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OPPORTUNISTIC
INFECTIONS IN HIV
ARWA M. AMIN MOSTAFA
P H D , M . P H A R M C L I N I C A L P H A R M A C Y , D I P . M A N A G E M E N T , B S C . P H A R M .
Arwa M. Amin
WHAT WE WILL DISCUSS TODAY?
• What are the common Opportunistic Infections (OIs) seen in
HIV infected subjects?
• What are the clinical manifestations of common OIs in HIV
infected subjects?
• How to Diagnose common OIs in HIV infected subjects?
• How to manage Common OIs in HIV infected subjects?
• How to prevent OIs in HIV infected subjects?
2
Arwa M. Amin
OPPORTUNISTIC INFECTIONS IN HIV
3
• Opportunistic infections (OIs) are caused by pathogens that take
the advantage opportunity of a very weakened host immunity.
• OIs occurs very often and very severe in HIV patients.
• OIs is associated with ↑↑ Morbidity and ↑↑ Mortality.
• As CD4 Cell count ↓↓ → The Risk of encountering OIs ↑↑.
• OIs type usually depends on CD4 count and
pathogens prevalence in the surroundings of the
HIV patient.
Arwa M. Amin
COMMON OPPORTUNISTIC INFECTIONS (OIS)
Examples of OIs frequent in HIV patients:
•Bacterial Infections: Tuberculosis, Pneumocystis jirovenci
(Pneumocystis carinii Pneumonia), Mycobacterium Avium
•Viral Infections: Cytomegalovirus, Varicella zoster virus,
Herpes simplex virus.
•Fungal Infections: Candidiasis, Cryptococcosis, Aspergillosis
•Parasitic Infections: Toxoplasmosis, Cryptosporidiosis.
4
Arwa M. Amin
COMMON OPPORTUNISTIC INFECTIONS (OIS) BASED ON BODY ORGANS
• Brain: Toxoplasmosis, CMV
Cryptococcal Meningitis
• Eyes: CMV
• Mouth: Candidiasis
• GI: Cryptosporidiosis,
Esophageal Candidiasis, CMV
• Respiratory: Tuberculosis
(TB), Pneumocystis,
Histoplasmosis
• Liver: HCV
• Reproductive: HPV, Cervical
Cancer, Vaginal Candidiasis
CMV: Cytomegalovirus, HCV: Hepatitis C Virus, HPV: Human papillomavirus 5
Natural history of opportunistic infections associated with HIV infection
Citation: Human Immunodeficiency Virus Infection, DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. Pharmacotherapy: A Pathophysiologic Approach, 10e; 2017. Available at:
https://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=146074012 Accessed: May 16, 2018. Reprinted with permission, © Courtney V. Fletcher, 2009.)
Copyright © 2018 McGraw-Hill Education. All rights reserved
6
Arwa M. Amin
TUBERCULOSIS
• TB is the Most Common OIs & HIV co-infection.
• Bacterial Pathogen: Mycobacterium
Tuberculosis.
• Route of Transmission: Inhaled Airborne
infectious droplet.
• TB is the leading cause of death among HIV
patients.
• Mainly affects the Lung, but M. Tuberculosis
bacteria can infect brain, spine and kidneys.
7
Figures’ sources:
• Tuberculosis - Causes –Symptoms and Treatment, https://reportshealthcare.com/tuberculosis-causes-
symptoms-and-treatment/
• What Is Tuberculosis? https://www.everydayhealth.com/tuberculosis/basics.aspx, Depositphotos.com
Arwa M. Amin
TUBERCULOSIS
Clinical Manifestations
8
• Fever & Chills
• Productive cough
• May bring up blood
• Weight Loss
• Night Sweats
• Lack of Appetite
• Muscle weakness & Fatigue
Arwa M. Amin
TUBERCULOSIS
Diagnosis:
• History & Physical Examination
• Chest X-Rays
• Laboratory tests:
• Sputum/Blood Acid Fast Bacilli (AFB)
Microscopy
• Sputum/Blood Mycobacterial culture
• Tuberculin Skin test (Mantoux test or PPD
test)
9
Arwa M. Amin
TUBERCULOSIS
10Image courtesy: medcomic.com by Jorge Muniz
Arwa M. Amin
TREATMENT OF TUBERCULOSIS IN HIV PATIENTS
11
TB Treatment Drug Regimen:
6 months of Intensive Drug Treatment divided into Two
Phases.
