3Human immunodeficiency virus (hiv) HIV = (virus)/AIDS = (Disease)Kills/damages immune systemProgressively destroys body’s ability to fight infections & certain cancersIncreases risk for opportunistic infections
4Origin and historyAIDS was first recognized in 19811983: 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.
5HIV Infection – AIDS is Final stage of HIV Infection 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 synthesisHIV evades IS via latency, vacuoles, antigenic changeFig 19.13An enzyme (protein) that's part of the human immunodeficiency virus reads the sequence of viral RNA nucleic acids that have entered the host cell and transcribes the sequence into a complementary DNA sequence. That enzyme is called "reverse transcriptase" . Without reverse transcriptase, the viral genome couldn't become incorporated into the host cell, and couldn't reproduce.
6How 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.
7How does hiv damage the host 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.
11Diagnoses of HIV Infection, by Age 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 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:
12Diagnoses 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:
13AIDS Diagnoses, by AgeIn 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:
14AIDS 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:
15AIDS Diagnoses, by Top 10 States/Dependent Areas These are the 10 states or dependent areas reporting the highest number of AIDS diagnoses in 2010:
16Types of hivThere 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.
17Hiv-2In 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
18The Stages of HIV Infection Phase 1: Asymptomatic or chroniclymphadenopathyPhase 2: Symptomatic; early indications of immune failurePhase 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 AIDSProgression from HIV infection to AIDS: 10 yThe life of an AIDS patient can be prolonged by the proper treatment of opportunistic infectionsPeople lacking CCR5 are resistant to HIV infectionCCR5, short for chemokine (C-C motif) receptor 5 is a protein which in humans is encoded by the CCR5 gene which is located on chromosome 3 on the short (p) arm at position 21. CCR5 has also recently been designated CD195 (cluster of differentiation 195).The CCR5 protein functions as a chemokine receptor. The natural chemokine ligands that bind to this receptor are RANTES, MIP-1α and MIP-1β. CCR5 is predominantly expressed on T cells, macrophages, dendritic cells and microglia. It is likely that CCR5 plays a role in inflammatory responses to infection, though its exact role in normal immune function is unclear. HIV uses CCR5 or another protein, CXCR4, as a co-receptor to enter its target cells. Several chemokine receptors can function as viral coreceptors, but CCR5 is likely the most physiologically important coreceptor during natural infection. A number of new experimental HIV drugs, called entry inhibitors, have been designed to interfere with the interaction between CCR5 and HIV, including PRO140 (), Vicriviroc (Schering Plough), Aplaviroc (GW ) (GlaxoSmithKline) and Maraviroc (UK ) (Pfizer). A potential problem of this approach is that, while CCR5 is the major co-receptor by which HIV infects cells, it is not the only such co-receptor. It is possible that under selective pressure HIV will evolve to use another co-receptor.
19Transmission of hiv Unprotected sex with infected partner Contact with infected bloodContaminated needles & syringes/other instrumentsFrequently spread among IV drug usersMaternal-Infant Transmission¼ ~1/3 of untreated pregnancies pass infection to babyReduced 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.Babies of AZT treated mothers delivered by C-section have ~1% risk for HIV
21Hiv symptomsMany people don’t have any symptoms after first becoming infected with HIVSome have flu-like illness within 1-2 months after exposureOften mistaken for other viral infectionFeverHeadachesTirednessEnlarged lymph nodes
22Hiv symptomsMore 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 persomSome people have symptoms within a few months and others remain symptom free > 10 years
23Effect 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 cellsDecline in number of CD4 + T cells (T4 cells)Are immune system’s key infection fighters
24Effect of hiv on immune response Advanced phase: As immune system worsens, many complications occurFor many: 1st signs of infection are large lymph nodes (swollen glands)
25AIDs: Most advanced stages of hiv infection All HIV infected people with <200 CD4+ Tcells per cubic millimeter of bloodHealthy adults: CD4+ T cell counts ≥ 1,000Also includes 26 clinical conditionsMost are opportunistic infectionsOften severe and sometimes fatalBody can’t fight off certain bacteria, viruses, fungi, parasites, other microbes
26Hiv/aids treatmentWithout treatment, nearly everyone with HIV will get AIDSThere'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 gogglesDo not recap needlesRisk of infection from infected needlestick injury is 0.3%