Zambian HIV Guidelines:: Tuberculosis, Active (Zambia specific)

	Zambia HIV National Guidelines
	Adverse Effects and Toxicity Adherence ARV Therapy for Individuals with Tuberculosis Co-Infection Baseline evaluation and Monitoring Changing or Stopping ART Cotrimoxazole Prophylaxis General Principles of Antiretroviral Therapy for Chronic HIV Infection in Adults and Adolescents HIV Counseling and Testing Immune Reconstitution Inflammatory Syndrome (IRIS) Initial Regimen for ARV Therapy Introduction Sexually Transmitted Infections (STIs) Nutrition Care and Support Palliative Care in HIV and AIDS Post Exposure Prophylaxis Stopping ARV Therapy Treatment Failure When to Start ARV Therapy for Chronic HIV Infection in Adults and Adolescents WHO Staging in Adults and Adolescents Calculations: Ideal Body Weight, Body Mass Index and Creatinine Clearance
	Guide Editors
	Editor In Chief Joel E. Gallant, MD, MPH Pharmacology Editor Paul Pham, PharmD, BCPS Zambia Guideline Team Peter Mwaba MMed PhD FRCP Alywn Mwinga MMed Isaac Zulu MMed MPH Velepie Mtonga MMed Albert Mwango MBChB Jabbin Mulwanda MMed FCS

Diagnosis>Opportunistic Infections>

Tuberculosis, Active (Zambia specific)

Yuka Manabe, M.D.
05-06-2008

PATHOGENS

M. tuberculosis
M. bovis

CLINICAL

Hx: cough >2 wks, fever, night sweats, weight loss, hemoptysis, shortness of breath, no response to broad-spectrum antibiotics, contact with known case of TB
CXR: upper lobe infiltrate classic (may be cavitary); atypical presentation in children or HIV+ adults; hilar lymphadenopathy, pleural effusions possible
Clinical and radiographic manifestations may be atypical in HIV+ persons, especially with low CD4 counts; can have lower-lobe infiltrates, adenopathy alone, and even normal CXR.
Extrapulmonary disease more common in HIV+ patients, especially with low CD4 counts.

DIAGNOSIS

Characteristic symptoms (see "Clinical")
Sputum AFB smear: 50% sensitive. Lower sensitivity in HIV+ pts
Culture: with suspected or known drug resistance, HIV+, complicated or severe disease, questionable Dx

TREATMENT

Adults

Intensive phase, 1st 2 months: Rx designed for rapid killing of actively growing bacilli and of semi-dormant bacilli. INH 5 mg/kg/d (300 mg max) + RIF 10-20 mg/kg (600 mg max) + PZA 15-30 mg/kg (2 g max) + EMB 15-20 mg/kg (1 g max), all PO. Once daily, fixed dose combination available.
Continuation phase: eliminates multiplying bacilli and reduces Rx failure/relapse. INH + EMB in fixed dose combination for 6 months (Note: INH & RIF more efficacious than INH + EMB, but more expensive and therefore not policy.
Re-treatment: streptomycin, RIF + INH + PZA+ EMB for 2 mos, then INH + RIF + PZA + EMB (fixed dose combo) for 1 month followed by 5 mos of INH EMB RIF (fixed dose combo)

Children

Intensive phase: INH + RIF + PZA only (directly observed at health clinic)
Continuation phase: INH + RIF in fixed dose combination for 4 months
Re-treatment: RIF + INH (fixed dose combo) + PZA + streptomycin for 2 mos

Treatment issues

Directly observed therapy (DOT) preferred for both adults and children
Monotherapy NEVER appropriate for treatment of TB
Caution regarding drug interactions, toxicity, paradoxical worsening or immune reconstitution inflammatory syndrome (especially after initiation of ART in severely immunosuppressed)
Avoid streptomycin during pregnancy.
Oral contraceptives may not be as efficacious while taking RIF.
Fixed dose combinations with EMB cannot be used in pts with renal impairment.
Sputum smear should be checked after 2, 5 and 8 months while on therapy.
Steroids may be useful adjunctive therapy in pts with meningitis, pericarditis, pleural effusion, massive lymphadenopathy or hypersensitivity to TB drugs.

