Management of Tb-Hiv Patients:: Current Status

MANAGEMENT OF TB-HIV PATIENTS :
CURRENT STATUS
Anna Uyainah ZN
Division of Pulmonology
Internal of Medicine
FKUI-RSCM

PERPARI BALI
May 21
th
, 2009
ISTC Training Modules 2008
Tn JA, 25 th
KU : Sesak napas memberat sejak 4 hari smrs
RPS :
Sesak (+), batuk (+), dahak (+) warna putih,
penurunan BB (+)
Diare (+), 3-4x sehari, warna kehijauan
3 bln yl : Batuk (+), dahak (-), demam (-)
berobat ke RSF dikatakan TBC,
mendapat terapi OAT (RHE),
1 minggu kmd gatal2 dan bentol merah diganti ESO
2 bln yl : nafsu makan menurun, mual-muntah, batuk (+) kering,
demam (-), dirawat di RSF anti HIV (+) mdpt ARV
(efavirens 1x1, stavir 2x1, hiviral 2x1) sampai sekarang
Riw IDU (+) 10 tahun yang lalu
TB-HIV, Perpari Bali 09
Pemeriksaan Fisik
TD : 120/80; HR : 88; RR : 20; S : 36
o
C
Leher : KGB (-) JVP 5-2 cmH2O
Paru : Vesikuler, Rh +/+ basah kasar, Wh (-)
Jtg : BJ I-II (N), mm (-), gl (-)
Abd : datar, lemas, NT (-), Hepar teraba 3 jbac, 2jbpx,
kenyal, tepi tumpul, limpa ttb, BU (+) N
Ext : dbn
LED : 105
Hb : 11,4 g/dL
Ht : 31,7 %
Lekosit : 6.300 /L
Diff b/e/net/limf/mn:
7.4/0.6/69/11/12
HbsAg : (-)
Anti HCV : (+)
CD 4 abs : 13
SGOT : 57 mg/dL
SGPT : 33 mg/dL
Prot : 6.1 mg/dL
Alb : 2.4 mg/dL
Glob : 3.7 mg/dL
LABORATORIUM
FOTO THORAX
Masalah :

SIDA on ARV
TB Paru on OAT
Hep C kronik
Diare akut

-Effusi pleura
-TB ekstraparu
Tatalaksana :
IVFD NaCl 0.9%
Kotrimoxazol 2x2 tab
Mycostatin 4x1 cc
Efavirens 1x600mg
Stavir 2x1 tab
Hiviral 2x1 tab
ESO : 1000/750/400mg
INH 1x300 mg
B6
Projected HIV for Jakarta
HOW TO MANAGE TB-HIV ?
Guidelines for collaborative TB-HIV (WHO)
( ~ The national strategic plans for TB-HIV)
International Standard for TB care (17 Standards )
o Standard 1- 7 : Diagnosis
o Standard 8 -15 : Treatment
o Standard 16 -17 : Public Health Resposibilities

The 3 Is
o Intensified Case Finding
o Isoniazid Preventive Therapy
o Infection Control
Recommended Collaborative TB/HIV activities
A. Establish the mechanisms for collaboration
Set up a coordinating body for TB/HIV activities effective at all levels
Conduct surveillance of HIV prevalence among people with TB
Carry out joint TB/HIV planning
Conduct monitoring and evaluation
B. Decrease the burden of TB among people living with HIV
Establish intensified TB case-finding
Introduce isoniazid preventive therapy
Ensure TB infection control in health care and congregate settings
C. Decrease the burden of HIV among people with TB
Provide HIV testing and counselling
Introduce HIV prevention methods
Introduce co-trimoxazole preventive therapy
Ensure HIV care and support
Introduce antiretroviral therapy
International Standard for TB care
17 Standards
~ TB-HIV
o Diagnosis : Standard 5
o Treatment : Standard 8, 12, 13
o Public Health Resposibilities : Standard 16

