Treating the Dually Infected Patient Tb 10 1

Unit 10: Treating the Dually Unit 10: Treating the Dually Infected PatientInfected Patient

Botswana National Tuberculosis Programme Manual Training for Medical Officers

Slide 10-2Unit 10: Treating the Dually Infected Patient

ObjectivesObjectives

At the end of this unit, participants will be able to:• Explain the relationship between TB and HIV • Describe the effects of immune suppression on TB

progression• Describe the ways in which TB and HIV care can be

integrated• Identify and address challenges to integrating TB

and HIV care• Describe the additional treatments for all TB/HIV

patients• Manage ART in a patient on TB therapy


• HIV/AIDS is the #1 infectious killer in the world—TB is #2

• Many people have both infections

• Botswana TB/HIV co-infection rate is 84%*

HIVHIV

TBTB

HIV & TBHIV & TB

*Source: BNTP, 2007. Source: WHO, 2006.

A Deadly Infectious DiseaseA Deadly Infectious Disease


The TB/HIV Relationship (1) The TB/HIV Relationship (1)

• TB increases HIV progression• Dually infected and untreated persons often

have very high HIV viral loads• Immunosuppression progresses more quickly,

and survival may be shorter despite successful treatment of TB

• Persons who were co-infected have a shorter survival period than persons with HIV who never had TB disease


The TB/HIV Relationship (2)The TB/HIV Relationship (2)

• Screen all HIV-infected patients for TB

• Conduct a complete history as well as a physical examination

• Screen all patients for TB who present in other situations where there is a high burden of HIV, such as medical wards, VCT centres and PMTCT facilities


Immune Suppression Immune Suppression and TB Progressionand TB Progression• HIV-positive person is more likely to progress to TB

disease following infection• HIV-positive person has a greater risk of reactivation• HIV-positive person has a high risk of relapse or

reinfection after treatment• HIV-positive person has a 10% annual risk of

developing active TB (versus 10% lifetime risk among HIV negative individuals)

Source: WHO, 2004


Natural History of TBNatural History of TB

New TBNew TBInfectionInfection

LatentLatentTB InfectionTB Infection

PrimaryPrimaryProgressiveProgressiveTB diseaseTB disease(children, (children,

rare adults,rare adults,HIV+)HIV+)

~~ 10% 10% reactivatereactivate

each each yearyear

~~ 5% 5% reactivate reactivate

after after 2 years 2 years till deathtill death

~~5 % 5 % reactivatereactivate

InIn1-2 years1-2 years

HIV +HIV +

HIV -HIV -


0

2

4

6

8

10

12

14

16

HIV-positive HIV negative

Death

within

6 m

onth

s o

f T

B d

iagnosis

(%

)

Mortality from TB Mortality from TB Before Era of ARTBefore Era of ART

Murray J et al, Am J Respir Crit Care Med, 1999.


Pattern of TB and Survival Pattern of TB and Survival of Patients with HIV-related TBof Patients with HIV-related TB

Whalen C, et al. AIDS, 1997.

PTB

EPTB

Both

Days from diagnosis of TB


Screening for HIV in TB PatientsScreening for HIV in TB Patients

• Purpose• Identify TB suspects and patients who are also HIV

positive

• All TB patients with HIV are eligible for ART, it’s just a matter of timing of ART initiation

• Method• At every health care encounter with TB patient:

• Counsel on HIV prevention strategies

• Offer Routine HIV testing if testing not previously done

• CD4 count should be obtained on any HIV positive individual


Screening for TB at HIV ClinicsScreening for TB at HIV Clinics

• Purpose• Identify HIV-positive persons eligible for IPT• Identify HIV-positive persons who may have active

TB

• Method• At each health care encounter, ask about:

• History of TB and prior treatment for TB• Current IPT or history of IPT• TB signs and symptoms