ART and TB

New TB: CD4<200 = TDF/FTC + EFV; CD4 > 200-350 = per guidelines
Smear(+) Retreatment - TDF/FTC + EFV
CD4 <200: start TB Rx immediately, start ART after TB meds tolerated (2-3 weeks), watch for signs and Sxs of IRIS
CD4 200-350: start TB Rx immediately, start ART after intensive phase according to guidelines (no rifampicin in continuation phase, so no interaction)
CD4 >350: start TB Rx, start ART after TB Rx complete, earlier if clinical deterioration
Smear (+) retreatment cases require RIF throughout TB Rx; so EFV-based regimen required
TB occurs on ART: switch NVP to EFV, continue ART, start TB Rx (consider increasing EFV dose to 800mg if pt > 60kg).
HIV diagnosed on TB Rx: in intensive and continuation phases (as above based on CD4), avoid RIF with NVP or with abnl LFT
Pregnant HIV+ woman develops TB: change NVP to EFV if not in first 1st trimester (otherwise consider AZT/3TC/ABC for 1st trimester), if clinical failure consider 2nd line
Pregnant TB pt Dx'ed with HIV: continue TB Rx, defer Rx (AZT/3TC/NVP) of HIV until after intensive phase of TB Rx or until 2nd trimester, unless re-Rx then AZT/3TC/EFV after 1st trimester

Adults: weight-based dosing for first episode

Intensive Phase 2 months - Weight 30-37 kg - RHZE=2*
Intensive Phase 2 months - Weight 38-54 kg - RHZE=3*
Intensive Phase 2 months - Weight 55-70 kg - RHZE=4*
Intensive Phase 2 months - Weight >71 kg - RHZE=5*
Continuation Phase 6 months - Weight 30-37 kg - EH=1*
Continuation Phase 6 months - Weight 38-54 kg - EH=2*
Continuation Phase 6 months - Weight 55-70 kg - EH=3*
Continuation Phase 6 months - Weight >71 kg - EH=3*
* = number of pills

Adults: weight-based dosing for smear(+) retreatment

Intensive Phase 3 months
2 months - Weight 30-37 kg - RHZE=2 + S=0.5g / 1 month RHZE=2*
2 months - Weight Kg 38-54 kg- RHZE=3 + S=0.75g / 1 month RHZE=3*
2 months - Weight Kg 55-70 kg - RHZE=4 + S=1g / 1 month RHZE=4*
2 months - Weight >71 kg - RHZE=5 + S=1g / 1 month RHZE=5*
Continuation Phase 5 months
Weight 30-37 kg - RHE=2*
Weight 38-54 kg - RHE=3*
Weight 55-70 kg - RHE=4*
Weight >71 kg - RHE=5*
* = number of pills

Children: weight-based dosing for first episode

Intensive Phase 2 months - Weight 6-11 kg - RH=0 + Z=0*
Intensive Phase 2 months - Weight 12-18 kg - RH=1 + Z=1*
Intensive Phase 2 months - Weight 19-26 kg - RH=1 + Z=1*
Intensive Phase 2 months - Weight 27-37 kg - RH=2 + Z=1*
Intensive Phase 2 months - Weight >38 kg - RH=3 + Z=2*
Continuation Phase 4 months - Weight 6-11 kg - RH=0*
Continuation Phase 4 months - Weight 12-18 kg - RH=1*
Continuation Phase 4 months - Weight 19-26 kg - RH=1*
Continuation Phase 4 months - Weight 27-37 kg - RH=2*
Continuation Phase 4 months - Weight >38 kg - RH=3*
* = number of pills

Children: weight-based dosing for retreatment: RIF / INH (fixed dose combo), PZA , Streptomycin for 2 mos Note that there's a link only for streptomycin

Intensive Phase 2 months - Weight 6-11 kg - RH=0 + Z=0 + S=0.1g
Intensive Phase 2 months - Weight 12-18 kg - RH=1 + Z=1 + S=0.2g
Intensive Phase 2 months - Weight 19-26 kg - RH=1 + Z=1 + S=0.5g
Intensive Phase 2 months - Weight 27-37 kg - RH=2 + Z=1 + S=0.5g
Intensive Phase 2 months - Weight >38 kg - RH=3 + Z=2 + S=0.5g
Continuation Phase 10 months - Weight 6-11 kg - RH=0*
Continuation Phase 10 months - Weight 12-18 kg - RH=1*
Continuation Phase 10 months - Weight 19-26 kg - RH=1*
Continuation Phase 10 months - Weight 27-37 kg - RH=2*
Continuation Phase 10 months - Weight >38 kg - RH=3*
* = number of pills

FOLLOW UP

Patients should receive directly observed therapy at district health clinic for intensive phase with monthly follow-up thereafter for signs/symptoms of toxicity.
Sputum smears to document treatment response
Patients should return if sign/sx of TB recur.

OTHER INFORMATION

After exposure to M. tuberculosis, clinically quiescent (latent) infection occurs in which patient do not manifest signs/Sx of TB, but are infected. Evidence for latent infection based on TB risk and size of induration on tuberculin skin testing. No recommendations for treatment of latent TB in Zambian guidelines, although treatment with INH has been shown to be efficacious in resource-limited settings. Based on the Zambian National TB Guidelines.

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