MDR TB/HIV INTEGRATION MDR TB WORKSHOP 18 SEPTEMBER 2015

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1 MDR TB/HIV INTEGRATION MDR TB WORKSHOP 18 SEPTEMBER 2015

2 HIV & MDR :Impact of early ART initiation Adjusted HR: 0.14; p = % reduction in mortality with ART Initiation during MDR-TB treatment

3 2015 ART Guidelines: ART initiation in TB Patients with MDR-TB eligible for ART irrespective of CD4 or WHO Stage If CD4< 100 do Cryptococcal Antigen test & if positive - Fluconazole prophylaxis prior to ART if no meningitis Initiation ART In TB co-infection start with TB treatment first, followed by ART as soon as possible and within 8 weeks If CD4 <50 cells/μl initiate ART within 2 weeks of starting TB treatment, when the patient s symptoms are improving and TB treatment is tolerated If CD4 >50 cells/μl initiate ART within 2-8 weeks of starting TB treatment In cryptococcal or TB meningitis: Defer ART initiation for 4-6 weeks

4 Choice of ART in ART Naive MDR REGIMEN MDR Guideline 2015 ART GUIDELINE Standard MDR regimen with no renal impairment at baseline Bedaquline due to renal impairment AZT+3TC+EFV (in injectable Phase) Change to Atroiza after injectable phase. KDHC Practice: Start Atroiza and monitor U+E and dipstix ABC+ 3TC + NVP CD4 <250 in women or CD4< 400 in men) Alluvia (CD4 >250 in women or CD4 > 400 in men) Check Hep B SAg If positive Give ATROIZA and monitor U+E and urine dipstix Check HEP B Sag status (Discuss with ID regarding adding TDFrenal dose if positive)

5 General management: Patients initiating nevirapine CD4 count: 400 (male) 250 (female) NVP should be avoided Prior to start: CD4 count; BL ALT CD4 count: <400 (male) <250 (female) Commence NVP 200mg daily TCA 14 days Tell the patient to return to clinic IMMEDIATELY if: 1. Rash, especially if mucocutaneous 2. Fever 3. Jaundice 4. Abdominal pain If no rash / hepatic symptoms: increase to 200mg twice daily 5

6 Initiating NVP Rash and/or hepatic symptoms Rash only (not severe) Any severe symptom or >2 symptoms Do not increase NVP dosing to 200mg twice daily until resolved ALT NCS increase: Repeat 7-14 days Hospitalisation If rash not resolved in 7 days or worsens: stop NVP; use alternative drug Stop all ART Investigate and monitor 6

7 Management of patients previously treated with ART Referred in on ART ART interrupted VL undetectable No side effects Previous regimen known or unknown Full history: why ART stopped Continue same regimen where possible NOT due to toxicity or VF IF PATIENT HAS FAILED A Check VL PREVIOUS REGIMEN, INITIATE Restart first line APPROPRIATE SECOND LINE Repeat VL at 2 months 7

8 Anaemia Anaemia Full history Examination FBC, smear, retics preart Early ART Established ART Common in low CD4 counts TB Other serious OI Poor prognostic factor Do not delay ART Consider: IRIS Disseminated TB AZT Other causes >6 months: Serious OI Unrelated to HIV Drugs (AZT; 3TC; cotrimoxazole) 8

9 Monitoring of patients on ART What? When? Why? CD4 count At 12 months on ART Immune response Viral load Creatinine FBC ALT Fasting TC and TG Months 6 and 12 on ART; then 12 monthly Months 3, 6 and 12 if on TDF; then 12 monthly Months 3 and 6 if on AZT; then annually If on NVP and develops rash or symptoms of hepatitis At month 3 if on LPV/r Treatment failure / adherence problems TDF toxicity / renal impairment AZT toxicity NVP toxicity LPV/r toxicity

