HIV & AIDS

objectives
Historical aspects Mode of transmission of HIV Pathogenesis of HIV infection Investigations Clinical staging Complications

Historical Background
June, 1981 : 5 cases of homosexual men with P. carinii pneumonia in Los Angeles, USA June27, 1982 : CDC names the new disease as AIDS Acquired Immuno- deficiency Syndrome April, 1984 : Viral aetiology of AIDS identified by two groups of scientists. March, 1985 :Tests Kits developed to detect antibodies to HIV 1986 : International Committee on Taxonomy of Viruses named the virus as Human Immunodeficiency Virus (HIV) 1986 HIV2: Probable origin: monkeys in West Africa. 1987 : Zidovudine marketed under the brand name of Retrovir.

 HIV classified as lentivirus , subfamily of retroviruses. HIV two distinct groups HIV-1 and HIV-2

HIV-1 was evolved from Pan troglodytes subspecies of chimpanzee.

Most common cause of HIV disease throught the world.

HIV -2 was transmited from sooty mangabeys, a traditional source of nutrition in subsaharan Africa.

Efficacy of different routes of HIV of transmission and their contribution to total number of cases

no Exposure route 1 Blood transfusion

Efficiency % of total India 90 95% 5 5.5

2
3

Perinantal
Sexual intercourse

20 40%
.01- 1.0 %

10
75

0.7
81

4
5 6

IDU
Needle exposure Others

0.5 1.0%
0.5%

10
0.1

5.2

7.6

Occupational transmission
Small

but definite risk of occupational transmission. Following skin puncture from needle, chance is 0.3%. Following mucous membrane exposure, chance is .09%. Transmission through intact skin not documented.

Mother to child transmission

Risk of trans mission from HIV infected mother to her babies are : 21 49% Transmission may occur during antepartum, intrapartum, postpartum, breast feeding. Prevention is possible through antenatal counseling and therapy

Cells affected by HIV

All cells expressing CD4 molecule T lymphocytes Monocytes & macrophages Dendritic/Langerhans cells

Viral pathogenesis & immune response

Historical Indications for HIV Antibody Testing

Men who have sex with men Persons with multiple sexual partners Current or past injection drug users Recipients of blood products between 1978 and 1985 Persons with current or past STD's Commercial sex workers and their contacts Pregnant women and women of child-bearing age Children born to HIV-infected mothers Sexual partners of those at risk for HIV infection Donors of blood products, semen, or organs Persons who consider themselves at risk or request testing

Clinical Indications for HIV Antibody Testing

Tuberculosis Syphilis Recurrent shingles Chronic constitutional symptoms Chronic generalized adenopathy Chronic diarrhea or wasting Encephalopathy Thrombocytopenia Unexplained thrush or chronic/recurrent vaginal candidiasis HIV-associated opportunistic diseases

Indicators Conditions in Case Definition of AIDS (Adults)Candidiasis of esophagus,trachea, bronchi, or lungs. Herpes simplex more than one month Cervical cancer Coccidioidomycosis- extra pulmonary Cryptococcosis

CMV of any organ

Histoplasmosis

HIV associated Dementia Weight loss >10% Kaposi Sarcoma Lymphoma

MAC
Mycobacterium Tuberculosis PCP

Pneumonia> 2 episode per year PML

Toxoplasmosis

ICCTC
Pretest counseling Informed consent HIV testing Post test counseling Follow up counseling

Diagnostic Tests for HIV Infection HIV antibody(IgG) testing is performed by using enzyme-linked immunosorbent assay (ELISA), which is highly sensitive If result is negative, the test is reported as negative If result is positive, the ELISA is repeated If the repeat test is positive, a Western blot (WB) assay is performed for confirmation

 If WB assay result is positive, the test is reported as positive WB results are occasionally described as indeterminate; supplemental testing may be recommended Standard HIV antibody testing may not detect HIV-2, which is common in West Africa A low CD4 cell count is not diagnostic of HIV disease IgG not reliable for babies

 IgG antibody to p24 (anti-p24).

can be detected from the earliest weeks of infection and through the asymptomatic phase. frequently lost as disease progresses

Genome detection assays. Nucleic acid-based

assays that amplify and test for components of the HIV genome used to aid diagnosis of HIV in the babies of HIVinfected mothers in early infection when antibody may not be present subtyping HIV variants for medicolegal reasons.

 Viral p24 antigen (p24ag). This is detectable shortly

after infection but has usually disappeared by 810 weeks after exposure. in individuals who have been infected recently but have not had time to mount an antibody response

Isolation of virus in culture. This is a specialized

technique available in some laboratories to aid diagnosis and as a research tool

CD4 Cell Count

Surrogate marker for HIV disease progression Normal value > 500/mm3 Average decline of 50-100 per year Variability between patients Intercurrent illnesses may affect value Main clinical uses are to determine need for antiretroviral therapy and prophylaxis against opportunistic pathogens

Improved understanding of "reconstituted" immunologic function

Viral Load Testing

Measurement of viral RNA by PCR or bDNA Level correlates with CD4 cell count decline and clinical progression; the lower, the better Normal variability of 0.3 log (3- to 5-fold) Intercurrent illnesses and immunizations may affect value Main clinical uses are to determine need for antiretroviral therapy and assess effectiveness

HIV Seroconversion Syndrome

Fever 96% Adenopathy 74% Pharyngitis 70% Rash 70% Diarrhoea 32% vomiting 27% Hepatosplenomegaly 14% Neurological symptom 12% Maculopapular rash

WHO Clinical Staging of HIV/AIDS

Clinical stage 1
Asymptomatic Persistent generalized lymphadenopathy (PGL):defined as lymphadenopathy (>1 cm) at two or more extra inguinal sites for more than 3 months in the absence of causes other than HIV infection.

