Clinical aspects of HIV

1. Clinical aspects of HIV Dr.AmajSaeed MB.CH.B MSc PhD Clinical virologist amanj.saeed@krg.org

2. HIV – global impact • 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

3. HIV – transmission 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

5. 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

6. The destruction of the CD4+ helper cell subset is particularly damaging to overall orchestrated immune response leads to appearance of opportunistic infection.

7. 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

8. Patients then proceed to full-blown AIDS (stage C) • Thrush • Herpes zoster • Pneumocystis cariniipneumonia • Death may occur if untreated (70%)

9. AIDS-defining conditions • 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

10. AIDS-defining conditions • 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

11. Initial 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- toxoplasmosis • exclude other active infection - syphilis, other STI- cervical cytology • immune status - CD4/CD8 lymphocyte counts

12. HIV-poor prognostic determinants • 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

13. HIV – infection complications • mucocutaneous • respiratory • gastrointestinal • neurological • eye (retina) • haematological

14. Major HIV-associated pathogens Viruses Cytomegalovirus Herpes simplex Varicella zoster Human papillomavirus Papovavirus Bacteria Salmonella spp Mycobacterium tuberculosis M. avium-intracellulare Streptococcus pneumoniae Staphylococcus aureus Haemophilus influenzae Moraxella catarrhalis Rhodococcus equii Bartonella quintana Nocardia

15. Major HIV-associated pathogens Protozoa Toxoplasma gondii Cryptosporidium parvum Microsporidia spp Leishmania donovani Isospora belli Fungi and yeasts Pneumocystis carinii Cryptococcus neoformans Candida spp Dermatophytes (Trichophyton) Aspergillus fumigatus Histoplasma capsulatum Coccidioides immitis

16. HIV – prevention of infectious complications • avoid exposure • food • protected sex • CMV & blood products • immunization • hepatitis A & B • chemoprophylaxis

17. HIV Lifecycle and Antivirals Entry inhibtors

18. Antiretroviral drugs 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)

19. HIV – treatment regimens (HAART) A) NRTI x 2 + NNRTI OR B) NRTI x 2 + PI (boosted)

20. HAART regimens (B) zidovudine & lamivudine + lopinavir/ritonavir (kaletra) OR atozanavir/ritonavir OR indinavir/ritonavir OR amprenavir/ritonavir (A) zidovudine & lamivudine + efavirenz OR nevirapine

21. Complications of HIV therapy • lipodystrophy • increased fat deposits (abdomen, breast, ‘buffalo hump’) •  lipids, cholesterol and glucose • mitochondrial toxicity •  lactic acid • immune reconstitution • flare in host response to OIeg. CMV, M. tuberculosis, HBV, VZ

22. HIV therapy – special situations • 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

23. HIV 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.