Standard 5 : Sputum smear, cxr,

The diagnosis of sputum smear-negative pulmonary TB
should be based on the following criteria: at least three
negative sputum smears (including at least one early-
morning specimen); chest radiography findings consistent
with TB; and lack of response to a trial of broad-spectrum
antimicrobial agents. (Since fl uoroquinolones are active
against M. tuberculosis complex, and thus may cause
transient improvement in persons with TB, they should be
avoided). For such patients, if facilities are available,
sputum cultures should be obtained. In persons with known
or suspected HIV infection, the diagnostic evaluation should
be expedited.
Standard 8 : OAT

All patients (including those with HIV infection) who have
not been treated previously should receive an internationally
accepted fi rst-line treatment regimen using drugs of known
bioavailability.
The initial phase should consist of two months of isoniazid,
rifampicin, pyrazinamide and ethambutol.
The preferred continuation phase consists of isoniazid and
rifampicin given for four months. Isoniazid and ethambutol
given for six months is an alternative continuation-phase
regimen that may be used when adherence cannot be
assessed, but it is associated with a higher rate of failure and
relapse, especially in patients with HIV infection.
Standard 8 (contd)

The doses of anti-TB drugs used should
confirm to international recommendations.
Fixed-dose combinations of two (isoniazid
and rifampicin), three (isoniazid, rifampicin
(or rifampin) and pyrazinamide), and four
(isoniazid, rifampicin, pyrazinamide and
ethambutol) drugs are highly recommended,
especially when medication ingestion is not
observed.

Standard 12 : Counseling

In areas with a high prevalence of HIV infection in
the general population and where TB and HIV
infection are likely to co-exist, HIV counseling and
testing are indicated for all TB patients as part of
their routine management.
In areas with lower prevalence rates of HIV, HIV
counseling and testing are indicated for TB patients
with symptoms and/or signs of HIV-related
conditions and in TB patients having a history
suggestive of high risk of HIV exposure.
Standard 13 : ART/OAT, consultation

All patients with TB and HIV infection should be
evaluated to determine if antiretroviral therapy is
indicated during the course of treatment for TB.
Appropriate arrangements for access to antiretroviral
drugs should be made for patients who meet indications
for treatment. Given the complexity of co-administration
of anti-TB treatment and antiretroviral therapy,
consultation with a physician who is expert in this area is
recommended before initiation of concurrent treatment
for tuberculosis and HIV infection, regardless of which
disease appeared fi rst. However, initiation of treatment
for TB should not be delayed. Patients with TB and HIV
infection should also receive cotrimoxazole as
prophylaxis for other infections.
Standard 16 : Evaluated to contact
All providers of care for patients with TB should
ensure that persons (especially children aged <5 yrs
and persons with HIV infection) who are in close
contact with patients who have infectious TB are
evaluated and managed in line with international
recommendations. Children aged <5 yrs and persons
with HIV infection who have been in contact with
an infectious case should be evaluated for both
latent infection with M. tuberculosis and for active
TB.
TB/HIV Goals: The 3 Is
Intensified Case Finding
Screening of all persons with or at risk of HIV for
TB, esp. in congregate settings and contacts
Isoniazid Preventive Therapy
Preventive therapy is safe and effective in people
with HIV (after excluding active TB)
Infection Control
TB infection control is essential to keep
vulnerable patients, healthcare workers and their
community safe from getting TB
Suspecting HIV
Question: When should you suspect
and test for HIV ?
Where High-prevalence areas
Who High-risk populations
How Presenting signs/symptoms that
should raise suspicion
When to suspect HIV
High-prevalence settings:
Sub-Saharan Africa
Indonesia: may include some areas of Papua,
Jakarta, East and West Java, Bali, Kepri , West
Kalimantan, Central Java, and North Sumatra
High-risk populations:
Intravenous drug user
Commercial sex worker
Multiple sexual partners
Men who have sex with men
Prisons
Clinical features suggestive of HIV coinfection in TB patients
Diagnosis of TB in HIV
Cannot rely on typical indicators of TB
Fever and weight loss are important symptoms
Cough is less common
Chest radiographic pattern more variable
More extrapulmonary and disseminated TB
Differential diagnosis is broader
CXR Pattern: Early vs. Advanced HIV
Early HIV
(CD4 >200)
Advanced HIV
(CD4 <200)
Pattern
Typical
(Reactivation)
Atypical
(Primary)
Infiltrate Upper lobes
Lower lobes,
multiple sites, or
miliary
Cavitation Common Uncommon
Adenopathy Uncommon Common
Effusion Uncommon More common
Seriously Ill TB Suspects
Immediate referral possible
No improvement 3-5 d
Antibiotic treatment, Sputum AFB
and Culture, HIV test, CXR
AFB Positive Yes TB
Immediate referral not possible
Antibiotic treatment,
? PCP treatment, Sputum AFB and
Culture, HIV test, CXR
AFB Negative
Improvement 3-5 d
TB treatment,
HIV care if HIV+
Reassess for TB,
HIV care if HIV+
No TB
Reassess for other
HIV assoc. disease
Treat for TB
HIV care if positive
Other
Diagnosis,
No TB
TB Diagnostic Algorithm: High HIV Prevalence
Ambulatory TB Suspects
AFB smears, HIV test
AFB Positive AFB Negative
Treat for bacterial infection and/or PCP
HIV care if positive, CPT
TB likely
Reassess
for TB
Treat for TB, CPT
HIV care if positive
AFB smears/culture, CXR,
clinical evaluation
TB not likely
No or poor
response
Response CPT = cotrimoxazole prophylaxis
TB Diagnostic Algorithm: High HIV Prevalence
TB/HIV: Common EPTB sites
Lymph Nodes: Cervical > axillary > inguinal
Serosal disease: pleural, pericardial
Genitourinary tract
Central nervous system: meningitis, tuberculoma
Bone and joint
Soft tissue abscesses
Disseminated disease

