HIV AIDS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [4]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [5]

The first case of AIDS was reported by CDC on June 5, 1981; in 1982, the term AIDS was coined. Although many cases have been identified as AIDS since then, the earliest cases of AIDS can be traced back to 1959 in Congo. A wide variety of theories has been postulated of the possible transmission of AIDS from animals to human like from Cameroon Chimpanzees and Congo Macaques. 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 throughout the world, while HIV-2 is less easily transmitted and is largely confined to West Africa.

AIDS, informally called the gay plague or GRIDS (Gay-related immune deficiency syndrome) was first reported June 5, 1981, when the U.S. Centers for Disease Control and Prevention recorded a clusters of Kaposi’s sarcoma and Pneumocystis pneumonia among gay males in California and New York City.^[1][2] By year-end of 1981, there is a cumulative total of 270 reported cases of severe immune deficiency among gay men, and 121 of those individuals have died. On September 24 1982, the term “AIDS” (acquired immune deficiency syndrome) was introduced by thee CDC, and the first case definition was published: “a disease at least moderately predictive of a defect in cell-mediated immunity, occurring in a person with no known case for diminished resistance to that disease. Soon after, clusters of Kaposi’s sarcoma and Pneumocystis pneumonia were also reported among Haitians recently entering the United States, ^[3] men with haemophilia, female sexual partners of AIDS patients, children born to possibly infected mothers, and among blood transfusion recipients with no obvious risk factors. The term AIDS (for acquired immune deficiency syndrome) was proposed ^[4] by Bruce Voeller, among other researchers, concerned with the accuracy of the disease’s name as the term “gay-related” did not accurately describe the full demographic that the disease affected.

In April 23, 1984, U.S. Department of Health and Human Services Secretary Margaret Heckler announced at a press conference that an American scientist, Dr. Robert Gallo, had discovered the probable cause of AIDS: the retrovirus subsequently named human immunodeficiency virus or HIV in 1986. The virus had previously been discovered by researchers at the Pasteur Institute in France, who called it lymphadenopathy-associated virus. It was given the acronym LAV and was subsequently renamed HIV. Three of the earliest known instances of HIV infection are a plasma sample taken in 1959 from an adult male living in Kinshasa, today part of the Democratic Republic of the Congo,^[5] HIV found in tissue samples from a 15 year old African-American teenager who died in St. Louis in 1969, and HIV found in tissue samples from Arvid Noe, a Norwegian sailor who died around 1976.^[6]

In May 1983, doctors from Dr. Luc Montagnier’s team at the Pasteur Institute in France, reported that they had isolated a new retrovirus from lymphoid ganglions that they believed was the cause of AIDS.^[7] The virus was later named lymphadenopathy-associated virus (LAV) and a sample was sent to the U.S. Centers for Disease Control, which was later passed to the National Cancer Institute (NCI).^{[8] [9]}

In May 1984 a team led by Robert Gallo of the United States confirmed the discovery of the virus, but they renamed it human T lymphotropic virus type III (HTLV-III).^{[10] [11]} The dual discovery led to considerable scientific disagreement, and it was not until President François Mitterrand of France and President Ronald Reagan of the USA met that the major issues were resolved.

In January 1985 a number of more detailed reports were published concerning LAV and HTLV-III, and by March it was clear that the viruses were the same, from the same source, and was the etiological agent of AIDS^{[12] [13]}

In May 1986, the International Committee on Taxonomy of Viruses ruled that both names should be dropped and a new name, HIV (Human Immunodeficiency Virus), be used. ^[14]

The 1985 World Health Organization AIDS surveillance case definition was developed in October 1985, at a conference of public health officials including representatives of the Centers for Disease Control (CDC) and World Health Organization (WHO) in Bangui, Central African Republic. For this reason, it became to be known as the Bangui definition for AIDS. It was developed to provide surveiling case definition of AIDS for use in countries where testing for HIV antibodies was not available.

It stated the following:

Exclusion criteria

1. Pronounced malnutrition
2. Cancer
3. Immunosuppressive treatment

The diagnosis of AIDS is established when the score is 12 or more.

The 1985 WHO AIDS surveillance case definition was heavily criticised, for both medical and political reasons. The 1994 expanded World Health Organization AIDS case definition was introduced in 1994 to incorporate the statement that HIV testing should be done. However, if testing was unavailable, then the Bangui definition should be used.

David Carr (November 1933 – August 31, 1959) was a sailor from Reddish, Manchester. He died at a relatively young age owing to multiple complications that were at the time inexplicable to his doctors at the Manchester Royal Infirmary. In 1990, more than three decades after his death, stored tissue samples from his body were tested positive for HIV. Given the date of his death, he was suspected to have been the first victim of AIDS in the West. The case gained wide coverage when the Sunday Express printed an exposé that revealed Carr’s identity to the public. However, further tests were carried out in the mid-1990s by the eminent American scientist Dr David Ho, who found that Carr’s tissue samples had been contaminated and who thus disproved the earlier AIDS diagnosis. Carr’s case is extensively documented in Edward Hooper’s massive work on the history of AIDS, The River.

The oldest documented case of the then-unknown syndrome was thought to have been detected that same year, when a 25-year-old British sailor who had traveled in the navy between 1955 and 1957 (but apparently not to Africa), sought help at the Royal Infirmary of Manchester, England. He reported to have been suffering from puzzling symptoms, among them purplish skin lesions, for nearly two years. His condition had taken a turn for worse during Christmas 195, when he started suffering from shortness of breath, extreme fatigue, rapid weight loss,night sweats and high fever. The doctors thought he might be suffering from tuberculosis and, even though they found no evidence of bacterial infection, they treated him for tuberculosis just to be safe, to no avail. The sailor continued to weaken and he died shortly after in August 1959. His autopsy revealed evidence of two unusual infections, cytomegalovirus and Pneumocystis carinii pneumonia (PCP, later, when redetermined as P. jirovecii, renamedPneumocystis pneumonia), very rare at the time but now commonly associated with AIDS patients. His case had puzzled his doctors, who preserved tissue samples from him and for years retained some interest in solving the mystery. Sir Robert Platt, then president of the Royal College of Physicians, wrote in the sailor’s hospital chart that he wondered “if we are in for a new wave of virus disease now that the bacterial illnesses are so nearly conquered.” It was only 31 years later, after the AIDS pandemic had become well-known and widespread, that they decided to perform HIV-tests on the preserved tissues of the sailor, which eventually turned out a positive result. The case was reported in the July 7, 1990 issue of the British medical journal The Lancet; their claim was retracted in a letter in the January 20, 1996 issue where they admitted that the tissue sample was contaminated in the laboratory (Corbitt G, Bailey A, Williams G. HIV infection in Manchester, 1959 . Lancet 1990; ii: 51.)

