitis is an infection of the meninx (the membrane covering the brain and spinal cord) by the fungus Cryptococcus neoformans. It can cause fevers, headache, fatigue, nausea, and vomiting. Patients may also develop seizures and confusion; left untreated, it 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 impairs 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, as is the case for AIDS patients. It progresses rapidly, usually causing death within months of diagnosis.[53]
AIDS dementia complex (ADC) is a metabolic encephalopathy induced by HIV infection and fueled by immune activation of HIV infected brain macrophages and microglia. These cells are productively infected by HIV and secrete neurotoxins of both host and viral origin.[54] Specific neurological impairments are manifested by cognitive, behavioral, and motor abnormalities that occur after years of HIV infection and are associated with low CD4+ T cell levels and high plasma viral loads.
Prevalence is 10–20% in Western countries[55] but only 1–2% of HIV infections in India.[56][57] This difference is possibly due to the HIV subtype in India. AIDS related mania is sometimes seen in patients with advanced HIV illness; it presents with more irritability and cognitive impairment and less euphoria than a manic episode associated with true bipolar disorder. Unlike the latter condition, it may have a more chronic course. This syndrome is less often seen with the advent of multi-drug therapy.
Tumors
Patients with HIV infection have substantially increased incidence of several cancers. This is primarily due to co-infection with an oncogenic DNA virus, especially Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpesvirus (KSHV) (also known as human herpesvirus-8 [HHV-8]), and human papillomavirus (HPV).[58][59]
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 signals of the AIDS epidemic. Caused by a gammaherpes virus called Kaposi’s sarcoma-associated herpes virus (KSHV), it 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’s lymphoma, Burkitt’s-like lymphoma, diffuse large B-cell lymphoma (DLBCL), and primary central nervous system lymphoma present more often 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 arises in extranodal sites such as the gastrointestinal tract.[60] When they occur in an HIV-infected patient, KS and aggressive B cell lymphomas confer a diagnosis of AIDS.
Invasive cervical cancer in HIV-infected women is also considered AIDS-defining, it is caused by human papillomavirus (HPV).[61]
In addition to the AIDS-defining tumors listed above, HIV-infected patients are at increased risk of certain other tumors, notably Hodgkin’s disease, anal and rectal carcinomas, hepatocellular carcinomas, head and neck cancers, and lung cancer. Some of these are causes by viruses, such as Hodgkin’s disease (EBV), anal/rectal cancers (HPV), head and neck cancers (HPV), and hepatocellular carcinoma (hepatitis B or C). Other contributing factors include exposure to carcinogens (cigarette smoke for lung cancer), or living for years with subtle immune defects.
Interestingly, the incidence of many common tumors, such as breast cancer or colon cancer, does not increase in HIV-infected patients. In areas where HAART is extensively used to treat AIDS, the incidence of many AIDS-related malignancies has decreased, but at the same time malignant cancers overall have become the most common cause of death of HIV-infected patients.[62] In recent years, an increasing proportion of these deaths have been from non-AIDS-defining cancers.
Other infections
AIDS patients often develop opportunistic infections that present with non-specific symptoms, especially low-grade fevers and weight loss. These include opportunistic infection with Mycobacterium avium-intracellulare and cytomegalovirus (CMV). CMV can cause colitis, as described above, and CMV retinitis can cause blindness.
Penicilliosis due to Penicillium marneffei is now the third most common opportunistic infection (after extrapulmonary tuberculosis and cryptococcosis) in HIV-positive individuals within the endemic area of Southeast Asia.[63]
An infection that often goes unrecognized in AIDS patients is Parvovirus B19. Its main consequence is anemia, which is difficult to distinguish from the effects of antiretroviral drugs used to treat AIDS itself.[64]
Cause
For more details on this topic, see
HIV.
A generalized graph of the relationship between HIV copies (viral load) and CD4 counts over the average course of untreated HIV infection; any particular individual’s disease course may vary considerably. CD4+ T Lymphocyte count (cells/mm³) 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.[65]
Once the number of CD4+ T cells per microliter (µL) of blood drops 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 amount of CD4+ T cells remaining in the blood, and/or the presence of certain infections, as noted above.[66]
In the absence of antiretroviral therapy, the median time of progression from HIV infection to AIDS is nine to ten years, and the median survival time after developing AIDS is only 9.2 months.[67] However, the rate of clinical disease progression varies widely between individuals, from two weeks up to 20 years.
Many factors affect the rate of progression. These include factors that influence the body’s ability to defend against HIV such as the infected person’s general immune function.[68][69] Older people have weaker immune systems, and therefore have a greater risk of rapid disease progression than younger people.
Poor access to health care and the existence of coexisting infections such as tuberculosis also may predispose people to faster disease progression.[67][70][71] The infected person’s genetic inheritance plays 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.[72] HIV is genetically variable and exists as different strains, which cause different rates of clinical disease progression.[73][74][75]
There are a number HIV and AIDS misconceptions. Three of the most common are that AIDS can spread through casual contact, that sexual intercourse with a virgin will cure AIDS, and that HIV can infect only homosexual men and drug users. Other misconceptions are that any act of anal intercourse between gay men can lead to AIDS infection, and that open discussion of homosexuality and HIV in schools will lead to increased rates of homosexuality and AIDS.[76][77]
Sexual transmission
Sexual transmission occurs with the contact between sexual secretions of one person with the rectal, genital or oral mucous membranes of another. Unprotected sexual acts are riskier for the receptive partner than for the insertive partner, and the risk for 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 both insertive and receptive oral sex.[78][79] Sexual assault greatly increases the risk of HIV transmission as condoms are rarely employed and physical trauma to the vagina or rectum occurs frequently, facilitating the transmission of HIV.[80]
Drug use has been studied as a possible predictor of HIV transmission. Perry N. Halkitis found that methamphetamine usage does significantly relate to unprotected sexual behavior. The study found methamphetamine users to be at a higher risk for contracting HIV.[81]
Other sexually transmitted infections (STI) increase the risk of HIV transmission and infection, because they cause the disruption of the normal epithelial barrier by genital ulceration and/or microulceration; and by accumulation of pools of HIV-susceptible or HIV-infected cells (lymphocytes and macrophages) in semen and vaginal secretions. Epidemiological studies from sub-Saharan 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 by about fourfold. There is also a significant although lesser increase in risk from STIs such as gonorrhea, chlamydia and trichomoniasis, which all cause local accumulations of lymphocytes and macrophages.[82]
Transmission of HIV depends on the infectiousness of the index case and the susceptibility of the uninfected partner. Infectivity seems to vary during the course of illness and is not constant between individuals. An undetectable plasma viral load does not necessarily indicate a low viral load in the seminal liquid or genital secretions.
However, each 10-fold increase in the level of HIV in the blood is associated with an 81% increased rate of HIV transmission.[82][83] 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.[84][85]
People who have been infected with one strain of HIV can still be infected later on 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 overlapping long-term sexual relationships. This allows the virus to quickly spread to multiple partners who in turn infect their partners. A pattern of serial monogamy or occasional casual encounters is associated with lower rates of infection.[86]
HIV spreads readily through heterosexual sex in Africa, but less so elsewhere. One possibility being researched is that schistosomiasis, which affects up to 50% of women in parts of Africa, damages the lining of the vagina.[87][88]
Blood products
CDC poster from 1989 highlighting the threat of AIDS associated with drug use
This transmission route is particularly relevant to intravenous drug users, hemophiliacs and recipients of blood transfusions and blood products. Sharing and reusing syringes contaminated with HIV-infected blood represents a major risk for infection with HIV.
Needle sharing is the cause of one third of all new HIV-infections in North America, China, and Eastern Europe. The risk of being infected with HIV from a single prick with a needle that has been used on an HIV-infected person is thought to be about 1 in 150 (see table above). Post-exposure prophylaxis with anti-HIV drugs can further reduce this risk.[89]
This route can also affect people who give and receive tattoos and piercings. Universal precautions are frequently not followed in both sub-Saharan Africa and much of Asia because of both a shortage of supplies and inadequate training.
The WHO estimates that approximately 2.5% of all HIV infections in sub-Saharan Africa are transmitted through unsafe healthcare injections.[90] Because of this, the United Nations General Assembly has urged the nations of the world to implement precautions to prevent HIV transmission by health workers.[91]
The risk of transmitting HIV to blood transfusion recipients is extremely low in developed countries where improved donor selection and HIV screening is performed. However, according to the WHO, the overwhelming majority of the world’s population does not have access to safe blood and between 5% and 10% of the world’s HIV infections come from transfusion of infected blood and blood products.[92]
Perinatal transmission
The transmission of the virus from the mother to the child can occur in utero during the last weeks of pregnancy and at childbirth. In the absence of treatment, the transmission rate between a mother and her child during pregnancy, labor and delivery is 25%.
However, when the mother takes antiretroviral therapy and gives birth by caesarean section, the rate of transmission is just 1%.[93] The risk of infection is influenced by the viral load of the mother at birth, with the higher the viral load, the higher the risk. Breastfeeding also increases the risk of transmission by about 4 %.[94]
Pathophysiology
The pathophysiology of AIDS is complex, as is the case with all syndromes.[95] Ultimately, HIV causes AIDS by depleting CD4+ T helper lymphocytes. This weakens the immune system and allows opportunistic infections. T lymphocytes are essential to the immune response and without them, the body cannot fight infections or kill cancerous cells. The mechanism of CD4+ T cell depletion differs in the acute and chronic phases.[96]
During the acute phase, HIV-induced cell lysis and killing of infected cells by cytotoxic T cells accounts for CD4+ T cell depletion, although apoptosis may also be a factor. During the chronic phase, the consequences of generalized immune activation coupled with the gradual loss of the ability of the immune system to generate new T cells appear to account for the slow decline in CD4+ T cell numbers.
Although the symptoms of immune deficiency characteristic of AIDS do not appear for years after a person is infected, the bulk of CD4+ T cell loss occurs during the first weeks of infection, especially in the intestinal mucosa, which harbors the majority of the lymphocytes found in the body.[97] The reason for the preferential loss of mucosal CD4+ T cells is that a majority of mucosal CD4+ T cells express the CCR5 coreceptor, whereas a small fraction of CD4+ T cells in the bloodstream do so.[98]
HIV seeks out and destroys CCR5 expressing CD4+ cells during acute infection. A vigorous immune response eventually controls the infection and initiates the clinically latent phase. However, CD4+ T cells in mucosal tissues remain depleted throughout the infection, although enough remain to initially ward off life-threatening infections.
