Presentation on theme: "Clinical aspects of HIV"— Presentation transcript:
1Clinical aspects of HIV Dr. Amaj Saeed MB.CH.B MSc PhD Clinical virologist
2HIV – global impact 4th commonest cause of death 34.5 x 106 infections worldwide24.5 x 106 in sub-Saharan Africa33% 15 year olds infected in some African countries impact on social, civil and economic stability
3HIV – transmissionSexually - 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
5HIV 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
6The destruction of the CD4+ helper cell subset is particularly damaging to overall orchestrated immune response leads to appearance of opportunistic infection.
7Mild 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 :feverWeight loss.Persistent lymphadenopathyNight sweatsDiarrhoeathe most important factor is gradual loss of CD+ T cells
8Patients then proceed to full-blown AIDS (stage C) ThrushHerpes zosterPneumocystis carinii pneumoniaDeath may occur if untreated (70%)
9AIDS-defining conditions Candidiasis of bronchi, trachea or lungsCandidiasis, oesophagealCervical carcinoma, invasiveCoccidioidomycocis, disseminated or extrapulmonaryCryptococcosis, extrapulmonaryCryptosporidiosis, chronic intestinal (1-month duration)Cytomegalovirus (CMV) disease (other than liver, spleen or nodes)CMV retinitis (with loss of vision)Encephalopathy, HIV-relatedHerpes simplex, chronic ulcers (1-month duration); or bronchitis, pneumonitis or oesophagitisHistoplasmosis, disseminated or extrapulmonaryIsosporiasis; chronic intestinal (1-month durations)Kaposi’s sarcoma
10AIDS-defining conditions Lymphoma, Burkitt’sLymphoma, immunoblastic (or equivalent term)Lymphoma (primary) of brainMycobacterium avium complex or M. kansasii, disseminated or extrapulmonaryMycobacterium tubereculosis, any siteMycobacterium, other species or unidentified species, disseminated or extrapulmonaryPneumocystis carinii pneumoniaPneumonia, recurrentProgressive multifocal leucoencephalopathySalmonella septicaemia, recurrentToxoplasmosis of brainWasting syndrome, due to HIV
11Initial management of 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 - toxoplasmosisexclude other active infection- syphilis, other STI - cervical cytologyimmune status- CD4/CD8 lymphocyte counts
19HIV – treatment regimens (HAART) A) NRTI x 2 + NNRTI OR B) NRTI x 2 + PI (boosted)
20(A) zidovudine & lamivudine + efavirenz OR nevirapine HAART regimens(A) zidovudine & lamivudine + efavirenz OR nevirapine(B) zidovudine & lamivudine + lopinavir/ritonavir (kaletra) OR atozanavir/ritonavir indinavir/ritonavir amprenavir/ritonavir
21Complications of HIV therapy lipodystrophyincreased fat deposits (abdomen, breast, ‘buffalo hump’) lipids, cholesterol and glucosemitochondrial toxicity lactic acidimmune reconstitutionflare in host response to OI eg. CMV, M. tuberculosis, HBV, VZ
23HIV vaccines 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.