Drug interactions with ART and Other medications must be
considered.
TB Treatment Initial Phase (2 months):
4 drugs intensive treatment: Isoniazid + Rifampicin +
Pyrazinamide + Ethambutol
TB Treatment Continuation Phase (4 months):
2 drugs treatment: Isoniazid + Rifampicin
TB: Tuberculosis, ART: Antiretroviral Therapy
Arwa M. Amin
CYTOMEGALOVIRUS (CMV)
• CMV Clinically Significant in HIV patients with CD4 < 50 cell/mm3.
• In HIV patients, CMV affects the Eyes, Brain, Lung & GI.
• Route of Transmission: Transmit through Body fluids
• Saliva, Blood, Urine, Semen, Tears and Breast Milk.
• Clinical Manifestations:
• Eye: Impaired vision, Blindness
• Lung: Hypoxia, Pneumonia
• GI: Swallowing difficulty, Diarrhea, Ulceration.
• Brain: Encephalitis, Seizures, Coma
12GI: Gastrointestinal Tract
Arwa M. Amin
CYTOMEGALOVIRUS (CMV)
13
Arwa M. Amin
CYTOMEGALOVIRUS (CMV)
Diagnosis:
• Clinical Examination & Evaluation
• Retinitis: Most common Clinical Manifestation of CMV in HIV patients.
• Diagnosis can’t be established by CMV biomarkers in Blood.
• Tissue biopsy:
• Histologic evidence of viral inclusions and inflammation
• CT scan
Treatment:
• IV Ganciclovir.
• IV Ganciclovir followed by Oral Valganciclovir. 14
Arwa M. Amin
CRYPTOCOCCOSIS (FUNGAL MENINGITIS)
• Cryptococcosis or Cryptococcus Meningitis is the common cause of Meningitis
in HIV patients.
• Life Threatening Fungal Infection.
• Fungal Pathogen: Cryptococcus Neoformans
• Route of Transmission: Inhaled Airborne infectious droplet.
15
• Clinical Manifestations:
•Headache: Severe
•Fever
•Fatigue
•Nausea & Vomiting
•CNS: Confusion, Memory Loss, Coma
•Sensitivity to Light
CNS: Central Nervous System
Arwa M. Amin
CRYPTOCOCCOSIS (FUNGAL MENINGITIS)
• Diagnosis
• Clinical Examination of signs and symptoms
• Laboratory tests:
• CSF Analysis
• India Ink Stain
• Cryptococcal Antigen Testing in Serum, CSF and Plasma.
16CSF: Cerebrospinal Fluids
Arwa M. Amin
CSF FINDINGS OF FUNGAL MENINGITIS
Fungal MeningitisNormal CSFParameter
↑↑< 150 mm H2OIntracranial Pressure
ClearClear/TransparentGross visual turbidity
Pleocytosis*
Lymphocytes
2 - 4 mm3
Monocytes
WBCs count
Differential**
↓↓45 – 80 mg/dL
(2/3 of serum)
Glucose conc.
↑↑15 – 50 mg/dLProtein conc.
(+) India Ink Stain (IIS)NAGm stain/ India Ink Stain
*Pleocytosis: ↑↑ WBCs, **Differential: Predominant Cell type in Differential
17
Arwa M. Amin
CSF FINDINGS OF BACTERIAL, VIRAL & FUNGAL MENINGITIS
Fungal
Meningitis
Viral MeningitisBacterial
Meningitis
Normal CSFParameter
↑↑Normal↑↑< 150 mm H2OPressure
ClearClearCloudyClear/TransparentGross visual
turbidity
Pleocytosis*
Lymphocytes
Pleocytosis*
Lymphocytes
Pleocytosis*
Neutrophils
2 - 4 mm3
Monocytes
WBCs count
Differential**
↓↓Normal↓↓45 – 80 mg/dL
(2/3 of serum)
Glucose conc.