Continuous HIV replication results in a state of generalized immune activation persisting throughout the chronic phase.[99] Immune activation, which is reflected by the increased activation state of immune cells and release of proinflammatory cytokines, results from the activity of several HIV gene products and the immune response to ongoing HIV replication. Another cause is the breakdown of the immune surveillance system of the mucosal barrier caused by the depletion of mucosal CD4+ T cells during the acute phase of disease.[100]
This results in the systemic exposure of the immune system to microbial components of the gut’s normal flora, which in a healthy person is kept in check by the mucosal immune system. The activation and proliferation of T cells that results from immune activation provides fresh targets for HIV infection. However, direct killing by HIV alone cannot account for the observed depletion of CD4+ T cells since only 0.01–0.10% of CD4+ T cells in the blood are infected.
A major cause of CD4+ T cell loss appears to result from their heightened susceptibility to apoptosis when the immune system remains activated. Although new T cells are continuously produced by the thymus to replace the ones lost, the regenerative capacity of the thymus is slowly destroyed by direct infection of its thymocytes by HIV. Eventually, the minimal number of CD4+ T cells necessary to maintain a sufficient immune response is lost, leading to AIDS
Cells affected
The virus, entering through which ever route, acts primarily on the following cells:[101]
The effect
The virus has cytopathic effects but how it does it is still not quite clear. It can remain inactive in these cells for long periods, though. This effect is hypothesized to be due to the CD4-gp120 interaction.[101]
- The most prominent effect of HIV is its T-helper cell suppression and lysis. The cell is simply killed off or deranged to the point of being function-less (they do not respond to foreign antigens). The infected B-cells can not produce enough antibodies either. Thus the immune system collapses leading to the familiar AIDS complications, like infections and neoplasms (vide supra).
- Infection of the cells of the CNS cause acute aseptic meningitis, subacute encephalitis, vacuolar myelopathy and peripheral neuropathy. Later it leads to even AIDS dementia complex.
- The CD4-gp120 interaction (see above) is also permissive to other viruses like Cytomegalovirus, Hepatitis virus, Herpes simplex virus, etc. These viruses lead to further cell damage i.e. cytopathy.
Molecular basis
For details, see:
Diagnosis
The diagnosis of AIDS in a person infected with HIV is based on the presence of certain signs or symptoms. Since June 5, 1981, many definitions have been developed for epidemiological surveillance such as the Bangui definition and the 1994 expanded World Health Organization AIDS case definition. However, clinical staging of patients was not an intended use for these systems as they are neither sensitive, nor specific. In developing countries, the World Health Organization staging system for HIV infection and disease, using clinical and laboratory data, is used and in developed countries, the Centers for Disease Control (CDC) Classification System is used.
WHO disease staging system
In 1990, the World Health Organization (WHO) grouped these infections and conditions together by introducing a staging system for patients infected with HIV-1.[102] An update took place in September 2005. Most of these conditions are opportunistic infections that are easily treatable in healthy people.
CDC classification system
There are two main definitions for AIDS, both produced by the Centers for Disease Control and Prevention (CDC). The older definition is to referring to AIDS using the diseases that were associated with it, for example, lymphadenopathy, the disease after which the discoverers of HIV originally named the virus.[15][16] In 1993, the CDC expanded their definition of AIDS to include all HIV positive people with a CD4+ T cell count below 200 per µL of blood or 14% of all lymphocytes.[103] The majority of new AIDS cases in developed countries use either this definition or the pre-1993 CDC definition. The AIDS diagnosis still stands even if, after treatment, the CD4+ T cell count rises to above 200 per µL of blood or other AIDS-defining illnesses are cured.
HIV test
Many people are unaware that they are infected with HIV.[104] Less than 1% of the sexually active urban population in Africa has been tested, and this proportion is even lower in rural populations. Furthermore, only 0.5% of pregnant women attending urban health facilities are counseled, tested or receive their test results. Again, this proportion is even lower in rural health facilities.[104] Therefore, donor blood and blood products used in medicine and medical research are screened for HIV.
HIV tests are usually performed on venous blood. Many laboratories use fourth generation screening tests which detect anti-HIV antibody (IgG and IgM) and the HIV p24 antigen. The detection of HIV antibody or antigen in a patient previously known to be negative is evidence of HIV infection. Individuals whose first specimen indicates evidence of HIV infection will have a repeat test on a second blood sample to confirm the results.
The window period (the time between initial infection and the development of detectable antibodies against the infection) can vary since it can take 3–6 months to seroconvert and to test positive. Detection of the virus using polymerase chain reaction (PCR) during the window period is possible, and evidence suggests that an infection may often be detected earlier than when using a fourth generation EIA screening test.
Positive results obtained by PCR are confirmed by antibody tests.[105] Routinely used HIV tests for infection in neonates and infants (i.e., patients younger than 2 years),[106] born to HIV-positive mothers, have no value because of the presence of maternal antibody to HIV in the child’s blood. HIV infection can only be diagnosed by PCR, testing for HIV pro-viral DNA in the children’s lymphocytes.[107]
Prevention
Estimated per act risk for acquisition
of HIV by exposure route (US only) [108]
| Exposure Route |
Estimated infections
per 10,000 exposures
to an infected source |
| Blood Transfusion |
9,000[109] |
| Childbirth (to child) |
2,500[93] |
| Needle-sharing injection drug use |
67[110] |
| Percutaneous needle stick |
30[111] |
| Receptive anal intercourse* |
50[112][113] |
| Insertive anal intercourse* |
6.5[112][113] |
| Receptive penile-vaginal intercourse* |
10[112][113][114] |
| Insertive penile-vaginal intercourse* |
5[112][113] |
| Receptive oral intercourse*§ |
1[113] |
| Insertive oral intercourse*§ |
0.5[113] |
* assuming no condom use
§ source refers to oral intercourse
performed on a man |
The three main transmission routes of HIV are sexual contact, exposure to infected body fluids or tissues, and from mother to fetus or child during perinatal period. It is possible to find HIV in the saliva, tears, and urine of infected individuals, but there are no recorded cases of infection by these secretions, and the risk of infection is negligible.[115] Anti-retroviral treatment of infected patients also significantly reduces their ability to transmit HIV to others, by reducing the amount of virus in their bodily fluids to undetectable levels.[116]
Sexual contact
The majority of HIV infections are acquired through unprotected sexual relations between partners, one of whom has HIV. The primary mode of HIV infection worldwide is through sexual contact between members of the opposite sex.[117][118][119]
During a sexual act, only male or female condoms can reduce the risk of infection with HIV and other STDs. The best evidence to date indicates that typical condom use reduces the risk of heterosexual HIV transmission by approximately 80% over the long-term, though the benefit is likely to be higher if condoms are used correctly on every occasion.[120]
The male latex condom, if used correctly without oil-based lubricants, is the single most effective available technology to reduce the sexual transmission of HIV and other sexually transmitted infections. Manufacturers recommend that oil-based lubricants such as petroleum jelly, butter, and lard not be used with latex condoms, because they dissolve the latex, making the condoms porous. If lubrication is desired, manufacturers recommend using water-based lubricants. Oil-based lubricants can be used with polyurethane condoms.[121]
Female condoms are commonly made from polyurethane, but are also made from nitrile and latex. They are larger than male condoms and have a stiffened ring-shaped opening with an inner ring designed to be inserted into the vagina keeping the condom in place; inserting the female condom requires squeezing this ring. Female condoms have been shown to be an important HIV prevention strategy by preliminary studies which suggest that overall protected sexual acts increase relative to unprotected sexual acts where female condoms are available.[122] At present, availability of female condoms is very low and the price remains prohibitive for many women.
Studies on couples where one partner is infected show that with consistent condom use, HIV infection rates for the uninfected partner are below 1% per year.[123] Prevention strategies are well-known in developed countries, but epidemiological and behavioral studies in Europe and North America suggest that a substantial minority of young people continue to engage in high-risk practices despite HIV/AIDS knowledge, underestimating their own risk of becoming infected with HIV.[124][125]
Randomized controlled trials have shown that male circumcision lowers the risk of HIV infection among heterosexual men by up to 60%.[126] It is expected that this procedure will be actively promoted in many of the countries affected by HIV, although doing so will involve confronting a number of practical, cultural and attitudinal issues. However, programs to encourage condom use, including providing them free to those in poverty, are estimated to be 95 times more cost effective than circumcision at reducing the rate of HIV in sub-Saharan Africa.[127]
Some experts fear that a lower perception of vulnerability among circumcised men may result in more sexual risk-taking behavior, thus negating its preventive effects.[128] However, one randomized controlled trial indicated that adult male circumcision was not associated with increased HIV risk behavior.[129]
Studies of HIV infection rates among women who have undergone female genital cutting (FGC) have reported mixed results; for details see Female genital cutting#HIV.
A three-year study in South Africa, completed in 2010, found that an anti-microbial vaginal gel could reduce infection rates among women by 50% after one year of use, and by 39% after two and a half years. The results of the study, which was conducted by the Centre for the Aids Programme of Research in South Africa (CAPRISA), were published in Science magazine in July 2010, and were then presented at an international aids conference in Vienna.[130]
Body fluid exposure
Health care workers can reduce exposure to HIV by employing precautions to reduce the risk of exposure to contaminated blood. These precautions include barriers such as gloves, masks, protective eyeware or shields, and gowns or aprons which prevent exposure of the skin or mucous membranes to blood borne pathogens. Frequent and thorough washing of the skin immediately after being contaminated with blood or other bodily fluids can reduce the chance of infection. Finally, sharp objects like needles, scalpels and glass, are carefully disposed of to prevent needlestick injuries with contaminated items.[131] Since intravenous drug use is an important factor in HIV transmission in developed countries, harm reduction strategies such as needle-exchange programmes are used in attempts to reduce the infections caused by drug abuse.[132][133]
Mother-to-child
Current recommendations state that when replacement feeding is acceptable, feasible, affordable, sustainable and safe, HIV-infected mothers should avoid breast-feeding their infant. However, if this is not the case, exclusive breast-feeding is recommended during the first months of life and discontinued as soon as possible.[134] It should be noted that women can breastfeed children who are not their own; see wet nurse.
Education
One way to change risky behavior is health education. Several studies[citation needed] have shown the positive impact of education and health literacy on cautious sex behavior. Education works only if it leads to higher health literacy and general cognitive ability. This ability is relevant to understand the relationship between own risky behavior and possible outcomes like HIV-transmission.[135] In July 2010, a UNAIDS Inter-Agency Task Team (IATT) on Education commissioned literature review found there was a need for more research into non-African (especially non-South African contexts), more research on the actual implementation of sex-education programmes (such as teacher training, access to related services through schools and the community, or parental attitudes to HIV and AIDS education) and more longitudinal studies on the deeper complexities of the relationship between education and HIV.[136]
Management
- See also HIV Treatment and Antiretroviral drug.
