Transcript TB-HIV Co-Infection - Ministry of Health

TB-H V Co-infection
by
Dr. Ker Hong Bee
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LEARNING OBJECTIVES
• To know & understand about TB-HIV coinfection in relation to:– interaction & prevalence
– diagnosis & treatment
– Isoniazid Prophylaxis Therapy (IPT)
– Highly Active Antiretroviral Therapy (HAART)
– Immune Reconstitution Inflammatory Syndrome
(IRIS)
– Co-trimoxazole (CTX) Prophylaxis
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TB & HIV:
A DEADLY HUMAN SYNDEMIC
TB is one of the leading
causes of death among HIV
patients
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TB-H V INTERACTION
HIV infection accelerates the
development of TB from
infection to advanced disease
TB depletes the CD4 count &
intensifying the
immunodepressant effect of HIV
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TB-H V INTERACTION
• HIV-positive patients have more than 2x risk
of primary MDR-TB.1,2
• Risk of mortality is 2.6x higher in HIV-positive
patients who develop TB compared to those
who do not.3
1Conaty
SJ et al., Epidemiol Infect, 2004
et al., PLoS ONE, 2009
3Straetemans et al., PLoS ONE, 2010
2Suchindran S
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PREVALENCE OF TB-H V CO-INFECTION
• At least one-third of HIV-positive persons worldwide
are infected with MTB.
• 8 - 10% of them develop clinical disease every
year1
1Swaminathan
S et al, Clin Infect Dis. 2010
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TB- H V INTERACTION
PTB (44.0 - 79.5%)
EPTB (14.0 - 18.8%)
Both PTB & EPTB (2.7 - 3.0%)
Zhou J et al., BMC Infect Dis, 2009
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DIAGNOSTIC CHALLENGES
Many HIV-TB co-infected patients:
• Have no cough & negative sputum
AFB smears
• Have lower AFB { } in sputum
– AFB density in sputum decreases with
decreasing CD4
• Have normal CXR even in cultureconfirmed PTB
• Have less cavitary disease on initial
CXR
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TB CULTURES
• Sputum/BAL TB cultures should be obtained in
all TB suspects with a normal CXR, particularly
HIV-positive persons.1
• Any biopsy specimen from extrapulmonary
sites should be sent for TB culture.
1Pepper
T et al., Int J Tuberc Lung Dis, 2008
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DIAGNOSTIC TESTS
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ANTITB FOR TB-H V CO-INFECTION
• Require prompt initiation of TB treatment1
• Treatment complicated by higher rate of TB
relapse & increased mortality rate during
treatment
1 Panel
on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected
adults and adolescents. Department of Health and Human Services.
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ANTITB FOR TB-H V CO-INFECTION
• 6 month regimen consisting of1,2
– 2EHRZ /4 HR
when the disease is caused by organisms
that are known or presumed to be
susceptible to the first-line drugs
1CDC.
Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents:
2Blumberg HM et al, ,Am J Respir Crit Care Med, 2003
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ANTITB FOR TB-H V CO-INFECTION
• Prolong the continuation phase if:– there is a slow or suboptimal response
(e.g. cultures are still positive after 2 months of
therapy)
– patients with EPTB
• All HIV patients should receive DAILY TB
treatment in maintenance phase.