↑↑slightly ↑↑↑15 – 50 mg/dLProtein conc.
(+) IISNA(+) Bacterial
presence, Gm
stain & Culture
NAGm stain/IIS***
Bacterial culture
*Pleocytosis: ↑↑ WBCs, **Differential: Predominant Cell type in Differential,***IIS: India Ink stain
18
Arwa M. Amin
MANAGEMENT OF CRYPTOCOCCAL MENINGITIS
Management of Cryptococcal Meningitis:
Amphotericin B, 3 to 4 mg/kg/day for at least 2 weeks
Maintain adequate Hydration and monitor Renal Function
+ Flucytosine, 100 mg/kg/q 6 h (4 doses)
Consider TDM to avoid bone marrow suppression
 Followed By: Fluconazole 400 mg/day oral for 8 weeks or until CSF cultures are
negative
 Repeated Lumbar puncture or Lumbar drain are recommended, why?
 To relief the ↑↑ ICP.
TDM: Therapeutic Drug Monitoring, ICP: intracranial Pressure, CSF: Cerebrospinal Fluids, ICP: Intracranial Pressure
19
Arwa M. Amin
MUCOCUTANEOUS CANDIDIASIS IN HIV PATIENTS
• Oral & Esophageal Candidiasis are common in HIV patients.
• Esophageal Candidiasis has high Morbidity & Mortality.
• Fungal Microbe: Candida Albicans
• Clinical Manifestations:
•Oral Thrush
•Creamy White plaque-like lesions
•Dysphagia
Diagnosis:
• Clinical Examination & Evaluation based on the appearance of the lesions.
20
Arwa M. Amin
MUCOCUTANEOUS CANDIDIASIS IN HIV PATIENTS
Treatment:
• Oral Candidiasis:
• Fluconazole 100mg Oral for(7-14) days.
• Esophageal Candidiasis:
• Fluconazole 100-400mg IV or Oral daily for (14-21) days.
21
Arwa M. Amin
TOXOPLASMIC ENCEPHALITIS IN HIV PATIENTS
• Toxoplasmic Encephalitis is a leading cause of Focal CNS
disease in AIDS patients.
• Parasitic Pathogen: Toxoplasma gondii
• Route of Transmission: Ingestion of Toxoplasma gondii in
food contaminated with cat feces or undercooked meat.
• Clinical Manifestations of Toxoplasmic Encephalitis disease is
Rare in HIV Patients with CD4 Cell count > 200 cell/mm3.
22
Arwa M. Amin
TOXOPLASMIC ENCEPHALITIS IN HIV PATIENTS
• Clinical Manifestations:
•Fever
•Focal neurological deficit (FND)
•Headache
•Motor Weakness
•Seizures
•Severe Dementia
•Confusion, altered mental state and coma
•Intracranial hemorrhage
23
Arwa M. Amin
TOXOPLASMIC ENCEPHALITIS IN HIV PATIENTS
• Diagnosis:
• CT brain scan
• Identification of Mass Lesion
• Brain Biopsy
• Detection of the Organism
• Detection of Toxoplasma gondii in Clinical
sample (CSF) by PCR
24
Arwa M. Amin
TOXOPLASMIC ENCEPHALITIS IN HIV PATIENTS
Treatment:
25
Preferred Treatment
Pyrimethamine 200 mg Orally once
followed by 50 – 70 mg daily
+ Sulfadiazine 1-1.5 g Orally four times
daily
+ Leucovorin* 10-25 mg Orally daily.
Primary Therapy: 6 weeks
Followed by long-term suppressive
therapy at reduced doses
Alternative Treatment
Trimethoprim 15-20 mg/Kg
+ Sulfamethoxazole 100mg IV or Oral BD
*Leucovorin is administered to prevent Pyrimethamine induced hematological toxicity
Arwa M. Amin
PREVENTING OIS IN HIV PATIENTS
• Best Prevention of OIs in HIV patients is Patient’s
adherence to HIV-ART.
• ART will restore Immunity by increasing CD4.
• Preventing Exposure to OIs.
• Vaccination to prevent first-episode disease.
