Human Immunodeficiency Virus

VIRUSES

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HUMAN IMMUNODEFICIENCY VIRUS (HIV)• HIV = (virus)/AIDS = (Disease)

• Kills/damages immune system

• Progressively destroys body’s ability to fight infections & certain cancers

• Increases risk for opportunistic infections

ORIGIN AND HISTORY• AIDS was first recognized in 1981

• 1983: Discovery of virus causing loss of immune function.

• 1986: Scientists started to identify the virus with "HIV" abbreviation.

• HIV is thought to have crossed the species barrier into humans in central Africa in the 1930s.

• Scientists identified a type of chimpanzee in West Africa as the source of HIV infection in humans. They believe that the chimpanzee version of the immunodeficiency virus (called simian immunodeficiency virus or SIV) most likely was transmitted to humans and mutated into HIV when humans hunted these chimpanzees for meat and came into contact with their infected blood.

• Over decades, the virus slowly spread across Africa and later into other parts of the world.

HIV: Retrovirus with ssRNA, RT (from viral RNA to DNA), and envelope with gp120 spikes.

Gp120 attach to CD4 on Helper T cells, M, dendritic cells.

Function of RT?

Provirus latent or directs active viron synthesis

HIV evades IS via latency, vacuoles, antigenic change

HIV INFECTION – AIDS IS FINAL STAGE OF HIV INFECTION

Fig 19.13

HOW DOES HIV DAMAGE THE HOST• HIV specifically damages T helper lymphocytes, called T4 because they have an antigen

CD4 on the surface of the cell. The CD4 receptors, plus a co-receptor, are the site of attachment for HIV. The viral envelope fuses with the cell membrane and releases the viral enzymes and two strands of RNA of the HIV genome.

• Many cells are killed as the virus replicates. The acute stage of the infection, lasting some where around 6 weeks or so, is marked by rapid viral replication and killing CD4 cells. Many people will have symptoms similar to other viral infections, such as fever, enlarged lymph nodes, rash, muscles aches, and headaches.

• The immune response to such and infection holds the viral replication in check, but does not eliminate the virus. A steady state of viral replication is then reached, which is the chronic phase. CD4 cell levels remain high enough to hold secondary infections in check.

• Eventually, the continued assault on the T4 cells leads to an imbalance in the ratio of (helper / suppressor / cytotoxic) lymphocytes. This leads to an even further suppression of the immune response. The course of the disease can vary tremendously from one individual to another.

• Since the T helper cells also help regulate the B cells, as well as macrophages, these immune functions are also damaged.

HOW DOES HIV DAMAGE THE HOST

PATHOGENESIS: HIV CELLULAR TARGETS

Th cells

APCs brain cell intestinal epithelium

OVERVIEW OF HIV INFECTION

DIAGNOSES OF HIV INFECTION, BY AGE

Diagnoses of HIV Infection, by AgeIn 2010, the estimated number of diagnoses of HIV infection in the 46 states with confidential name-based HIV infection reporting, by age at diagnosis, was as follows:• In 2010, the estimated number of diagnoses of HIV infection in the 46 states with

confidential name-based HIV infection reporting, by age at diagnosis, was as follows:

DIAGNOSES OF HIV INFECTION, BY RACE/ETHNICITY

• In 2010, the estimated number of diagnoses of HIV infection in the 46 states with confidential name-based HIV infection reporting, by race or ethnicity, was as follows:

AIDS DIAGNOSES, BY AGE• In 2010, the estimated number of AIDS diagnoses in the 50 states and the District of

Columbia, by distribution of ages at time of diagnosis, was as follows:

AIDS DIAGNOSES, BY RACE/ETHNICITY• In 2010, the estimated number of AIDS diagnoses in the 50 states and the District of

Columbia, by race or ethnicity was as follows:

AIDS DIAGNOSES, BY TOP 10 STATES/DEPENDENT AREAS

• These are the 10 states or dependent areas reporting the highest number of AIDS diagnoses in 2010:

TYPES OF HIV• There are two types of HIV, HIV-1 and HIV-2. In the United States, unless otherwise

noted, the term “HIV” primarily refers to HIV-1.