10 Management of patients with VL> 1000 copies /ml on EFV first line ART Increase adherence interventions Repeat VL after 2 months Pull FBC, ALT and Hep Bsag Change to second line if repeat VL >1000 copies/ml If Hep BSAg+ (TDF as part of second line regimen)

11 Diagnosis of second line failure VL >1000 copies/ml on second line >1 year Adherence; compliance; tolerability; drug interactions; psychological Repeat VL in 6 months VL 1000 copies/ml Continue second line VL>1000 copies/ml Specialist referral GENOTYPE Management as per specialist 11

12 Additive Toxicities HIV and MDR TB Side-effect Antiretroviral drug MDR TB Therapy GIT S/E Hepatitis Peripheral neuropathy Rash AZT Alluvia Nevirapine Efavirenz D4T, DDI NVP, EFV, ABC Ethionamide PAS (Pyrazinamide) Rifampicin, Isoniazid Pyrazinamide (Moxiflox) Isoniazid Terizidone, Linezolid INH, PZA Psychosis Marrow suppression EFV AZT INH, Terizidone Linezolid Renal Toxicity Tenofovir 2 nd line injectables

13 Revisiting the DILI Definition in the South African context: ALT level > 120 IU/l and symptomatic ( Nausea, vomiting, abdominal pain, jaundice) or ALT level >200 IU/l and asymptomatic or Total serum bilirubin concentration > 40 micromols/l

14 Patterns of Hepatic dysfunction and commonly associated drugs HEPATOCELLULAR Increase in serum ALT> ALP MIXED CHOLESTASIS Increased ALP and Bilirubin ARVS Sulphonamides Rifampicin INH Cotrimoxazole Amoxyclav PZA Phenytoin Macrolides Herbal meds Phenobarbitol Phenothiazines Valproate Nitrofurantoin TCA Ketoconazole Anabolic steroids NSAIDS OCP Allopurinol

15 Mild DILI (Clinically well with elevated ALT <200 and total Bili <40) Continue TB drugs Continue ART if already receiving Repeat ALT and Bili in 1 week If ALT and bili improving or normal then stop Lab monitoring If ALT and Bili continue to rise and meet DILI definition, continue as below

16 Moderate DILI (Clinically well and elevated ALT> 200 irrespective of total Bili) Discontinue TB regimen Discontinue Bactrim prophylaxis and other hepatotoxic drugs Stop ART unless on a stable ART regimen for > 6 months Repeat ALT and Bili in 3 (Inpt) or 7 (Otpt) days When ALT < 100 and Bili is normal, attempt rechallenge

17 Severe DILI Clinically not well (Nausea, vomiting, abdominal pain), meets DILI definition Admit and consult ID Assess liver synthetic function with INR and monitor blood glucose Stop standard TB treatment, Bactrim and all other hepatotoxic drugs Stop ART Repeat ALT and Bili after 2-3 days Rechallenge TB drugs when ALT <100 and Bilirubin is normal Monitor ALT weekly for 4 weeks after rechallenge

18 Impact of the TB HIV Integrated on health service delivery Co-located services scored higher that single service clinics in integrated TB-ART service delivery ART coverage improved by 60% Time to ART initiation reduced by 72 days 71% provide IPT 71% offered ART 76% of HIV infected patients screened for TB

19 Models of TB - HIV service integration Source: Legido-Quigley et al., Trop Med Int Health, 2011

20 Acknowledgements Dr Kogie Naidoo (Slides on TB/HIV Integration) Dr Iqbal Master (Principles of Management of MDR TB) Dr Mitesh Singh (Drug Induced Liver Injury) NDOH slides on 2015 ART Guidelines

21 Acknowledgements This training was supported by the Grant or Cooperative Agreement Number U2G GH001142, funded by the Centers for Disease Control and Prevention. Its contents are solely the responsibility of the presenters and do not necessarily represent the official views of the U.S. Centers for Disease Control and Prevention or the U.S. Department of Health and Human Services