There is currently no publicly available vaccine for HIV or cure for HIV or AIDS. The only known methods of prevention are based on avoiding exposure to the virus or, failing that, an antiretroviral treatment directly after a highly significant exposure, called post-exposure prophylaxis (PEP).[137] PEP has a very demanding four week schedule of dosage. It also has very unpleasant side effects including diarrhea, malaise, nausea and fatigue.[138]
Antiviral therapy
Abacavir – a nucleoside analog reverse transcriptase inhibitor (NARTI or NRTI)
The chemical structure of Abacavir
Current treatment for HIV infection consists of highly active antiretroviral therapy, or HAART.[139] This has been highly beneficial to many HIV-infected individuals since its introduction in 1996 when the protease inhibitor-based HAART initially became available.[13] Current optimal HAART options consist of combinations (or “cocktails”) consisting of at least three drugs belonging to at least two types, or “classes,” of antiretroviral agents.
Typical regimens consist of two nucleoside analogue reverse transcriptase inhibitors (NARTIs or NRTIs) plus either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor (NNRTI). Because HIV disease progression in children is more rapid than in adults, and laboratory parameters are less predictive of risk for disease progression, particularly for young infants, treatment recommendations are more aggressive for children than for adults.[140] In developed countries where HAART is available, doctors assess the viral load, CD4 counts, rapidity of CD4 decline and patient readiness while deciding when to recommend initiating treatment.[141] Traditionally, treatment has been recommended for otherwise asymptomatic patients when CD4 cell counts fall to 200-250 cells per microliter of blood. However, beginning treatment earlier (at a CD4 level of 350 cells/microliter) may significantly reduce the risk of death.[142]
Standard goals of HAART include improvement in the patient’s quality of life, reduction in complications, and reduction of HIV viremia below the limit of detection, but it does not cure the patient of HIV nor does it prevent the return, once treatment is stopped, of high blood levels of HIV, often HAART resistant.[143][144] Moreover, it would take more than the lifetime of an individual to be cleared of HIV infection using HAART.[145]
Despite this, many HIV-infected individuals have experienced remarkable improvements in their general health and quality of life, which has led to the plummeting of HIV-associated morbidity and mortality.[146][147][148] In the absence of HAART, progression from HIV infection to AIDS occurs at a median of between nine to ten years and the median survival time after developing AIDS is only 9.2 months.[67] HAART is thought to increase survival time by between 4 and 12 years.[149][150]
For some patients, which can be more than fifty percent of patients, HAART achieves far less than optimal results, due to medication intolerance/side effects, prior ineffective antiretroviral therapy and infection with a drug-resistant strain of HIV. Non-adherence and non-persistence with therapy are the major reasons why some people do not benefit from HAART.[151] The reasons for non-adherence and non-persistence are varied. Major psychosocial issues include poor access to medical care, inadequate social supports, psychiatric disease and drug abuse. HAART regimens can also be complex and thus hard to follow, with large numbers of pills taken frequently.[152][153][154]
Side effects can also deter people from persisting with HAART, these include lipodystrophy, dyslipidaemia, diarrhoea, insulin resistance, an increase in cardiovascular risks and birth defects.[155] Anti-retroviral drugs are expensive, and the majority of the world’s infected individuals do not have access to medications and treatments for HIV and AIDS. However, the costs of anti-retroviral drugs have fallen recently in low-income countries. Moreover, patients’ quality of life indices benefit from anti-retroviral treatment especially if healthcare services are adequate.[156] In the absence of a cure for AIDS, anti-retroviral treatment is likely to be a cost-effective strategy for enhancing well-being of AIDS patients and their dependents.
Complementary and alternative medicine
In the US, approximately 60% of HIV patients use various forms of complementary or alternative medicine (CAM).[157] Despite the widespread use of CAM by people living with HIV/AIDS, the effectiveness of these therapies has not been established.[158] A 2005 Cochrane review of existing high-quality scientific evidence concluded: “There is insufficient evidence to support the use of herbal medicines in HIV-infected individuals and AIDS patients.”[159] Acupuncture has only been proposed for symptomatic relief, but not to treat or cure HIV or AIDS.[160]
Vitamin or mineral supplementation has shown benefit in some studies. Daily doses of selenium can suppress HIV viral burden with an associated improvement of the CD4 count. Selenium can be used as an adjunct therapy to standard antiviral treatments,[161] but cannot itself cure the infection. More evidence is needed before it can be established that selenium supplementation reduces mortality rates. There is some evidence that vitamin A supplementation in children reduces mortality and improves growth.[162] A large Tanzanian trial in immunologically and nutritionally compromised pregnant and lactating women showed a number of benefits to daily multivitamin supplementation for both mothers and children.[162] Dietary intake of micronutrients at RDA levels by HIV-infected adults is recommended by the World Health Organization (WHO).[163] The WHO further states that several studies indicate that supplementation of vitamin A, zinc, and iron can produce adverse effects in HIV positive adults.[163]
Prognosis
Without treatment, the net median survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype,[8] and the median survival rate after diagnosis of AIDS in resource-limited settings where treatment is not available ranges between 6 and 19 months, depending on the study.[164] In areas where it is widely available, the development of HAART as effective therapy for HIV infection and AIDS reduced the death rate from this disease by 80%, and raised the life expectancy for a newly diagnosed HIV-infected person to about 20 years.[165]
As new treatments continue to be developed and because HIV continues to evolve resistance to treatments, estimates of survival time are likely to continue to change. Without antiretroviral therapy, death normally occurs within a year after the individual progresses to AIDS.[67] Most patients die from opportunistic infections or malignancies associated with the progressive failure of the immune system.[166] The rate of clinical disease progression varies widely between individuals and has been shown to be affected by many factors such as host susceptibility and immune function[68][69][72] health care and co-infections,[67][166] as well as which particular strain of the virus is involved.[74][167][168]
Even with anti-retroviral treatment, over the long term HIV-infected patients may experience neurocognitive disorders, osteoporosis, neuropathy, cancers, nephropathy, and cardiovascular disease. It is not always clear whether these conditions result from the infection, related complications, or are side effects of treatment.[169][170][160][58][59][171][155][172]
The largest cause of AIDS morbidity today, globally, is tuberculosis co-infection, see AIDS#Pulmonary_infections. In Africa, HIV is the single most important factor contributing to the increase in the incidence of TB since 1990.[173]
Epidemiology
Main article:
AIDS pandemic
Estimated prevalence of HIV among young adults (15–49) per country at the end of 2005.
Estimated number of people living with HIV/AIDS by country
Disability-adjusted life year for HIV and AIDS per 100,000 inhabitants.
no data
≤ 10
10-25
25-50
50-100
100-500
500-1000
1000-2500
2500-5000
5000-7500
7500-10000
10000-50000
≥ 50000
The AIDS pandemic can also be seen as several epidemics of separate subtypes; the major factors in its spread are sexual transmission and vertical transmission from mother to child at birth and through breast milk.[6] Despite recent, improved access to antiretroviral treatment and care in many regions of the world, the AIDS pandemic claimed an estimated 2.1 million (range 1.9–2.4 million) lives in 2007 of which an estimated 330,000 were children under 15 years.[8] Globally, an estimated 33.2 million people lived with HIV in 2007, including 2.5 million children. An estimated 2.5 million (range 1.8–4.1 million) people were newly infected in 2007, including 420,000 children.[8]
Sub-Saharan Africa remains by far the worst affected region. In 2007 it contained an estimated 68% of all people living with AIDS and 76% of all AIDS deaths, with 1.7 million new infections bringing the number of people living with HIV to 22.5 million, and with 11.4 million AIDS orphans living in the region. Unlike other regions, most people living with HIV in sub-Saharan Africa in 2007 (61%) were women. Adult prevalence in 2007 was an estimated 5.0%, and AIDS continued to be the single largest cause of mortality in this region.[8]
South Africa has the largest population of HIV patients in the world, followed by Nigeria and India.[174] South & South East Asia are second worst affected; in 2007 this region contained an estimated 18% of all people living with AIDS, and an estimated 300,000 deaths from AIDS.[8] India has an estimated 2.5 million infections and an estimated adult prevalence of 0.36%.[8] Life expectancy has fallen dramatically in the worst-affected countries; for example, in 2006 it was estimated that it had dropped from 65 to 35 years in Botswana.[6]
In the United States, young African-American women are also at unusually high risk for HIV infection.[175] African Americans make up 10% of the population but about half of the HIV/AIDS cases nationwide.[176] This is due in part to a lack of information about AIDS and a perception that they are not vulnerable, as well as to limited access to health-care resources and a higher likelihood of sexual contact with at-risk male sexual partners.[177]
There are also geographic disparities in AIDS prevalence in the United States, where it is most common in rural areas and in the southern states, particularly in the Appalachian and Mississippi Delta regions and along the border with Mexico.[178] Approximately 1.1 million persons are living with HIV/AIDS in the United States, and more than 56,000 new infections occur every single year.[179]
Society and culture
Stigma
AIDS stigma exists around the world in a variety of ways, including ostracism, rejection, discrimination and avoidance of HIV infected people; compulsory HIV testing without prior consent or protection of confidentiality; violence against HIV infected individuals or people who are perceived to be infected with HIV; and the quarantine of HIV infected individuals.[180] Stigma-related violence or the fear of violence prevents many people from seeking HIV testing, returning for their results, or securing treatment, possibly turning what could be a manageable chronic illness into a death sentence and perpetuating the spread of HIV.[181]
AIDS stigma has been further divided into the following three categories:
- Instrumental AIDS stigma—a reflection of the fear and apprehension that are likely to be associated with any deadly and transmissible illness.[182]
- Symbolic AIDS stigma—the use of HIV/AIDS to express attitudes toward the social groups or lifestyles perceived to be associated with the disease.[182]
- Courtesy AIDS stigma—stigmatization of people connected to the issue of HIV/AIDS or HIV- positive people.[183]
Often, AIDS stigma is expressed in conjunction with one or more other stigmas, particularly those associated with homosexuality, bisexuality, promiscuity, prostitution, and intravenous drug use.
In many developed countries, there is an association between AIDS and homosexuality or bisexuality, and this association is correlated with higher levels of sexual prejudice such as anti-homosexual attitudes.[184] There is also a perceived association between AIDS and all male-male sexual behavior, including sex between uninfected men.[182]
Economic impact
Changes in life expectancy in some hard-hit African countries. Botswana Zimbabwe Kenya South Africa Uganda
HIV and AIDS affects economic growth by reducing the availability of human capital.[185] Without proper nutrition, health care and medicine that is available in developed countries, large numbers of people suffer and die from AIDS-related complications. They will not only be unable to work, but will also require significant medical care. The forecast is that this will probably cause a collapse of economies and societies in countries with a significant AIDS population. In some heavily infected areas, the epidemic has left behind many orphans cared for by elderly grandparents.[186]
The increased mortality has results in a smaller skilled population and labor force. This smaller labor force consists of increasingly younger people, with reduced knowledge and work experience leading to reduced productivity. An increase in workers’ time off to look after sick family members or for sick leave lowers productivity. Increased mortality reduces the mechanisms that generate human capital and investment in people, through loss of income and the death of parents.