Prevent HIV among TB patients
Prevent TB among HIV patients
Test patients and contacts for both conditions
Coordinate treatment / drugs
TB/HIV Collaboration
Coordinate treatment for TB and HIV:
Avoid drug interactions
Maximize adherence: DOT/supportive care
Ensure timely start or continuation of anti-
retrovirals (ARV) and cotrimoxazole preventive
therapy (CPT)
ARV therapy alone can reduce the risk of progression
to active TB in latently infected individuals by 80-
92%
TB/HIV Collaboration: Treatment
TB treatment regimens are the same in HIV-positive
and HIV-negative patients ( ISTC standard 8)
All patients who have not been previously treated
should receive an internationally accepted treatment
regimen:
Initial phase: 2 months INH, RIF, PZA, and EMB
Continuation phase: 4 months INH and RIF, or
6 months of INH and EMB (higher failure in HIV)
2 RHZE, 4 RH
Fixed-dose combinations are highly recommended
HIV is associated with increased mortality during TB
treatment
TB/HIV: Treatment Outcomes
Antiretroviral Therapy (ARV)
significantly reduces TB incidence
Decrease in TB
incidence after
starting ART in
resource-limited,
high-burden area
Lawn SD, et al, Am J Respir Crit Care Med, 2008;177:680-685
ARV Improves Outcomes
Standard 13: TB/HIV
All patients with TB and HIV infections should
be evaluated to determine if antiretroviral therapy
is indicated during the course of treatment for
TB.
Appropriate arrangements for access to
antiretroviral drugs should be made for patients
who meet indications for treatment.
Standard 13: TB/HIV
Given the complexity of co-administration of anti-
TB treatment and antiretroviral therapy, consultation
with a physician who is expert in this area is
recommended before initiation of concurrent
treatment for TB and HIV infection, regardless of
which disease appeared first.
However, initiation of treatment for
tuberculosis should not be delayed

