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History
1984: Virus isolated in the U.S. (called HTLV-III and AIDS-Related Virus, ARV). 1985: Development and implementation of antibody test to screen blood donors
History
1986:
Consensus name Human Immunodeficiency Virus (HIV-1), first case in India was detected in Chennai
Related virus (HIV-2) identified 1992: AIDS becomes the leading cause of death
among adults ages 25-44 in the U.S. 1997: Mortality rates of AIDS starts to decline due to the introduction of new drug cocktails 2001: World Health Organization predicts up to 40 million infected individuals. More than 22 million have already died.
HIV Virus
RNA virus HIV-I: A,D: East, West, North, Central Africa B: US, Europe, East Asia, Brazil C: India, South Africa E: Thailand F: East Europe, Brazil HIV-II : West Africa, Brazil, South West Asia Less transmissible Associated with lower viral load , Slower rate of clinical progression Not susceptible to NNRTI, possible PI resistance
Group O - west-central Africa Group N - discovered in 1998 in Cameroon - is extremely rare Group M - nine genetically distinct subtypes A, B, C, D, F, G, H, J and K
gag pol env (tat, rev, nef, vif, vpr, vpu) tev
Virus binds to surface molecule (CD4) of T helper cells and macrophages. - Coreceptors: Required for HIV infection - CXCR4 and CCR5 mutants are resistant to infection Fusion: Viral envelope fuses with cell membrane, releasing contents into the cell
Reverse transcriptase
RNA ------------------------> DNA Reverse transcriptase is the target of several HIV drugs: AZT, ddI and ddC. Integration: Viral DNA is inserted into host cell chromosome by unique enzyme integrase. Integrated viral DNA may remain latent for years and is called a provirus.
Transmission Categories
Transmission Categories
Sexual Perinatal Blood and blood products Injecting drug users Number of cases 93,964 3,957 2,201 2,661
%
85.93 3.62 2.01 2.43
6,566
109,349
6.00
100%
Pathogenesis
Viral transmission
2-3 wks
Recovery + Seroconversion
2-4 wks
Death
Natural History
Women
Children under 15 years
Source: Joint United Nations Programme on HIV AIDS (UNAIDS) and WHO 2006
AIDS deaths in 2006 Total Adults Children under 15 years 2.9 million (2.5-3.5 million) 2.6 million (2.2-3.0 million) 3,80,000 (2,90,000-5,00,000)
Source: Joint United Nations Programme on HIV AIDS (UNAIDS) and WHO 2006
Revised WHO clinical staging of HIV/AIDS for Adults and Adolescents (2005)
Asymptomatic
Acute retroviral syndrome
Clinical stage 1
Asymptomatic
Persistent generalized lymphadenopathy
Revised WHO clinical staging of HIV/AIDS for Adults and Adolescents (2005)
Clinical stage 2
Moderate and unexplained weight loss (<10% of presumed or measured body weight) Recurrent respiratory tract infections Herpes Zoster Recurrent oral ulcerations Papular pruritic eruptions
Seborrhoeic dermatitis
Fungal nail infections
Revised WHO clinical staging of HIV/AIDS for Adults and Adolescents (2005)
Clinical stage 3
Conditions where a presumptive diagnosis can be made on the basis of clinical signs or simple investigations
Unexplained chronic diarrhoea for longer than one month Unexplained persistent fever Severe weight loss (>10% of presumed or measured body weight) Oral candidiasis Oral hairy leukoplakia
Revised WHO clinical staging of HIV/AIDS for Adults and Adolescents (2005)
Clinical stage 3 Pulmonary tuberculosis (TB) diagnosed in last two years Severe bacterial infections Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis
Conditions where confirmatory diagnostic testing is necessary
Unexplained anaemia (< 80 g/l), and or neutropenia (<500/l) and or thrombocytopenia (<50 000/ l) for more than one month
Revised WHO clinical staging of HIV/AIDS for Adults and Adolescents (2005)
Clinical stage 4
Conditions where a presumptive diagnosis can be made on the basis of clinical signs or simple investigations
HIV wasting syndrome Pneumocystis pneumonia Recurrent severe or radiological bacterial pneumonia Chronic herpes simplex infection (orolabial, genital or anorectal of more than one months duration)
