1. 1 Guidance on Cotrimoxazole Prophylactic Therapy for HIV Exposed/Infected Children HAIVN Harvard Medical School AIDS Initiative in Vietnam

2. 2 By the end of this session, participants should be able to: Explain indications of Cotrimoxazole Prophylactic Therapy (CPT) for HIV- exposed and HIV-infected children Describe clinical and testing follow up while taking CTX Prophylactic Therapy Can explain when stop taking CTX Prophylactic Therapy Learning Objectives

3. 3 Introduction

4. 4 Anti-retrovirus treatment could prevent OIs Some medications (mainly CTX) have been proved that they could prevent OIs Counseling people who provide care for infected children: Food hygiene Good nutrition Regular check up OI Prophylactic Therapies

5. 5 Primary prophylaxis: Giving medication to prevent an OI from occurring in the first place Secondary prophylaxis: Giving medication after an OI is treated to prevent it from recurring Also known as maintenance therapy Two Types of OI Prophylaxis

6. 6 Cotrimoxazole (CTX): Combination of sulfamethoxazole and trimethoprim Broad-spectrum antibiotics for gram positive and negative bacteria, fungi and protozoa Cotrimoxazole prophylaxis: Overview (1)

7. 7 CTX prophylaxis: A part of a standardized Care and Treatment Package for HIV/AIDS patients High effective, simple, and economical intervention Need to be maintained until having evidence of immunological recovery. Cotrimoxazole prophylaxis: Overview (2)

8. 8 Prevents: PCP (Pneumocystis jiroveci pneumonia) Cerebral toxoplasmosis Reduces the occurrence of: Pneumonia due to streptococcus pneumoniae, Nocardia, Haemophilus Influenzae, S. aureus, gram-negative bacilli Diarrheas due to Salmonella, Isospoiaris and protozoa Malaria Cotrimoxazole prophylaxis: Overview (3)

9. 9 PCP is the most common OI in infants and young children Mortality associated with PCP in infants is as high as 40% despite treatment CPT is highly effective at preventing PCP CPT has been shown to reduce mortality in infants and children CTX prophylaxis for PCP

10. 10 High Rate of PCP in Infants Age 2-8 Months Age in Months Number of Cases 0 0 50 100 150 200 250 300 350 400 450 24681012141618202224 Other AIDS-defining conditions Pneumocystis carinii pneumonia

11. 11 Indications and Dose for Cotrimoxazole Prophylaxis

12. 12 Prevent OIs: PCP Cerebral toxoplasmosis Some diarrheas Pneumonia due to bacterium Objective of CTX prophylaxis

13. 13 All HIV-exposed infants/children: Starting at 4–6 weeks of age and Continued until HIV infection is excluded Indications for Primary Cotrimoxazole Prophylaxis Hướng dẫn Quốc gia về Chẩn đoán và Điều trị HIV/AIDS. Bộ Y tế, Việt Nam, 2011.

14. 14 HIV-confirmed children < 24 months old All children regardless of symptoms or CD4 count 24-60 months old Clinical stages 2, 3, 4 regardless of CD4 count or CD4 ≤ 25% or CD4 ≤ 750 cells/ml regardless of clinical stage ≥ 5 years old Clinical stages 1, 2 with CD4 ≤ 350 cells/ml Clinical stages 2, 3, and 4 if CD4 unavailable or Clinical stages 3, 4 regardless of CD4 count Indications for Primary Cotrimoxazole Prophylaxis (2) National Guidelines for the Diagnosis and Treatment of HIV/AIDS. Ministry of Health, Vietnam. 2011.

15. 15 Exposed/infected children who acquired: PCP Cerebral toxoplasmosis Indications for Secondary Cotrimoxazole Prophylaxis Hướng dẫn Quốc gia về Chẩn đoán và Điều trị HIV/AIDS. Bộ Y tế, Việt Nam, 2011.

16. 16 Thành phần Trimethoprim (TMP) and Sulfamethoxazole (SMX) Dosing 5 mg TMP/kg/day once a day Formulations Liquid 8mg TMP/40mg SMX per 1ml Tablet 80mg TMP/400mg SMX (480mg tablet) Or 160mg TMP/800mg SMX (960mg tablet) CTX Prophylaxis: dosing

17. 17 Nausea, vomiting Rash can occur during first 1-2 weeks Severe side effects: Anemia Granulocytopenia Hypersensitivity reaction Hepatotoxicity Cotrimoxazole Side Effects (1)

18. 18 Need to counsel for care givers and children: Side effects How to manage Check up immediately when suspected signs of severe side effect occur Do complete blood count, liver enzymes measuring when anemia or hepatotoxicity is suspected Cotrimoxazole Side Effects (2)

19. 19 Divided into 4 groups Topics of discussion: Group 1: manifestations/symptoms of rash at grade 1 and how to manage Group 2: manifestations/symptoms of rash at grade 2 and how to manage Group 3: manifestations/symptoms of rash at grade 3 and how to manage Group 4: manifestations/symptoms of rash at grade 4 and how to manage Time: 10 minutes Group Discussion

20. 20 GradeClinical descriptionManagement Grade 1 (mild) Erythema-Continue CPT with careful follow up. -Provide symptomatic treatment and anti- histamine Grade 2 (moderate) Diffuse maculopapular rash, dry desquamation Grade 3 (severe) Bulla, mucosal ulceration- Hospitalization with supportive treatment - CTX should be permanently discontinued Grade 4 (very severe) Exfoliative dermatitis, Steven Johnson syndrome or erythema multiforms, moist desquamation Rash due to CTX and management

21. 21 There are no adequate data on CTX desensitization in children Other medications need to be noticed and may be overlapping drug toxicity: EFV NVP Isoniazid… Rash due to CTX and management

22. 22 Indication: allergy to CTX Dose: 2mg/kg/day, once a day or 4mg/kg/time, once a week Note: Less effect than CTX in terms of PCP prevention Can not prevent Toxoplasma Alternative Therapy: Dapson

23. 23 Indication of discontinuing CPT

24. 24 Discontinuing CPT for HIV-exposed Children Stop CTX prophylaxis when HIV infection has been definitively excluded Infants <18 monthsChildren >18 months Confirmed negative HIV virological test and antibody test 6 weeks after complete cessation of breastfeeding Confirmed negative HIV antibody test 6 weeks after complete cessation of breastfeeding

25. 25 Discontinuing CPT for HIV-infected Children (While on ARV) National Guidelines for the Diagnosis and Treatment of HIV/AIDS. Ministry of Health, Vietnam. 2009. 0-24 months old Do not discontinue 24-60 months old Discontinue when: CD4 count > 25% for at least 6 months 5 years old Discontinue when: CD4 count > 200 for at least 6 months

26. 26 Case Study

27. 27 CPT is highly effective for prevention of PCP in infants and children All HIV-exposed infants should receive CPT starting at 4–6 weeks of age Follow up closely CTX side effects and manage them timely Indication of discontinuing CPT: Exposed infants: HIV infection has been definitively excluded Infected infants/children: after ARV treatment and CD4 higher the threshold as MOH required for each age group for 6 months continuously. Key Points

28. 28 Thank you! Questions?