HIV / AIDS

HIV/AIDS in short

• AIDS (acquired immunodeficiency syndrome) is a set of symptoms and infections resulting from immune system damage caused by the human immunodeficiency virus (HIV)
• 33,4 million people live with HIV worldwide
• AIDS is the leading cause of death in Africa, which is home to two-thirds of all individuals living with HIV
• 2.7 million people were newly infected in 2008
• an estimated 2 million people died of AIDS every year

HIV/AIDS in detail

Pathogenic agent
The human immunodeficiency virus (HIV) is an enveloped retrovirus belonging to the genus Lentiviridae. Two variants of HIV exist: HIV‑1 and HIV‑2. HIV‑2 accounts for only 1% of all HIV infections worldwide and occurs only in some West African regions.

Transmission/pathogenesis
HIV is spread by direct contact of mucous membranes or the bloodstream with a bodily fluid (blood, semen, vaginal fluid, preseminal fluid, breast milk) containing the virus. Transmission can occur during sexual intercourse, blood transfusion or sharing of needles by intravenous drug users as well as between mother and baby during pregnancy, birth or breastfeeding.

HIV infects cells in the immune system and central nervous system but is especially fond of T helper (CD4+) lymphocytes. After entering the cell, the core of the virus disassembles, and the viral RNA is transcribed into a DNA copy via the virus’s own reverse transcriptase enzyme. This provirus is then transported into the nucleus for integration into the host genome, where the virus remains latent and invisible to the immune system. Because latency is established very early, in the first days to weeks after infection, the time during which HIV is vulnerable to the immune system is very short. After integration into the host cell DNA, production of new HIV can start.

The mutability and the resulting genetic diversity of HIV, especially of the envelope protein, enables the virus to evade the immune system.

Infection leads to depletion of CD4+ T cells within all lymphoid tissues and qualitative defects of CD8+ and CD4+ T cells, resulting in an immunodeficient state that leaves the infected individual vulnerable to infections and cancer. Without treatment, HIV infection is almost always progressive,

Symptoms
Symptoms of acute HIV infection may occur in some individuals days to weeks after contact with the virus. These signs are unspecific (fatigue, fever, rash, joint pain) and are often mistaken as symptoms of a "common cold" or mononucleosis. During this phase of infection, the CD4+ T cell count is usually depleted and viraemia is high. After acute infection, a balance between viral replication and the immune response is usually reached, and years may pass before clinical manifestations appear. When the level of CD4+ T cells is depleted below 200/µl, the risk of many AIDS-defining illnesses increases rapidly.

The diagnosis of AIDS is based on the presence of certain signs and symptoms. Both the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) have developed staging systems for HIV/AIDS. The WHO classification, which is based on symptoms, is used in developing countries, while the CDC system based on clinical conditions and CD4+ T cell count is used in developed countries. AIDS-defining illnesses include opportunistic infections and malignancies that usually do not occur in patients with a healthy immune system:

- candidiasis
- cryptosporidiosis
- cytomegalovirus disease
- encephalopathy (HIV-related)
- chronic Herpes simplex
- Kaposi's sarcoma
- lymphoma characterized by swollen lymph nodes (lymphadenopathy)
- Pneumocystis carinii pneumonia
- recurrent pneumonia
- toxoplasmosis of the brain
- tuberculosis
- wasting syndrome

CDC Case Definition for AIDS:
www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm

Treatment
There are different classes of antiretroviral substances used in the treatment of HIV:

- Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NRTIs)
- Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
 -Protease Inhibitors (PIs)
- Fusion Inhibitors
- Entry Inhibitors

Shortly after the first NRTI azidothymidine (AZT) became available in 1987, drug resistance appeared. Current treatment for HIV consists of a combination of different agents to prevent the development of resistance. This regimen, often called highly active antiretroviral therapy (HAART), was induced in 1996 and has transformed AIDS into a chronic disease in developed countries. However, for most people in developing countries HAART treatment is unaffordable; in low- and middle-income countries, approximately one in five people who need antiretroviral drugs are receiving them. In 2005 the G8 countries and the United Nations announced their commitment to the establishment of a framework for scaling up HIV prevention, treatment, care and support, with the aim of coming as close as possible to the goal of universal access to treatment for all those who need it by 2010.

