Wikipedia

HIV/AIDS

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AIDS (Acquired Immunodeficiency Syndrome or Acquired Immune Deficiency Syndrome, rarely written Aids) is the result of infection with Human immunodeficiency virus HIV, a lentivirus. [1] A person with antibodies to HIV, who has a CD4+ T cell count below 200/mm3 or one of 26 of AIDS defining conditions, is diagnosed with AIDS. [2]

File:Red ribbon.jpg
The Red Ribbon symbol is used internationally to represent the fight against AIDS.

HIV infection is acquired through penetrative (anal or vaginal) and oral sex; blood transfusion; the sharing of contaminated needles in health care settings and through drug injection; and, between mother and infant, during pregnancy, childbirth and breastfeeding. [3].

AIDS is thought to have originated in sub-Saharan Africa during the twentieth century and is now a global epidemic. The World Health Organization estimated that, worldwide, between 2.8 and 3.5 million people with AIDS died in 2004. [4]

Global epidemic

UNAIDS and the World Health Organization estimated that between 36 and 44 million people around the world were living with HIV in December 2004 [5]. It was estimated that during 2004, between 4.3 and 6.4 million people were newly infected with HIV and between 2.8 and 3.5 million people with AIDS died. Sub-Saharan Africa remains by far the worst-affected region, with 23.4 million to 28.4 million people living with HIV at the end of 2004. Just under two thirds (64%) of all people living with HIV are in sub-Saharan Africa, as are more than three quarters (76%) of all women living with HIV. [6] South & South East Asia are second most affected with 15%. AIDS accounts for the deaths of 500,000 children.

World region Estimated adult prevalence of HIV infection
(ages 15–49)		 Estimated adult and child deaths
during 2004
Sub-Saharan Africa 6.9% to 8.3% 2.1 to 2.6 million
Caribbean 1.5% to 4.1% 24,000 to 61,000
Asia 0.3% to 0.6% 350,000 to 810,000
Eastern Europe and Central Asia 0.5% to 1.2% 39,000 to 87,000
Latin America 0.5% to 0.8% 73,000 to 120,000
Oceania 0.1% to 0.3% fewer than 1,700
Middle East and North Africa: 0.1% to 0.7% 12,000 to 72,000
North America, Western and Central Europe 0.3% to 0.6% 15,000 to 32,000
UNAIDS and the WHO 2004 estimates. The ranges define the boundaries within which the actual numbers lie, based on the best available information. [7]

Prevention

File:R402a1t1.gif
CDC 2005

The effective use of condoms and screening of blood transfusion in North America, Western and Central Europe is credited with the low rates of AIDS in these regions. Adopting these effective prevention methods in other regions has proved controversial and difficult. The Vatican opposes the use of condoms [8] and many countries do not screen blood transfusions for HIV antibodies.

Safer sex

Health organizations endorse the "ABC Approach" to lower the risk of acquiring AIDS during sex:

  • Abstinence or delay of sexual activity
  • Be faithful and reduce partner numbers
  • Condom use

Health experts around the world advocate the proper use of condoms to prevent the spread of AIDS. Using a condom significantly reduces the risk of acquiring AIDS.

HIV blood screening

Blood tranfusions remain a source of new HIV infections. According to the WHO [9], "between 5% and 10% of HIV infections worldwide are transmitted through the transfusion of infected blood and blood products." In those countries where improved donor selection and antibody tests have been introduced, the risk of transmitting HIV infection to blood transfusion recipients has been effectively eliminated.

Medical procedures

Medical workers who follow universal precautions or body substance isolation such as wearing latex gloves when giving injections and washing the hands frequently can help prevent infection of HIV. The risk of being infected with HIV from a single prick with a needle that has been used on an HIV infected person though is thought to be about 1 in 150 (see table above). Post-exposure prophylaxis with anti-HIV drugs can further reduce that small risk. [10]

Health clinics in some countries are responsible for as much as 30% of HIV transmission worldwide. There is an urgent need to address medical transmission as a priority in these countries. see HIV transmission in the medical setting.

