Human Immunodeficiency Virus HIV

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• HIV-1 is the most prevalent HIV type
  throughout the world
• HIV-2 has been found in Africa

In June 1981, the centers for disease control of
the United States reported that five young
homosexual men in the Los Angeles area had
contracted the AIDS Etiology human
immunodeficiency virus (HIV)
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Human immunodeficiency virus (HIV) cause acquired
immune deficiency syndrome (AIDS)
More than 25 million people have died of AIDS
since 1981. Africa has 12 million AIDS
orphans. At the end of 2006, women accounted for
48 of all adults living with HIV worldwide, and
for 59 in sub-Saharan Africa. Young people
(15-24 years old) account for half of all new HIV
infections worldwide - around 6,000 become
infected with HIV every day. In developing and
transitional countries, 6.8 million people are in
immediate need of life-saving AIDS drugs of
these, only 1.65 million are receiving the drugs.
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Human Immunodeficiency Virus (HIV)

• Member of lentivirus slow virus , HIV is a
  retrovirus encodes genome in RNA
• HIV is transmitted through direct contact of a
  mucous membrane or the bloodstream with a bodily
  fluid containing HIV, such as blood, semen,
  vaginal fluid, preseminal fluid, and breast milk.
• Five groups of adults at high risk for developing
  AIDS
• ? Homosexual or bisexual males ? Intravenous
  drug abusers ? Hemophiliacs
• ? Recipients of blood and blood components ?
  Heterosexual contacts
• Tropism for hematopoietic and nervous systems
  (Infects macrophages, and later, helper T cells)
• Virus replicates and bursts out of the helper T
  cell, killing it
• Loss of helper T cells prevents B cell activation
• Infections occur because the immune system not
  functional
• Replicates rapidly, mutates easily, and can hide
• Variation in disease presentation, Variation in
  time of onset of disease
• Infect non-diving cells
• 3 infection stages acute, latent, high levels of
  viral production
• Results of TH cell depletion
• opportunistic infections
• tumors develop

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Opportunistic Infections and Cancers That Kill
AIDS Patients
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• AIDS Associated Disease Categories
• 1. Gastrointestinal Cause most of illness and
  death of late AIDS.
• Pathogens Candida albicans, cytomegalovirus,
  Microsporidia, and Cryptosporidia.
• 2. Respiratory 70 of AIDS patients develop
  serious respiratory problems.
• 3. Neurological Opportunistic diseases and
  tumors of central nervous system.
• 4. Skin Disorders 90 of AIDS patients develop
  skin or mucous membrane disorders.
• 5. Eye Infections 50-75 patients develop eye
  conditions.

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Extensive tumor lesions of Kaposiss sarcoma in
AIDS patient.
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• HIV-2 shares 40 nucleotide homology with HIV-1
• Genome consists of 9200 nucleotides

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The HIV Genome
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HIV-1 Genotypes

• There are 3 HIV-1 genotypes M (Main), O
  (Outlayer), and N (New)
• M group comprises of a large number subtypes and
  recombinant forms
• Subtypes - (A, A2, B, C, D, F1, F2, G, H, J and
  K)
• Recombinant forms - AE, AG, AB, DF, BC, CD
• O and N group subtypes not clearly defined,
  especially since there are so few N group
  isolates.
• As yet, different HIV-1 genotypes are not
  associated with different courses of disease nor
  response to antiviral therapy.
• However, certain subgroups may be difficult to
  detect by certain commercial assays.

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Life Cycle of HIV

• 1. Virus attaches and penetrates host cells-
  gp120 binds CD4 TH cells
• 2. Viral RNA converts to viral DNA
• 3. Viral DNA integrates into human chromosome
• 4. Infected host cells produce new virus
  particles
• 5. New virus particles bud from host cell
  one-by-one, taking host cell's membrane along as
  envelope
• HIV high mutation rate impedes immune response

The time required to complete a single HIV
life-cycle is approximately 1.5 days.
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Development of HIV Disease

• Time Periods
• 1. weeks 1-3 virus enters body, circulates,
  and makes infected person contagious
• 2. weeks 1-8 acute viral syndrome
• short term
• mild or severe flu-like symptoms
• fever, fatigue, rash, aching muscle and joints,
  sore throat, enlarged lymph nodes

• 3. 6 weeks - 6 months positive HIV
  antibody test
• seronegative negative test
• seropositive positive test for HIV
• 4. 2 yrs onset of longer-lasting symptoms
• 5. 6 months-15 yrs development of AIDS

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Human immunodeficiency virus (HIV) cause acquired
immune deficiency syndrome (AIDS)
HIV infects CD4 cells and macrophages CD4 is a
receptor for the virus CCR5 (a chemokine
receptor) is a co-receptor
CD4 cells in HIV infected individuals
For us, AIDS is defined as fewer than 200 CD4
cells per ml of blood
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Progression of HIV Infection
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Mechanisms of CD4 T cell depletion-Dysfunction
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• Accumulation of unintegrated viral DNA
• Loss of plasma membrane integrity due to viral
  budding
• Elimination of infected cells by HIV-specific
  immune effectors
• Syncytium formation
• Autoimmunity
• Superantigenic stimulation
• Apoptosis
• Infection of stem cells and interference with
  lymphopoiesis

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The multiple effects of loss of CD4 T cells as a
result of HIV infection
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Diagnosis of AIDS

• ELISA test
• Western Blot
• PCR test
• HIV viral load - HIV viral load in serum may be
  measured by assays which detect HIV-RNA e.g.
  RT-PCR, NASBA, or bDNA. HIV viral load has now
  been established as having good prognostic value,
  and in monitoring response to antiviral
  chemotherapy.
• HIV Antigen tests - they were widely used as
  prognostic assays. It was soon apparent that
  detection of HIV p24 antigen was not as good as
  serial CD4 counts. The use of HIV p24 antigen
  assays for prognosis has now been superseded by
  HIV-RNA assays.

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Possible HIV Therapies

• Preventing assembly of HIV virus
• HIV protease
• Inhibit reverse transcription
• AZT (azidothymidine)
• Other nucleotide analogs
• Gene Therapy
• Antisense RNA
• Introduce into stem cells
• Preventing entry of HIV into uninfected cells
• gp120/viral envelope
• CD4 on the cell surface
• Vaccines recombinant or attenuated virus
  (risky?)

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Therapeutic targets
























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Treatment

• There is currently no vaccine or cure for HIV or
  AIDS.
• The only known methods of prevention are based on
  avoiding exposure to the virus.
• Abacavir a nucleoside analog reverse
  transcriptase inhibitors (NARTIs or NRTIs)
• The chemical structure of Abacavir

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• Atazanavir a protease inhibitor
• Current treatment for HIV infection consists of
  highly active antiretroviral therapy, or HAART.
• This has been highly beneficial to many
  HIV-infected individuals since its introduction
  in 1996 when the protease inhibitor-based HAART
  initially became available.
• Current optimal HAART options consist of
  combinations (or "cocktails") consisting of at
  least three drugs belonging to at least two
  types, or "classes," of anti-retroviral agents.
• Typical regimens consist of two nucleoside
  analogue reverse transcriptase inhibitors (NARTIs
  or NRTIs) plus either a protease inhibitor or a
  non-nucleoside reverse transcriptase inhibitor
  (NNRTI).