Early Diagnosis: Better OutcomesEarly Diagnosis: Better Outcomes

• Decrease in mortality for treated patients• Decrease in period of transmission to others

especially family members who may be HIV infected

• Decrease in transmission in the community• Identification of at-risk contacts in a timely

manner


TB and HIV Care StrategiesTB and HIV Care Strategies

Persons with TB• Rapid diagnosis and

initiation of TB treatment• Test all TB patients for HIV• Maximise treatment

completion rates• Offer cotrimoxazole

preventive therapy to HIV+ in TB system

• Assess HIV+ for ART eligibility and refer

HIV-positive Persons• Screen for active TB at

every health system encounter

• Rapid TB diagnosis and initiation of TB treatment

• Reduce TB incidence with IPT

• Reduce TB incidence with effective ART

• Minimise exposures to active TB cases


TB and HIV Treatment StrategiesTB and HIV Treatment Strategies

TB Care and Treatment• Individual

• Control their disease• Restore health and ADL*• Preserve their position in

family and community

• Community• Decrease the spread of TB

infection • Mitigate against TB stigma

from society• Enforce prevention

HIV Care and Treatment• Individual

• Control their disease• Restore health and ADL*• Preserve their position in

family and community

• Community• Decrease the spread of HIV

infection • Mitigate against HIV stigma

from society• Enforce prevention


Challenges to Integration Challenges to Integration

What do you think are the challenges to

integrating the two services?

What strategies can you suggest to address these

potential challenges?


Treating a Person with HIV and TBTreating a Person with HIV and TB

• Common scenario in Botswana

• TB case definitions are the same regardless of HIV status

• TB treatment is the priority

• Clinician should decide the optimal timing for initiation of ART during TB treatment guided by National policy


When to Start ART When to Start ART During TB TherapyDuring TB Therapy• All HIV-infected TB patients qualify for ART

• CD4<100 should start ART within one to two weeks after start of ATT

• CD4 100 – 200 should start ART within two to four weeks after start of ATT

• CD4s>200 may defer ART until end of ATT

• HIV-infected patients already on ART who develop TB should begin anti-TB meds immediately

• Management of TB patients on ART is complex and patient care needs to be coordinated with IDCC


ART in the Botswana ART in the Botswana National ProgrammeNational Programme

Special Order:

ABC (Abacavir), TDF (Tenofovir)

NRTIs NNRTIs PIs

AZT (Zidovudine) 3TC (Lamivudine)d4T (Stavudine)ddI (Didanosine)

(AZT+3TC) (Combivir)

EFV (Efavirenz)NVP (Nevirapine)

LPV/r (Kaletra or Alluvia)RTV (Ritonavir)SQV (Saquinavir)


TB Disease Progression TB Disease Progression with HIV Co-infection with HIV Co-infection

Source: de Jong BC et al, Annu Rev Med, 2004.

• TB progresses more rapidly with HIV co-infection• Up to 10% of co-infected individuals develop active

tuberculosis each year• 10%–20% lifetime risk among those without HIV infection

• ART alone can reduce the risk of progression to active tuberculosis in latently infected individuals by as much as 80%–92%

• Patients on or about to start ART should still be offered IPT if they meet the criteria


Years of enrollment

Baseline CD4 cell count

Use of ART during TB treatment

Death within 1 year of start of TB therapy

Death or new OI within 1 year of start of TB therapy

TBTC 23ARV

1999-2002

90

80%

4.5%

15.7%

CPCRA/ACTGNo ARV

1993-1995

85

0%

20%

38.9%

HIV Disease Progression on HIV Disease Progression on TB Treatment, ARTTB Treatment, ART

Source: Burman et al, CROI, 2003.


• Appropriate treatment of TB• TB treatment regimens are the same for HIV-

infected patients as for non-infected patients

• Assure adherence with TB treatment (use of directly observed therapy, DOT)

• Cotrimoxazole prophylaxis

• ART

How To Improve How To Improve Outcomes of HIV-Related TB?Outcomes of HIV-Related TB?