By affecting mainly young adults, AIDS reduces the taxable population, in turn reducing the resources available for public expenditures such as education and health services not related to AIDS resulting in increasing pressure for the state’s finances and slower growth of the economy. This results in a slower growth of the tax base, an effect that is reinforced if there are growing expenditures on treating the sick, training (to replace sick workers), sick pay and caring for AIDS orphans. This is especially true if the sharp increase in adult mortality shifts the responsibility and blame from the family to the government in caring for these orphans.[186]
On the level of the household, AIDS results in both the loss of income and increased spending on healthcare by the household. The income effects of this lead to spending reduction as well as a substitution effect away from education and towards healthcare and funeral spending. A study in Côte d’Ivoire showed that households with an HIV/AIDS patient spent twice as much on medical expenses as other households.[187]
Religion and AIDS
The topic of religion and AIDS has become highly controversial in the past twenty years, primarily because many prominent religious leaders have publicly declared their opposition to the use of condoms,[188] which scientists feel is currently the only means of stopping the epidemic.[citation needed] However, there is a growing openness to faith-based methods due to the failure rates associated with condoms.[188] Other issues involve religious participation in global health care services[citation needed] and collaboration with secular organizations such as UNAIDS and the World Health Organization.[citation needed]
The religious approach to prevent the spread of AIDS according to a report by American health expert Matthew Hanley titled The Catholic Church and the Global Aids Crisis argues that cultural changes are needed including a re-emphasis on fidelity within marriage and sexual abstinence outside of it.[188]
AIDS denialism
Main article:
AIDS denialismA small number of activists question the connection between HIV and AIDS,[189] the existence of HIV,[190] or the validity of current treatment methods (even going so far as to claim that the drug therapy itself was the cause of AIDS deaths). Though these claims have been examined and thoroughly rejected by the scientific community,[191] they continue to be promulgated through the Internet[192] and have had a significant political impact. In South Africa, former President Thabo Mbeki’s embrace of AIDS denialism resulted in an ineffective governmental response to the AIDS epidemic that has been blamed for hundreds of thousands of AIDS-related deaths.[193][194]
KGB disinformation
Operation INFEKTION was a worldwide Soviet active measures operation to spread information that the United States had created HIV/AIDS. Surveys show that a significant number of people believed – and continue to believe – in such claims.[195]
Government reaction
In 2010, former US President Bill Clinton said that countries receiving aid to combat the epidemic should redirect funding to local organizations who could spend it most effectively and efficiently. He said,
- “In too many countries, too much money goes to pay for too many people to go to too many meetings, [and] get on too many airplanes.” [196]
Research directions
It has been postulated that only a vaccine can halt the pandemic because a vaccine would possibly cost less, thus being affordable for developing countries, and would not require daily treatments. However, even after almost 30 years of research, HIV-1 remains a difficult target for a vaccine.[197]
Research to improve current treatments includes decreasing side effects of current drugs, further simplifying drug regimens to improve adherence, and determining the best sequence of regimens to manage drug resistance. A number of studies have shown that measures to prevent opportunistic infections can be beneficial when treating patients with HIV infection or AIDS. Vaccination against hepatitis A and B is advised for patients who are not infected with these viruses and are at risk of becoming infected.[198] Patients with substantial immunosuppression are also advised to receive prophylactic therapy for Pneumocystis jiroveci pneumonia (PCP), and many patients may benefit from prophylactic therapy for toxoplasmosis and Cryptococcus meningitis as well.[138]
Researchers have discovered an abzyme that can destroy the protein gp120 CD4 binding site. This protein is common to all HIV variants as it is the attachment point for B lymphocytes and subsequent compromising of the immune system.[199]
Researchers from the Hebrew University of Jerusalem have also discovered that a combination of peptides that stimulate integration together with the protease inhibitor Ro 31-8959 caused apoptotic cell death of HIV-infected cells with total extermination of the virus but did not harm healthy cells.[200][201] It could take several years before a commercial treatment based on this discovery becomes available.[202]
Reactivation of the retrocyclin pseudogene has been proposed as a possible prevention method, as was demonstrated in a proof-of-concept study in tissue culture cells.[203]
In Berlin, Germany, a 42-year-old leukemia patient, Timothy Ray Brown (also referred to as the “Berlin Patient”),[204] infected with HIV for more than a decade was given an experimental transplant of bone marrow with cells that contained an unusual natural variant of the CCR5 cell-surface receptor. This CCR5-Δ32 variant has been shown to make some cells from people who are born with it resistant to infection with some strains of HIV. Almost two years after the transplant, and even after the patient reportedly stopped taking antiretroviral medications, HIV has not been detected in the patient’s blood.[205] As of December 2010, three years after the transplant, Brown was still free of any detectable HIV in his blood and was described, in a paper in the journal Blood, as “cured.”[204][206]
See also
Notes and references
- ^ Sepkowitz KA (June 2001). “AIDS–the first 20 years”. N. Engl. J. Med. 344 (23): 1764–72. doi:10.1056/NEJM200106073442306. PMID 11396444.
- ^ Weiss RA (May 1993). “How does HIV cause AIDS?”. Science (journal) 260 (5112): 1273–9. doi:10.1126/science.8493571. PMID 8493571.
- ^ Cecil, Russell (1988). Textbook of Medicine. Philadelphia: Saunders. pp. 1523, 1799. ISBN 0721618480.
- ^ Divisions of HIV/AIDS Prevention (2003). “HIV and Its Transmission”. Centers for Disease Control & Prevention. Archived from the original on February 4, 2005. Retrieved 2006-05-23.
- ^ San Francisco AIDS Foundation (2006-04-14). “How HIV is spread”. Retrieved 2006-05-23.
- ^ a b c Kallings LO (2008). “The first postmodern pandemic: 25 years of HIV/AIDS”. J Intern Med 263 (3): 218–43. doi:10.1111/j.1365-2796.2007.01910.x. PMID 18205765.
- ^ “Worldwide AIDS & HIV Statistics”. AVERT. 31 December 2009. Retrieved 26 January 2011.
- ^ a b c d e f g UNAIDS, WHO (December 2007). “2007 AIDS epidemic update” (PDF). Retrieved 2008-03-12.
- ^ Data.unaids.org
- ^ Gao F, Bailes E, Robertson DL, et al. (1999). “Origin of HIV-1 in the Chimpanzee Pan troglodytes troglodytes”. Nature 397 (6718): 436–441. doi:10.1038/17130. PMID 9989410.
- ^ a b Worobey M, Gemmel M, Teuwen DE, et al. (October 2008). “Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960″. Nature 455 (7213): 661–4. doi:10.1038/nature07390. PMID 18833279. Retrieved 2009-03-31.
- ^ Gallo RC (2006). “A reflection on HIV/AIDS research after 25 years”. Retrovirology 3: 72. doi:10.1186/1742-4690-3-72. PMC 1629027. PMID 17054781.
- ^ a b Palella FJ Jr, Delaney KM, Moorman AC, et al. (1998). “Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators”. N. Engl. J. Med 338 (13): 853–860. doi:10.1056/NEJM199803263381301. PMID 9516219.
- ^ Gottlieb MS (2006). “Pneumocystis pneumonia–Los Angeles. 1981″. Am J Public Health 96 (6): 980–1; discussion 982–3. PMC 1470612. PMID 16714472. Retrieved 2009-03-31.
- ^ a b Centers for Disease Control (CDC) (1982). “Persistent, generalized lymphadenopathy among homosexual males.”. MMWR Morb Mortal Wkly Rep. 31 (19): 249–251. PMID 6808340.
- ^ a b Barré-Sinoussi F, Chermann JC, Rey F, et al. (1983). “Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS)”. Science 220 (4599): 868–871. Bibcode 1983Sci…220..868B. doi:10.1126/science.6189183. PMID 6189183.
- ^ a b Centers for Disease Control (CDC) (1982). “Opportunistic infections and Kaposi’s sarcoma among Haitians in the United States”. MMWR Morb Mortal Wkly Rep. 31 (26): 353–354; 360–361. PMID 6811853.
- ^ Altman LK (1982-05-11). “New homosexual disorder worries officials”. The New York Times.
- ^ “Making Headway Under Hellacious Circumstances” (PDF). American Association for the Advancement of Science. 2006-07-28. Retrieved 2008-06-23.
- ^ Kher U (1982-07-27). “A Name for the Plague”. Time. Retrieved 2008-03-10.
- ^ Centers for Disease Control (CDC) (1982). “Update on acquired immune deficiency syndrome (AIDS)—United States.”. MMWR Morb Mortal Wkly Rep. 31 (37): 507–508; 513–514. PMID 6815471.
- ^ Gilbert MT, Rambaut A, Wlasiuk G, Spira TJ, Pitchenik AE, Worobey M (2007). “The emergence of HIV/AIDS in the Americas and beyond”. Proc. Natl. Acad. Sci. U.S.A. 104 (47): 18566–70. doi:10.1073/pnas.0705329104. PMC 2141817. PMID 17978186.
- ^ Kalish ML, Wolfe ND, Ndongmo CD, McNicholl J, Robbins KE, et al. (2005). “Central African hunters exposed to simian immunodeficiency virus”. Emerg Infect Dis 11 (12): 1928–30. PMID 16485481.
- ^ Sharp, P. M.; Bailes, E.; Chaudhuri, R. R.; Rodenburg, C. M.; Santiago, M. O.; Hahn, B. H. (2001). “The origins of acquired immune deficiency syndrome viruses: where and when?”. Philosophical Transactions of the Royal Society B: Biological Sciences 356: 867–76. doi:10.1098/rstb.2001.0863. PMC 1088480. PMID 11405934.
- ^ Marx PA, Alcabes PG, Drucker E (2001). “Serial human passage of simian immunodeficiency virus by unsterile injections and the emergence of epidemic human immunodeficiency virus in Africa”. Philos Trans R Soc Lond B Biol Sci 356 (1410): 911–20. doi:10.1098/rstb.2001.0867. PMC 1088484. PMID 11405938.
- ^ Chitnis, Amit; Rawls, Diana; Moore, Jim (2000). “Origin of HIV Type 1 in Colonial French Equatorial Africa?”. AIDS Research and Human Retroviruses 16 (1): 5–8. doi:10.1089/088922200309548. PMID 10628811.
