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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
BacteriaSalmonella sppMycobacterium tuberculosisM. avium-intracellulareStreptococcus pneumoniaeStaphylococcus aureusHaemophilus influenzaeMoraxella catarrhalisRhodococcus equiiBartonella quintanaNocardia
VirusesCytomegalovirusHerpes simplexVaricella zosterHuman papillomavirusPapovavirus
Fungi and yeastsPneumocystis cariniiCryptococcus neoformansCandida sppDermatophytes (Trichophyton)Aspergillus fumigatusHistoplasma capsulatumCoccidioides immitis
ProtozoaToxoplasma gondiiCryptosporidium parvumMicrosporidia sppLeishmania donovaniIsospora belli
avoid exposure◦food◦protected sex◦CMV & blood products
immunization◦hepatitis A & B
chemoprophylaxis
HIV lifecycle and antivirals
Reverse transcription and integration
Reverse transcriptase blockers nucleoside analogs: AZT, 3TC, d4T
non-nucleosides: delaviradine, nevirapine
Protease blockers e.g., indinavir,
ritonavir
T cell or macrophage
Assembly, Budding
&Maturation
CD4
Co Receptor
Entry inhibtors
NRTI Nucleoside reverse transcriptase inhibitors – (nucleoside analogues NA)
abacavir, didanosine, lamivudine, stavudine, zalcitabine, zidovudineNNRTI Non-nucleoside RTIs
efavirenz, nevirapineProtease 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/ritonavirOR
indinavir/ritonavirOR
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.
