Guidance on Cotrimoxazole Prophylactic Therapy for HIV ExposedInfected

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

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

Introduction 3

OI Prophylactic Therapies n n n 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 4

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

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

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

Cotrimoxazole prophylaxis: Overview (3) n Prevents: • PCP (Pneumocystis jiroveci pneumonia) • Cerebral toxoplasmosis n 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 8

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

High Rate of PCP in Infants Age 2 -8 Months 450 400 Pneumocystis carinii pneumonia Number of Cases 350 300 Other AIDS-defining conditions 250 200 150 100 50 0 0 2 4 6 8 10 12 14 16 18 20 22 24 Age in Months 10

Indications and Dose for Cotrimoxazole Prophylaxis 11

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

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

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

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

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

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

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

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

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

Rash due to CTX and management n n 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… 21

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

Indication of discontinuing CPT 23

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

Discontinuing CPT for HIV-infected Children (While on ARV) 0 -24 months old Do not discontinue Discontinue when: 24 -60 months old CD 4 count > 25% for at least 6 months Discontinue when: 5 years old CD 4 count > 200 for at least 6 months 25

Case Study 26

Key Points n n 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 CD 4 higher the threshold as MOH required for each age group for 6 months continuously. 27

Thank you! Questions? 28