Human Immunodeficiency Virus

An Overview

Human Immunodeficiency Virus

Acquired Immunodeficiency syndrome (AIDS)

first described in 1981

Belong to the lentivirus subfamily of the

retroviridae

Enveloped RNA virus, 120nm in diameter

Mode of transmission

Sexual transmission

Blood/blood products

Vertical transmission - the transmission from mother to

the newborn

HIV IS FOUND IN BODY FLUIDS

Semen

Breast milk

Blood

Vaginal fluid

3

Tears

Saliva

Sweat

Urine

You CANNOT get HIV from…

HIV-1 and HIV-2

HIV-1 and HIV-2 are

• Transmitted through the same routes

• Associated with similar opportunistic infections

HIV-2 is less easily transmitted

HIV-1 is more common worldwide

HIV-2 is found in West Africa, Mozambique.

HIV-2 is less pathogenic

Duration of HIV-2 infection is shorter

HIV particles

(HIV)

Icosahedral or Wedge-

shaped Nucleocapsi

d

Reverse Transcript

ase

Lipid Membrane

single stranded (+) sense

RNA

gp120

gp41gp160

(NIH, 2005)

Replication The first step of infection is the binding of gp120

to the CD4 receptor of the T helper cell

Macrophages, monocytes and dendritic cells express

CD4 receptors and also infected by the virus

which is followed by penetration and uncoating.

The gp41 mediates fusion of the viral envelope

with the cell membrane,

The RNA genome is then reverse transcribed

into a DNA provirus which is integrated into the

cell genome.

This is followed by the synthesis and maturation

of virus progeny.

Clinical Features1-The acute stage:

Begins 2-4 weeks after infection with a mononucleosis-

like picture

it resolves spontaneously in 2 weeks.

2-A latent stage:

For up to 10 years follows.

The patient is asymptomatic.

AIDS-related complex or persistent generalized

lymphadenopathy.

3-Full-blown AIDS.

AIDS

Opportunistic infection

Protozoal pneumocystis carinii , Toxoplasmosis

Fungal Candidiasis, crytococcosis, histoplasmosis

Bacterial Mycobacterium avium, MTB, AMB

Viral CMV, HSV, VZV, JCV

tumors

The most frequent opportunistic tumour, Kaposi's sarcoma

Malignant lymphomas

The most frequent neurological disorder is AIDS

encephalopathy

Other manifestations include characteristic skin

eruptions and persistent diarrhoea.

Kaposi’s Sarcoma

HIV Pathogenesis Immunosuppression in AIDS is due to depletion of T

helper cells.

Antibodies to HIV appear 3-4 weeks after infection.

An immune response, by cytotoxic T cells and humoral

immunity, controls the infection in the acute stage

In the acute stage, HIV is present at a high level in blood

It then derease to a certain low level during the Latent

stage.

AIDS develop when severe decrease in CD4 cells occur.

Laboratory Diagnosis

Decreased CD4 count and inversion of the

CD4/CD8 ratio

Serology detects antibodies against p24 or gp41,

gp120 or gp160 and others by ELISA and RIBA.

Detection of viral nucleic acid in clinical samples

by PCR

Detection of viral antigens i.e. p24 by ELISA,

Virus isolation from lymphocytes, bone marrow or

plasma

Treatments Reverse Transcriptase (RT) Inhibitors – interrupt

early stage of viral replication

1) Nucleoside/nucleotide RT inhibitors• Insert faulty DNA building blocks into HIV genome

• Prevents completion of DNA chain → no replication

2) Non-nucleoside RT inhibitors• Bind to reverse transcriptase and prevents reverse transcription

Protease Inhibitors – interrupt late stage of viral replication in the HIV life cycle

Fusion Inhibitors – new class of drugs• Fuzeon interferes with HIV ability to enter the cell

Nevirapine

Zidovudine

Indinavir Ritonavir Saquinavir

HAART

HAART (highly active anti-retroviral therapy): 2

nucleoside reverse transcriptase inhibitors and a

protease inhibitor. e.g. AZT, lamivudine and

indinavir.

Since the use of HAART, mortality from HIV has

declined dramatically in the developed world.

It may be possible to reduce toxicity, improve

efficacy and prevent resistance.

Reduces the amount of virus circulating in blood

to nearly undetectable levels.