1. Clinical aspects of HIV
Dr. Amaj Saeed MB.CH.B MSc PhD Clinical virologist

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 carinii pneumonia
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
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

15. Major HIV-associated pathogens
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

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. (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

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 OI eg. 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.