HIV/AIDS

• 1. Virology And Pathogenesis

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  Human immunodeficiency virus is a retrovirus that primarily infects components of the human immune system such as CD4+ T cells, macrophages and dendritic cells. It directly and indirectly destroys these critical white blood cells. HIV is a member of the genus Lentivirus, part of the family Retroviridae. Lentiviruses share many morphological and biological characteristics with other long-duration illnesses. Many species of mammals are infected by lentiviruses which are characteristically responsible for chronic conditions with long incubation periods. Upon entry into the target cell, the viral RNA genome is converted into double-stranded DNA by a virally encoded reverse transcriptase. The resulting viral DNA is then imported into the cell nucleus and integrated into the cellular DNA by a virally encoded integrase. Once integrated, the virus may become latent allowing the virus and its host cell to avoid detection by the immune system. Alternatively, the virus may be transcribed producing new RNA genomes and viral proteins that are packaged and released from the cell as new virus particles. This process begins the replication cycle anew. Two types of HIV have been characterized: HIV-1 and HIV-2. HIV-1 is the virus that was originally discovered and initially referred to also as LAV or HTLV-III. It is more virulent, more infective, and is the cause of the majority of HIV infections globally.

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• 2. Transmission Dynamics And Risk

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  HIV is spread primarily by unprotected sex including anal oral and vaginal sex contaminated hypodermic needles or blood transfusions and from mother to child during pregnancy delivery or breastfeeding. Some bodily fluids such as saliva sweat and tears do not transmit the virus. Oral sex has little risk of transmitting the virus but it is still present. The per-act risk is estimated at 0, 0.04% for receptive oral intercourse. In settings involving prostitution in low-income countries risk of female-to-male transmission has been estimated as 2.4% per act and of male-to-female transmission as 0.05% per act. The risk of transmission from anal intercourse is especially high estimated as 1.4, 1.7% per act in both heterosexual and homosexual contacts. During the first 2.5 months of an HIV infection a person's infectiousness is twelve times higher due to the high viral load associated with acute HIV. If the person is in the late stages of infection rates of transmission are approximately eightfold greater. Genital ulcers increase the risk approximately fivefold. Other sexually transmitted infections such as gonorrhea chlamydia trichomoniasis and bacterial vaginosis are associated with somewhat smaller increases in risk of transmission.

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• 3. Clinical Progression And Staging

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  There are three main stages of HIV infection: acute infection clinical latency and AIDS. The initial period following infection with HIV is called acute HIV primary HIV or acute retroviral syndrome. Many individuals develop an influenza-like illness mononucleosis or glandular fever 2, 4 weeks after exposure while others have no significant symptoms. Symptoms occur in 40, 90% of cases and most commonly include fever large tender lymph nodes throat inflammation a rash headache tiredness and/or sores of the mouth and genitals. The rash which occurs in 20, 50% of cases presents itself on the trunk and is maculopapular classically. Some people also develop opportunistic infections at this stage. Gastrointestinal symptoms such as vomiting or diarrhea may occur. Neurological symptoms of peripheral neuropathy or Guillain, Barré syndrome also occur. The duration of the symptoms varies but is usually one or two weeks. These symptoms are not often recognized as signs of HIV infection. Family doctors or hospitals can misdiagnose cases as one of the many common infectious diseases with similar symptoms. Someone with an unexplained fever who may have been recently exposed to HIV should consider testing to find out if they have been infected.

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• 4. Diagnostic Methods And Testing

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  HIV/AIDS is diagnosed via laboratory testing and then staged based on the presence of certain signs or symptoms. HIV screening is recommended by the United States Preventive Services Task Force for all people 15 years to 65 years of age including all pregnant women. Additionally testing is recommended for those at high risk which includes anyone diagnosed with a sexually transmitted illness. In many areas of the world a third of HIV carriers only discover they are infected at an advanced stage of the disease when AIDS or severe immunodeficiency has become apparent. Most people infected with HIV develop seroconverted antigen-specific antibodies within three to twelve weeks after the initial infection. Diagnosis of primary HIV before seroconversion is done by measuring HIV-RNA or p24 antigen. Positive results obtained by antibody or PCR testing are confirmed either by a different antibody or by PCR. Antibody tests in children younger than 18 months are typically inaccurate due to the continued presence of maternal antibodies. Thus HIV infection can only be diagnosed by PCR testing for HIV RNA or DNA or via testing for the p24 antigen. Much of the world lacks access to reliable PCR testing and people in many places simply wait until either symptoms develop or the child is old enough for accurate antibody testing.

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• 5. Antiretroviral Therapies And Prevention

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  Treatment consists of highly active antireviral therapy ART which slows progression of the disease. As of 2022 39 million people globally were living with HIV and 29.8 million people were accessing ART. Current ART options are combinations or cocktails consisting of at least three medications belonging to at least two types or classes of antiretroviral agents. There are eight classes of antiretroviral agents including nucleoside/nucleotide reverse transcriptase inhibitors non-nucleoside reverse transcriptase inhibitors protease inhibitors integrase strand transfer inhibitors a fusion inhibitor a CCR5 antagonist a CD4 T lymphocyte post-attachment inhibitor and a gp120 attachment inhibitor. The World Health Organization and the United States recommend antiretrovirals in people of all ages including pregnant women as soon as the diagnosis is made regardless of CD4 count. Once treatment is begun it is recommended that it is continued without breaks or holidays. Many people are diagnosed only after treatment ideally should have begun. The desired outcome of treatment is a long-term plasma HIV-RNA count below 50 copies/mL. Levels to determine if treatment is effective are initially recommended after four weeks and once levels fall below 50 copies/mL checks every three to six months are typically adequate.

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• 6. Global Epidemiology And Demographics

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  The first news story on the disease appeared on the 18th of May 1981 in the gay newspaper New York Native. AIDS was first clinically reported on the 5th of June 1981 with five cases in the United States. The initial cases were a cluster of injecting drug users and gay men with no known cause of impaired immunity who showed symptoms of Pneumocystis carinii pneumonia PCP a rare opportunistic infection that was known to occur in people with very compromised immune systems. Soon thereafter a large number of homosexual men developed a generally rare skin cancer called Kaposi's sarcoma KS. Many more cases of PCP and KS emerged alerting U.S. Centers for Disease Control and Prevention CDC and a CDC task force was formed to monitor the outbreak. In the early days the CDC did not have an official name for the disease often referring to it by way of diseases associated with it such as lymphadenopathy the disease after which the discoverers of HIV originally named the virus. They also used Kaposi's

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• 7. Historical Origins And Discovery

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  sarcoma and opportunistic infections the name by which a task force had been set up in 1981. At one point the CDC referred to it as the 4H disease as the syndrome seemed to affect heroin users homosexuals hemophiliacs and Haitians.

  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. 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. The gross domestic product of the most affected countries has decreased due to the lack of human capital. Without proper nutrition health care and medicine large numbers of people die from AIDS-related complications. Before death they will not only be unable to work but will also require significant medical care. It is estimated that as of 2007 there were 12 million AIDS orphans. Many are cared for by elderly grandparents. Returning to work after beginning treatment for HIV/AIDS is difficult and affected people often

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• 8. Social Stigma And Economic Impact

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  work less than the average worker. Unemployment in people with HIV/AIDS also is associated with suicidal ideation memory problems and social isolation.

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