Revised WHO clinical staging of HIV/AIDS for Adults and Adolescents (2005)
Clinical stage 4 Oesophageal candidiasis Extrapulmonary Tuberculosis Kaposis sarcoma Central nervous system toxoplasmosis HIV encephalopathy
Conditions where confirmatory diagnostic testing is necessary
Revised WHO clinical staging of HIV/AIDS for Adults and Adolescents (2005)
Clinical stage 4 Disseminated non-tuberculous mycobacteria infection Progressive multifocal leukoencephalopathy Candida of trachea, bronchi or lungs Cryptosporidiosis Isosporiasis Visceral herpes simplex infection
Revised WHO clinical staging of HIV/AIDS for Adults and Adolescents (2005)
Clinical stage 4 Cytomegalovirus infection Any disseminated mycosis (e.g. histoplasmosis, coccidiomycosis, penicilliosis) Recurrent non-typhoidal salmonella septicaemia Lymphoma (cerebral or B cell non-Hodgkin) Invasive cervical carcinoma Visceral leishmaniasis
Clinical Axis
Stage II Early HIV 2A 2B 2C Stage III Intermediate (ARC) +++ 3A 3B 3C Stage IV late AIDS 4A 4B 4C
Double ELISA
In Pediatrics :
Baseline investigations
To Rule Out Underlying O.Is X-ray chest Montoux test Sputum for AFB USG abdomen FNAC/Biopsy of lymphnodes VDRL HbsAg
Baseline investigations
For Monitoring ARV Hb CBC LFT RFT Blood sugar Urine & Stool S. Cholesterol S.Triglycerides S. Uric acid S.Creatinine S. Lactic acid S. Amylase Prognostic Investigations CD4 lymphocyte enumeration Plasma Viral load assays
Side-effects of ART
Adherence & compliance Failure of therapy Extended counseling for relatives & friends Safe sex-practices
Aim of ART
Improve symptom free longevity by maximal, sustainable & durable suppression of viral replication (<50 copies/ml)
Indications of ART
AIDS defining HIV illness regardless of CD4 count and viral load levels - eg. esophageal candidiasis CD4 counts < 200; Viral load > 1,00,000 copies/ml Total lymphocyte count < 1200 cells/ml
WHO Guidelines
CD4 count available WHO stage IV WHO stage I / II / III CD4 <200/cu.mm CD4 count not available WHO stage IV WHO stage II / III TLC <1200 cells/cu.mm
PI
Saquinavir soft gel hard gel Indinavir Ritonavir Nelfinavir Amprenavir Lopinavir Atazanavir Fosamprenavir SQV SGC HGC IDV RTV NFV APV LPV ATV f-APV
NNRTI
Nevirapine Efavirenz Delavirdine
Fusion Inhibitor
Enfuvirtide T-20
ART Regimens
3 Drug combination 2 NRTI + 1 NNRTI 2 NRTI + 1 PI 1 NRTI + 1 NNRTI + 1 PI 3 NRTI
Cutaneous Infections
Bacterial: Staphylococcus Aureus: Bullous Impetigo, Ecthyma, Folliculitis Bartonella: Bacillary Angiomatosis Pseudomonas Aeruginosa Mycobacterial Infection: Scrofuloderma, TB Gumma, Atypical mycobacterial infections
Cutaneous Infections
Viral: Herpes Simplex Virus Varicella Zoster: Multidermatomal, Recurrent, Bullous, Hemorrhagic and Necrotic Molluscum Contagiosum Human Papillomavirus (Warts) Acute HIV exanthem & enanthem
Superficial Infections: Thrush, Dermatophytosis Deep (Systemic) Fungal Infections: Cryptococcosis, Histoplasmosis, Sporotrichosis, Aspergillosis, Candidiasis, Coccidioidomycosis, Actinomycosis, and Phaeohyphomycosis
Inflammatory conditions
Psoriasis Reiter's Syndrome Xerosis and Ichthyosis Seborrheic Dermatitis, Atopic Dermatitis Pruritic Papular Eruptions Eosinophillic Folliculitis Insect Bite Reactions Photosensitivity Porphyria Cutanea Tarda (PCT) Aphthosis
Drug Reactions
Morbilliform drug eruptions Urticaria Fixed drug eruption Erythema multiforme Stevens Johnson syndrome Toxic epidermal necrolysis Erythroderma
Drug Reactions
Morbilliform drug eruptions Urticaria Fixed drug eruption Erythema multiforme Stevens Johnson syndrome Toxic epidermal necrolysis Erythroderma
Kaposi's Sarcoma Basal cell carcinomas Squamous cell carcinomas HIV-associated lymphoma of either T or B cells
Diffuse alopecia, telogen effluvium, alopecia areata Elongation of the eyelashes and softening and straightening of the scalp hair Beau lines, pallor of the nail beds Longitudinal, transverse, or diffuse melanin pigmentation of the nails (Zidovudine or HIV associated) Proximal subungual onychomycosis
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