Dr. Amaj Saeed

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Clinical aspects of HIV

• Dr. Amaj Saeed
• MB.CH.B MSc PhD
• Clinical virologist
• amanj.saeed_at_krg.org

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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

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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

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• 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

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

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• 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

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• Patients then proceed to full-blown AIDS (stage
  C)
• Thrush
• Herpes zoster
• Pneumocystis carinii pneumonia
• Death may occur if untreated (70)

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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)
• Kaposis sarcoma

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AIDS-defining conditions

• Lymphoma, Burkitts
• 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

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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

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HIV-poor prognostic determinants

• low CD4 count
• high VL - gt 10,000 copies/ml
• gt 35 years
• low BMI (weight (kg) / height (m)2)
• coinfection CMV
• complicating systemic infections
• complicating malignancies eg. Lymphoma

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HIV infection complications

• mucocutaneous
• respiratory
• gastrointestinal
• neurological
• eye (retina)
• haematological

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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

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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

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HIV prevention of infectious complications

• avoid exposure
• food
• protected sex
• CMV blood products
• immunization
• hepatitis A B
• chemoprophylaxis

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HIV Lifecycle and Antivirals
Entry inhibtors
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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)

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HIV treatment regimens (HAART)

• A) NRTI x 2 NNRTI
• OR
• B) NRTI x 2 PI (boosted)

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HAART regimens

• (A) zidovudine lamivudine
• efavirenz OR nevirapine

• (B) zidovudine lamivudine
• lopinavir/ritonavir (kaletra)
• OR
• atozanavir/ritonavir
• OR
• indinavir/ritonavir
• OR
• amprenavir/ritonavir

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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

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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

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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.