Intravenous drug use

HIV can be transmitted by the sharing of needles by users of intravenous drugs. Cumulative data from 1981 to 2001 has shown that 31% of people with AIDS in the United States are injection drug users [11]. All AIDS-prevention organisations advise drug-users not to share needles and to use a new or properly sterilized needle for each injection. Information on cleaning needles using bleach is available from health care and addiction professionals and from needle exchanges. In the United States and other western countries, clean needles are available free in some cities, at needle exchanges or safe injection sites.

Mother to child transmisson

About one in four babies born to HIV infected mothers are infected with HIV. Studies have shown that antiretroviral drugs, cesarean delivery and formula feeding reduce the chance of transmission of HIV from mother to child. [12]

When replacement feeding is acceptable, feasible, affordable, sustainable and safe, avoiding breastfeeding by HIV infected mothers is recommended. Otherwise, exclusive breastfeeding is recommended during the first months of life and should be discontinued as soon as possible. [13]

Transmission and infection

 
HIV daughter particles being shed from an infected T cell.

Patterns of HIV transmission vary in different parts of the world. In Africa, which accounts for an estimated 60% of new HIV infections worldwide, controversy rages over the respective contribution of medical procedures, heterosexual sex and the bush meat trade. In the United States, sex between men (35%) and needle sharing by intravenous drug users (15%) remain prominent sources of new HIV infections. [14] In January 2005, Anthony S. Fauci, M.D., director of NIAID said, "Individual risk of acquiring HIV and experiencing rapid disease progression is not uniform within populations". NIH press release Some epidemiological models suggest that over half of HIV transmission occurs in the weeks following primary HIV infection before antibodies to the virus are produced. [15] [16] Investigators have shown that viral loads are highest in semen and blood in the weeks before antibodies develop and estimated that the likelihood of sexual transmission from a given man to a given woman would be increased about 20-fold during Primary HIV infection as compared with the same couple having the same sex act 4 months later. [17] Most people who are infected typically suffer from days to weeks of fever with or without muscle and joint aches, fatigue, headache, sore throat, swollen glands and sometimes rash. This "acute retroviral syndrome" is rarely diagnosed because it is difficult to distinguish from other very common ailments.

CDC reported a cluster of HIV infections in 13 of 42 young women who reported sexual contact with the same HIV infected man in a rural county in upstate New York between February and September 1996 [18]

The risk of oral sex has always been controversial, because most AIDS could be attributed to anal sex or vaginal sex. As the use of condoms became more widespread, there were reports of AIDS acquired by oral sex. [19]

Heterosexual transmission of HIV-1 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. Each 10 fold increment of seminal HIV RNA is associated with an 81% increased rate of HIV transmission. [bmj.bmjjournals.com/cgi/content/full/324/7353/1586] During 2003 in the United States, 19% of new infections were attributed to heterosexual transmission [20]

Genetic susceptibility

File:HIV Viron.png
Diagram of the HIV virus

The Centers for Disease Control in the United States has released findings that genes influence susceptibility to HIV infection and progression to AIDS. HIV enters cells through an interaction with both CD4 and a chemokine receptor of the 7 Tm family. They first reviewed the role of genes in encoding chemokine receptors (CCR5 and CCR2) and chemokines (SDF-1). While CCR5 has multiple variants in its coding region, the deletion of a 32-bp segment results in a nonfunctional receptor, thus preventing HIV entry; two copies of this gene provide strong protection against HIV infection, although the protection is not absolute. This gene is found in up to 20% of Europeans but is rare in Africans and Asians. Multiple studies of HIV-infected persons have shown that presence of one copy of this gene delays progression to AIDS by about 2 years.