CLINICAL STAGE : 2 (Adult)

Weight loss < 10% body weight Minor mucocutaneous manifestation (seborrhoeic

dermatitis, prurigo, fungal nail infections, recurrent

oral ulcerations, and angular chelitis) Herpes zoster, within last 5 years Recurrent upper respiratory infections (I.e., bacterial sinusitis)

And or performance scale 2: symptomatic , normal

otherwise

CLINICAL STAGE : 3 (Adult)

Weight loss > 10% body weight Unexplained chronic diarrhoea, >1 month Unexplained prolonged fever (intermittent or constant), > 1 month Oral candidiasis (thrush)

Oral hairy leukoplakia

Pulmonary tuberculosis, within the past year Severe bacterial infections (I.e. pneumonia, pyomyositis) And / or performance scale 3: bed-ridden <50% of the day during the last month

CLINICAL STAGE : 4
HIV wasting syndrome : weight loss of > 10%, plus either unexplained chronic diarrhoea > 1 month, or

chronic weakness and unexplained prolonged fever

> 1 month Pneumocystis carinii pneumonia Toxoplasmosis of the brain Cryptosporidiosis with diarrhoea, > 1 month

Cryptococcosis, extrapulmonary
Cytomegalovirus (CMV) disease of an organ other

than liver, spleen or lymph nodes

CLINICAL STAGE : 4
Herpes simplex virus (HSV) infection, mucocutaneous > 1 month, or visceral Progressive multifocal leukoencephalopathy (PML) Any disseminated endemic mycosis ( I.e.) histoplasmosis, coccidioidmycosis Candidiasis of the oesophagus, trachea, bronchi or lungs

Atypical mycobateriosis, disseminated

Non-typhoid Salmonella septicaemia

CLINICAL STAGE : 4
Extrapulmonary tuberculosis Lymphoma

Kaposis Sarcoma (KS)

HIV encephalopathy (Clinical findings of disabling cognitive and / or motor dysfunction interfering with activities of daily living, progression over weeks or months, in the absence ofa concurrent illness or condition other than HIV infection that could explain findings) And / or Performance scale 4: bed ridden , > 50 of the

day during the last month

CDC classification of HIV infection

Spectrum of HIV Infection

CD4 cell count > 500/mm3 Most patients asymptomatic Bacterial infections, TB, shingles CD4 cell count 500-200/mm3 Some patients asymptomatic Generalized lymphadenopathy, KS, thrush

CD4 cell count < 200/mm3 PCP, cryptococcosis, toxoplasmosis

CD4 cell count < 50/mm3 CMV and MAC infections Increased risk of lymphoma Mortality highest

Systemic Complications in HIV/AIDS

Oral complications
Candidiasis Herpes Simplex Kaposis Sarcoma Oral Hairy Leukoplakia

Gastrointestinal Complications
Anorxia, nausea, vomiting Aphthous ulcers Esophageal Candidiasis Diarrhoea

Liver Diseases
Viral hepatitis B,C Cholangiopathy Pancreatitis

Dermatlogic Complications

Pulmonary Complications
Pneumonia Pulmonary Tuberculosis Pneumocystis Carinni Histoplasmosis Crytococcosis MAC Lymphocylic interstitial Pneumonia

Cardio Pulmonary Complications

Dilated Cardiomyopathy Pulmonary hypertension Tricuspid Valve endocarditis

Neurological Complications
Distal Sensory Neuropathy Polyradiculitis Myelopathy AIDP Monneuritis multiplex Dementia Toxoplasmosis Cryptococcal Meningitis Primary CNS lymphoma Tubercular Meningitis

Genitourinary Complications
HIV Nephropathy Renal Stone UTI Vulvo- vaginal candidiasis

HAEMATOLOGICAL COMPLICATIONS
Anaemia Thrombocytopenia Persistent generalised lymphadenopathy Lymphopenia Neutropenia Pancytopenia Drug induced

Malignancies
Kaposi Sarcoma Non-Hodgkin,s lymphoma Primary CNS lymphoma

Ophthalamological Complications
CMV Retinitis Acute retinal necrosis syndrome Chorioretinitis due to toxoplasma

Major hiv associated pathogens

conclusion
HIV is a lente virus, subfamily of retrovirus It has varied modes of transmission, most important being blood transfusion, sexual and perinatal All the cells with CD4 molecule are affected by HIV Clinical staging is important for both therapeutic and prognostic reasons Any system may be involved in HIV infection