- ^ Sousa, João Dinis de; Müller, Viktor; Lemey, Philippe; Vandamme, Anne-Mieke; Vandamme, Anne-Mieke (2010). “High GUD Incidence in the Early 20th Century Created a Particularly Permissive Time Window for the Origin and Initial Spread of Epidemic HIV Strains”. PLoS ONE 5 (4): e9936. doi:10.1371/journal.pone.0009936. PMC 2848574. PMID 20376191.
- ^ Donald G. McNeil, Jr. (September 16, 2010). “Precursor to H.I.V. Was in Monkeys for Millennia”. New York Times. Retrieved 2010-09-17. “Dr. Marx believes that the crucial event was the introduction into Africa of millions of inexpensive, mass-produced syringes in the 1950s. … suspect that the growth of colonial cities is to blame. Before 1910, no Central African town had more than 10,000 people. But urban migration rose, increasing sexual contacts and leading to red-light districts.”
- ^ [1]
- ^ [2]
- ^ [3]
- ^ [4]
- ^ [5]
- ^ [6]
- ^ [7]
- ^ Curtis T (1992). “The origin of AIDS”. Rolling Stone (626): pp. 54–59, 61, 106, 108. Archived from the original on February 17, 2008. Retrieved 2008-03-10.
- ^ Hooper E (1999). The River : A Journey to the Source of HIV and AIDS (1st ed.). Boston, MA: Little Brown & Co. pp. 1–1070. ISBN 0-316-37261-7.
- ^ Worobey M, Santiago ML, Keele BF, et al. (2004). “Origin of AIDS: contaminated polio vaccine theory refuted”. Nature 428 (6985): 820. doi:10.1038/428820a. PMID 15103367.
- ^ Berry N, Jenkins A, Martin J, et al. (2005). “Mitochondrial DNA and retroviral RNA analyses of archival oral polio vaccine (OPV CHAT) materials: evidence of macaque nuclear sequences confirms substrate identity”. Vaccine 23 (14): 1639–1648. doi:10.1016/j.vaccine.2004.10.038. PMID 15705467.
- ^ “Oral Polio Vaccine and HIV / AIDS: Questions and Answers”. Centers for Disease Control and Prevention. 2004-03-23. Retrieved 2006-11-20.
- ^ Holmes CB, Losina E, Walensky RP, Yazdanpanah Y, Freedberg KA (2003). “Review of human immunodeficiency virus type 1-related opportunistic infections in sub-Saharan Africa”. Clin. Infect. Dis. 36 (5): 656–662. doi:10.1086/367655. PMID 12594648.
- ^ Guss DA (1994). “The acquired immune deficiency syndrome: an overview for the emergency physician, Part 1″. J. Emerg. Med. 12 (3): 375–384. doi:10.1016/0736-4679(94)90281-X. PMID 8040596.
- ^ Guss DA (1994). “The acquired immune deficiency syndrome: an overview for the emergency physician, Part 2″. J. Emerg. Med. 12 (4): 491–497. doi:10.1016/0736-4679(94)90346-8. PMID 7963396.
- ^ Feldman C (2005). “Pneumonia associated with HIV infection”. Curr. Opin. Infect. Dis. 18 (2): 165–170. doi:10.1097/01.qco.0000160907.79437.5a. PMID 15735422.
- ^ Kwara A, Ramachandran G, Swaminathan S (January 2010). “Dose adjustment of the non-nucleoside reverse transcriptase inhibitors during concurrent rifampicin-containing tuberculosis therapy: one size does not fit all”. Expert Opinion on Drug Metabolism & Toxicology 6 (1): 55–68. doi:10.1517/17425250903393752. PMC 2939445. PMID 19968575.
- ^ who.int
- ^ Decker CF, Lazarus A (August 2000). “Tuberculosis and HIV infection. How to safely treat both disorders concurrently”. Postgraduate Medicine 108 (2): 57–60, 65–8. PMID 10951746.
- ^ Zaidi SA, Cervia JS (2002). “Diagnosis and management of infectious esophagitis associated with human immunodeficiency virus infection”. Journal of the International Association of Physicians in AIDS Care 1 (2): 53–62. doi:10.1177/154510970200100204. PMID 12942677.
- ^ Pollok RC (2001). “Viruses causing diarrhoea in AIDS”. Novartis Foundation Symposium 238: 276–83; discussion 283–8. doi:10.1002/0470846534.ch17. PMID 11444032.
- ^ Guerrant RL, Hughes JM, Lima NL, Crane J (1990). “Diarrhea in developed and developing countries: magnitude, special settings, and etiologies”. Reviews of Infectious Diseases 12 (Suppl 1): S41–50. PMID 2406855.
- ^ Gazzard, B; Balkin, A; Hill, A (2010). “Analysis of neuropsychiatric adverse events during clinical trials of efavirenz in antiretroviral-naive patients: a systematic review”. AIDS reviews 12 (2): 67–75. PMID 20571601.
- ^ Luft BJ, Chua A (August 2000). “Central Nervous System Toxoplasmosis in HIV Pathogenesis, Diagnosis, and Therapy”. Current Infectious Disease Reports 2 (4): 358–362. doi:10.1007/s11908-000-0016-x. PMID 11095878.
- ^ Sadler M, Nelson MR (June 1997). “Progressive multifocal leukoencephalopathy in HIV”. International Journal of STD & AIDS 8 (6): 351–7. doi:10.1258/0956462971920181. PMID 9179644.
- ^ Gray F, Adle-Biassette H, Chretien F, Lorin de la Grandmaison G, Force G, Keohane C (2001). “Neuropathology and neurodegeneration in human immunodeficiency virus infection. Pathogenesis of HIV-induced lesions of the brain, correlations with HIV-associated disorders and modifications according to treatments”. Clinical Neuropathology 20 (4): 146–55. PMID 11495003.
- ^ Grant I, Sacktor H, McArthur J (2005). “HIV neurocognitive disorders”. In H. E. Gendelman, I. Grant, I. Everall, S. A. Lipton, and S. Swindells. (ed.) (PDF). The Neurology of AIDS (2nd ed.). London, UK: Oxford University Press. pp. 357–373. ISBN 0-19-852610-5.
- ^ Satishchandra P, Nalini A, Gourie-Devi M, et al. (January 2000). “Profile of neurologic disorders associated with HIV/AIDS from Bangalore, south India (1989-96)”. The Indian Journal of Medical Research 111: 14–23. PMID 10793489.
- ^ Wadia RS, Pujari SN, Kothari S, et al. (March 2001). “Neurological manifestations of HIV disease”. The Journal of the Association of Physicians of India 49: 343–8. PMID 11291974.
- ^ a b Boshoff C, Weiss R (2002). “AIDS-related malignancies”. Nat. Rev. Cancer 2 (5): 373–382. doi:10.1038/nrc797. PMID 12044013.
- ^ a b Yarchoan R, Tosato G, Little RF (2005). “Therapy insight: AIDS-related malignancies — the influence of antiviral therapy on pathogenesis and management”. Nat. Clin. Pract. Oncol. 2 (8): 406–415. doi:10.1038/ncponc0253. PMID 16130937.
- ^ Ho-Yen C and Chang F (June 1, 2008). “Gastrointestinal Malignancies in HIV/AIDS”. The AIDS Reader 18 (6).
- ^ Palefsky J (2007). “Human papillomavirus infection in HIV-infected persons”. Top HIV Med 15 (4): 130–3. PMID 17720998.
- ^ Bonnet F, Lewden C, May T, et al. (2004). “Malignancy-related causes of death in human immunodeficiency virus-infected patients in the era of highly active antiretroviral therapy”. Cancer 101 (2): 317–324. doi:10.1002/cncr.20354. PMID 15241829.
- ^ Skoulidis F, Morgan MS, MacLeod KM (2004). “Penicillium marneffei: a pathogen on our doorstep?”. J. R. Soc. Med. 97 (2): 394–396. doi:10.1258/jrsm.97.8.394. PMC 1079563. PMID 15286196.
- ^ Silvero AM, Acevedo-Gadea CR, Pantanowitz L “et al”; (June 4, 2009). “Unsuspected Parvovirus B19 Infection in a Person With AIDS”. The AIDS Reader 19 (6).
- ^ Alimonti JB, Ball TB, Fowke KR (2003). “Mechanisms of CD4+ T lymphocyte cell death in human immunodeficiency virus infection and AIDS.”. J. Gen. Virol. 84 (7): 1649–1661. doi:10.1099/vir.0.19110-0. PMID 12810858.
- ^ M.C.I. Lipman, R. W. Baker and M.A. Johnson ; with a foreword by P.A. Volberding. (2003). An Atlas of Differential Diagnosis in HIV Disease, Second Edition. CRC Press-Parthenon Publishers. pp. 22–27. ISBN 1-84214-026-4.
- ^ a b c d e Morgan D, Mahe C, Mayanja B, Okongo JM, Lubega R, Whitworth JA (2002). “HIV-1 infection in rural Africa: is there a difference in median time to AIDS and survival compared with that in industrialized countries?”. AIDS 16 (4): 597–632. doi:10.1097/00002030-200203080-00011. PMID 11873003.
- ^ a b Clerici M, Balotta C, Meroni L, et al. (1996). “Type 1 cytokine production and low prevalence of viral isolation correlate with long-term non progression in HIV infection”. AIDS Res. Hum. Retroviruses. 12 (11): 1053–1061. doi:10.1089/aid.1996.12.1053. PMID 8827221.
- ^ a b Morgan D, Mahe C, Mayanja B, Whitworth JA (2002). “Progression to symptomatic disease in people infected with HIV-1 in rural Uganda: prospective cohort study”. BMJ 324 (7331): 193–196. doi:10.1136/bmj.324.7331.193. PMC 64788. PMID 11809639.
- ^ Gendelman HE, Phelps W, Feigenbaum L, et al. (1986). “Transactivation of the human immunodeficiency virus long terminal repeat sequences by DNA viruses”. Proc. Natl. Acad. Sci. U. S. A. 83 (24): 9759–9763. doi:10.1073/pnas.83.24.9759. PMC 387220. PMID 2432602.
- ^ Bentwich Z, Kalinkovich, A, Weisman Z (1995). “Immune activation is a dominant factor in the pathogenesis of African AIDS.”. Immunol. Today 16 (4): 187–191. doi:10.1016/0167-5699(95)80119-7. PMID 7734046.
- ^ a b Tang J, Kaslow RA (2003). “The impact of host genetics on HIV infection and disease progression in the era of highly active antiretroviral therapy”. AIDS 17 (Suppl 4): S51–S60. doi:10.1097/00002030-200317004-00006. PMID 15080180.