• Both types of HIV damage a person’s body by destroying specific blood cells, called CD4+ T cells, which are crucial to helping the body fight diseases.

HIV-2• In 1986, a second type of HIV, called HIV-2, was isolated from AIDS patients in West

Africa.

• HIV-2 has the same modes of transmission as HIV-1 and is associated with similar opportunistic infections and AIDS.

• In persons infected with HIV-2, immunodeficiency seems to develop more slowly and to be milder, and those with HIV-2 are comparatively less infectious early in the course of infection. As the disease advances, HIV-2 infectiousness seems to increase; however, compared with HIV-1, the duration of this increased infectiousness is shorter.

• The first case of HIV-2 infection in the United States was diagnosed in 1987

THE STAGES OF HIV INFECTION

• Phase 1: Asymptomatic or chroniclymphadenopathy

• Phase 2: Symptomatic; early indications of immune failure• Phase 3 is AIDS: Characterized by indicator conditions, such as: CMV,

TB, Pneumocystis, toxoplasmosis, and Kaposi's sarcoma (see Table 19.5)

• Phases 1 and 2 are reported as AIDS if CD4+ T cells <200 cells/µl; Phase 3 always reported as AIDS

• Progression from HIV infection to AIDS: 10 y• The life of an AIDS patient can be prolonged by the proper treatment of

opportunistic infections• People lacking CCR5 are resistant to HIV infection

TRANSMISSION OF HIV• Unprotected sex with infected partner

• Contact with infected blood

• Contaminated needles & syringes/other instruments

• Frequently spread among IV drug users

• Maternal-Infant Transmission

• ¼ ~1/3 of untreated pregnancies pass infection to baby

• Reduced risk of perinatal transmission with prenatal zidovudine (AZT)

• The most common routes of transmission in the US are sexual contact, IV drug use, and vertical passage from infected mothers to offspring.

• Since 1985, transmission by blood transfusion has been rare due to good testing of blood supply and heat treatment of plasma products.

HIV SYMPTOMS• Many people don’t have any symptoms after first becoming infected with HIV

• Some have flu-like illness within 1-2 months after exposure

• Often mistaken for other viral infection

• Fever

• Headaches

• Tiredness

• Enlarged lymph nodes

HIV SYMPTOMS• More persistent or sever symptoms may not appear for ≥ 10 years or more after infection

(adults)

• Within 2 years in kids born infected

• “Asymptomatic” period varies by persom

• Some people have symptoms within a few months and others remain symptom free > 10 years

EFFECT OF HIV ON IMMUNE RESPONSE• Initial period after infection: HIV begins to disable or destroy immune system cells without

causing symptoms

• “Asymptomatic” period: virus actively multiplies, infects, and kills immune system cells

• Decline in number of CD4 + T cells (T4 cells)

• Are immune system’s key infection fighters

EFFECT OF HIV ON IMMUNE RESPONSE• Advanced phase: As immune system worsens, many complications occur

• For many: 1st signs of infection are large lymph nodes (swollen glands)

AIDS: MOST ADVANCED STAGES OF HIV INFECTION• All HIV infected people with <200 CD4+ Tcells per cubic millimeter of blood

• Healthy adults: CD4+ T cell counts ≥ 1,000

• Also includes 26 clinical conditions

• Most are opportunistic infections

• Often severe and sometimes fatal

• Body can’t fight off certain bacteria, viruses, fungi, parasites, other microbes

HIV/AIDS TREATMENT• Without treatment, nearly everyone with HIV will get AIDS

• There's no cure for HIV/AIDS, but a variety of drugs can be used in combination to control the virus.

• Each of the classes of anti-HIV drugs blocks the virus in different ways. It's best to combine at least three drugs from two different classes to avoid creating strains of HIV that are immune to single drugs.

• Prevention- Health care workers use Universal Precautions:• Wear gloves, gowns, masks, and goggles• Do not recap needles• Risk of infection from infected needlestick injury

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