TB Treatment and TB Treatment and Outcome of HIV-Related TBOutcome of HIV-Related TB• Poor adherence to TB treatment is associated with

the following adverse outcomes• Treatment failure: patient suffers morbidity or mortality of

TB• Increased risk of TB drug resistance or MDR complicating

future treatment of the patient• Continued transmission of TB and development of new

cases of active TB• Possible transmission of drug resistant or MDR TB

• DOT can lead to improved outcomes by supporting better adherence practices


Cotrimoxazole Preventative Cotrimoxazole Preventative Therapy (CPT) (1)Therapy (CPT) (1)• Reduces the risk of

• Pneumocystis jiroveci pneumonia (PCP)• Toxoplasmosis• Bacterial infections

• Reduces deaths and hospitalisations

• Also effective against:• Pneumococcus, salmonella, nocardia and malaria


CPT (2)CPT (2)

• All HIV-positive TB patients should receive CPT regardless of the CD4 count for, at least, the duration of anti-TB treatment

• Extend CPT beyond the end of anti-TB treatment if the CD4 cell count is less than 200 cells/mm3

Source: WHO, 2006


Cotrimoxazole DosingCotrimoxazole Dosing

AGE (weight) OF CHILD

RECOMMENDED DAILY DOSE

SUSPENSION(5ML syrup = 200mg/40mg)

Child tablet (100mg/20mg)

Single strength adult tablet (400mg/80mg)

6 weeks to 6 months(<5kg)

100mg sulfamethoxazole/ 20mg trimethoprim

2.5ml One tablet

6 months – 5 years (5-15kg)


5ml Two tablets Half tablet

6 to post-pubertal


10ml Four tablets One tablet

Post-pubertal Adolescents and Adults


Two tablets


• Identification of patients who will benefit from antiretroviral therapy

• Drug-drug interactions• Immune reconstitution events• Overlapping ARV and TB medicine side effect • Adherence with multi-drug therapy for two infections• Coordinating care between TB and HIV care

providers

Issues in Using Issues in Using ART During TB TherapyART During TB Therapy


Immune Function and Immune Function and Survival During TB TreatmentSurvival During TB Treatment

Source: Mansouthi W et al., J Acquir Immune Defic Syndr, 2006.

• Survival during TB treatment is associated with level of immune function

• ART can substantially reduce mortality among HIV/TB co-infected patients

• Initiation of ART within six months of TB diagnosis can improve survival


Who Would Benefit from ARVsWho Would Benefit from ARVsDuring TB Therapy?During TB Therapy?• HIV is associated with markedly increased

mortality during TB treatment

• Early deaths (< 30 days after TB diagnosis) often due to TB; later deaths - other complications of HIV

• All HIV+ patients with TB are stage 3 (pulmonary) or 4 (extra-pulmonary) and are eligible for ART


Benefits and RisksBenefits and Risks

• Benefits:• Strengthen immune system for fighting TB and other

infections

• Avoid deaths due to OIs and AIDS during TB therapy

• Risks• Drug interactions limit ART regimens

• Immune reconstitution inflammatory syndrome

• Drug toxicity


Treatment of TB for HIV-Positive Treatment of TB for HIV-Positive PersonsPersons

Initial treatment phase should consist of

• Isoniazid (H)

• Rifampicin (R)

• Pyrazinzamide (Z)

• Ethambutol (E)


Rifampicin Decreases Rifampicin Decreases Blood Levels of NVP and EFVBlood Levels of NVP and EFV

NNRTI Effect of rifampicin

Nevirapine ↓ 37-58%

Efavirenz ↓ 13-26%


ART and Rifampicin-BasedART and Rifampicin-BasedTB TherapyTB Therapy

• AZT/3TC/EFV* • Men• Women outside of child bearing years • Children >3 years old

• AZT/3TC/NVP*• Women of child bearing age• Children < 3 years old

*Note: if Hb < 7.5, substitute AZT with d4T


Rifampicin Markedly Rifampicin Markedly Decreases Blood Levels of all PIsDecreases Blood Levels of all PIs