• Basic Food Hygiene and Eating well cooked meat.
• Secondary Chemoprophylaxis to prevent disease recurrence.
26
ART: Antiretroviral Therapy
Arwa M. Amin

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Opportunistic Infections in HIV

  • 1. OPPORTUNISTIC INFECTIONS IN HIV ARWA M. AMIN MOSTAFA P H D , M . P H A R M C L I N I C A L P H A R M A C Y , D I P . M A N A G E M E N T , B S C . P H A R M .
  • 2. Arwa M. Amin WHAT WE WILL DISCUSS TODAY? • What are the common Opportunistic Infections (OIs) seen in HIV infected subjects? • What are the clinical manifestations of common OIs in HIV infected subjects? • How to Diagnose common OIs in HIV infected subjects? • How to manage Common OIs in HIV infected subjects? • How to prevent OIs in HIV infected subjects? 2
  • 3. Arwa M. Amin OPPORTUNISTIC INFECTIONS IN HIV 3 • Opportunistic infections (OIs) are caused by pathogens that take the advantage opportunity of a very weakened host immunity. • OIs occurs very often and very severe in HIV patients. • OIs is associated with ↑↑ Morbidity and ↑↑ Mortality. • As CD4 Cell count ↓↓ → The Risk of encountering OIs ↑↑. • OIs type usually depends on CD4 count and pathogens prevalence in the surroundings of the HIV patient.
  • 4. Arwa M. Amin COMMON OPPORTUNISTIC INFECTIONS (OIS) Examples of OIs frequent in HIV patients: •Bacterial Infections: Tuberculosis, Pneumocystis jirovenci (Pneumocystis carinii Pneumonia), Mycobacterium Avium •Viral Infections: Cytomegalovirus, Varicella zoster virus, Herpes simplex virus. •Fungal Infections: Candidiasis, Cryptococcosis, Aspergillosis •Parasitic Infections: Toxoplasmosis, Cryptosporidiosis. 4
  • 5. Arwa M. Amin COMMON OPPORTUNISTIC INFECTIONS (OIS) BASED ON BODY ORGANS • Brain: Toxoplasmosis, CMV Cryptococcal Meningitis • Eyes: CMV • Mouth: Candidiasis • GI: Cryptosporidiosis, Esophageal Candidiasis, CMV • Respiratory: Tuberculosis (TB), Pneumocystis, Histoplasmosis • Liver: HCV • Reproductive: HPV, Cervical Cancer, Vaginal Candidiasis CMV: Cytomegalovirus, HCV: Hepatitis C Virus, HPV: Human papillomavirus 5
  • 6. Natural history of opportunistic infections associated with HIV infection Citation: Human Immunodeficiency Virus Infection, DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. Pharmacotherapy: A Pathophysiologic Approach, 10e; 2017. Available at: https://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=146074012 Accessed: May 16, 2018. Reprinted with permission, © Courtney V. Fletcher, 2009.) Copyright © 2018 McGraw-Hill Education. All rights reserved 6
  • 7. Arwa M. Amin TUBERCULOSIS • TB is the Most Common OIs & HIV co-infection. • Bacterial Pathogen: Mycobacterium Tuberculosis. • Route of Transmission: Inhaled Airborne infectious droplet. • TB is the leading cause of death among HIV patients. • Mainly affects the Lung, but M. Tuberculosis bacteria can infect brain, spine and kidneys. 7 Figures’ sources: • Tuberculosis - Causes –Symptoms and Treatment, https://reportshealthcare.com/tuberculosis-causes- symptoms-and-treatment/ • What Is Tuberculosis? https://www.everydayhealth.com/tuberculosis/basics.aspx, Depositphotos.com
  • 8. Arwa M. Amin TUBERCULOSIS Clinical Manifestations 8 • Fever & Chills • Productive cough • May bring up blood • Weight Loss • Night Sweats • Lack of Appetite • Muscle weakness & Fatigue
