HIV and AIDS

HIV
Human Immunodeficiency Virus H = Infects only Human beings I = Immunodeficiency virus weakens the immune system and increases the risk of infection V = Virus that attacks the body

AIDS
Acquired Immune Deficiency Syndrome A = Acquired, not inherited I = Weakens the Immune system D = Creates a Deficiency of CD4+ cells in the immune system S = Syndrome, or a group of illnesses taking place at the same time

HIV and AIDS

When the immune system becomes weakened by HIV, the illness progresses to AIDS
Some blood tests, symptoms or certain infections indicate progression of HIV to AIDS

HIV-1 and HIV-2

HIV-1 and HIV-2 are

Transmitted through the same routes

Associated with similar opportunistic

infections
HIV-1 is more common worldwide

HIV-2 is found in West Africa, Mozambique,

and Angola

HIV-1 and HIV-2

HIV-2 is less easily transmitted
HIV-2 is less pathogenic Duration of HIV-2 infection is shorter MTCT is relatively rare with HIV-2 MTCT of HIV-2 has not been reported from India

Transmission of HIV
HIV is transmitted by Direct contact with infected blood Sexual contact: oral, anal, or vaginal Direct contact with semen or vaginal and cervical secretions HIV-infected mothers to infants during pregnancy, delivery, or breastfeeding

Transmission of HIV
HIV is not transmitted by
Coughing, sneezing
Insect bites Touching, hugging
Public baths

Water, food
Kissing

Handshakes Work or school contact Using telephones Sharing cups, glasses, plates, or other utensils

DR. S.K CHATURVEDI

Worldwide Distribution of HIV-1 Viral Subtypes

B
Western Europe: 540,000

B
Northern America: 920,000

Eastern Europe & Central Asia: 700,000

C
Eastern Asia & the Pacific: 640,000

Caribbean: 390,000

Northern Africa & Middle East: 400,000

C,E

Latin America: 1.4 million

C
Sub - Saharan Africa:

Southern & Southeastern Asia:

7 million
Australia & New Zealand: 15,000

25.3 million

B
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Viruses
A virus is the simplest, most primitive life form on earth. A virus is unable to replicate (reproduce) on its own and must first infect a living cell in order to replicate. HIV is a retrovirus. A retrovirus is an RNA virus which uses DNA as an intermediary for its replication.
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Human Immunodeficiency Virus

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HIV-1 Particle

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HIV Life Cycle

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HIV Life Cycle

HIV RNA
Reverse Transcriptase RNA Protease RNA RNA RNA DNA RNA RNA Proviral DNA RNA RNA

CD4 T -Lymphocyte

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HIV Variability

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HIV Variability
HIV has enormous potential for change (mutations)
The HIV copies in an infected person are not all identical but are rather like a swarm of closely related viruses. Reverse Transcriptase is a very error-prone enzyme.
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Effects of HIV Mutations

Mostly of no consequence. Viral fitness increased or decreased.

Viral infectivity/pathogenicity increased or decreased. Escape from immune control.

ARV drug resistance.
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Immunology

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Host Defense System

Self versus Non-Self (antigen)

Innate Immunity

Adaptive Immunity
B-Lymphocytes T-Lymphocytes

-Skin, mucosa -Cells

White blood cells Macrophages -Complement

Plasma cells

CD4 cells

CD8 cells

High Specificity/ Memory Cells 19

Helper Function of CD4 Cells

Macrophage

T helper cell (CD4) B Lymphocyte Cytotoxic T Lymphocyte

(CD8) Infected cell

Antibody secreting (plasma) cell

Killed 20

White Blood Cell Distribution

Absolute/Total cells/uL
Neutrophils

Percent

4000

55% WBC 30% Lymphocytes

Lymphocytes CD4 1000

CD8
Basophils Eosinophils Monocytes

500

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CD4 Counts in Botswana

Uninfected: 750 cells/uL (IQR: 560-900) Asymptomatic HIV-1 positive: 350 cells/uL (IQR: 268-574) Patients with AIDS: 121 cells/uL (IQR: 50-250)
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Surrogate Markers of HIV Disease

CD4 is an indicator of the strength of the
immune system.

Viral Load is an indicator of the amount of

viral replication.

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Natural History of HIV Infection

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Acute Retroviral Syndrome

Non-specific flu-like symptoms;
Fever Fatigue Pharyngitis Lymphadenopathy Rash

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Pathogenesis of Acute HIV-1 Infection

Initial infection of CD4 cells and macrophages at site of exposure.
Dissemination of infection to lymph nodes.

Burst of viral replication results in intense viremia.

Development of humoral immunity (HIVspecific antibodies). Development of cellular immunity (HIV-specific CD4 and CD8 cells). 26

Clinical Latency
At CD4 cell counts over 500 cells/uL many complications overlap with conditions found in uninfected populations (bacterial pneumonia, tuberculosis, minor skin conditions), but they may be more frequent. At CD4 counts between 200 and 500 cells/uL other conditions and opportunistic infections may begin to appear (Kaposis sarcoma, oral/genital candidiasis, herpes 27 zoster, etc.).

Pathogenesis of Chronic HIV-1 Infection

High turnover of CD4 cells.
Continuous destruction and compensatory increased production of CD4 Lymphocytes.

Viral load plateaus at viral set point.

Non-specific, generalized, immune activation resulting in immune dysfunction. Viral reservoirs in resting infected cells.
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Immune Evasion by HIV

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Inability to Eradicate HIV-1 Infection

CD4 T cell decline CTL response inadequate Viral reservoir
Viral infection in sanctuaries (brain and genito-urinary tract) Viral persistence in lymphoid tissue Latency archiving in resting cells

Mutational Potential of HIV-1

Escape of HIV from CD8 immune response and neutralizing antibodies
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Immune Response in Children

Viral set point is higher in children. Disease progression similar to adults.

15-20% of children develop AIDS or die within 1 year.

10% survive for a prolonged period (5-6 years).

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Immune Response in Children (2)

Because the infants immune system is immature, disease progression is expressed as CD4%.

CD4% is the percent of total lymphocytes that are CD4 cells.

e.g., if total lymphocytes are 4000 cells per uL and 1000 of these cells are CD4 cells, the CD4% is 25%. 32

HIV Transmission and Prevention

Modes of Transmission
Mucosa (genital/rectal) Blood (transfusion, MTCT, needle stick injury) Breast Feeding

Prevention
Avoidance of infected mucosal secretions Safe blood transfusion service Post-exposure prophylaxis Prevention of Mother-to-Child Transmission Avoidance of breast feeding

Universal precautions
Hand washing Safe disposal of infected material
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Summary
HIV life cycle involves transcription of viral RNA into DNA and integration into human genome. Mutational potential of HIV-1 results in worldwide diversity (subtypes), viral escape from immune response and development of drug resistance. Viral replication persists throughout infection.

Fundamental pathology is the inability of the host immune system to eradicate HIV infection, which results in progressive destruction of the immune system.
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