Protease Inhibitor Rifampicin effect

Saquinavir ↓ by 80%

Ritonavir ↓ by 35%Indinavir ↓ by 90%

Nelfinavir ↓ by 82%

Lopinavir/ritonavir ↓ by 75%


Treatment Options: ART During Treatment Options: ART During Rifampicin-Based TB TherapyRifampicin-Based TB Therapy

Ritonavir boosting of other PIs can achieve adequate blood levels: • Lopinavir/ritonavir, 400mg/400mg BD

• = 3 capsules Kaletra + 3 capsules ritonavir BD• =2 tablets Alluvia* + 3 capsules ritonavir BD

• Lopinavir/ritonavir, 800mg/200mg BD• =6 capsules Kaletra BD• =4 tablets Alluvia* BD


Case Study: M.L. (1)Case Study: M.L. (1)

• 31 year old female with HIV infection diagnosed 5 years ago

• She has been non-adherent to ART• She presented with fever and cough of 2-3

weeks duration• Exam: a small (1 cm) submandibular lymph

node was found on the right side• Lab: CD4 count 26, Sputum smears x 2

positive for AFB



• M.L. was started on TB medications (EHRZ) plus ART as inpatient

• 2 wks after starting medications, she developed increased cervical lymphadenopathy with worsening respiratory symptoms

• Repeat CD4 count was 120 • A CXR was done


Courtesy of: © M. Narita, 2006.

What do you think is happening?

What would you do next?



• HIV medications were discontinued

• TB medications were continued

• Repeat CXR was done• M.L.’s CD4 decreased

to 34


Courtesy of: © M. Narita, 2006.



• ART resumed 3 months into TB treatment

• TB was cured

• At the end of TB treatment her CD4 was 342


• Improved immune response against MTB leads to new or worsening signs or symptoms despite effective TB treatment

• Closely associated with starting ARV (days to weeks), but rarely associated with starting TB therapy

• Natural history• Duration - days to months• Waxing and waning is common

Immune Reconstitution Immune Reconstitution Inflammatory Syndrome (IRIS)Inflammatory Syndrome (IRIS)


• Fever• New or worsening lymphadenitis - peripheral or

central nodes• New or worsening pulmonary infiltrates, including

respiratory failure• New or worsening pleuritis, pericarditis, or ascites• Intracranial tuberculomas, worsening meningitis• Disseminated skin lesions• Epididymitis, hepatosplenomegaly, soft tissue

abscesses

IRIS Among Patients with HIV/TBIRIS Among Patients with HIV/TB


• Shorter time from the initiation of TB therapy to the initiation of antiretroviral therapy (e.g., within six weeks)

• Low initial CD4 count or high viral load at ART initiation• CD4 count rises rapidly on ART

• Good immunological and virological response during ART

• Extrapulmonary or disseminated diseaseSource: Colebunders R, et al., Int J Tuberc Lung Dis, 2006.

Risk Factors for IRISRisk Factors for IRIS


Managing IRIS Managing IRIS

• Inform patients about the possibility of an event after starting ART– may feel like the “TB is coming back”

• Evaluate for possible TB treatment failure • Drug resistance, non-adherence, malabsorption

• Assess for other HIV-related complications, e.g., another opportunistic infection

• Management of symptoms, e.g., use non-steroidal anti inflammatory drugs

• For severe symptoms may need to use steroids (prednisolone), 1 mg/kg or even stop ART temporarily


Case Study: MikaCase Study: Mika

• A 40 year-old male from Gaborone presents with fever for 4 weeks, cough with bloody sputum, sweats and weight loss of 7kg

• Chest X-ray shows right lobe infiltrate• Sputum AFB x 1 results “scanty” • His HIV test is positive and CD4 is180

cell/cu mm


Case Study: Case Study: Mika at 2 months ATTMika at 2 months ATT

• Mika returns after two months

• His fevers, cough, and night sweats have stopped and he has gained 5kg

• His TB regimen is changed to the continuous phase (R/H)