- ^ Quiñones-Mateu ME, Mas A, Lain de Lera T, Soriano V, Alcami J, Lederman MM, Domingo E (1998). “LTR and tat variability of HIV-1 isolates from patients with divergent rates of disease progression”. Virus Research 57 (1): 11–20. doi:10.1016/S0168-1702(98)00082-3. PMID 9833881.
- ^ a b Campbell GR, Pasquier E, Watkins J, et al. (2004). “The glutamine-rich region of the HIV-1 Tat protein is involved in T-cell apoptosis”. J. Biol. Chem. 279 (46): 48197–48204. doi:10.1074/jbc.M406195200. PMID 15331610.
- ^ Kaleebu P, French N, Mahe C, et al. (2002). “Effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D on disease progression in a large cohort of HIV-1-positive persons in Uganda”. J. Infect. Dis. 185 (9): 1244–1250. doi:10.1086/340130. PMID 12001041.
- ^ Blechner MJ (1997). Hope and mortality: psychodynamic approaches to AIDS and HIV. Hillsdale, NJ: Analytic Press. ISBN 0-88163-223-6.
- ^ Kirby DB, Laris BA, Rolleri LA (March 2007). “Sex and HIV education programs: their impact on sexual behaviors of young people throughout the world”. J Adolesc Health 40 (3): 206–17. doi:10.1016/j.jadohealth.2006.11.143. PMID 17321420.
- ^ Rothenberg RB, Scarlett M, del Rio C, Reznik D, O’Daniels C (1998). “Oral transmission of HIV”. AIDS 12 (16): 2095–2105. doi:10.1097/00002030-199816000-00004. PMID 9833850.
- ^ Mastro TD, de Vincenzi I (1996). “Probabilities of sexual HIV-1 transmission”. AIDS 10 (Suppl A): S75–S82. doi:10.1097/00002030-199601001-00011. PMID 8883613.
- ^ Koenig MA, Zablotska I, Lutalo T, Nalugoda F, Wagman J, Gray R (2004). “Coerced first intercourse and reproductive health among adolescent women in Rakai, Uganda”. Int Fam Plan Perspect 30 (4): 156–63. doi:10.1363/ifpp.30.156.04 (inactive 2009-11-21). PMID 15590381.
- ^ Halkitis PN, Pandey Mukherjee P, Palamar JJ (2008). “Longitudinal Modeling of Methamphetamine Use and Sexual Risk Behaviors in Gay and Bisexual Men”. AIDS and Behavior 13 (4): 783–791. doi:10.1007/s10461-008-9432-y. PMID 18661225.
- ^ a b Laga M, Nzila N, Goeman J (1991). “The interrelationship of sexually transmitted diseases and HIV infection: implications for the control of both epidemics in Africa”. AIDS 5 (Suppl 1): S55–S63. PMID 1669925.
- ^ Tovanabutra S, Robison V, Wongtrakul J, et al. (2002). “Male viral load and heterosexual transmission of HIV-1 subtype E in northern Thailand”. J. Acquir. Immune. Defic. Syndr. 29 (3): 275–283. PMID 11873077.
- ^ Sagar M, Lavreys L, Baeten JM, et al. (2004). “Identification of modifiable factors that affect the genetic diversity of the transmitted HIV-1 population”. AIDS 18 (4): 615–619. doi:10.1097/00002030-200403050-00005. PMID 15090766.
- ^ Lavreys L, Baeten JM, Martin HL, et al. (March 2004). “Hormonal contraception and risk of HIV-1 acquisition: results of a 10-year prospective study”. AIDS 18 (4): 695–7. PMID 15090778.
- ^ Epstein, Helen (2007). The invisible cure: Africa, the West, and the fight against AIDS. New York: Farrar, Straus, and Giroux. ISBN 0-374-28152-1.
- ^ Parasitic worms may boost African HIV rates
- ^ Agnès-Laurence Chenine, Ela Shai-Kobiler, Lisa N. Steele, Helena Ong, Peter Augostini, Ruijiang Song, Sandra J. Lee, Patrick Autissier, Ruth M. Ruprecht, W. Evan Secor Acute Schistosoma mansoni Infection Increases Susceptibility to Systemic SHIV Clade C Infection in Rhesus Macaques after Mucosal Virus Exposure PLoS Neglected Tropical Diseases DOI: 10.1371/journal.pntd.0000265
- ^ Fan H (2005). Fan, H., Conner, R. F. and Villarreal, L. P. eds. ed. AIDS: science and society (4th ed.). Boston, MA: Jones and Bartlett Publishers. ISBN 0-7637-0086-X.
- ^ “WHO, UNAIDS Reaffirm HIV as a Sexually Transmitted Disease”. WHO. 2003-03-17. Retrieved 2006-01-17.
- ^ “Financial Resources Required to Achieve, Universal Access to HIV Prevention, Treatment Care and Support” (PDF). UNAIDS. Retrieved 2008-04-11.
- ^ “Blood safety….for too few”. WHO. 2001. Retrieved 2006-01-17.
- ^ a b Coovadia H (2004). “Antiretroviral agents—how best to protect infants from HIV and save their mothers from AIDS”. N. Engl. J. Med. 351 (3): 289–292. doi:10.1056/NEJMe048128. PMID 15247337.
- ^ Coovadia HM, Bland RM (2007). “Preserving breastfeeding practice through the HIV pandemic”. Trop. Med. Int. Health. 12 (9): 1116–1133. doi:10.1111/j.1365-3156.2007.01895.x. PMID 17714431.
- ^ Guss DA (1994). “The acquired immune deficiency syndrome: an overview for the emergency physician, Part 1″. J Emerg Med 12 (3): 375–84. doi:10.1016/0736-4679(94)90281-X. PMID 8040596.
- ^ Hel Z, McGhee JR, Mestecky J (June 2006). “HIV infection: first battle decides the war”. Trends Immunol. 27 (6): 274–81. doi:10.1016/j.it.2006.04.007. PMID 16679064.
- ^ Mehandru S, Poles MA, Tenner-Racz K, Horowitz A, Hurley A, Hogan C, Boden D, Racz P, Markowitz M (September 2004). “Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract”. J. Exp. Med. 200 (6): 761–70. doi:10.1084/jem.20041196. PMC 2211967. PMID 15365095.
- ^ Brenchley JM, Schacker TW, Ruff LE, Price DA, Taylor JH, Beilman GJ, Nguyen PL, Khoruts A, Larson M, Haase AT, Douek DC (September 2004). “CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract”. J. Exp. Med. 200 (6): 749–59. doi:10.1084/jem.20040874. PMC 2211962. PMID 15365096.
- ^ Appay V, Sauce D (January 2008). “Immune activation and inflammation in HIV-1 infection: causes and consequences”. J. Pathol. 214 (2): 231–41. doi:10.1002/path.2276. PMID 18161758.
- ^ Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, Kazzaz Z, Bornstein E, Lambotte O, Altmann D, Blazar BR, Rodriguez B, Teixeira-Johnson L, Landay A, Martin JN, Hecht FM, Picker LJ, Lederman MM, Deeks SG, Douek DC (December 2006). “Microbial translocation is a cause of systemic immune activation in chronic HIV infection”. Nat. Med. 12 (12): 1365–71. doi:10.1038/nm1511. PMID 17115046.
- ^ a b Textbook of Pathology by Harsh Mohan, ISBN 81-8061-368-2
- ^ World Health Organization (1990). “Interim proposal for a WHO staging system for HIV infection and disease”. WHO Wkly Epidem. Rec. 65 (29): 221–228. PMID 1974812.
- ^ “1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults”. CDC. 1992. Retrieved 2006-02-09.
- ^ a b Kumaranayake L, Watts C (2001). “Resource allocation and priority setting of HIV/AIDS interventions: addressing the generalized epidemic in sub-Saharan Africa”. J. Int. Dev. 13 (4): 451–466. doi:10.1002/jid.798.
- ^ Weber B (2006). “Screening of HIV infection: role of molecular and immunological assays”. Expert Rev. Mol. Diagn. 6 (3): 399–411. doi:10.1586/14737159.6.3.399. PMID 16706742.
- ^ eMedicine – HIV Infection (Pediatrics: General Medicine)
- ^ Tóth FD, Bácsi A, Beck Z, Szabó J (2001). “Vertical transmission of human immunodeficiency virus”. Acta Microbiol Immunol Hung 48 (3–4): 413–27. doi:10.1556/AMicr.48.2001.3-4.10. PMID 11791341.
- ^ Smith DK, Grohskopf LA, Black RJ, et al. (2005). “Antiretroviral Postexposure Prophylaxis After Sexual, Injection-Drug Use, or Other Nonoccupational Exposure to HIV in the United States”. MMWR 54 (RR02): 1–20. Retrieved 2009-03-31.
- ^ Donegan E, Stuart M, Niland JC, et al. (1990). “Infection with human immunodeficiency virus type 1 (HIV-1) among recipients of antibody-positive blood donations”. Ann. Intern. Med. 113 (10): 733–739. PMID 2240875.
- ^ Kaplan EH, Heimer R (1995). “HIV incidence among New Haven needle exchange participants: updated estimates from syringe tracking and testing data”. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 10 (2): 175–176. PMID 7552482.
- ^ Bell DM (1997). “Occupational risk of human immunodeficiency virus infection in healthcare workers: an overview.”. Am. J. Med. 102 (5B): 9–15. doi:10.1016/S0002-9343(97)89441-7. PMID 9845490.
- ^ a b c d European Study Group on Heterosexual Transmission of HIV (1992). “Comparison of female to male and male to female transmission of HIV in 563 stable couples”. BMJ. 304 (6830): 809–813. doi:10.1136/bmj.304.6830.809. PMC 1881672. PMID 1392708.
- ^ a b c d e f Varghese B, Maher JE, Peterman TA, Branson BM,Steketee RW (2002). “Reducing the risk of sexual HIV transmission: quantifying the per-act risk for HIV on the basis of choice of partner, sex act, and condom use”. Sex. Transm. Dis. 29 (1): 38–43. PMID 11773877.
- ^ Leynaert B, Downs AM, de Vincenzi I (1998). “Heterosexual transmission of human immunodeficiency virus: variability of infectivity throughout the course of infection. European Study Group on Heterosexual Transmission of HIV”. Am. J. Epidemiol. 148 (1): 88–96. PMID 9663408.
- ^ “Facts about AIDS & HIV”. avert.org. Retrieved 2007-11-30.
- ^ NPR.org
- ^ Johnson AM, Laga M (1988). “Heterosexual transmission of HIV”. AIDS 2 (suppl. 1): S49–S56. doi:10.1097/00002030-198800001-00008. PMC 2545554. PMID 3130121.
- ^ N’Galy B, Ryder RW (1988). “Epidemiology of HIV infection in Africa”. Journal of Acquired Immune Deficiency Syndromes 1 (6): 551–558. PMID 3225742.