  • 9. Arwa M. Amin TUBERCULOSIS Diagnosis: • History & Physical Examination • Chest X-Rays • Laboratory tests: • Sputum/Blood Acid Fast Bacilli (AFB) Microscopy • Sputum/Blood Mycobacterial culture • Tuberculin Skin test (Mantoux test or PPD test) 9
  • 10. Arwa M. Amin TUBERCULOSIS 10Image courtesy: medcomic.com by Jorge Muniz
  • 11. Arwa M. Amin TREATMENT OF TUBERCULOSIS IN HIV PATIENTS 11 TB Treatment Drug Regimen: 6 months of Intensive Drug Treatment divided into Two Phases. Drug interactions with ART and Other medications must be considered. TB Treatment Initial Phase (2 months): 4 drugs intensive treatment: Isoniazid + Rifampicin + Pyrazinamide + Ethambutol TB Treatment Continuation Phase (4 months): 2 drugs treatment: Isoniazid + Rifampicin TB: Tuberculosis, ART: Antiretroviral Therapy
  • 12. Arwa M. Amin CYTOMEGALOVIRUS (CMV) • CMV Clinically Significant in HIV patients with CD4 < 50 cell/mm3. • In HIV patients, CMV affects the Eyes, Brain, Lung & GI. • Route of Transmission: Transmit through Body fluids • Saliva, Blood, Urine, Semen, Tears and Breast Milk. • Clinical Manifestations: • Eye: Impaired vision, Blindness • Lung: Hypoxia, Pneumonia • GI: Swallowing difficulty, Diarrhea, Ulceration. • Brain: Encephalitis, Seizures, Coma 12GI: Gastrointestinal Tract
  • 14. Arwa M. Amin CYTOMEGALOVIRUS (CMV) Diagnosis: • Clinical Examination & Evaluation • Retinitis: Most common Clinical Manifestation of CMV in HIV patients. • Diagnosis can’t be established by CMV biomarkers in Blood. • Tissue biopsy: • Histologic evidence of viral inclusions and inflammation • CT scan Treatment: • IV Ganciclovir. • IV Ganciclovir followed by Oral Valganciclovir. 14
  • 15. Arwa M. Amin CRYPTOCOCCOSIS (FUNGAL MENINGITIS) • Cryptococcosis or Cryptococcus Meningitis is the common cause of Meningitis in HIV patients. • Life Threatening Fungal Infection. • Fungal Pathogen: Cryptococcus Neoformans • Route of Transmission: Inhaled Airborne infectious droplet. 15 • Clinical Manifestations: •Headache: Severe •Fever •Fatigue •Nausea & Vomiting •CNS: Confusion, Memory Loss, Coma •Sensitivity to Light CNS: Central Nervous System
  • 16. Arwa M. Amin CRYPTOCOCCOSIS (FUNGAL MENINGITIS) • Diagnosis • Clinical Examination of signs and symptoms • Laboratory tests: • CSF Analysis • India Ink Stain • Cryptococcal Antigen Testing in Serum, CSF and Plasma. 16CSF: Cerebrospinal Fluids
  • 17. Arwa M. Amin CSF FINDINGS OF FUNGAL MENINGITIS Fungal MeningitisNormal CSFParameter ↑↑< 150 mm H2OIntracranial Pressure ClearClear/TransparentGross visual turbidity Pleocytosis* Lymphocytes 2 - 4 mm3 Monocytes WBCs count Differential** ↓↓45 – 80 mg/dL (2/3 of serum) Glucose conc. ↑↑15 – 50 mg/dLProtein conc. (+) India Ink Stain (IIS)NAGm stain/ India Ink Stain *Pleocytosis: ↑↑ WBCs, **Differential: Predominant Cell type in Differential 17
  • 18. Arwa M. Amin CSF FINDINGS OF BACTERIAL, VIRAL & FUNGAL MENINGITIS Fungal Meningitis Viral MeningitisBacterial Meningitis Normal CSFParameter ↑↑Normal↑↑< 150 mm H2OPressure ClearClearCloudyClear/TransparentGross visual turbidity Pleocytosis* Lymphocytes Pleocytosis* Lymphocytes Pleocytosis* Neutrophils 2 - 4 mm3 Monocytes WBCs count Differential** ↓↓Normal↓↓45 – 80 mg/dL (2/3 of serum) Glucose conc. ↑↑slightly ↑↑↑15 – 50 mg/dLProtein conc. (+) IISNA(+) Bacterial presence, Gm stain & Culture NAGm stain/IIS*** Bacterial culture *Pleocytosis: ↑↑ WBCs, **Differential: Predominant Cell type in Differential,***IIS: India Ink stain 18