• He is started on ART

X-ray shows improvement

Source: I-TECH, Tanzania


Case study: Mika at 4 Months ATTCase study: Mika at 4 Months ATT

• Mika comes back for his 2nd ART monitoring visit

• He reports fever, cough and night sweats have returned

• He has taken his ARTs as prescribed but thinks they are making him more sick and would like to stop them


Case Study: MikaCase Study: MikaFindings at 4 Months ATTFindings at 4 Months ATT• Mika reports excellent

adherence and denies nausea, vomiting or diarrhoea

• His oxygen saturation is 96% on room air

• Heart rate, respiratory rate and other vital signs are normal

• Remainder of physical exam is normal

• Sputum smear is 1+ for AFB

New CXR



Case Study: Mika Case Study: Mika 2 Weeks Later2 Weeks Later• He is worse• Sputum culture from last visit

shows no growth to date (2 weeks)

• Sputum smear is still 1+ AFB• On physical exam is

tachypnoeic• Oxygen saturations is 90% on

room air• Crackles heard in right lung

field

X-ray shows worsening



Adverse Events During Adverse Events During Combined TB+HIV Treatment (1)Combined TB+HIV Treatment (1)

Common adverse events include:• Peripheral neuropathy - more common with

use of ddI & d4T• Skin rash

• TB drugs• Cotrimoxazole• Nevirapine • Other drugs

• Hepatitis, due to TB drugs or unknown causesSource: Dean GL, et.al., AIDS, 2002.


Overlapping Side Effects ofOverlapping Side Effects ofAnti-TB and ARV DrugsAnti-TB and ARV Drugs

Side EffectPossible Causes

Antituberculosis Drugs

Antiretroviral drugs

Skin rash S, Z, R, H nevirapine, efavirenz, abacavir

Nausea, vomiting Z, R, H zidovudine, ritonavir, protease inhibitors

Hepatitis Z, R, H nevirapine, efavirenz, protease inhibitors

Leukopenia, anemia R zidovudine


Adverse Events During Adverse Events During Combined TB+HIV Treatment (2)Combined TB+HIV Treatment (2)

• Some adverse events related to advanced AIDS, some to other infections or malignancies, and some to their treatment

• Few events result in permanent discontinuation of first-line TB drugs, even though therapy may have been temporarily discontinued

Do not give up on the first-line TB drugs unless it is clear that one of them is causing a

severe side effect!Source: Dean GL, et.al., AIDS, 2002.


Managing Adverse EventsManaging Adverse Events

• Do one thing at a time-- makes it easier to decide the cause of an event

• Stop medications for severe adverse events• Use sequential re-challenge to decide the cause of

an event• Don’t switch from the first-line TB drugs (especially

INH and RIF) without evidence of an association with a significant side effect

• Remember IRIS as a possible cause of adverse events during treatment


Increasing TB/HIV Increasing TB/HIV Treatment Adherence Treatment Adherence • TB treatment uses directly observed therapy

(DOT)-- use DOT visits for TB treatment to enhance adherence to antiretroviral therapy

• Try to coordinate medication pickups where possible


Preventing Active TB Preventing Active TB Among HIV-Infected PersonsAmong HIV-Infected PersonsFour strategies:

1. INH Preventive Treatment2. Antiretroviral Therapy3. Infection Control

• HIV+ Health Care Workers should avoid TB exposure (medical and TB wards)

1. TB case finding• Early case-detection and effective TB therapy

(effective DOTS program)


Key PointsKey Points

• Both TB and HIV increase the other’s disease progression

• Early Diagnosis of TB has better outcomes for patients, families and community

• Standard TB treatment correctly implemented cures TB in TB/HIV

• ART for eligible patients greatly improves survival• Different ART regimens are required because of

drug interactions with rifampicin

Date post:	15-Jul-2015
Category:	Health & Medicine
Upload:	alemu-chemeda
View:	48 times
Download:	2 times

Treating the Dually Infected Patient Tb 10 1

Health & Medicine