Opportunistic infections

Pharmacotherapeutics of Opportunistic infections in HIV patients

1. Opportunistic Infections Dr.V . S. Swathi Assistant Professor

2. Definition Opportunistic infections (OIs) are infections that occur more often or are more severe in people with weakened immune systems (people living with HIV) than in people with healthy immune systems.

3. Epidemiology About 90% of HIV-related morbidity and mortality is due to opportunistic infections in World In one study it was found that Tuberculosis was the most frequent opportunistic infections accounting for 50% of all opportunistic infections, followed by Candidiasis in 49% of cases. Pneumocystosis was seen in 16%, Cryptococcal infection in 09% and parasitic diarrhoea in 15% in India

4. Risk factors Elders Malnutrition Patients with HIV Patients with Inflammatory bowel disease Patients with Leukopenia Patients with diabetes mellitus Patients who uses immunosupressants

5. Types of opportunistic infections in HIV patients Fungal infections P. jiroveci Pneumonia Oropharangeal Candiasis Cryptococcus neoformans infection   Protozoal infections Toxoplasmosis Cryptospordiasis   Bacterial infection Mycobacterium Tuberculosis   Viral infection Cytomegalo virus infection

6. P . jiroveci Pneumonia Cause: Pneumocystitis jerovecii (Yeast like fungus) Clinical Presentation: Non productive cough Shortness of breath on exertion Inability to take deep breath Fever Anorexia Weight loss Diagnosis : Exercise induced oxygen desaturation Chest radiographic appearance of bilateral interstitial shadowing Nucleic acid amplification technique Bronchoalveolar lavage CD4 count is less than 200cells/mm 3

7. Oropharangeal Candiasis Cause: Candida albicans (Fungus) Clinical Presentation: White plaques on oral mucosa Erythamatous plaques on oral mucosa Angulus chelitis Dysphagia Odynophagia Diagnosis: Based on clinical presentation

8. Cryptococcus neoformans Infection Cause: Cryptococcus neoformans (Fungus) Clinical Presentation: Fever Head ache Diagnosis: CSF analysis Blood culture

9. Toxoplasmosis Cause: Toxoplasma gondii (Protozoa) Clinical Presentation: Fever Head ache Confusion Seizures Diagnosis: CT Scan-Ring Enhancing Lesion Brain biopsy

10. Cryptospordiosis Cause: Cryptospordium parvum (Protozoa) Clinical Presentation: Abdominal pain Diarrhea Weight loss Diagnosis: Stool analysis

11. Mycobacterium Infection Cause: Mycobacterium tuberculosis (Bacteria) Clinical Presentation: Persistent cough Coughing with blood Chest pain while coughing and breathing Unintentional weight loss Fatigue Fever Night sweats Chills   Diagnosis: Tuberculin test Sputum Culture

12. Cytomegalovirus Infection Cause: Cytomegalovirus (Virus) Clinical Presentation: Blurred vision Visual field defects Blindness Diagnosis: Based on clinical presentation  

13. Pathophysiology of P.jerovecii Pneumonia P.jerovecii Inhalation   Enter in to HIV patient   Residing in alveoli   Multiplication of P. jerovecii   Alteration of alveolar capability   Impairment of gaseous exchange   Ventilation - Perfusion mismatch   Respiratory Arrest

14. Pathophysiology of Toxoplasmosis T.gondii   Food   Enter in to HIV patient   Reach to CNS via systemic circulation   Perivascular inflammatory response   Fibrosis or Necrosis   Hemorrhage or Thrombosis   Neurological signs and symptoms  

15. Pathophysiology of Tuberculosis Coughing and Sneezing of Patients with active pulmonary TB Generate droplet nuclei of M. tuberculosis   Enter in to lungs of HIV patients Bacteria is deposited in terminal airways (alveoli) and ingested by macrophages Inflammatory changes in lungs TB spreads to remaining organs

16. Pathophysiology of Cytomegalo virus infection Cytomegalovirus   Enter in to body of HIV patient through saliva, breast milk and genital secretion   Reach to eye via systemic circulation   Inflammatory response in eye   Edema , Hemorrage   Necrosis   Diminished visual acuity   Blindness