  • 19. Arwa M. Amin MANAGEMENT OF CRYPTOCOCCAL MENINGITIS Management of Cryptococcal Meningitis: Amphotericin B, 3 to 4 mg/kg/day for at least 2 weeks Maintain adequate Hydration and monitor Renal Function + Flucytosine, 100 mg/kg/q 6 h (4 doses) Consider TDM to avoid bone marrow suppression  Followed By: Fluconazole 400 mg/day oral for 8 weeks or until CSF cultures are negative  Repeated Lumbar puncture or Lumbar drain are recommended, why?  To relief the ↑↑ ICP. TDM: Therapeutic Drug Monitoring, ICP: intracranial Pressure, CSF: Cerebrospinal Fluids, ICP: Intracranial Pressure 19
  • 20. Arwa M. Amin MUCOCUTANEOUS CANDIDIASIS IN HIV PATIENTS • Oral & Esophageal Candidiasis are common in HIV patients. • Esophageal Candidiasis has high Morbidity & Mortality. • Fungal Microbe: Candida Albicans • Clinical Manifestations: •Oral Thrush •Creamy White plaque-like lesions •Dysphagia Diagnosis: • Clinical Examination & Evaluation based on the appearance of the lesions. 20
  • 21. Arwa M. Amin MUCOCUTANEOUS CANDIDIASIS IN HIV PATIENTS Treatment: • Oral Candidiasis: • Fluconazole 100mg Oral for(7-14) days. • Esophageal Candidiasis: • Fluconazole 100-400mg IV or Oral daily for (14-21) days. 21
  • 22. Arwa M. Amin TOXOPLASMIC ENCEPHALITIS IN HIV PATIENTS • Toxoplasmic Encephalitis is a leading cause of Focal CNS disease in AIDS patients. • Parasitic Pathogen: Toxoplasma gondii • Route of Transmission: Ingestion of Toxoplasma gondii in food contaminated with cat feces or undercooked meat. • Clinical Manifestations of Toxoplasmic Encephalitis disease is Rare in HIV Patients with CD4 Cell count > 200 cell/mm3. 22
  • 23. Arwa M. Amin TOXOPLASMIC ENCEPHALITIS IN HIV PATIENTS • Clinical Manifestations: •Fever •Focal neurological deficit (FND) •Headache •Motor Weakness •Seizures •Severe Dementia •Confusion, altered mental state and coma •Intracranial hemorrhage 23
  • 24. Arwa M. Amin TOXOPLASMIC ENCEPHALITIS IN HIV PATIENTS • Diagnosis: • CT brain scan • Identification of Mass Lesion • Brain Biopsy • Detection of the Organism • Detection of Toxoplasma gondii in Clinical sample (CSF) by PCR 24
  • 25. Arwa M. Amin TOXOPLASMIC ENCEPHALITIS IN HIV PATIENTS Treatment: 25 Preferred Treatment Pyrimethamine 200 mg Orally once followed by 50 – 70 mg daily + Sulfadiazine 1-1.5 g Orally four times daily + Leucovorin* 10-25 mg Orally daily. Primary Therapy: 6 weeks Followed by long-term suppressive therapy at reduced doses Alternative Treatment Trimethoprim 15-20 mg/Kg + Sulfamethoxazole 100mg IV or Oral BD *Leucovorin is administered to prevent Pyrimethamine induced hematological toxicity
  • 26. Arwa M. Amin PREVENTING OIS IN HIV PATIENTS • Best Prevention of OIs in HIV patients is Patient’s adherence to HIV-ART. • ART will restore Immunity by increasing CD4. • Preventing Exposure to OIs. • Vaccination to prevent first-episode disease. • Basic Food Hygiene and Eating well cooked meat. • Secondary Chemoprophylaxis to prevent disease recurrence. 26 ART: Antiretroviral Therapy