One of the earliest documented HIV-1 infection was discovered in a preserved blood sample taken in 1959 from a man from Leopoldville, Belgian Congo (now Kinshasa, Democratic Republic of the Congo).^[15] However, it is unknown whether this anonymous person ever developed AIDS and died of its complications. ^[5]

Another early case was probably detected that same year, 1959, in a 48-year-old Haitian, who 30 years before had immigrated to the United States and at the time was working as a shipping clerk for a garment manufacturer in Manhattan. He developed similar symptoms to those just described for the British sailor, and died the same year, apparently of the same very rare kind of pneumonia. Many years later, Dr. Gordon R. Hennigar, who had performed this man’s autopsy, was asked whether he thought his patient had died of AIDS; he replied “You bet” and added “It was so unusual at the time. Lord knows how many cases of AIDS have been autopsied that we didn’t even know had AIDS. I think it’s such a strong possibility that I’ve often thought about getting them to send me the tissue samples.”

In 1969, a 15-year-old African-American male known to medicine as Robert R. died at the St. Louis City Hospital from aggressive Kaposi’s sarcoma. AIDS was suspected as early as 1984, and in 1987, researchers at Tulane University School of Medicine confirmed this, finding HIV-1 in his preserved blood and tissues. The doctors who worked on his case at the time suspected he was a prostitute, though the patient did not discuss his sexual history with them in detail.^[16]

In 1976, a Norwegian sailor named Arvid Noe, his wife, and his nine-year-old daughter died of AIDS. The sailor had first presented symptoms in 1969, 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).^{[17][18] [6]}

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.

A variety of theories exist explaining the transfer of HIV to humans, but no single hypothesis is unanimously accepted, and the topic remains controversial.

The most widely accepted theory is so called ‘Hunter’ Theory according to which transference from ape to human most likely occurred when a human was bitten by an ape or was cut while butchering one, and the human became infected.

Researchers announced in May 2006 that HIV most likely originated in wild chimpanzees in the southeastern rain forests of Cameroon (modern East Province) ^{[19] [20]} rather than in Kinshasa, Democratic Republic of Congo (formerly Zaire), as had previously been believed. Seven years of research and 1,300 chimpanzee genetic samples led Dr. Beatrice Hahn of the University of Alabama, Birmingham, to identify chimpanzee communities near Cameroon’s Sanaga River as the most likely originators. Presumably, someone in rural Cameroon was bitten by a chimp or was cut while butchering one and became infected with the ape virus. That person passed it to someone else.

Calculating based on a fixed mutation rate, the jump from chimpanzee to human likely occurred during the French colonial period (1919–1960). Comparative primatologist Jim Moore suggests that this may have been the result of colonial practices of forced labour, which could have suppressed the immune system of the initial hunter enough to allow the virus to infect and take hold. Likewise, forced immunisations (using one needle on many patients) may have sped the virus’s spread through Cameroon and beyond.

The Times published an article in 1987 stating that WHO suspected some kind of connection with its vaccine program and AIDS-epidemic. The story was almost entirely based on statements given by one unnamed WHO advisor. The theory was supported only by weak circumstantial evidence and is now disproven by unraveling the genetic code of the virus and finding out that the virus dates back to the 1930s.

Freelance journalist Tom Curtis discussed one controversial possibility for the origin of HIV/AIDS in a 1992 Rolling Stone magazine article. He put forward what is now known as the OPV AIDS hypothesis, which suggests that AIDS was inadvertently caused in the late 1950s in the Belgian Congo by Hilary Koprowski‘s research into a polio vaccine.

Although subsequently retracted due to libel issues surrounding its claims, the Rolling Stone article motivated another freelance journalist, Edward Hooper, to probe more deeply into this subject. Hooper’s research resulted in his publishing a 1999 book, The River, in which he alleged that an experimental oral polio vaccineprepared using chimpanzee kidney tissue was the route through which simian immunodeficiency virus (SIV) crossed into humans to become HIV, thus starting the human AIDS pandemic.^[21]

This theory is contradicted by an analysis of genetic mutation in primate lentivirus strains that estimates the origin of the HIV-1 strain to be around 1930, with 95% certainty of it lying between 1910 and 1950.^[22]

In February 2000 one of the original developers of the polio vaccine, Philadelphia based Wistar Institute found from its stores a vial of the original vaccine used in the vaccination program. It was analyzed in April 2001 and no traces of either HIV-1 or SIV were found in the sample.^[23] A second analysis showed that only macaque monkey kidney cells, which cannot be infected with SIV or HIV, were used to produce the vaccine.^[24] While the analysis was done on only one vial of vaccine, some scientists have concluded that the polio vaccine theory of the origins of HIV is not possible.

However the sample tested was never used in the Congo nor was it ever claimed by Hooper that the original vaccines were contaminated, the OPV hypothesis claims instead that HIV was introduced in the Congo at the Stanlyvile laboratory as the local administers amplified the original vaccine using infected Chimp kidneys (local amplification was widely practiced at the time) for the 1 million to whom it was forcefully administered. As such there is no hard evidence to dismiss the OPV hypothesis.