Vaccination
A successful HIV vaccine may need to induce both neutralizing antibodies to eliminate viral load and cytotoxic T lymphocytes to eliminate infected cells. Phase III studies of vaccine candidates based on viral surface proteins and a recombinant adenovirus vector containing HIV proteins recently failed. Some scientists estimate that it will take at least another decade to develop another candidate ready for a phase III study.

Incidence and mortality
In 2007, an estimated 33 million people were living with HIV worldwide. There were 2.7 million new HIV infections and 2 million AIDS-related deaths. Rates of new HIV infections are rising rapidly in many countries including China, Kenya, Mozambique, the Russian Federation, Ukraine and Vietnam.

Africa is home to two-thirds of all people living with HIV, with sub-Saharan Africa remaining by far the worst affected region: 76% of all AIDS deaths occur in sub-Saharan Africa, and 11.4 million AIDS orphans live in the region. Adult prevalence was estimated to be 5.0% in 2007, and AIDS continues to be the leading cause of death.

For more information see HIV prevalence on worldmapper.org:
www.worldmapper.org/display.php?selected=227
and HIV/AIDS deaths on worldmapper.org:
www.worldmapper.org/display_extra.php?selected=374

HIV/AIDS and other infectious diseases
The symptoms of AIDS are mainly caused by opportunistic infections (bacteria, viruses, fungi and parasites) that usually do not occur in patients with a healthy immune system (see list above).

Tuberculosis (TB) is of special importance: the majority of TB deaths occur in HIV-infected individuals. As HIV weakens the immune system, HIV patients are much more likely to develop active TB after being infected with Mycobacterium tuberculosis, and TB patients with HIV are twice as likely to have multidrug-resistant TB as HIV-negative patients. To combat the lethal duo, the WHO and its partners have formed a TB/HIV working group.
For more information on HIV and tuberculosis see: www.who.int/tb/challenges/hiv/en/.

For more information
- WHO: www.who.int/hiv/en/
- Robert Koch Institute (in German only): www.rki.de/cln_100/nn_196658/DE/Content/InfAZ/H/HIVAIDS/hiv__node.html?__nnn=true
UNAIDS, 2008 Report on the global AIDS epidemic: www.unaids.org/en/KnowledgeCentre/HIVData/GlobalReport/2008/
- CDC on tuberculosis: www.cdc.gov/tb

Literature
- UNAIDS: The United Nations Joint Programme on HIV/AIDS: www.unaids.org/en/
- Robert Koch Institute (in German only): www.rki.de/cln_100/nn_196658/DE/Content/InfAZ/H/HIVAIDS/hiv__node.html?__nnn=true
- Centers for Disease Control and Prevention: www.cdc.gov/hiv/
- The Global Fund to Fight AIDS, Tuberculosis and Malaria: www.theglobalfund.org/en/
- WHO-UNAIDS HIV Vaccine Initiative: www.who.int/vaccine_research/diseases/hiv/en/index.html
- WHO working group TB/HIV: www.who.int/tb/challenges/hiv/en/
- Henry J. Kaiser Family Foundation, Global HIV/AIDS Timeline: www.kff.org/hivaids/timeline
- Hoffmann C, Jürgen K, Rockstroh JK. HIV.NET 2008:Open-Access-Book HIV Medicine (2008 edition in German only; 2007 edition available in English), pdf downloads: www.hivmedicine.com
- Wainberg MA, Jeang KT. 25 years of HIV-1 research – progress and perspectives. BMC Medicine (2008) 6: 31. doi:10.1186/1741-7015-6-31
- Sepkowitz KA. One Disease, Two Epidemics – AIDS at 25. N Engl J Med (2006) 354: 2411–14. http://content.nejm.org/cgi/content/full/354/23/2411
- Merson MH. The HIV–AIDS Pandemic at 25 – The Global Response.N Engl J Med (2006) 354: 2414–2417. http://content.nejm.org/cgi/content/full/354/23/2414
- Johnston MI, Fauci AS. An HIV Vaccine – Challenges and Prospects. N Engl J Med (2008) 359: 888–890. http://content.nejm.org/cgi/content/full/359/9/888