Transcript Slide 1
Dr. Amaj Saeed MB.CH.B MSc PhD Clinical virologist [email protected] 4th commonest cause of death 34.5 x 106 infections worldwide 24.5 x 106 in sub-Saharan Africa 33% 15 year olds infected in some African countries impact on social, civil and economic stability Sexually - heterosexual - same sex Vertically - in utero - during delivery (15-40%) - breast milk (20%) Contaminated - IV drug misuse needles - needle stick injuries Blood products - transfusion/tissues factor VIII HIV initially infect CD4+ lymphocytes, macrophages and dendritic cells. HIV can infect macrophages. As the disease progress B lymphocyte function are affected through their regulation by CD4+ Th cells The destruction of the CD4+ helper cell subset is particularly damaging to overall orchestrated immune response leads to appearance of opportunistic infection. Mild influenza like illness (incubation time of about 3-4 weeks) Vigorous immune response resulting in dramatic fall of virus until the virus reach a set point (stage B). 60% of asymptomatic cases move in to AIDS related complex in the next 4 years : fever Weight loss. Persistent lymphadenopathy Night sweats Diarrhoea the most important factor is gradual loss of CD+ T cells Patients then proceed to full-blown AIDS (stage C) Thrush Herpes zoster Pneumocystis carinii pneumonia Death may occur if untreated (70%) Candidiasis of bronchi, trachea or lungs Candidiasis, oesophageal Cervical carcinoma, invasive Coccidioidomycocis, disseminated or extrapulmonary Cryptococcosis, extrapulmonary Cryptosporidiosis, chronic intestinal (1-month duration) Cytomegalovirus (CMV) disease (other than liver, spleen or nodes) CMV retinitis (with loss of vision) Encephalopathy, HIV-related Herpes simplex, chronic ulcers (1-month duration); or bronchitis, pneumonitis or oesophagitis Histoplasmosis, disseminated or extrapulmonary Isosporiasis; chronic intestinal (1-month durations) Kaposi’s sarcoma Lymphoma, Burkitt’s Lymphoma, immunoblastic (or equivalent term) Lymphoma (primary) of brain Mycobacterium avium complex or M. kansasii, disseminated or extrapulmonary Mycobacterium tubereculosis, any site Mycobacterium, other species or unidentified species, disseminated or extrapulmonary Pneumocystis carinii pneumonia Pneumonia, recurrent Progressive multifocal leucoencephalopathy Salmonella septicaemia, recurrent Toxoplasmosis of brain Wasting syndrome, due to HIV establish diagnosis - HIV antibody present (ELISA, Western blot) - determine VL (HIV RNA assays – bDNA, RT-PCR, NASBA) determine past exposure to OI - hepatitis A, B, C - CMV - toxoplasmosis exclude other active infection - syphilis, other STI - cervical cytology immune status - CD4/CD8 lymphocyte counts low CD4 count high VL - > 10,000 copies/ml > 35 years low BMI (weight (kg) / height (m)2) coinfection – CMV complicating systemic infections complicating malignancies eg. Lymphoma mucocutaneous respiratory gastrointestinal neurological eye (retina) haematological Bacteria Salmonella spp Mycobacterium tuberculosis M. avium-intracellulare Streptococcus pneumoniae Staphylococcus aureus Haemophilus influenzae Moraxella catarrhalis Rhodococcus equii Bartonella quintana Nocardia Viruses Cytomegalovirus Herpes simplex Varicella zoster Human papillomavirus Papovavirus Fungi and yeasts Pneumocystis carinii Cryptococcus neoformans Candida spp Dermatophytes (Trichophyton) Aspergillus fumigatus Histoplasma capsulatum Coccidioides immitis Protozoa Toxoplasma gondii Cryptosporidium parvum Microsporidia spp Leishmania donovani Isospora belli avoid exposure ◦ food ◦ protected sex ◦ CMV & blood products immunization ◦ hepatitis A & B chemoprophylaxis HIV lifecycle and antivirals Re vers e tran scriptas e bl ock e rs nucleoside analogs: AZT , 3T C, d4T non-nucleosides: delaviradine, nevirapine CD4 Prote ase bl ock e rs e.g., indinavir, ritonavir T ce ll or macroph age Co Receptor Entry inhibtors Re ve rs e tran s cri pti on an d in te gration As se m bl y, Bu ddin g &Matu ration NRTI Nucleoside reverse transcriptase inhibitors – (nucleoside analogues NA) abacavir, didanosine, lamivudine, stavudine, zalcitabine, zidovudine NNRTI Non-nucleoside RTIs efavirenz, nevirapine Protease inhibitors (PIs) amprenavir, indinavir*, nelfinavir, ritonavir, saquinavir*, lopinavir* (* combined with ritonavir – boosted) Fusion inhibitors enfuvirtide (T-20) A) NRTI x 2 + NNRTI OR B) NRTI x 2 + PI (boosted) (A) zidovudine & lamivudine + efavirenz OR nevirapine (B) zidovudine & lamivudine + lopinavir/ritonavir (kaletra) OR atozanavir/ritonavir OR indinavir/ritonavir OR amprenavir/ritonavir lipodystrophy ◦ increased fat deposits (abdomen, breast, ‘buffalo hump’) ◦ lipids, cholesterol and glucose mitochondrial toxicity ◦ lactic acid immune reconstitution ◦ flare in host response to OI eg. CMV, M. tuberculosis, HBV, VZ pregnancy ◦ avoid vertical transmission (AZT, combination therapy) newborn ◦ treat vertical infection (AZT, combination therapy) post-exposure prophylaxis ◦ needle stick injuries in HCW (AZT, 3TC, indinavir) acute seroconversion illness ◦ HAART Chemically inactivated whole virus vaccine (in effective) Recombinant DNA technology (expression of HIV env protein) Live attenuated HIV vaccine is under investigation (nef gene has been mutated) Prime boost approach : HIV env gene has been cloned in to harmless pox virus (canary pox), injection to the arm and subsequent replication of the pox virus DNA containing the HIV env gene prime the immune system, this will be followed by injection of recombinant env protein.