- ^ Deschamps MM, Pape JW, Hafner A, Johnson WD Jr. (1996). “Heterosexual transmission of HIV in Haiti”. Annals of Internal Medicine 125 (4): 324–330. PMID 8678397.
- ^ Cayley WE Jr. (2004). “Effectiveness of condoms in reducing heterosexual transmission of HIV”. Am. Fam. Physician 70 (7): 1268–1269. PMID 15508535.
- ^ “Module 5/Guidelines for Educators” (Microsoft Word). Durex. Archived from the original on March 13, 2006. Retrieved 2006-04-17.
- ^ PATH (2006). “The female condom: significant potential for STI and pregnancy prevention”. Outlook 22 (2).
- ^ “Condom Facts and Figures”. WHO. August 2003. Retrieved 2006-01-17.
- ^ Patel VL, Yoskowitz NA, Kaufman DR, Shortliffe EH (2008). “Discerning patterns of human immunodeficiency virus risk in healthy young adults”. Am J Med 121 (4): 758–764. doi:10.1016/j.amjmed.2008.04.022. PMC 2597652. PMID 18724961.
- ^ Dias SF, Matos MG, Goncalves, A. C. (2005). “Preventing HIV transmission in adolescents: an analysis of the Portuguese data from the Health Behaviour School-aged Children study and focus groups”. Eur. J. Public Health 15 (3): 300–304. doi:10.1093/eurpub/cki085. PMID 15941747.
- ^ Weiss HA (February 2007). “Male circumcision as a preventive measure against HIV and other sexually transmitted diseases”. Curr. Opin. Infect. Dis. 20 (1): 66–72. doi:10.1097/QCO.0b013e328011ab73. PMID 17197884.
- ^ Mcallister RG, Travis JW, Bollinger D, Rutiser C, Sundar V (Fall 2008). “The cost to circumcise Africa”. International Journal of Men’s Health (Men’s Studies Press) 7 (3): 307–316. doi:10.3149/jmh.0703.307. ISBN 1532-6306 (Print) 1933-0278 (Online).
- ^ Eaton LA, Kalichman S (December 2007). “Risk compensation in HIV prevention: implications for vaccines, microbicides, and other biomedical HIV prevention technologies”. Curr HIV/AIDS Rep 4 (4): 165–72. doi:10.1007/s11904-007-0024-7. PMC 2937204. PMID 18366947.
- ^ Mattson, C.L.; R.T. Campbell, R.C. Bailey, K. Agot, J.O. Ndinya-Achola, S. Moses (June 18 2008). “Risk compensation is not associated with male circumcision in Kisumu, Kenya: a multi-faceted assessment of men enrolled in a randomized controlled trial”. PLoS One 3 (6): e2443. doi:10.1371/journal.pone.0002443. PMC 2409966. PMID 18560581.
- ^ Scientists say vaginal gel cuts HIV-infections by half, BBC News, 19 July 2010, accessed 19 July 2010
- ^ Centers for Disease Control (CDC) (August 1987). “Recommendations for prevention of HIV transmission in health-care settings”. MMWR 36 (Suppl 2): 1S–18S. PMID 3112554.
- ^ Kerr T, Kimber J, Debeck K, Wood E (December 2007). “The role of safer injection facilities in the response to HIV/AIDS among injection drug users”. Current HIV/AIDS Reports 4 (4): 158–64. doi:10.1007/s11904-007-0023-8. PMID 18366946.
- ^ Wodak A, Cooney A (2006). “Do needle syringe programs reduce HIV infection among injecting drug users: a comprehensive review of the international evidence”. Substance Use & Misuse 41 (6-7): 777–813. doi:10.1080/10826080600669579. PMID 16809167.
- ^ WHO HIV and Infant Feeding Technical Consultation (2006). “Consensus statement” (PDF). Retrieved 2008-03-12.
- ^ Lakhanpal, M; Ram, R (2008). “Educational attainment and HIV/AIDS prevalence: A cross-country study”. Economics of Education Review 27: 14–21. doi:10.1016/j.econedurev.2006.09.003.; Rindermann, H; Meisenberg, G (2009). “Relevance of education and intelligence at the national level for health: The case of HIV and AIDS”. Intelligence 37: 383–395. doi:10.1016/j.intell.2009.03.005.
- ^ Fiona Samuels (2010) Improving research quality: how good is the literature on the impact of education on HIV and AIDS? Overseas Development Institute
- ^ Hamlyn E, Easterbrook P (August 2007). “Occupational exposure to HIV and the use of post-exposure prophylaxis”. Occup Med (Lond) 57 (5): 329–36. doi:10.1093/occmed/kqm046. PMID 17656498.
- ^ a b “A Pocket Guide to Adult HIV/AIDS Treatment February 2006 edition”. Department of Health and Human Services. February 2006. Retrieved 2006-09-01.
- ^ “A Pocket Guide to Adult HIV/AIDS Treatment February 2006 edition”. Department of Health and Human Services. February 2006. Retrieved 2006-09-01.
- ^ “Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection” (PDF). Department of Health and Human Services Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children. 2005-11-03. Retrieved 2006-01-17.
- ^ “Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents” (PDF). Department of Health and Human Services Panel on Clinical Practices for Treatment of HIV Infection. 2005-10-06. Retrieved 2006-01-17.
- ^ Siegfried, N.; Uthman, O.; Rutherford, G. (2010). “Optimal time for initiation of antiretroviral therapy in asymptomatic, HIV-infected, treatment-naive adults”. Cochrane Database of Systematic Reviews (3): CD008272. doi:10.1002/14651858.CD008272.pub2. PMID 20238364.
- ^ Martinez-Picado J, DePasquale MP, Kartsonis N, et al. (2000). “Antiretroviral resistance during successful therapy of human immunodeficiency virus type 1 infection”. Proc. Natl. Acad. Sci. U. S. A. 97 (20): 10948–10953. doi:10.1073/pnas.97.20.10948. PMC 27129. PMID 11005867.
- ^ Dybul M, Fauci AS, Bartlett JG, Kaplan JE, Pau AK; Panel on Clinical Practices for Treatment of HIV. (2002). “Guidelines for using antiretroviral agents among HIV-infected adults and adolescents”. Ann. Intern. Med. 137 (5 Pt 2): 381–433. PMID 12617573.
- ^ Blankson JN, Persaud D, Siliciano RF (2002). “The challenge of viral reservoirs in HIV-1 infection”. Annu. Rev. Med. 53: 557–593. doi:10.1146/annurev.med.53.082901.104024. PMID 11818490.
- ^ Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD (1998). “Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection”. N. Engl. J. Med. 338 (13): 853–860. doi:10.1056/NEJM199803263381301. PMID 9516219.
- ^ Wood E, Hogg RS, Yip B, Harrigan PR, O’Shaughnessy MV, Montaner JS (2003). “Is there a baseline CD4 cell count that precludes a survival response to modern antiretroviral therapy?”. AIDS 17 (5): 711–720. doi:10.1097/00002030-200303280-00009. PMID 12646794.
- ^ Chene G, Sterne JA, May M, Costagliola D, Ledergerber B, Phillips AN, Dabis F, Lundgren J, D’Arminio Monforte A, de Wolf F, Hogg R, Reiss P, Justice A, Leport C, Staszewski S, Gill J, Fatkenheuer G, Egger ME and the Antiretroviral Therapy Cohort Collaboration (2003). “Prognostic importance of initial response in HIV-1 infected patients starting potent antiretroviral therapy: analysis of prospective studies”. Lancet 362 (9385): 679–686. doi:10.1016/S0140-6736(03)14229-8. PMID 12957089.
- ^ King JT, Justice AC, Roberts MS, Chang CH, Fusco JS and the CHORUS Program Team (2003). “Long-Term HIV/AIDS Survival Estimation in the Highly Active Antiretroviral Therapy Era”. Medical Decision Making 23 (1): 9–20. doi:10.1177/0272989X02239652. PMID 12583451.
- ^ Tassie JM, Grabar S, Lancar R, Deloumeaux J, Bentata M, Costagliola D and the Clinical Epidemiology Group from the French Hospital Database on HIV (2002). “Time to AIDS from 1992 to 1999 in HIV-1-infected subjects with known date of infection”. Journal of acquired immune deficiency syndromes 30 (1): 81–7. doi:10.1097/00126334-200205010-00011. PMID 12048367.
- ^ Becker SL, Dezii CM, Burtcel B, Kawabata H, Hodder S. (2002). “Young HIV-infected adults are at greater risk for medication nonadherence”. MedGenMed. 4 (3): 21. PMID 12466764.
- ^ Nieuwkerk P, Sprangers M, Burger D, Hoetelmans RM, Hugen PW, Danner SA, van Der Ende ME, Schneider MM, Schrey G, Meenhorst PL, Sprenger HG, Kauffmann RH, Jambroes M, Chesney MA, de Wolf F, Lange JM and the ATHENA Project (2001). “Limited Patient Adherence to Highly Active Antiretroviral Therapy for HIV-1 Infection in an Observational Cohort Study”. Arch. Intern. Med. 161 (16): 1962–1968. doi:10.1001/archinte.161.16.1962. PMID 11525698.
- ^ Kleeberger C, Phair J, Strathdee S, Detels R, Kingsley L, Jacobson LP (2001). “Determinants of Heterogeneous Adherence to HIV-Antiretroviral Therapies in the Multicenter AIDS Cohort Study”. J. Acquir. Immune Defic. Syndr. 26 (1): 82–92. PMID 11176272.
- ^ Heath KV, Singer J, O’Shaughnessy MV, Montaner JS, Hogg RS (2002). “Intentional Nonadherence Due to Adverse Symptoms Associated With Antiretroviral Therapy”. J. Acquir. Immune Defic. Syndr. 31 (2): 211–217. PMID 12394800.
- ^ a b Burgoyne RW, Tan DH (March 2008). “Prolongation and quality of life for HIV-infected adults treated with highly active antiretroviral therapy (HAART): a balancing act”. J. Antimicrob. Chemother. 61 (3): 469–73. doi:10.1093/jac/dkm499. PMID 18174196.
- ^ Bhargava, A.; Booysen, F. L. (2010). “Healthcare infrastructure and emotional support are predictors of CD4 cell counts and quality of life indices of patients on antiretroviral treatment in Free State Province, South Africa”. AIDS Care 22 (1): 1–9. doi:10.1080/09540120903012585. PMID 20390475.
- ^ Littlewood RA, Vanable PA (September 2008). “Complementary and alternative medicine use among HIV-positive people: research synthesis and implications for HIV care”. AIDS Care 20 (8): 1002–18. doi:10.1080/09540120701767216. PMC 2570227. PMID 18608078.