Treatment

There is currently no cure or vaccine for HIV or AIDS. Current optimal treatment options consist of combinations ("cocktails") consisting of at least three drugs belonging to at least two types, or "classes," of anti-retroviral agents. Typical regimens consist of two nucleoside analogue reverse transcriptase inhibitors (NRTIs) plus either a protease inhibitor or a non nucleoside reverse transcriptase inhibitor (NNRTI). This treatment is frequently referred to as HAART (highly-active anti-retroviral therapy). [21] Anti-retroviral treatments, along with medications intended to prevent AIDS-related opportunistic infections, have played a part in delaying complications associated with AIDS, reducing the symptoms of HIV infection, and extending patients' life spans. Over the past decade the success of these treatments in prolonging and improving the quality of life for people with AIDS has improved dramatically. [22], [23].

There are several concerns about anti-retroviral regimens. The drugs can have serious side effects. Regimens can be complicated, sometimes requiring patients to take several pills at various times during the day, although most dosing and regimen schedules have been simplified greatly in recent years. If patients miss doses, drug resistance can develop [24]. Anti-retroviral drugs are costly, and the majority of the world's infected individuals do not have access to medications and treatments for HIV and AIDS.

The current guidelines for anti-retroviral therapy from the World Health Organization recommend that anti-retroviral therapy should start when a patient's CD4 count drops below 200/mm3, or an AIDS defining illness is diagnosed. The Department of Health and Human Services (DHHS), the federal agency responsible for overseeing HIV/AIDS healthcare policies in the United States, recommends that anti-retroviral therapy be started when the CD4 cell count is between 200 and 350/mm3. DHHS recommends that doctors should assess the viral load, rapidity in CD4 decline, and patient readiness while deciding when to begin treatment. [25]

Research to improve current treatments includes decreasing side effects of current drugs, simplifying drug regimens to improve adherence, and determining the best sequence of regimens to manage drug resistance.

Alternative medicine

Ever since AIDS entered the public consciousness, various forms of alternative medicine have been used to treat its symptoms. In the first decade of the epidemic when no useful conventional treatment was available, a large number of people with AIDS experimented with alternative therapies (massage, herbal and flower remedies and acupuncture). Interest in these therapies has declined over the past decade as conventional treatments have improved. People with AIDS, like people with other illnesses such as cancer, also sometimes use marijuana to treat pain, combat nausea and stimulate appetite.

Research

Origins of HIV

 
Scanning electron micrograph of HIV-1 budding from cultured lymphocyte. Multiple round bumps on cell surface represent sites of assembly and budding of virions.

Two species of HIV infect humans: HIV-1 and HIV-2. HIV-1 is more virulent and more easily transmitted. HIV-1 is the source of the majority of HIV infections thoughout the world, while HIV-2 is less easily transmitted and is largely confined to West Africa. [26]

Both species of the virus (HIV-1 and HIV-2) are believed to have originated in West-Central Africa and jumped species (zoonosis) from primates to humans. HIV-1 evolved from a Simian Immunodeficiency Virus (SIVcpz) found in the chimpanzee subspecies Pan troglodyte troglodyte. [27] DNA sequencing indicates that HIV-1 (group M) entered the human population in the early 20th century, probably sometime between 1915 and 1941. [28] [29] HIV-2 crossed species from a different strain of SIV, this one found in sooty mangabeys (an Old World monkey) of Guinea-Bissau. [30]

The earliest documented HIV-1 infection dates from 1959, and was discovered in the preserved blood sample of a man from what is now known as Kinshasa in the Democratic Republic of the Congo. [31] In 1969, a 15-year-old African-American male died at the St. Louis City Hospital from aggressive Kaposi's sarcoma. AIDS was suspected as early as 1988, and in 1999, researchers at Tulane University School of Medicine confirmed this, finding HIV-1 in his preserved blood and tissues. [32] [33] [34]

In 1976, a Norwegian sailor, his wife, and his nine-year-old daughter died of AIDS. The sailor had first presented symptoms in 1966, four years after he had spent time in ports along the West African coastline. Tissue samples from the sailor and his wife were tested in 1988 and found to contain the HIV-1 virus (Group O). [35] [36] The next documented western death from AIDS was that of Dr. Grethe Rask in 1977. Rask, a Danish surgeon, had worked in the Congo in the early 1970s.

