Wednesday, June 1, 2011

Human Immunodeficiency Viruses

ssRNA genome


Infection is transmitted in a manner identical to that of hepatitis B.

1.) Blood products

• Blood transfusions

• Intra-venous drug abusers - sharing of needles

• Health care workers:

needlestick injuries - risk approximately 0.36% (depends on extent of the injury)

muco-cutaneous exposure - no sero-conversion incidents have been reported

2.) Organ transplants

3.) Sexual intercourse

Both homosexual and hetero-sexual exposure

Increased risk of transmission if partners have other sexually transmitted diseases

4.) Vertical Transmission

10-40% of babies born of HIV-infected mothers will be infected.

Infection may occur

in utero

during birth

post-natally, through breast feeding

Primary infection

About 90% of patients develop a flu-like illness which co-incides with seroconversion, between 2 and 4 weeks post exposure. Symptoms include, fever, night sweats, sore throat, lymphadenopathy, diarrhoea. The illness is self limiting.

Asymptomatic phase

Of variable duration, from 2 to 10 years. Patients are clinically well, but infectious.

Prodromal phase

This period is heralded by the insidious onset of a variety of prodromal disorders, including: weight loss, fever, persistant lymphadenopathy, oral candidiasis and diarrhoea. These symptoms precede the progression to AIDS.

Acquired Immunodeficiency Syndrome (AIDS)

Syndrome with the following features:

1) Constitutional disease: fever, diarrhoea, weight loss, skin rashes

2) Neurological disease: dementia, myelopathy, peripheral neuropathy

3) Immunodeficiency: Increased susceptibility to opportunistic infections: (see table 1)

4) Rare malignancies: Kaposi sarcoma, oral hairy leukoplakia, lymphomas.

Kaposi sarcoma - is a tumour of endothelial cells. Prior to the AIDS epidemic, this tumuor was rare and only found in middle aged African and Mediterranean Jewish men, in whom it was an indolent condition. AIDS patients develop a disseminated highly aggressive form of the disease.

Paediatric Infection

Following infection in the perinatal period, babies may develop a progressive illness in the first few months of life (No latent period). Clinical features include: Failure to thrive, diarrhoea, lymphadenopathy, susceptibility to opportunistic infections hepato-splenomegaly, lymphoid interstitial pneumonia and parotitis.


HIV infects CD4 cells

Disseminated infection

Specific immune Response


Cell mediated immunity

Clearance of most virus

Some persistence

a) Gradual loss of CD4 cells

b) Destruction of microenvironment of lymphoid tissue


Cell tropism: CD4+ T cells, Macrophages

Destruction of CD4 cells occurs through the following mechanisms:

direct lysis of infected cells

syncytium formation

Infection of precursor cells and destruction of microenvironment

Impairment of CD4 cell function



IgG develops 4-6 weeks post exposure and remains detectable for life. Its presence in serum therefore indicates infection.

Exception: Uninfected infants of HIV positive mothers

Direct detection of virus

p24 antigen ELISA

culture from PBMC's



There is no effective vaccine available for HIV. Attempts have been made to develop a vaccine, using:

• purified viral envelope glycoproteins, gp120 or 160

• whole inactivated virus

• live attenuated HIV strains (lacking certain genes)

• live recombinant virus vectors, expressing HIV proteins.

A major difficulty is the fact that neutralizing antibody in the serum does not protect the host from infection with HIV: Possible reasons for this include:

• Antibody enhancement of infection

• Rapid virus mutation may result in variation of envelope antigens (escape mutants)

• HIV can infect cells in sites that are sequestered from antibody

• Host may be infected by whole virus-infected cells

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