AIDS

Megha J Nair6th Batch

INTRODUCTION

Acquired Immunodeficiency Syndrome

First indication in 1981 with reports from New York and Los Angeles-sudden outbreak of two rare diseases-kaposi’s sarcoma and Pnuemocystis carinii

HUMAN IMMUNODEFICIENCY VIRUS

Causative agent of AIDS Spherical enveloped virus about 90-120 nm in

size Genome is diploid composed of two identical

single stranded positive RNA copies Along with viral RNA – reverse transcriptase

enzyme-characteristic feature of retrovirus When virus infects cell-reverse trancriptase

transcribe the single stranded RNA to double stranded RNA nand then to double stranded DNA(PROVIRUS)-integrates into human genome!

During viral replication , when the virus buds out of the host cell surface membrane-acquires a lipoprotein envelop-consists of lipid derived from the host cell membrane and glycoproteins which are virus coded

Major virus coded envelop protein –projecting knob like spikes and anchoring transmembrane pedicles

Spikes-major surface component of virus which binds to CD4 receptors on host cells…transmembrane proteins help in cell fusion

PATHOGENESIS

Transmitted mainly through sexual contact or through blood transfusion

Transmitted when the virus enters the blood or the tissues and come in contact with suitable host cells

Receptor for virus –CD4 antigen-thus infect any cells bearing CD4 antigen on surface-primarily the CD4+ helper T cell

Others include B lymphocytes,monocytes and macrophages such as specialised macrophages of lungs langerhan cells in dermis.

After fusion of virus with the cell-HIV genome uncoated and internalised into the cell

Action of reverse transcriptase enzyme-double stranded DNA integrated into the human genome with the help of integrase-causes latent infection

Long and variable incubation period is due to latency

Primary pathogenic mechanism-due to damage caused to the CD4 T lymphocytes

T4 cells decrease in number,CMI reduces T4:T8 ratio reverses Helper T cell function-essential for B cell

function-polyclonal activation of Bcells -hypergammaglobulinemia

CLINICAL MANIFESTATIONS

Not primarily to viral cytopathology but due to failure of immune responses

AIDS – only the last stage in the wide spectrum of clinical features

STAGES OF EVOLUTION

Acute HIV infection

Asymptomatic or latent infection

Persistent generalised lymphadenopathy

AIDS related complex

AIDS

ACUTE HIV INFECTION

Within 3-6 weeks of infection

Low grade fever,malaise,head ache,lymphadenopathy,sometimes with rashes arthropathy resembling glandular fever.Spontaneous resolution within weeks

Tests for HIV antibodies negative in early stage and get positive during its course-seroconversion illness.

ASYMPTOMATIC AND LATENT INFECTION

Symptomless infection Positive HIV antibodies test Passes through various stages-CD4

lymphocytopaenia,minor oppurtunistic infection,persistent generalised lymphadenopathy,ARC and full blown AIDS

Viral multiplication goes on-immune response mounnted by host-only helps in limiting viral load

Tcell-500 from 1000/microlitre-acute infection and when 200 or less , clinical AIDS

PGL

Enlarged lymph nodes

Atleast 1 cm or more

In two or more non contiguous extrainguinal sites-that persists for more than 3 months in the absence of any current illness or medication

PGL

ARC

Patients with considerable immunodeficiency suffering from various constitutional symptoms or minor oppurtunistic infections

Fatigue , unexplained fever , persistent diarrhoe , marked weight lose-symptoms-also gen. lymphadenopathy and splenomegaly

Oppurtunistic inf.-oral candidiasis,herpes zoster,hairy cell luekoplakia,salmanellosis or tb

ORAL THRUSH

AIDS

• End stage disease-irreversible breakdown of immune system-progressive oppurtunistic infection and malignancies.

• Dry cough , dyspnea , fever , recurrent pneumonia

• GIT-thrush , herpetic steatites , gingivitis , hairy luekoplakia or kaposi’s sarcoma.A characteristic intestinal pathogen is cryptosporidium

HAIRY LEUKOPLAKIA

CNS-toxoplasmosis and cryptococcosis,lymphomas of CNS also seen.also can cross blood brain barrier and cause encephalopathy leading to loss of higher function-then dementia

Malignancies-kaposi’s sarcoma(nonmetastasing mucosal or cutaneous tuour of endothelial orgin)Hodgkin and Non Hodgkin lymphomas

Babies born to infected mothers-also positive-

KAPOSI’S LESIONS

DIAGNOSIS

IMMUNOLOGICAL TESTS: Total luecocyte and lymphocyte count Tcell subset assay-ratio inversion.Absolute

CD4 cell count less than 200/cubic mm Platelet cout will show thrombocytopaenia Raised IgG and IgA levels Diminished CMI by skin tests Lymph node biopsy

Specific tests: Antigen detection:major core antigen-

p24-earliest marker-p24 antigen capture assay

Viral isolation:cocultivation of patient’s lymphocyte with uninfected lymphocyte in the presence of interluekin 2.viral replicatio detected by demo of reverse transcriptase activity as well as antigen

PCR:golden standard for diagnosis of all stages of HIV infection

Antibody detection: ELISA Test

Western blot test-HIV proteins seperated by their electrophoretic mobility by poly acrylamide gel electrophoresis are blotted on to the strips of nitrocellulose paper.strips are reacted with test sera and then with enzyme conjugated anti human globulin

TREATMENT

Treatment and prophylaxis of infections and tumours

General managementImmunorestortive

measures(administration of interluekin 2,thymic factors etc)

Specific anti-HIV drugs(anti retroviral drugs)

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