HIV AIDS overview

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Serge Korjian M.D., Tarek Nafee, M.D. [2], Marjan Khan M.B.B.S.[3]

Overview

Acquired immune deficiency syndrome (AIDS) is a disease caused by the human immunodeficiency virus (HIV) that leads to the progressive deterioration of the immune system.In late stages of the condition, individuals become susceptible to opportunistic infections and neoplastic proliferation. HIV is transmitted via direct contact of an exposed mucous membrane or the bloodstream with bodily fluids (e.g., blood, semen, vaginal fluid, preseminal fluid, or breast milk) that contain HIV particles. HIV is a global pandemic with an estimated 35 million individuals living with the disease. Although several treatment regimens for HIV exist, they serve only to decelerate the progression of the virus. There is currently no known cure. Still, modern antiretroviral therapy has significantly decreased the morbidity and mortality associated with the disease.

Classification

Many definitions have been developed for epidemiological surveillance of HIV/AIDS; these include 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, which 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 chiefly based on CD4 T-lymphocyte counts.

Pathophysiology

HIV causes AIDS by depleting the body's supply of CD4+ T helper lymphocytes. The virus is acquired via either sexual contact, exposure to contaminated blood, or mother-to-child transmission. Once the virus is acquired, it disseminates to the majority of lymphoid organs where it enters a period of rapid viral replication. This leads to the acute phase of the infection, which is characterized by a very elevated viral titer and an acute drop in CD4 T-lymphocyte count. As the immune response mounts, viral replication and the CD4 T cell depletion rate drops. The immune system continues to deteriorate, but at a slower pace. This is known as the chronic phase of HIV infection. The HIV virus causes CD4 T cell death through a variety of mechanisms, including cytopathic single-cell destruction, syncytia formation, autoimmunity, and superantigen formation.

Causes

AIDS is caused by the human immunodeficiency virus (HIV). HIV is a retrovirus classified into the family Retroviridae and the sub-family orthoretroviridae. Two main subspecies of HIV exist: HIV-1 and HIV-2. HIV-1 is composed of two copies of single-stranded RNA enclosed by a conical capsid comprising the viral protein p24. The genome consists of several major genes that code for structural and functional proteins. These include the gag, pol, env, tat, and nef genes. Two enzymes that are critical for all retroviruses are reverse transcriptase, which transcribes the viral RNA into double-stranded DNA and integrase, which integrates this newly formed DNA into the host genome. It is a well known fact that no two HIV genomes are the same, not even from the same person, causing some to speculate that HIV is a "quasispecies" of a virus.

Differentiating AIDS from other Diseases

Epidemiology and Demographics

  • HIV is a global pandemic. In 2013, an estimated 35 million people worldwide were living with the disease.
  • An estimated 39 million people have died from AIDS or AIDS-related causes, including approximately 1.5 million patients in 2013 alone.
  • Over three-fourths of these deaths are confined to Sub-Saharan Africa. 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.[2]
  • At the end of 2013, 11.7 million people were receiving ART in low- and middle-income countries, which represents just 36% of people living with HIV in these countries.

Risk Factors

  • 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 throughout the course of the disease and is closely associated with the HIV viral load.

Screening

  • The primary determinant of the morbidity and mortality of HIV infections is adequate antiretroviral therapy. For that reason, early detection is essential in improving outcomes.[3]
  • In 2006, the Centers for Disease Control announced an initiative for voluntary, routine testing of all Americans aged 13–64 during visits to healthcare facilities. An estimated 25% of infected individuals were unaware of their status.[4]
  • Routine prenatal HIV testing was also recommended for all women as part of their normal gestational screening tests.

Natural history, complications, and prognosis

Opportunistic infections

HIV Co-infections

  • Tuberculosis, hepatitis B and hepatitis C are three of the most common co-infections found in patients with HIV owing mostly to their mode of transmission and epidemiological distribution.
  • Co-infetions may manifest differently in patients with HIV due to the altered immune response. Accordingly, screening for these infections is recommended in all patients diagnosed with HIV.

HIV and pregnancy

  • Approximately one in four HIV-positive women are unaware of their disease status, which puts them at high risk of passing the virus to their children.
  • Mother-to-child transmission is the most common way in which children become infected with HIV.
  • Virtually all AIDS cases in U.S. children are the result of mother-to-child transmission.
  • HIV transmission is reduced from 25% to less than 2% in women taking antiretroviral therapy (ART) before and during birth, and if their babies are given therapy after birth. Accordingly, universal “opt-out” HIV testing is recommended for all pregnant women early in every pregnancy.
  • Triple therapy should be administered to all pregnant women diagnosed with HIV. However, regardless of the antenatal ART regimen, zidovudine should be administered to the mother as an intravenous infusion during labor, and to the neonate orally for 6 months after birth.