Edward Hooper rejects the dates calculated using a fixed mutation rate on the basis that phylogenetic dating of “the most recombinogenic organisms known to medical science”, immunodeficiency viruses, is “inherently incapable of making any allowance for recombination.”^[25][21]

The Durban declaration was a statement signed by over 5,000 physicians and scientists at the 2000 International AIDS Conference in Durban, South Africa, affirming that HIV is the cause of AIDS. The declaration was drafted in response to statements by South Africa president Thabo Mbeki, who questioned the link between HIV and AIDS. At the Durban conference, 5,000 scientists from all over the world, including eleven Nobel prize winners, signed a statement calling the evidence that HIV causes AIDS “clear-cut, exhaustive and unambiguous.”^[26]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Many definitions have been developed for epidemiological surveillance of HIV/AIDS such as the Bangui definition and the 1994 Expanded World Health Organization AIDS Case Definition. However, these systems are neither sensitive nor specific for clinical staging. In developing countries, the World Health Organization staging system for HIV infection and disease that uses clinical and laboratory data is widely employed. The Centers for Disease Control (CDC) Classification System for HIV/AIDS is another primary system used that is primarily based on CD4 T-lymphocyte counts.

The table below shows the HIV infection stage, based on age-specific CD4+ T-lymphocyte count or CD4+ T-lymphocyte percentage of total lymphocytes. ^[2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ujjwal Rastogi, MBBS, Ammu Susheela, M.D. [2]

Acute HIV infection may be asymptomatic or may cause a mononucleosis-like syndrome. It should be differentiated from similar diseases that cause fever, fatigue, sore throat, myalgia, and lymphadenopathy such as acute toxoplasmosis, acute CMV/EBV infections, and acute viral hepatitis. On the other hand, AIDS should be considered in all patients presenting with symptoms of immunodeficiency or opportunistic infections. It should be distinguished from various medical states that cause immunosuppression including common variable immune deficiency (CVID), chemotherapy treatment, steroid therapy, and severe malnutrition.^[1]

The table shown bellow describes the most common conditions that should be differentiated from AIDS as they all cause immunodeficiency and patients with those diseases are prone to opportunistic infections.

AIDS must be differentiated from other causes of rash and arthritis^[5][6][7]

AIDS should be differentiated from other conditions presenting with fever, fatigue, weight loss, arthralgia, myalgia, rash and soft tissue swelling. The differentials include the following:^{[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]}

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2]Ammu Susheela, M.D. [3]

HIV is a global pandemic. In 2013, an estimated 35 million people were living with the disease worldwide. An estimated 39 million people have died from AIDS or AIDS-related causes, including and approximate 1.5 million patients in 2013 alone. Over three-fourths of these deaths are confined to Sub-Saharan Africa. Owing to the development and success of ART over the past 25 years, the population of individuals with HIV infection is aging. Despite advances in antiretroviral therapy (ART) and reduction of both the mortality and the morbidity of HIV infection with regular use of these agents, routine access to ART is not available in all countries.^[1] At the end of 2013, 11.7 million people were receiving ART in low- and middle-income countries representing 36% of people living with HIV in these countries. In 2015,the number of new HIV cases in New York City fell below 2,500 for the first time since the beginning of the AIDS epidemic in 1981.

• HIV/AIDS was first reported in the early 1980s.^[2]
• In 2005, approximately 5 million people were newly infected with HIV and approximately 3 million people with AIDS died, an increase from 2004 and the highest number since 1981 (UNAIDS, 2005).
• Between 2011 and 2017, among patients receiving standard ART regimens, the difference in the incidence of death at 5 years after diagnosis between patients receiving ART and age-matched controls was just 2.7%.^[3]
• In 2013, approximately 6000 new individuals were infected with HIV every day . ^[4]
• In 2014, approximately 37,600 Americans became newly infected with HIV.
• In 2015, an estimated 44% of new infections occurred among key populations and their partners.
• Between 2000 and 2016, new HIV infections fell by 39% due to the antiretroviral therapy.
• In 2016, approximately 36.7 million people were found to be infected with HIV and among them 1.8 million people were newly infected with HIV.
• In 2018, approximately 38,000 new HIV cases were detected in the United States.
• Between 2014 and 2018, the incidence of HIV cases in adolescents and adults decreased by only 7%.^[5]

• More than 1.1 million people in the U.S. are living with HIV today, and 1 in 7 of them do not know it.

In 2013, the prevalence estimates were as follows:

• Total = 35 million
• Adults = 31.8 million
• Women = 16 million
• Children (<15 years) = 3.2 million

• Globally, an estimated 2.5 million children are living with HIV. An estimated 400,000 children are infected yearly.^[6]

^[6]

The following table demonstrates the estimated number of AIDS diagnoses in the United States in 2011 distributed by age at time of diagnosis:

• Owing to the development and success of ART over the past 25 years, the population of individuals with HIV infection is aging.
• For example, in the United States, more than half of the patients receiving care for HIV infection are older than 50 years of age and 18% are older than 60 years.^[7]

In the United States, males are more commonly affected than females. This may be related to the higher prevalence of HIV in homosexual men.

• The most common method of transmission is sexual contact.
• Unprotected male-to-male sexual contact is the major factor, followed by unprotected male-to-female sexual contact.
• In the United States, one out of seven individuals with HIV infection is unaware of having the infection. The HIV transmission from them represents at least one third of new infections each year.

• HIV type 1 (HIV-1) is the most common and predominant type in the United states; however, HIV type 2 (HIV-2) is endemic in other countries (e.g., West Africa).^[8]
• In the United States, HIV is most common among African-American males and females from Native Hawaiian, Hispanic, and Latin origin.

• UNAIDS and the WHO estimate that AIDS has killed more than 25 million people since it was first recognized in 1981, making it one of the most destructive epidemics in recorded history.
• The total number of deaths attributable to HIV/AIDS in 2013 according to the WHO:
  • Total = 1.5 million
  • Adults = 1.3 million
  • Children (>15 years) = 190,000

• In 2016, 1.0 million people died from HIV-related causes globally.
• HIV is a major global public health issue and has claimed more than 35 million lives so far.
• Between 2000 and 2016, HIV-related deaths fell by one third with 13.1 million lives saved due to ART.

• The number of patients receiving antiretroviral therapy has been on the rise since the introduction of these agents.
• In 2013, approximately 12.5 million individuals were receiving antiretroviral therapy.
• Between 2000 and 2016, new HIV infections fell by 39% due to the antiretroviral therapy.
• Between 2000 and 2016, HIV-related deaths fell by one third with 13.1 million lives saved due to ART.
• Global ART coverage for pregnant and breastfeeding women living with HIV is high at 76%.
• In 2016, almost 8 out of 10 pregnant women living with HIV, or 1.1 million women, received antiretrovirals (ARVs).
• In mid-2017, 20.9 million people living with HIV were receiving antiretroviral therapy globally.
• 54% of adults living with HIV are currently receiving lifelong antiretroviral therapy (ART).
• 43% of children living with HIV are currently receiving lifelong antiretroviral therapy (ART).