(2 of 3)
Standard 13: TB/HIV
Patients with TB and HIV infection should also
receive cotrimoxazole as prophylaxis for other
infections
All HIV-positive TB patients should receive
Cotrimoxazole Preventative Therapy (CPT) regardless
of the CD4 count, for at least the duration of anti-TB
treatment.
CPT is recommended for all patients with CD4 cell count
less than 200 cells/mm3
[WHO recommendations]
(3 of 3)
TB/HIV issues to consider:
Drug-drug interactions
Role of antiretroviral therapy (ART)
Overlapping drug toxicities
Immune-reconstitution inflammatory
syndrome (IRIS)
Adherence issues
Warning : TB/HIV Treatment
TB and ARV Therapy (ART)
Indications for ART in TB/HIV patients
depend upon:
Status of HIV disease (CD4 level)
Success of current TB treatment regimen
Adherence and toxicity issues
If TB develops Then
Within 6 months of
starting ART
Start first-line TB rx and
change ART regimen if
necessary
After 6 months of
starting ART evidence
of clinical
immunological failure
Consider ART failure and
change to second-line
ART
Key point: Start TB treatment immediately
TB Care: If Already on ART
When to Start Antiretrovirals
If CD4 count not available:
Clinical Presentation ART
Any pulmonary TB and
signs of advanced HIV, or
no clinical improvement ,
extrapulmonary TB
Start ART as soon as
TB rx tolerated
Smear-negative pulmonary TB,
gaining weight on rx,
no other signs/sx of advanced HIV
Start ART after the
intensive phase of TB
rx
Smear-positive pulmonary TB,
gaining weight on rx,
no other signs/sx of advanced HIV
Defer ART until TB rx
done
CD4 Consider starting ART
< 200
28 weeks after start of TB rx
>200 and <350 8 weeks after start of TB rx
> 350
Defer ART (re-evaluate at 8
weeks and end of TB rx)
When to Start Antiretrovirals
If CD4 count available:
TB/HIV Co-infection Treatment Scheme
ARV Therapy
No
Yes
CD4 <200 CD4 200-350 CD4 > 350
Start ARV
after anti-TB
tolerable
(2 mgg-2 bl)
Start Anti-TB
Start ARV
after anti-
TB is
finished
Finishing anti-TB
If VL > 55,000
start ARV
Continue and
adjust dose if
necessary
ARV in Indonesia
Generic Name Group Branded Name
Zidovudine/AZT NRTI Zidovex, Antivir
Lamivudine/3TC NRTI Hiviral
Stavudine NRTI Stavir, Zerit
Didanosine NRTI Videx
Nevirapine NNRTI Neviral
Nelfinavir PI Nelvex
Efavirenz/EFZ NNRTI Stocrin
Zidovudine + Lamivudine Duviral
Stavudine + Lamivudine Coviro-LS3*
Stavudine + Lamivudine + Nevirapine Triomune, GPOVir
Overlapping Side Effects
Side Effect TB Drug ARV
Skin rash* PZA, RIF, INH
Nevirapine
Efavirenz
Abacavir
Nausea,
vomiting
PZA, RIF, INH

Zidovudine
Ritonavir
Amprenavir
Indinavir
Burman et al, Am J Respir Crit Care Med 2001
* May also see rash with cotrimoxazole
Side Effect TB Drug ARV
Hepatitis PZA, RIF, INH
Nevirapine
Protease
inhibitors
IRIS
(with chronic
hepatitis)
Leukopenia,
anemia
RIF Zidovudine
Overlapping Side Effects
Burman et al, Am J Respir Crit Care Med 2001
IRIS
Immune Reconstitution Inflammatory
Syndrome (IRIS)
Clinical worsening in the setting of an adequate
response to ART
Paradoxical worsening of previously known
treated (completed or ongoing) opportunistic
pathogen
Timing of onset
Usually within first 6 weeks of ART (often 23 weeks, but
can be months after ART started)
Refer to specialist if suspect

IRIS
Clinical presentation:
Fever
Nodal enlargement
Worsening pulmonary
infiltrates (with or
without respiratory
symptoms)
Local worsening in
extrapulmonary sites
IRIS Differential Diagnosis
Differential diagnosis of IRIS:
TB treatment failure
Drug-resistant TB
Other opportunistic (or non-opportunistic)
infections
Lymphoma, Kaposis sarcoma
Hypersensitivity drug reactions
ART failure (if symptoms occur late in the course
of ART therapy)
IRIS Evaluation and Treatment
TB treatment should be continued
Exclude TB treatment failure
Adequate treatment and adherence?
Drug resistance?
Exclude additional/new diagnosis
Continue ART (unless life-threatening)
Consider NSAIDS, steroids
Drainage of lesions
Source: Tuberculosis Care with TB-HIV Co-management, IMAI
Example: Co-treatment Regimen

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