HUMAN IMMUNODEFICIENCY VIRUS (HIV)

Structure & Property	Transmission	Pathogenesis	Clinical findings	Laboratory diagnosis	Treatment	
Family: retrovirus

Genome: single strand, 2 segments, +ve polarity RNA.

Genes:
- gag: core proteins – p24.
- pol: reverse transcriptase & integrase.
- env: envelop glycoproteins gp160 cleaved to gp 41 & gp120
- tat: enhances viral mRNA synthesis, suppress MHC class I expression.

Size: 100nm

Icosahedral nucleocapsid.

Enveloped virion with central wedge-shape core.

Two types:
- HIV-1
- HIV-2	HIV-1: main cause of the world-wide AIDS pandemic.

HIV-2: West Africa

Routes:
- sexual
- paraenterally by infected blood or blood products, needle-sharing among drug abusers.
- in utero from mother to child, perinatally or via breast milk.

Infected mothers transmit HIV to their babies in about 20% of cases:
- transplacentally: to cause infection in utero.
- during delivery or in the perinatal period.
- through breastfeeding.	Replication:
- binding of gp120 to CD4 protein on cell surface
- gp41 mediates fusion of viral envelope with cell membrane.
- virion RNA-dependent DNA polymerase transcribe genome RNA into dsDNA which integrates into host cell DNA.
- viral mRNA transcribed and cleaved.
- assembled virions released from cells by budding.

Pathology:
- infects helper T cells and kills them, resulting in suppression of cell-mediated immunity.
- virus causes disseminated infection and affect many organs.
- cells recruited into syncytia die.
- HIV-infected cells killed by immunologic attack by cytotoxic CD8 cells.
- HIV acts as a superantigen, activates many helper T cells.

Chronic infection for life.	Three stages of HIV infection:

Acute primary infection:
- often symptomless
- sometimes with an infectious mononucleosis-like illness some 2 weeks to 3 months after exposure with:
- fever, rash, sore throat, night sweats, malaise, lymphadenopathy, diarrhea and lymphocytosis.

Variable symptomless period:
- usually around 1-10 years.
- active viral replication in lymphoid tissues; mainly lymphocytes and macrophages.
- patients may show depressed counts of CD4 lymphocytes.

Symptomatic stage:
- leading into full-blown AIDS.
- presents with persistent lymphadenopathy and other infections associated with defective cell-mediated immunity:
- fever, diarrhea, fatigue, candidiasis, zoster, hairy leukoplakia of tongue
- idiopathic thrombocytopenic purpura.

Progression to AIDS correlates with:
- decrease in CD4 count
- appearance of p24 in blood.

AIDS:
- characterized by an extreme degree of immunodeficiency, with low and decreasing CD4 counts.
- results in a serious of opportunistic infections and certain tumors.

Symptoms of infected infants:
- failure to thrive
- fever, diarrhea, frequent infections.
- lymphadenopathy, lymphoid intestinal pneumonia
- parotitis
- hepatosplenomegaly
- progressive encephalopathy and dementia.	Tissue culture:
- grows in lymphocytes with variable CPE.
- cocultivation with certain other cells results in syncytium formation and allows easier detection of virus growth.

Diagnosis: 
- detection by ELISA but there are some false-positives.
- definitive test is made by Western blot.
- positive test requires presence of bands at gp24, gp31, gp41, gp120.

PCR for the detection of:
- virus RNA in blood and other body fluids.
- virus load: quantification of amount of virus in blood to monitor progress of disease.

Infection in infants:
- difficult to diagnose because of persistent of maternal antibody in all babies born to infected mothers.
- HIV antibody persisting around 15 months is strong evidence of infection.
- use of PCR for detection or isolation of virus from the infant’s leukocytes.	Treatment aimed at two targets:
- HIV: AZT does not eradicate virus but improves survival.
- associated opportunistic infections and tumors are treated with antimicrobial drugs and chemotherapy.
 
Current treatment of choice: 2 nucleoside inhibitors and a protease inhibitor.

No vaccine is available.

Prevention:
- avoid exposure to virus: use of condoms, not sharing needles, discarding donated blood contaminated with HIV.
- AZT given perinatally to HIV-infected mothers who should not breast-feed.