HIV infection in infants

  • The use of ART during pregnancy in HIV-infected women has resulted in a dramatic decrease in the rate of transmission to infants, which is currently less than 2% in the United States.
  • The number of infants with AIDS in the United States continues to decline. For infants born to mothers with unknown HIV status, rapid HIV antibody testing of the mother and/or infant is recommended as soon as possible after birth, with immediate initiation of infant antiretroviral prophylaxis if the rapid test is positive.
  • Virologic assays that directly detect HIV must be used to diagnose HIV infection in infants younger than 18 months.
  • HIV antibody testing cannot establish HIV infection in this age group because maternal HIV antibodies may persist and interfere with the interpretation of a positive HIV antibody test.
  • The treatment of children living with HIV infection is associated with challenges of adherence, drug resistance, reproductive health planning, management of multiple drugs, and long-term complications from HIV and its treatments.

Diagnosis

Case Definition

  • AIDS is defined as an the presence of either of the following in a patient with HIV infection: a CD4+ T cell count below 200 cells/µl, a CD4+ T cell percentage of total lymphocytes of less than 15%, or the presence of any of the 27 specified AIDS-defining illnesses.

History and symptoms

Physical examination

Laboratory Findings

  • Important laboratory tests for the initial evaluation of patients with suspected HIV infection include screening tests with high sensitivity such as ELISA, dot blot, and latex agglutination assays; and confirmatory tests with high specificity such as Western blot assays, P24 antigen assays, and nucleic acid testing. Two surrogate markers, the CD4 T cell count (CD4 count) and the plasma HIV RNA viral load, are routinely used to asses immune function and levels of viremia.
  • Resistance testing is becoming of greater importance in the management of HIV/AIDS patients given the increased resistance to certain antiretroviral agents.

Electrocardiogram

Chest X Ray

CT

MRI

Treatment

Medical Therapy

Surgery

  • HIV-infected patients may require surgery to treat infections and diseases associated with the condition. Childbirth and organ transplant are two of the many conditions that may necessitate surgery in an HIV-positive patient.

Primary Prevention

Secondary Prevention

  • Secondary prevention encompasses measures to reduce the complications of HIV as well as spread of the disease in the population.[1]

Cost-Effectiveness of Therapy

  • HIV and AIDS slow economic growth by destroying human capital. Without proper nutrition, health care, and medicine that is available in developed countries, large numbers of people are falling victim to AIDS. They will not only be unable to work, but will also require significant and expensive medical care.
  • It is expected that this will likely cause a collapse of economies and societies in certain regions. In some heavily infected areas, the epidemic has left behind many orphans who are cared for by elderly grandparents.[9]

Future or Investigational Therapies

Research to improve current treatments includes decreasing side effects of current drugs, further simplifying drug regimens to improve adherence, and determining the best sequence of regimens to manage drug resistance. To learn more about HIV vaccine click here.

References

  1. 1.0 1.1 "AIDSinfo".
  2. {{ cite journal | author=Palella FJ Jr, Delaney KM, Moorman AC, et al | title=Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators | journal=N. Engl. J. Med | year=1998 | pages=853–860 | volume=338 | issue=13 | pmid=9516219
  3. Long EF, Brandeau ML, Owens DK (2010). "The cost-effectiveness and population outcomes of expanded HIV screening and antiretroviral treatment in the United States". Ann Intern Med. 153 (12): 778–89. doi:10.7326/0003-4819-153-12-201012210-00004. PMC 3173812. PMID 21173412.
  4. CDC fact sheet
  5. Vergis EN, Mellors JW (2000). "Natural history of HIV-1 infection". Infect Dis Clin North Am. 14 (4): 809–25, v–vi. PMID 11144640.
  6. Giles M, Workman C (2009). "Clinical manifestations and the natural history of HIV" (PDF). Australian Society for HIV Management: 125–32. ISBN 9781920773571.
  7. Knoll B, Lassmann B, Temesgen Z (2007). "*Current status of HIV infection: a review for non-HIV-treating physicians". Int J Dermatol. 46 (12): 1219–28. doi:10.1111/j.1365-4632.2007.03520.x. PMID 18173512.
  8. Gunthardt, HF; Saag, Michael; Benson, C (Jul 21, 2016). "Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society–USA Panel". JAMA. The JAMA Network (published 2016). 316 (2): 191–210. doi:10.1001/jama.2016.8900. PMC 5012643. PMID 27404187.
  9. Greener R (2002). "AIDS and macroeconomic impact". In S, Forsyth (ed.). State of The Art: AIDS and Economics. IAEN. pp. 49&ndash, 55.

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