17. Complications of Opportunistic Infections Acute Respiratory Distress Syndrome (ARDS) Encephalitis Meningitis Blindness

18. Treatment Algorithm of Opportunistic Infections in HIV Patients

19. Drugs used in Treatment of Opportunistic Infections

20. Drug Category Mode of Action Dose Adverse Effects Trimethoprim + Sulpha methoxazole Sulphonamides Inhibit folic acid synthesis in bacteria Moderate–severe: 120mg/kg i.v in 2–4 divided doses for 3 days, then 90mg/kg for 18 days Mild: 1920mg p.o . three times daily for 3 weeks Prophylaxis: 480 or 960mg p.o . daily or 960mg three times per week (960mg daily if on rifampicin ) Nausea Vomiting Diarrhoea Rash Hyperkalaemia Dapsone Antileprosy Agents Inhibit folic acid synthesis in bacteria 100mg p.o . daily (with trimethoprim 10–15mg/kg/ day in divided doses for 3 weeks for PCP treatment) Anorexia Nausea Vomiting Rash Dapsone syndrome

21. Clindamycin Lincosamide Inhibit protein synthesis in bacteria 600mg i.v./p.o. four times daily for 3 weeks 600mg i.v./p.o. four times daily for at least 6 weeks 1.2g p.o. daily in 3–4 divided doses Diarrhoea Abdominal discomfort Oesophagitis Abnormal LFTs Thrombophlebitis Primaquine Anti malarial drug Disrupts Plasmodium mitochondria 15–30mg p.o. daily for 3 weeks Nausea Vomiting Anorexia Abdominal pain Haemolytic anaemia

22. Flucanazole Anti fungal drug Disrupts fungal cell membrane 100mg p.o. daily for 2 weeks 50mg p.o. daily for 7–14 days 400mg i.v./p.o. daily for ≥8 weeks 200mg p.o. daily Headache Abdominal pain Diarrhoea Flatulence Abnormal LFTs Amphotericin B Anti fungal drug Disrupts fungal cell membrane Test dose of 1mg i.v. (over 10–30min, depending on product), followed by once daily i.v.: 1. 0.25–1.0mg/kg (increased over 3–5 days as tolerated) 2. 1–3.0mg/kg (increased over 2–3 days) 3. 5mg/kg. Duration: 2–6 weeks (total induction period at least 6 weeks) Fever Weight loss Myalgia Thrombophlebitis Epigastric pain

23. Flucytosine Anti fungal agent Inhibit protein synthesis in fungus 100mg/kg daily p.o./i.v. in four divided doses for 2 weeks (with i.v. amphotericin) Nausea Vomiting Diarrhoea Rash Hepatotoxicity Sulphadiazine Sulphonamide Inhibit folic acid synthesis in bacteria 1–1.5g i.v ./ p.o . four times daily for at least 6 weeks. 2g p.o . daily in divided doses Nausea Vomiting Rash Bone marrow suppression Crystalluria Pyrimethamine Antimalarial agent Inhibit folic acid synthesis in parasite 100mg on day 1, then 50mg p.o . once daily for at least 6 weeks Different in SPC 25mg p.o . once daily Anaemia Leucopenia Thrombocytopenia Rash

24. Nitazoxanide Anti Parasitic agent Inhibits growth of sporozoites and oocysts of Cryptosporidium and trophozoites of Giardia 500 mg PO q12hr x 3 days Headache Abdominal pain Diarrhea Nausea Chromaturia Cidofovir Anti viral agent Inhibits DNA synthesis in virus 5mg/kg weekly for two doses, then every 2 weeks thereafter Infection Chills Fever Headache Amnesia Anxiety Atovaquone Anti malarial agent Inhibits electron transport chain in Plasmodium 750mg p.o. twice daily with food for 3 weeks 1.5g p.o. twice daily for at least 6 weeks Diarrhoea Insomnia Increased LFTs Decreased sodium Anaemia

25. Resources https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931281/pdf/nihms796285.pdf www.ijmm.org/temp/IndianJMedMicrobiol33178-2534228_070222.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055535/pdf/nihms-545048.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820438/pdf/1471-2180-10-11.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877069/pdf/pone.0083643.pdf