CLINICAL SPECTRUM OF HIV INFECTION y y y y Duration between primary infection and progression to clinical disease about 10years once

infected, remain infected for life death occurs within two years after onset of clinical symptoms clinical picture = manifestations of the dysfunction of the immune system + pathogenesis resulting from viral infection Clinical Latency (asymptomatic chronic infection)
y y can last as long as ten years very few infected cells found in peripheral blood not a time of true latency as virus expressing cells present in lymphoid organs

Primary infection (Acute retroviral syndrome)

y y y viral replication occurs at local LNs 4-11days, viraemia is detectable Level of virus in blood very high for 8-12weeks In this viraemic seronegative phase, patient highly infectious

Persistent generalized lymphadenopathy (PGL)

y definition: symmetrical enlargement of LN >1cm sites: two or more extrainguinal sites duration: >3months dt. reactive hyperplasia in LN LN is firm, mobile, not tender, preserved

Chronic constitutional disease (symptomatic infection)

y y y Formerly: AIDS related complex (ARC) Prodromal phase Main constitutional symptoms: 1. Fever more than 1month 2. Chronic diarrhea more than 1month 3. Loss of body weight more than 10%
y

AIDS (final stage)

Characterized by: 1. Tumours mainly: - Kaposi sarcoma Def: malignancy of endothelial cells of blood vessels Affects skin, LN and visceral organs Kaposi sarcoma associated herpes virus or HHV-8 causally related to cancer. 2. Oppurtunistic infections: - Pneumicystis carinii

y y y y

Virus widely disseminated in the body Lymphoid organs seeded with the virus Immune response occurs 1week3months after infection 50-75% of patients may develop acute mononucleosis like syndrome After seroconversion (seropositive), plasma viraemia drops and virus trapped in lymphoid tissues

y y

clinical latency occurs despite active virus replication low level chronicity state, virus multiplies and infects more cells decline in circulating CD4 lymphocytes count of this cells remain beyond critical level of immunodeficiency (<500) infected person exhibits no signs, no symptoms (except PGL) patient is considered as HIV carrier

y y

architecture As disease progresses, disrupted architecture of LN and regression in size (bad sign) This degeneration leads to: 1. Loss of the virustrapping function 2. Allows release of virus into circulation Resulting in rise of HIV in blood PGL may overlap with clinical latency or chronic constitutional disease

(wasting syndrome) 4. Various skin manifestations 5. Severe and recurrent forms of common infections (respond to treatment with difficulty): i. Infections with candida ii. HSV (persistent progressive mucotaneous HS) iii. HZV herpes zoster virus (persistent or disseminated) iv. TB v. Salmonella infections

pneumonia CMV retinitis Eneteritis Pneumonitis Cryptococcal meningitis Pulmonary infections dt. M.avium intracellulare - Progressive multifocal leucoencephalopathy (JC virus) 3. Severe forms of common infections 4. Neurologic diseases: - Peripheral neuropathy - Myelopathy - Myopathy - Aseptic meningitis - AIDS encephalopathy - AIDS dementia complex Neurologic abnormalities common in late stages (AIDS defining condition) Direct and indirect pathogenic mechanism might explain neuropsychiatric manifestations

i. -

TRANSMISSION OF HIV - HIV is extremely fragile and spread by specific preventable behaviours - Virus demonstrated in high titers in semen and cervical secretions - Also detected in saliva, tears, urine and breast milk - These sources have not been shown infectious except breast milk. HORIZONTAL TRANSMISSION VERTICAL TRANSMISSION Sexual transmission ii. Blood & blood products i. Congenital ii. Intranatal Hetero and - Transfusion of infectious - Transplacental - During birth, homosexual blood or blood products passage of virus from tansplacental Infection by breaks - Effective route for HIV - From mother's bleeding or in the epithelial transmission blood through contact of surface (provide placenta to the abrasions with direct access to - Sharing contaminated fetus virus containing underlying tissues syringe needle common fluids (cervical or blood stream) among intravenous drug secretions and and other STDs abusers blood) STDs especially genital ulcer disease increases risk of transmission During passage along the birth canal

iii. Early postnatal - Mainly through breast milk - Regimen of AZT therapy of mother reduced the risk of perinatal transmission by 60-70%: 1. During pregnancy 2. During birth process 3. baby after birth

LABORATORY DIAGNOSIS o Objectives of HIV testing:

1. 2. 3. 4. 5. Transfusion / donation safety Surveillance (incindence of HIV infection and pattern of spread) Diagnosis of HIV infection Research To monitor disease progression and response to treatment

IMMUNOLOGIC FEATURES
(degree of immune deficiency) Analysis of T-lymphocytes subsets: Great reduction in the absolute number of CD 4 lymphocytes Low ratio of helper to suppressor lymphocytes (CD4/CD8 ratio) y After person becomes infected with HIV: No. of CD 4 lymphocytes begin to drop gradually (CD4 slope) (about 50-100cells/mm 3/year) normal level of CD4 lymphocytes: 1000cells/mm 3 y

DETECTION OF VIRAL AG AND VIRAL NUCLEIC ACID

y Target for viral Ag detection viral core antigen p24 - Detected in serum by ELISA technique and in infected cells by IF Detection viral nucleic acid using PCR - Most sensitive method in newborn Antigen or N.A. detection is used in: 1. Early infection in the viraemic seronegative phase y -

VIRAL ISOLATION
most sensitive virus isolation technique cocultivate test sample with uninfected mitogen stimulated PBMC (peripheral blood mononuclear cells) Viral infection of susceptible lymphocyte cell line detected by testing culture supernatant fluids after 714days for: 1. Reverse transcriptase assay measures enzymatic activity of

ANTIBODY ASSAY (ANTI-HIV TESTS)

y routine screening of anti-HIV is done by using ELISA technique

+ve ELISA test should always be repeated Repeatedly reactive test should be confirmed y Tests used to confirm seropositive results are 1. Western Blot technique (WB) 2. Immunofluorescent assay Places with no facilities for

y CD4 cell count :

Clinical latency (patient is still beyond the critical level of immunodeficiency) <500 Chronic constitutional disease (degree of immunodeficiency) 500-200 Frank AIDS - <200 y y T4 lymphocyte counts: Best predictors of short term risk of developing an opportunistic disease.

2. To monitor disease progression and response to treatment 3. To detect infection in newborn 4. To detect antigen in supernatant fluids from cultures Viral load (amount of HIV in blood): Best predictor of long term clinical outcome Predictive marker of disease progression (high viral load predict rapid progression of disease) to monitor the effectiveness of antiviral therapy

released HIV particle 2. Indirect IF assay measures percentage of infected cells 3. RT-PCR Amplification assay measure HIV N.A.

confirmatory tests: Confirmation is done by retesting the repeatedly reactive sample using another screening assay having: 1. Different test principle or 2. Method of antigen preparation