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TREATMENT REGIMEN FOR TB-H V CO-INFECTION
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RIFAMYCIN & ANTIRETROVIRAL (ARV) DRUGS
• Includes rifampin (rifampicin) & rifabutin
• Regimens in which rifampin is only used for the first
2 months  higher rates of Rx failure & relapse1
• Recommend to include rifamycin for the full course
of TB treatment unless• the Mycobacterium is resistant to rifamycin
• the patient has a severe side effect that is clearly due to the
rifamycin
1Jindani A
et al., Lancet, 2004
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RIFAMYCIN & ARV DRUGS
• Rifampicin:
– the most potent inducer of CYP450 system
– significant interactions with most ARVs including all
protease inhibitors (PIs)
• Rifabutin*
– has much less effect on drugs metabolism through the
CYP3A system
– as effective as rifampicin1
*Not registered in Malaysia
1Panel
on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1infected adults and adolescents. Department of Health and Human Services
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RIFAMYCIN & ARV DRUGS
*Not registered in Malaysia
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ISONIAZID PROPHYLAXIS THERAPY (IPT)
FOR H V INFECTED PATIENTS
• HIV infection
significantly
increases the risk of
progression from
latent to active TB
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CONCERN OF TB REACTIVATION
Latent TB
Annual risk of
TB reactivation
5 - 10%1
Risk of TB
reactivation
Active TB
Lifetime risk
5 - 10%
1Narain
JP et al., Tuber Lung Dis, 1992
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IPT FOR H V INFECTED PATIENTS
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Isoniazide 5mg/kg OD
(max 300 mg)
+
Pyridoxine 50 mg OD
for 6 months
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ANTITB + HAART = SURVIVAL
• Highly Active Antiretroviral Therapy (HAART)
during TB treatment1
o protective against mortality
o result in earlier conversion of sputum & cultures
to negative
1Nahid
P et al., Am J Respir Crit Care Med, 2007
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TIMING TO INITIATE HAART
• Initiation of earlier-HAART in patients with
CD4 <50/cubic ml improves survival.1
• In HIV-associated TB meningitis, immediate
HAART is associated with an increase in grade
4 adverse events  safer to defer HAART.2
1Abdool
Karim SS et al., N Engl J Med.2011
ME et al., Clin Infect Dis2011
2Torok
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TIMING OF HAART
CD4 count
(cells/µl)
Timing of HAART initiation
<50
2 weeks after starting intensive phase of
antiTB treatment
>50 but
<350
After completion of intensive phase of
antiTB treatment
>350
Continue antiTB treatment & monitor
CD4. Commence HAART if CD4 drops
<350 cells/µl.
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ARV REGIME
Antiretroviral drugs
Interactions with rifampicin
NRTIs
No clinically significant interaction
NNRTIs
Efavirenz: the preferred NNRTI
Nevirapine:
 can be continued if already on a
nevirapine-based HAART with close
monitoring of LFT;
 if need to start, please d/w ID physician
PIs
Referral to an ID Physician if patient already
on PI-based regimen
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HAART IN H V-TB CO-INFECTION
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DRUG INTERACTIONS BETWEEN
HAART & ANTITB REGIMEN
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IMMUNE RECONSTITUTION
INFLAMMATORY SYNDROME (IRIS)
• An augmented inflammatory
response that occurs in
patients started on HAART &
antiTB
• Usually occurs within 3
months of TB treatment
o typically within 2 to 12 weeks
after the initiation of HAART
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IRIS
• The major manifestations of IRIS are fever &
lymphadenitis.1
• HAART & antiTB treatment should not be
stopped while managing IRIS.
1Dibyendu
D et al., Braz J Infect Dis2011
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CO-TRIMOXAZOLE (CTX) PROPHYLAXIS IN
TB-H V CO-INFECTION
• A RCT showed that CTX prophylaxis in TB-HIV co-infected
adults was associated with a 21% reduction in all cause
mortality.1
• CTX is generally safe & well-tolerated.1,2
• CTX should be initiated as soon as possible & given
throughout TB treatment.3
1Nunn
2Boeree
AJ et al., BMJ, 2008
MJ et al., Trop Med Int Health, 2005
3WHO, 2010
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TAKE HOME MESSAGES
1. Active TB should be ruled out in all HIV-positive
patients.
2. Sputum TB culture should be done regardless of
CXR/smear AFB status in TB-HIV suspect.
3. AntiTB regimen offered to HIV +ve adults should be
the same as for HIV -ve individual .
o Caution on drug interaction with HAART
o Daily maintenance phase
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TAKE HOME MESSAGES
4. IPT for 6 months should be offered to all HIV
patients with LTBI after ruling out active TB.
4. For patients with CD4 <50 cells/μl, initiate
HAART 2 weeks after starting antiTB
treatment.
4. CTX prophylaxis should be given to HIV
patients on antiTB treatment.
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THANK YOU
[email protected]
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