• Sub-Saharan Africa remains by far the worst affected region, with an estimated 23.8 to 28.9 million people currently living with HIV. More than 60% of all people living with HIV are in Sub-Saharan Africa, as are more than three quarters (76%) of all women living with HIV.

• In 2007, Sub-Saharan Africa accounted for 76% of all AIDS deaths and approximately 35% of all new infections worldwide. 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.^[6] South Africa has the largest population of HIV patients in the world, followed by Nigeria and India.^[9] South & South East Asia are the second worst affected regions; in 2007, an estimated 18% of all people living with AIDS, and an estimated 300,000 deaths from AIDS were attributable to these regions.^[6] The estimated adult prevalence of AIDS in India is approximately 0.36%.^[6] 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.^[10]

• This strategy has been adopted by the United States since 2019
• The target is reduction of the number of new HIV infections by 75% by 2025 and by 90% by 2030.
• It includes 4 elements:
  • Early identification of all cases of HIV infection
  • Successful treatment with ART
  • Prevention of new infections
  • Rapid response to outbreaks

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2] ; Alejandro Lemor, M.D. [3]

The majority of HIV infections are acquired through unprotected sexual intercourse. The exposures with the highest risk of contracting disease include contaminated blood transfusions, childbirth, needle sharing, and receptive anal intercourse. Needle sharing is the cause of one third of all new HIV-infections. Infectivity varies along the course of the disease and is closely associated with the HIV viral load.

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.^[9][10][11] Sexual transmission occurs with the contact between sexual secretions of one partner with the rectal, genital or oral mucous membranes of another. Unprotected receptive sexual acts are riskier than unprotected insertive sexual acts, with the risk for transmitting HIV from an infected partner to an uninfected partner through unprotected anal intercourse greater than the risk for transmission through vaginal intercourse or oral sex. Oral sex is not without its risks as HIV is transmissible through both insertive and receptive oral sex.^[12] The risk of HIV transmission from exposure to saliva is considerably smaller than the risk from exposure to semen; contrary to popular belief, one would have to swallow liters of saliva from a carrier to run a significant risk of becoming infected.^[13]

Approximately 30% of women in ten countries representing “diverse cultural, geographical and urban/rural settings” report that their first sexual experience was forced or coerced, making sexual violence a key driver of the HIV/AIDS pandemic.^[14] Sexual assault greatly increases the risk of HIV transmission as protection is rarely employed and physical trauma to the vaginal cavity frequently occurs which facilitates the transmission of HIV.^[15]

• 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 have suggested that there is approximately a four times greater risk of becoming infected with HIV in the presence of a genital ulcer such as those caused by syphilis and/or chancroid. There is also a significant though lesser increased risk in the presence of STIs such as gonorrhea, Chlamydial infection and trichomoniasis which cause local accumulations of lymphocytes and macrophages.^[16]

• 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. Each 10-fold increment of blood plasma HIV RNA is associated with an 81% increased rate of HIV transmission.^[16][17]
• 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.^[18][19]
• People who are infected with HIV can still be infected by other, more virulent strains.

• During a sexual act, only male or female condoms can reduce the chances of infection with HIV and other STDs and the chances of becoming pregnant. 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.^[20]
• The effective use of condoms and screening of blood transfusion in North America, Western and Central Europe is credited with contributing to the low rates of AIDS in these regions. Promoting condom use, however, has often proved controversial and difficult. Many religious groups, most noticeably the Roman Catholic Church, have opposed the use of condoms on religious grounds, and have sometimes seen condom promotion as an affront to the promotion of marriage, monogamy and sexual morality. Defenders of the Catholic Church’s role in AIDS and general STD prevention state that, while they may be against the use of contraception, they are strong advocates of abstinence outside marriage.^[21] This attitude is also found among some health care providers and policy makers in sub-Saharan African nations, where HIV and AIDS prevalence is extremely high.^[22]
• They also believe that the distribution and promotion of condoms is tantamount to promoting sex amongst the youth and sending the wrong message to uninfected individuals. However, no evidence has been produced that promotion of condom use increases sexual promiscuity,^[23] and abstinence-only programs have been unsuccessful in the United States both in changing sexual behavior and in reducing HIV transmission.^[24]
• Evaluations of several abstinence-only programs in the US showed a negative impact on the willingness of youths to use contraceptives, due to the emphasis on contraceptives’ failure rates.^[25]
• 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 necessary, manufacturers recommend using water-based lubricants. Oil-based lubricants can however be used with polyurethane condoms.^[26]
• Latex condoms degrade over time, making them porous, which is why condoms have expiration dates. In Europe and the United States, condoms have to conform to European (EC 600) or American (D3492) standards to be considered protective against HIV transmission.

• The female condom is an alternative to the male condom and is made from polyurethane, which allows it to be used in the presence of oil-based lubricants. They are larger than male condoms and have a stiffened ring-shaped opening, and are designed to be inserted into the vagina. The female condom contains an inner ring, which keeps the condom in place inside the vagina – inserting the female condom requires squeezing this ring. However, at present availability of female condoms is very low and the price remains prohibitive for many women. Preliminary studies suggest that, where female condoms are available, overall protected sexual acts increase relative to unprotected sexual acts, making them an important HIV prevention strategy.^[27]

• With consistent and correct use of condoms, there is a very low risk of HIV infection. 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.^[28]

• In December 2006, the last of three large, randomized trials confirmed that male circumcision lowers the risk of HIV infection among heterosexual African men by around 50%. It is expected that this intervention will be actively promoted in many of the countries worst affected by HIV, although doing so will involve confronting a number of practical, cultural and attitudinal issues. 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.^[29]
• Furthermore, South African medical experts are concerned that the repeated use of unsterilized blades in the ritual circumcision of adolescent boys may be spreading HIV.^[30]

• Prevention strategies are well-known in developed countries, however, recent epidemiological and behavioral studies in Europe and North America have suggested that a substantial minority of young people continue to engage in high-risk practices and that despite HIV/AIDS knowledge, young people underestimate their own risk of becoming infected with HIV.^[31]

• Needle sharing is the cause of one third of all new HIV-infections and 50% of hepatitis C 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 that small risk.^[32]
• Health care workers (nurses, laboratory workers, doctors etc) are also concerned, although more rarely. This route can 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.^[33]
• Because of this, the United Nations General Assembly, supported by universal medical opinion on the matter, has urged the nations of the world to implement universal precautions to prevent HIV transmission in health care settings.^[34]
• Drug abuse has an additional effect of an increased tendency to engage in unprotected sexual intercourse.^[35]

• 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 HIV infections worldwide are transmitted through the transfusion of infected blood and blood products”.^[36]

• 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 by HIV.