- ^ Mills E, Wu P, Ernst E (June 2005). “Complementary therapies for the treatment of HIV: in search of the evidence”. Int J STD AIDS 16 (6): 395–403. doi:10.1258/0956462054093962. PMID 15969772.
- ^ Liu JP, Manheimer E, Yang M (2005). “Herbal medicines for treating HIV infection and AIDS”. Cochrane Database Syst Rev (3): CD003937. doi:10.1002/14651858.CD003937.pub2. PMID 16034917.
- ^ a b Nicholas PK, Kemppainen JK, Canaval GE, et al. (February 2007). “Symptom management and self-care for peripheral neuropathy in HIV/AIDS”. AIDS Care 19 (2): 179–89. doi:10.1080/09540120600971083. PMID 17364396.
- ^ Hurwitz BE, Klaus JR, Llabre MM, et al. (January 2007). “Suppression of human immunodeficiency virus type 1 viral load with selenium supplementation: a randomized controlled trial”. Arch. Intern. Med. 167 (2): 148–54. doi:10.1001/archinte.167.2.148. PMID 17242315.
- ^ a b Irlam JH, Visser ME, Rollins N, Siegfried N (2005). “Micronutrient supplementation in children and adults with HIV infection”. Cochrane Database Syst Rev (4): CD003650. doi:10.1002/14651858.CD003650.pub2. PMID 16235333.
- ^ a b World Health Organization (2003-05). Nutrient requirements for people living with HIV/AIDS: Report of a technical consultation. Geneva. Retrieved 2009-03-31.
- ^ Zwahlen M, Egger M (2006) (PDF). Progression and mortality of untreated HIV-positive individuals living in resource-limited settings: update of literature review and evidence synthesis. UNAIDS Obligation HQ/05/422204. Retrieved 2008-03-19.
- ^ Knoll B, Lassmann B, Temesgen Z (2007). “Current status of HIV infection: a review for non-HIV-treating physicians”. Int J Dermatol 46 (12): 1219–28. doi:10.1111/j.1365-4632.2007.03520.x. PMID 18173512.
- ^ a b Lawn SD (2004). “AIDS in Africa: the impact of coinfections on the pathogenesis of HIV-1 infection”. J. Infect. Dis. 48 (1): 1–12. doi:10.1016/j.jinf.2003.09.001. PMID 14667787.
- ^ Campbell GR, Watkins JD, Esquieu D, Pasquier E, Loret EP, Spector SA (2005). “The C terminus of HIV-1 Tat modulates the extent of CD178-mediated apoptosis of T cells”. J. Biol. Chem. 280 (46): 38376–39382. doi:10.1074/jbc.M506630200. PMID 16155003.
- ^ Senkaali D, Muwonge R, Morgan D, Yirrell D, Whitworth J, Kaleebu P (2005). “The relationship between HIV type 1 disease progression and V3 serotype in a rural Ugandan cohort”. AIDS Res. Hum. Retroviruses. 20 (9): 932–937. doi:10.1089/aid.2004.20.932. PMID 15585080.
- ^ Woods, S.; Moore, D.; Weber, E.; Grant, I. (2009). “Cognitive neuropsychology of HIV-associated neurocognitive disorders”. Neuropsychology review 19 (2): 152–168. doi:10.1007/s11065-009-9102-5. PMC 2690857. PMID 19462243.
- ^ Brown, T.; Qaqish, R. (2006). “Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review”. AIDS (London, England) 20 (17): 2165–2174. doi:10.1097/QAD.0b013e32801022eb. PMID 17086056.
- ^ Post, F. .; Holt, S. . (2009). “Recent developments in HIV and the kidney”. Current opinion in infectious diseases 22 (1): 43–48. doi:10.1097/QCO.0b013e328320ffec. PMID 19106702.
- ^ AIDS Patients Now Living Longer, But Aging Faster
- ^ “Tuberculosis“. World Health Organization (WHO).
- ^ McNeil DG Jr (2007-11-20). “U.N. agency to say it overstated extent of H.I.V. cases by millions”. New York Times. Retrieved 2008-03-18.
- ^ “Report: Black U.S. AIDS rates rival some African nations“. CNN.com. July 29, 2008.
- ^ “White House summit on AIDS’ impact on black men“. San Francisco Chronicle. June 3, 2010.
- ^ >Arya M, Behforouz HL, and Viswanath K (March 9, 2009). “African American Women and HIV/AIDS: A National Call for Targeted Health Communication Strategies to Address a Disparity”. The AIDS Reader 19 (2).
- ^ >Chu C and Selwyn PA (March 1, 2008). “Current Health Disparities in HIV/AIDS”. The AIDS Reader 18 (3).
- ^ “Obama Ends U.S. Travel Ban On Visitors, Immigrants With HIV-AIDS“. ABC News. October 30, 2009.
- ^ “The impact of AIDS on people and societies” (PDF). 2006 Report on the global AIDS epidemic. UNAIDS. 2006. ISBN 9291734799. Retrieved 2006-06-14.
- ^ Ogden J, Nyblade L (2005). “Common at its core: HIV-related stigma across contexts” (PDF). International Center for Research on Women. Retrieved 2007-02-15.
- ^ a b c Herek GM, Capitanio JP (1999). “AIDS Stigma and sexual prejudice” (PDF). American Behavioral Scientist 42 (7): 1130–1147. doi:10.1177/0002764299042007006. Retrieved 2006-03-27.
- ^ Snyder M, Omoto AM, Crain AL (1999). “Punished for their good deeds: stigmatization for AIDS volunteers”. American Behavioral Scientist 42 (7): 1175–1192. doi:10.1177/0002764299042007009.
- ^ Herek GM, Capitanio JP, Widaman KF (2002). “HIV-related stigma and knowledge in the United States: prevalence and trends, 1991-1999″ (PDF). Am J Public Health 92 (3): 371–7. doi:10.2105/AJPH.92.3.371. PMC 1447082. PMID 11867313. Retrieved 2008-03-10.
- ^ Bell C, Devarajan S, Gersbach H (2003) (PDF). The long-run economic costs of AIDS: theory and an application to South Africa. World Bank Policy Research Working Paper No. 3152. Retrieved 2008-04-28.
- ^ a b Greener R (2002). “AIDS and macroeconomic impact”. In S, Forsyth (ed.). State of The Art: AIDS and Economics. IAEN. pp. 49–55.
- ^ Over M (1992) (PDF). The macroeconomic impact of AIDS in Sub-Saharan Africa, Population and Human Resources Department. The World Bank. Retrieved 2008-05-03.
- ^ a b c Thirty years after AIDS discovery, appreciation growing for Catholic approach
- ^ Duesberg PH (1988). “HIV is not the cause of AIDS”. Science 241 (4865): 514, 517. doi:10.1126/science.3399880. PMID 3399880.
- ^ Papadopulos-Eleopulos E, Turner VF, Papadimitriou J, et al. (2004). “A critique of the Montagnier evidence for the HIV/AIDS hypothesis”. Med Hypotheses 63 (4): 597–601. doi:10.1016/j.mehy.2004.03.025. PMID 15325002.
- ^ For evidence of the scientific consensus that HIV is the cause of AIDS, see (for example):
- ^ Smith TC, Novella SP (2007). “HIV denial in the Internet era”. PLoS Med. 4 (8): e256. doi:10.1371/journal.pmed.0040256. PMC 1949841. PMID 17713982.
- ^ Chigwedere P, Seage GR, Gruskin S, Lee TH, Essex M (October 2008). “Estimating the Lost Benefits of Antiretroviral Drug Use in South Africa”. Journal of acquired immune deficiency syndromes (1999) 49: 410. doi:10.1097/QAI.0b013e31818a6cd5. PMID 18931626. Lay summary.
- ^ Baleta A (2003). “S Africa’s AIDS activists accuse government of murder”. Lancet 361 (9363): 1105. doi:10.1016/S0140-6736(03)12909-1. PMID 12672319.
- ^ Operation INFEKTION – Soviet Bloc Intelligence and Its AIDS Disinformation Campaign. Thomas Boghardt. 2009
- ^ Oleksyn, Veronika (20 July 2010). “Clinton and Gates urge change in AIDS strategy”. Burlington, Vermont: Burlington Free Press. pp. 3A.
- ^ Karlsson Hedestam GB, Fouchier RA, Phogat S, Burton DR, Sodroski J, Wyatt RT (February 2008). “The challenges of eliciting neutralizing antibodies to HIV-1 and to influenza virus”. Nat. Rev. Microbiol. 6 (2): 143–55. doi:10.1038/nrmicro1819. PMID 18197170.
- ^ Laurence J (2006). “Hepatitis A and B virus immunization in HIV-infected persons”. AIDS Reader 16 (1): 15–17. PMID 16433468.
- ^ Planque S, Nishiyama Y, Taguchi H, Salas M, Hanson C, Paul S (June 2008). “Catalytic antibodies to HIV: Physiological role and potential clinical utility”. Autoimmun Rev 7 (6): 473–9. doi:10.1016/j.autrev.2008.04.002. PMC 2527403. PMID 18558365.
- ^ Even, Dan (3 September 2010). “Hebrew U. researchers develop treatment to kill HIV cells”. Haaretz. Retrieved 11 October 2010.
- ^ Levin, Aviad; Hayouka, Zvi; Friedler, Assaf; Loyter; Abraham (19 August 2010). “Specific eradication of HIV-1 from infected cultured cells”. AIDS Research and Therapy 7 (31): 31. doi:10.1186/1742-6405-7-31. PMC 2933580. PMID 20723214. Retrieved 11 October 2010.
- ^ Klein Leichman, Abigail (7 October 2010). “On the HIV warpath”. Israel 21c Innovation News Service. Retrieved 11 October 2010.
- ^ Retrocyclin pseudogene reactivation as defense to AIDS
- ^ a b “German HIV patient cured after stem cell transplant”. Belfast Telegraph. 15 December 2010. Retrieved 15 December 2010.
- ^ Schoofs, Mark (November 2008). “A Doctor, a Mutation and a Potential Cure for AIDS: A Bone Marrow Transplant to Treat a Leukemia Patient Also Gives Him Virus-Resistant Cells; Many Thanks, Sample 61″. Wall Street Journal. Retrieved 2008-11-12.
- ^ Allers, K.; Hutter, G.; Hofmann, J.; Loddenkemper, C.; Rieger, K.; Thiel, E.; Schneider, T. (2010). “Evidence for the cure of HIV infection by CCR5 32/ 32 stem cell transplantation”. Blood 117 (10): 2791–2799. doi:10.1182/blood-2010-09-309591. PMID 21148083.
Further reading
External links
International political commitment is needed to expand HIV treatment, scientists and activists say. Shannon Stapleton/Reuters