HIV infection clinical picture and

treatment
Mona Bozchelouei & Tsz Yuen Au
Overview

- Sexually transmitted
- RNA retrovirus
- infects CD4 T cells (leading to clinical features) & Macrophages
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- AIDS (advanced stage)

- susceptible to unique opportunistic infection (low CD4 T cells count)
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- Early stage infection: macrophage; Later stage: CD4 T cell

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HIV morphology
Key features:
- gp-120: “docking protein” binds
to CD4 protein
- gp-41: mediates fusion of viral
envelop with cell membrane
Key enzymes
- reverse transcriptase: RNA→
DNA
- Asparatate protease: cleaves
protein
- Integrase: Integrate HIV DNA
to host DNA
Transmission
- sexual contact: unprotected sex
- Exposure to contaminated blood: sharing needles; needle stick
- Perinatal transmission: HIV positive mother to baby
- In general, higher viral load, higher the risk
Markers of disease progression
1. CD4 T cell count
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- flow cytometry
- For AIDS, cell count< 200 cells/µL (Normal ~ 1,000 cells/µL)
1. Viral load
- RT-PCR
- quantification of HIV RNA
Clinical Stages
1. Acute HIV infection
- Shortly after exposure
- Rapid increase in viral load (viral RNA)
1. Chronic HIV infection
- slowly decrease CD4+ T cell count
- relatively low viral load
- last for many years
1. AIDS (late stage)
Acute Infection Syndrome
- 2 to 4 weeks after exposure
- classical symptoms of viral infection (similar to mononucleosis)
- Fever, myalgia, sore throat
- cervical lymphadenopathy(like in mononucleosis)
- sometimes patient also experience maculopapular rash
Chronic infection
- viral load stablised
- decreased CD4 T cells
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- could last for around 8 to 10 years without treatment

- may have subtle symptoms e.g. presistant diffuse lymphedenopathy, fatigue,
malaise
- Candida infection
- Seborrheic dermatitis is also common
Acquired immunodeficiency syndrome (AIDS)
- end-stage
- severe immunodeficiency
- average of 8 years from exposure
- CD4 T cells < 200 cells/µL and/or AIDS-defining infections
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- Clinical features: opportunistic infection

Diagnosis
1. Combination antigen/ antibody test (4th generation)
- p24 antigen
- anti-HIV antibody
1. HIV-1 & HIV-2 antibody differentiation assay
- HIV-1 is more pravalent (worldwide)
- HIV-2 (west Africa)
Parenatal HIV
- antibody-based test will be positive anyway (mother’s antibodies in babies
body)
- HIV virologic test: detecting HIV RNA
Opportunistic infection
3 most common opportunistic infection:
- Pneumocystis pneumonia
- Cryptococcal meningitis
- Toxoplasmosis
HIV patients are required to take prophylaxis
- they are based on cell count
Prophylaxis
Highlights for prophylaxis
1. standard ART keeps the number of CD4+ T cells high
2. for almost all HIV patients
- Tuberculosis test (PPD test or Interferon-gamma release assay IGRAs)
1. CD4+ T cells < 250 cells/µL
- test for Coccidiomyocosis IgM and IgG
- only in endemic area
- treatment: fluconazole
1. CD4+ T cells < 200 cells/µL
- Pneumocystic pneumonia
- treatment: TMP-SMX Bactrium (if allergic: dapsone)
1. CD4+ T cells < 150 cells/µL
- histoplasmosis (endemic area)
1. CD4+ T cells < 100 cells/µL
- Toxoplasmosis
- treatment TMP-SMX
Vaccination
- avoid live attenuated vaccines (e.g. MMR, Zoster, Vericella)
- For HIV adults: Pneumococcal, meningococcal, HepA & B
- plus standard vaccines
Antiretroviral therapy (ART)
- multiple medications
- keep the viral load low
- maintain a high CD4+ T cell count
- initial antiretroviral regimen: two NRTIs in combination with a third active
drug from one of the following classes (NNRTI, PI); boosted with ritonavir or
cobicistat, or an INSTI
HIV drugs
- Nucleoside reverse transcrpitase (NRTI)
- Non-nucleoside reverse transcrpitase (NNRTI)
- Integrase strand transfer inhibitors (INTIs)
- Protease Inhibitors (PIs)
- Other agents
NRTIs
- target: reverse transcriptase
- inhibits RNA→ DNA (stops viral replication)
- nucleoside that competes with normal ones
- list of NRTIs: Zidovudine, lamivudine, abcavir, didanosine, tenofovir,
emtricitabine
- often given in pairs to enhance the effectiveness
- some common adverse effects: Mitochondrial toxicity, Lactic acidosis,
Lipoatrophy, Hepatotoxicity, Renal dysfunction (Tenofovir)
NNTRIs
- List of drugs: Efavirenz, rilpivirine, doravirine
- not nucleoside
- binds to a different site → inhibition of enzymes
- Adverse effetct vary by drugs; most commonly CNS toxicity (Efavirenz and
rilpivirine)
INTIs
- List of drugs: Ralteravir, Elvitegravir, Dolutegravir, Bictegavir
- inhibit HIV enzyme, Integrase
- stops integration of viral DNA to host DNA
- usually well tolerated
- Adverse effetct vary by drugs
- Elvitegravir given with cobicistat (inhibits CYP3A; boost the level of the drug)
PIs
- list of drugs: Lopinavir, ritonavir, indinavir
- inhibits HIV protease
- stops the cleavage of polypeptides into smaller functional proteins
- inhibit productions of all other enzymes
- Virus particles cannot be mature
- Adverse effects: Insulin resistance, hyoperglycemia, hyperlipidemia,
lipodystrophy, hepatoxicity
- Ritonavir: inhibits p450 which boost other drugs
Protease Inhibitors
1. Enfuvirtide
- Binds gp41
- inhibis viral entry
1. Maraviroc
- Blocks CCR5 on macrophages
- Impairs viral ability to bind macrophages
Thank you !