• All AIDS-prevention organizations advise drug-users not to share needles and other material required to prepare and take drugs (including syringes, cotton balls, the spoons, water for diluting the drug, straws, crack pipes, etc). It is important that people use new or properly sterilized needles for each injection. Information on cleaning needles using bleach is available from health care and addiction professionals and from needle exchanges. In some developed countries, clean needles are available free in some cities, at needle exchanges or safe injection sites. Additionally, many nations have decriminalized needle possession and made it possible to buy injection equipment from pharmacists without a prescription.

• Transmission of HIV between intravenous drug users has clearly decreased, and HIV transmission by blood transfusion has become quite rare in developed countries.

• In the absence of treatment, the transmission rate between the mother to the child during pregnancy, labor and delivery is 25%. However, when the mother has access to antiretroviral therapy and gives birth by caesarean section, the rate of transmission is just 1%.^[3] A number of factors influence the risk of infection, particularly the viral load of the mother at birth (the higher the viral load, the higher the risk). Breastfeeding increases the risk of transmission by 4.04%.^[37]
• This risk depends on clinical factors and may vary according to the pattern and duration of breast-feeding.^[37]

• Studies have shown that antiretroviral drugs, caesarean delivery and formula feeding reduce the chance of transmission of HIV from mother to child.^[38]
• 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.^[39] In 2005, around 700,000 children under 15 contracted HIV, mainly through MTCT, with 630,000 of these infections occurring in Africa.^[40] Of the children currently living with HIV, almost 90% live in sub-Saharan Africa.

• In Africa, the number of MTCT and the prevalence of AIDS is beginning to reverse decades of steady progress in child survival.^[41]
• Countries such as Uganda are attempting to curb the MTCT epidemic by offering VCT (voluntary counseling and testing), PMTCT (prevention of mother-to-child transmission) and ANC (ante-natal care) services, which include the distribution of antiretroviral therapy.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-in-Chief: Ujjwal Rastogi, MBBS ; Ammu Susheela, M.D. [2]

The major determinant of the morbidity and mortality of HIV infections is adequate antiretroviral therapy. For that reason, early detection is essential in improving outcomes.^[1] In 2006, the Centers for Disease Control announced an initiative for voluntary, routine testing of all Americans aged 13–64 during health care encounters. An estimated 25% of infected individuals were unaware of their status.^[2] Routine prenatal HIV testing was also recommended for all women as part of their normal gestational screening tests.

• According to the U.S. guidelines, all sexually active individuals have to be tested at least once for HIV at ages 15–65 years.^[3]
• Recommended for all persons seeking STI evaluation who are not already known to have HIV infection at the time of the STI evaluation.^[4]
• At least annual testing is recommended for those with an ongoing high risk of infection (sexual partners of individuals with sexually transmitted infections, individuals with more than one sexual partner since their most recent HIV test, injection-drug users, and individuals who exchange sex for drugs or money).^[5]
• Providers should assess eligibility of all persons seeking STI services for HIV PrEP and PEP. For persons with substantial risk whose results are HIV negative, providers should offer or provide referral for PrEP services, unless the last potential HIV exposure occurred <72 hours, in which case PEP might be indicated.^[4]

• People who are infected with HIV but not aware of it are not able to take advantage of the therapies that can keep them healthy and extend their lives, nor do they have the knowledge to protect their sex or drug-use partners from becoming infected. Knowing whether one is positive or negative for HIV confers great benefits in healthy decision making.
• Cohort studies have demonstrated that many infected persons decrease behaviors that help transmit infection to sex or needle-sharing partners once they are aware of their positive HIV status.^[6][7][8]
• HIV-infected persons who are unaware of their infection do not reduce risk behaviors.^[9][10][11]
• Persons tested for HIV who do not return for test results might even increase their risk for transmitting HIV to partners.^[12]
• Early referral to medical care could prevent HIV transmission in communities while reducing a person’s risk for HIV-related illness and death, because medical treatment that lowers HIV viral load might also reduce risk for transmission to others.^[13]
• Several patients with undiagnosed HIV infection had multiple health care visits before getting an HIV test.^[14]
• Approximately 38% of new HIV cases are transmitted by individuals with undiagnosed HIV infection.^[15]
• HIV infection is consistent with all generally accepted criteria that justify screening:

1. HIV infection is a serious health disorder that can be diagnosed before symptoms develop.
2. HIV can be detected by reliable, inexpensive, and noninvasive screening tests.
3. Infected patients have years of life to gain if treatment is initiated early, before symptoms develop.
4. The costs of screening are reasonable in relation to the anticipated benefits.^[16] Among pregnant women, screening has proven substantially more effective than risk-based testing for detecting unsuspected maternal HIV infection and preventing perinatal transmission.^[17][18][19]

• The use of “opt-out” testing (i.e., all adults are informed that an HIV test could be done; however, they can opt out if they want) has been shown to be more reliable in detection of HIV cases and cost-effective.^[20][21][22]

• Sexually active gay, bisexual, and other men who have sex with men, should be screened for HIV at least annually.^[4]