The official date for the beginning of the AIDS epidemic is marked as June 18, 1981, when the US Center for Disease Control and Prevention reported in its Morbidity and Mortality Weekly Report newsletter that unusual clusters of Pneumocystis carinii pneumonia had been discovered in gay men in Los Angeles in the early 1980s. [37] Over the next eighteen months, more Pneumocystis carinii clusters were discovered among otherwise healthy men in cities throughout the country, along with other opportunistic diseases (such as Kaposi's sarcoma [38] and lymphadenopathy [39]), common in immunosuppressed patients.

The AIDS report of opportunistic infections for gay male intravenous drug users from the 1980s was initially termed 'GRID' (Gay Related Immune Deficiency) [40]. However, the same opportunistic infections also began to be reported among hemophiliacs [41], heterosexual IV drug users, and Haitian immigrants [42]. By September of 1982, the Centers for Disease Control had adopted the more general name of AIDS for the disease. [43]

Some past studies of AIDS in Africa have used a very loose definition that results in the overdiagnosis of AIDS, even when HIV is not present, because this definition avoids expensive tests. This complicates epidemiological comparisons. The controversial OPV AIDS hypothesis raises speculation that the origin of AIDS is due to the oral polio vaccination program that took place in the late 1950s of Africa.

Circumcision

Many studies have explored the suggestion that uncircumcised men may be more vulnerable to HIV infection due to a specific type of cell found in the foreskin tissue. "It will not take very much of an increase in risk behavior to overcome the benefit from circumcision," said Carolyn Williams, an American researcher involved in the Kenya circumcision study. AIDS experts insist that circumcision will have to be accompanied by intensive counseling.

The argument about the exact incidence of HIV transmission per act of intercourse is academic. Infectivity depends critically on social, cultural, and political factors as well as the biological activity of the agent. Whether the epidemic grows or slows depends on infectivity plus two other variables: the duration of infectiousness and the average rate at which susceptible people change sexual partners. [44]

A review and meta-analysis investigating earlier studies of different design claims this reduced risk may have been repeatedly been reported with bias, and concluded that there is no scientific basis for circumcision as a prevention for HIV infection in humans (International Journal of STD & AIDS 1999) [45]. Some critics have claimed that that study inappropriately combines data from differing studies.[46][47] Another review and meta-analysis reported a protective effect of circumcision among adult men in Africa.[48] A 2003 Cochrane review found a strong epidemiological association between male circumcision and prevention of HIV, but recommended waiting for the outcome of randomised controlled trials.[49]

Results of the first randomised controlled trial to investigate the issue were described in the Wall Street Journal[50] on the prevention of HIV transmission claimed that adult men circumcised during the study had a reduced the risk of contracting HIV. Limiting the analysis exclusively to the female-to-male pathway of infection, a reduction of 70 percent was reported. According to the newspaper account, the study in South Africa was stopped by the data and safety monitoring board for ethical concerns. Female-to-male sexual transmission is an uncommon route of HIV infection in the Western world, but is more common in Africa.

The researchers suggested that uncircumcised men may be more vulnerable to HIV infection due to a specific type of cell found in the foreskin tissue, a suggestion supported by other research.[51] Other researchers have suggested that these risks have more to do with hygiene practices, or with the presence of other sexually transmitted infections causing breaks in the skin.[52]

South African medical experts are concerned that the repeated use of unsterilised blades in the ritual circumcision of adolescent boys might be spreading HIV. [53]

Vaccine research

Main article: HIV vaccine

There no vaccine for HIV.

Alternative theories

Main article: AIDS reappraisal

A number of scientists and activists question the connection between HIV and AIDS, or the existence of HIV, or the validity of current testing methods.


References

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