HIV can be transmitted to a person receiving blood or organs from an infected donor. To reduce this risk, blood banks and organ donor programs screen donors, blood, and tissues thoroughly. People who received blood transfusions or clotting products between 1977 and 1985 (before screening for the virus became standard practice) are at highest risk for getting HIV. Basic screening lab tests and regular cervical Pap smears are important to monitor in HIV infection, due to the increased risk of cervical cancer in women with a compromised immune system. Tests selected to screen donor blood and tissue must provide a high degree of confidence that HIV will be detected if present (that is, a high sensitivity is required). A combination of antibody, antigen and nucleic acid tests are used by blood banks in Western countries. The World Health Organization estimated that, inadequate blood screening had resulted in 1 million new HIV infections worldwide. In the USA, since 1985, all blood donations are screened with an ELISA test for HIV-1 and HIV-2, as well as a nucleic acid test. These diagnostic tests are combined with careful donor selection. The risk of transfusion-acquired HIV in the U.S. was approximately one in 2.5 million for each transfusion.^[23]

• Public health services (PHS) recommends that all pregnant women in the United States be tested for HIV infection. All health-care providers should recommend HIV testing to all of their pregnant patients, pointing out the substantial benefit of knowledge of HIV status for the health of women and their infants. HIV screening should be a routine part of prenatal care for all women.
• A second test during the third trimester, preferably at <36 weeks’ gestation, should be considered and is recommended for women who are at high risk.^[4]
• HIV testing should be voluntary and free of coercion. Informed consent before HIV testing is essential. Information regarding consent can be presented orally or in writing and should use language the client understands. Accepting or refusing testing must not have detrimental consequences to the quality of prenatal care offered. Documentation of informed consent should be in writing, preferably with the client’s signature. State or local laws and regulations governing HIV testing should be followed. HIV testing should be presented universally as part of routine services to pregnant women, and confidential informed consent should be maintained.
• Although HIV testing is recommended, women should be allowed to refuse testing. Women should not be tested without their knowledge.
• Women who refuse testing should not be coerced into testing, denied care for themselves or their infants, or threatened with loss of custody of their infants or other negative consequences.
• Discussing and addressing reasons for refusal (e.g., lack of awareness of risk or fear of the disease, partner violence, potential stigma, or discrimination) could promote health education and trust-building and allow some women to accept testing at a later date.
• Women who refuse testing because of a previous history of a negative HIV test should be informed of the importance of retesting during pregnancy. All logistical reasons for not testing (e.g., scheduling) should be addressed as well. Health-care providers should remember that some women who initially refuse testing might accept at a later date, particularly if their concerns are discussed.
• Some women who refuse confidential testing might be willing to obtain anonymous testing. However, they should be informed that if they choose anonymous testing, no documentation of the results will be recorded in the medical chart, and their providers might have to retest them, potentially delaying provision of antiretroviral drugs for therapy or perinatal prophylaxis. Some women will continue to refuse testing, and their decisions should be respected.
• Before HIV testing, health-care providers should provide the following minimum information. Although a face-to-face counseling session is ideal, other methods can be used (e.g., brochure, pamphlet, or video) if they are culturally and linguistically appropriate.
  • HIV is the virus that causes AIDS. HIV is spread through unprotected sexual contact and injection-drug use. Approximately 25% of HIV-infected pregnant women who are not treated during pregnancy can transmit HIV to their infants during pregnancy, during labor and delivery, or through breast feeding.
  • A woman might be at risk for HIV infection and not know it, even if she has had only one sex partner.
  • Effective interventions (e.g., highly active combination antiretrovirals) for HIV-infected pregnant women can protect their infants from acquiring HIV and can prolong the survival and improve the health of these mothers and their children.
  • For these reasons, HIV testing is recommended for all pregnant women.
  • Services are available to help women reduce their risk for HIV and to provide medical care and other assistance to those who are infected.
  • Women who decline testing will not be denied care for themselves or their infants.
• Health-care providers should perform HIV testing in consenting women as early as possible during pregnancy to promote informed and timely therapeutic decisions. Retesting in the third trimester, preferably before 36 weeks of gestation, is recommended for women known to be at high risk for acquiring HIV (e.g., those who have a history of sexually transmitted diseases [STDs], who exchange sex for money or drugs, who have multiple sex partners during pregnancy, who use illicit drugs, who have sex partner[s] known to be HIV-positive or at high risk, and who have signs and symptoms of seroconversion). Routine universal retesting in the third trimester may be considered in health-care facilities with high HIV seroprevalence among women of childbearing age. Retesting for syphilis during the third trimester and again at delivery also is recommended for pregnant women at high risk. [4]
• Some states mandate syphilis screening at delivery for all pregnant women.
• Women admitted for labor and delivery with unknown or undocumented HIV status should be assessed promptly for HIV infection to allow for timely prophylactic treatment. Expedited testing by either rapid return of results from standard testing or use of rapid testing (with confirmation by a second licensed test when available) is recommended for these women. The goal is to identify HIV-infected women or their infants as soon as possible because the efficacy of prophylactic therapy is greatest if given during or as soon after exposure as possible (i.e., within 12 hours of birth). Informed consent is essential for women tested prenatally, and women in labor with unknown status should be allowed to refuse testing without undue consequences. After delivery, standard confirmatory testing should be done for women with positive rapid test results.

• Regulations, laws, and policies regarding HIV screening of pregnant women and infants are not standardized throughout all states and U.S. territories. Health-care providers should be familiar with and adhere to state/local laws, regulations, and policies concerning HIV screening of pregnant women and infants.
• Routine prenatal HIV testing with streamlined counseling and consent procedures has increased the number of pregnant women tested substantially.

Per the United States Preventive Services Task Force (USPSTF)^[24][25]:

• “Current CDC guidelines recommend testing for HIV infection with an antigen/antibody immunoassay approved by the US Food and Drug Administration that detects HIV-1 and HIV-2 antibodies and the HIV-1 p24 antigen, with supplemental testing following a reactive assay to differentiate between HIV-1 and HIV-2 antibodies. If supplemental testing for HIV-1/HIV-2 antibodies is nonreactive or indeterminate (or if acute HIV infection or recent exposure is suspected or reported), an HIV-1 nucleic acid test is recommended to differentiate acute HIV-1 infection from a false-positive test result.”

The UNAIDS/WHO policy statement on HIV Testing states that conditions under which people undergo HIV testing must be anchored in a human rights approach that pays due respect to ethical principles.^[26] According to these principles, the conduct of HIV testing of individuals must be

• Confidential.
• Accompanied by counseling (for those who test positive).
• Conducted with the informed consent of the person being tested.

Considerable controversy exists over the ethical obligations of health care providers to inform the sexual partners of individuals infected with HIV that they are at risk of contracting the virus.^[27] Some legal jurisdictions permit such disclosure, while others do not. More state funded testing sites are now using confidential forms of testing. This allows for monitoring of infected individuals easily, compared to anonymous testing that has a number attached to the positive test results. Controversy exists over privacy issues.

In developing countries, home-based HIV testing and counseling (HBHTC) is an emerging approach for addressing confidentiality issues. HBHTC allows individuals, couples, and families to learn their HIV status in the convenience and privacy of their home environment. Rapid HIV tests are most often used, so results are available for the client between 15 and 30 minutes. Furthermore, when an HIV positive result is communicated, the HTC provider can offer appropriate linkages for prevention, care, and treatment.

Testing that has only a number attached to the specimen that will be delivered for testing. Items that are confirmed positive will not have the HIV infected individual’s name attached to the specimen. Sites that offer this service advertise this testing option.

• Specific testing includes syphilis serology and NAAT for N. gonorrhoeae and C. trachomatis at the anatomic site of exposure.^[4]
• Women should also be screened for trichomoniasis at the initial visit and annually thereafter.^[4]
• Women should be screened for cervical cancer precursor lesions per existing guidelines.^[4]

• History taking
• Physical examination
• Screening test for HIV antibody and antigen,
• Measurement of HIV RNA (viral load), CD4 count, and assessment of HIV resistance genotype if ART initiated at time and place of diagnosis or if acute HIV seroconversion suspected
• Liver and kidney function tests
• Complete blood count (CBC) with differential
• Initiation of prophylaxis against Pneumocystis jiroveci pneumonia, if P. jiroveci pneumonia clinically suspected

• History taking
• Physical examination
• Measurement of HIV RNA (viral load), CD4 count, and assessment of HIV resistance genotype are not needed if ART initiated at time and place of diagnosis
• Assessment of resistance to ART
• Liver and kidney function tests
• Complete blood count (CBC) with differential
• Serum lipid profile
• Urinanalysis
• HBV and HCV serologic tests
• Pregnancy test if the woman in the childbearing age
• Prophylaxis against Pneumocystis jiroveci pneumonia when CD4 count is <200 cells/mm3
• Cryptococcal antigen screening if CD4 counts <100 cells/mm3
• Urine test for histoplasmosis antigen if CD4 count <100 cells/mm3 in areas where histoplasmosis endemic
• Screening for sexually transmitted infection
• Testing for HLA-B*5701 before prescribing abacavir
• Tropism assay (CCR5) before prescribing maraviroc
• Assessment of psychosocial factors (substance abuse, alcohol abuse, depression, anxiety, suicidality, housing, food insecurity, domestic violence)
• Counseling on the effects of an HIV diagnosis, the value of disclosure of the patient’s HIV infection status to some trusted friends or relatives for support and their sexual partners
• Counseling on the different ways of prevention of transmission to others such as the consistent use of condoms during sexual activity and avoidance of sharing needles with others

• History taking
• Physical examination
• Measurement of HIV RNA (viral load)
• CD4 count every 6 months until HIV RNA sustained (<100 copies/ml) for 1 year and CD4 >250 cells/mm3; then no longer check is needed
• Liver and kidney function tests
• Complete blood count (CBC) with differential
• Serum lipid profile
• Urinanalysis
• HBV or HCV if any unexplained increase in serum AST or ALT level or annually in patients who remain at high risk for infection or reinfection (high-risk sexual exposure or ongoing injection drug use).
• Pregnancy test if the woman in the childbearing age
• Screening for sexually transmitted infection
• Annual evaluation for cervical cancer/anal cancer with pap smears, if available or at least digital rectal examination (DRE)
• Assessment of psychosocial factors (medication adherence, substance abuse, alcohol abuse, depression, anxiety, suicidality, housing, food insecurity, domestic violence, social isolation, polypharmacy)

• Assessment of cognitive function in patients older than 60 year of age or as indicated clinically, every 2 years

• History taking
• Physical examination
• Measurement of HIV RNA (viral load), CD4 count, and assessment of HIV resistance genotype at time of confirmed virologic failure (detectable viremia)
• Assessment of resistance to ART at time of confirmed virologic failure (detectable viremia)
• Liver and kidney function tests
• Complete blood count (CBC) with differential
• Initiation of prophylaxis against Pneumocystis jiroveci pneumonia in case of virologic failure
• Cryptococcal antigen screening, each year
• Assessment for medication adherence
  

• It is recommended that follow-up visits should be scheduled 4 to 6 weeks after the initiation of ART and then every 3 months until virologic suppression is reached.

• After maintaining the virologic suppression for a year, follow-up visits should be scheduled every 6 months.^[28]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2] ; Alejandro Lemor, M.D. [3]

There is currently no cure for HIV/AIDS. HIV infection leads to progressive decline in CD4+ T-lymphocyte count increasing the risk for opportunistic infections and malignancies. Despite having a variable rate of progression determined by specific host and viral factors, the median time from infection to the development of AIDS ranges from 8 to 10 years among untreated individuals.^[1] With the advent of highly active antiretroviral therapy (HAART), both morbidity and mortality have dramatically decreased. Survival and the rate of CD4-count recovery is influenced by age, baseline CD4 cell count, baseline viral load and initial and sustained viral suppression.^[2] In areas where HAART 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 near normal (assuming full compliance to HAART).^[3] HIV infection makes individuals highly susceptible to severe opportunistic infections and neoplastic disease. Major complications of HIV/AIDS include Pneumocystis jirovecii pneumonia, disseminated Mycobacterium avium complex infection, cryptococcal meningitis, cytomegalovirus retinitis, Kaposi sarcoma, and primary CNS lymphoma.

In the early days of the HIV epidemic, knowledge about the natural history of HIV accrued rapidly. However, the widespread use of effective antiretroviral therapy (ART) brought a shift in focus of the research community away from studies of natural history to those of treated infection.^[4] HIV infection leads to progressive decline in CD4+ T-lymphocyte count increasing the risk for opportunistic infections and malignancies. Despite having a variable rate of progression determined by specific host and viral factors, the median time from infection to the development of AIDS ranges from 8 to 10 years among untreated individuals.^[1] With the advent of highly active antiretroviral therapy (HAART), both morbidity and mortality have dramatically decreased. Survival and the rate of CD4-count recovery is influenced by age, baseline CD4 cell count, baseline viral load and initial and sustained viral suppression.^[2]

Approximately half of patients that acquire HIV develop a mononucleosis-like syndrome within 3-6 weeks during which the viral titers are very elevated. Common symptoms include acute but brief and nonspecific influenza-like retroviral syndrome that can include fever, malaise, lymphadenopathy, pharyngitis, arthritis, or skin rash.^[5] This causes a rapid drop in CD4 T-Cell count as these cells are the primary host for viral replication. Within several weeks patients mount a strong immune response to the virus that causes a drop in the viral titers. However, this response is not adequate to completely suppress viral replication. Although viremia may become undetectable, replication persists in the lymphoid organs. Although a significant number of patients do not have an acute HIV syndrome, these processes do occur albeit without symptoms.^[6]

This period is sometimes called asymptomatic HIV infection or chronic HIV infection. After the initial phase, the majority of patients with HIV develop a clinical latency period that lasts several years. During this period, all patients have a progressive decline in immune status and gradual depletion of CD4 T-cells. This period does not represent a true microbiological or pathological latency, but rather defines a time period without clinically manifest disease. People who are on highly active antiretroviral therapy (HAART) may live with clinical latency for several decades.^[6]

The eventual outcome of most HIV infections is gradual immune system deterioration resulting in AIDS. Clinically apparent disease is classically diagnosed following an AIDS-defining illness i.e. an opportunistic infection or neoplasm that demonstrates a significant compromise of the immune system. Another diagnostic sign, although not strictly clinical, is the decline of CD4 T-cell count below 200 cells/mm³. Without treatment, individuals diagnosed with AIDS may survive approximately 1-3 years.^[6]

The natural course of untreated HIV infection varies widely. The past decade has seen considerable interest in the identification of subgroups of HIV-positive persons who exhibit distinct patterns of disease progression:^[4]

• Long-term nonprogressors (LTNP) are individuals who remain asymptomatic for a prolonged period of time off ART with a high CD4 cell count. Although it is widely reported that 1–5% of the HIV-positive population are LTNP, these estimates are complicated by the fact that there is no standardized definition of a LTNP, and thus definitions used (and the way in which they are applied, particularly in the presence of varying follow-up and irregularly measured CD4 cell counts) differ widely. LTNP status can be lost, and thus the reported prevalence of LTNP within a study will depend on the required period of follow-up. Predictors of loss of LTNP status are a high baseline HIV DNA level and a more rapid increase in HIV DNA over the first year of follow-up, suggesting the presence of ongoing (but low-grade) viral replication. Indeed, HIV RNA levels in plasma increased by 0.04 log10 copies/ml per year over the first 8 years after diagnosis. As such, it is likely that virtually all HIV-positive persons will eventually experience disease progression if left untreated.^[4]

• Elite controllers or viral controllers are individuals who are able to suppress HIV replication to such an extent that viral load levels remain undetectable in the absence of ART. As with LTNP, several studies have attempted to identify factors associated with elite controller status. Loss of naive CD4 T cells seems to be a universal feature of elite controllers, despite the ability of such individuals to maintain undetectable viral loads. However, CD4 naive lymphocytes from elite controllers tend to be less susceptible to HIV infection than such lymphocytes from progressors or uninfected individuals. This specific feature was linked with upregulation of a cellular kinase (p21). HIV-specific CD4 activation is a hallmark of viral control but, many other host factors have been linked with this phenotype, including cellular restriction factors such as APOBEC, tetherin, and SAMHD1. In addition, several viral factors may also play a role, including deletions or mutations with the viral genes that may have an impact on the ability of the virus to replicate. ^[4]

HIV infection makes individuals highly susceptible to severe opportunistic infections and neoplastic disease. The following complications are classically observed among patients with significant immunocompromise and rarely manifest among patients with a CD4 count greater than 350 cells/mm³.

• Pneumocystis jirovecii pneumonia
• Tuberculosis
• Disseminated Mycobacterium avium complex
• Salmonellosis (Septicemia)
• Cytomegalovirus retinitis
• Candidiasis
• Cryptococcal meningitis
• Cerebral Toxoplasmosis
• Cryptococcal meningitis
• Disseminated Coccidiomycosis
• Disseminated Histoplasmosis
• Cryptosporidiosis
• Isosporiasis

• Kaposi Sarcoma
• AIDS-related lymphomas

• Non-Hodgkin’s Lymphoma
• Hodgkin’s Lymphoma
• Primary CNS Lymphoma
• Burkitt’s Lymphoma
• Large B-cell Lymphoma

• Invasive cervical cancer
• Invasive anal cancer

• HIV associated nephropathy
• HIV induced pericarditis
• HIV-associated wasting syndrome
• Aortitis
• AIDS dementia complex
• Lymphoid interstitial pneumonia

Without treatment, the net median survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype, 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.^[7] 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 near normal (assuming full compliance to HAART).^[8]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [18]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [19]; Jesus Rosario Hernandez, M.D. [20]

It is important to recognize that the relationship between opportunistic infections (OIs) and HIV infection is bi-directional. HIV causes the immunosuppression that allows opportunistic pathogens to cause disease in HIV-infected persons. OIs, as well as other co-infections that may be common in HIV-infected persons, such as sexually transmitted infections (STIs), can adversely affect the natural history of HIV infection by causing reversible increases in circulating viral load that could accelerate HIV progression and increase transmission of HIV. The widespread use of ART starting in the mid-1990s has had the most profound influence on reducing OI-related mortality in HIV-infected persons in those countries in which these therapies are accessible and affordable. Major OIs characteristic of AIDS include viral infections such as CMV retinitis, mucosal HSV, and varicella zoster, bacterial infections such as bacillary angiomatosis, tuberculosis, mycobacterium avium complex, and syphilis, and fungal infections such as cryptococcosis, mucocutaneous candidiasis, coccidiomycosis, and pneumocystis jirovecii pneumonia.