Paradoxical Reaction

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Transcript Paradoxical Reaction

The danger Numero Uno
That’s how it reaches you
• Unprotected sexual intercourse
• Intravenous drug abuse and shared
• From a HIV positive mother to her infant
during breastfeeding
No ,Not this way
I am no less
• World Population is six billion
• Two billion have me
• The Tubercle Bacilli.
Transmission and Pathogenesis
• Prospective cohort studies have
documented high rates of TB (5-10% per
year) among HIV infected populations,
particularly injection drug users.
Exogenous re infection with another strain
of M. tuberculosis has been documented
in patients with advanced HIV disease.
• The risk of TB has been estimated to be
over 9 times greater in HIV positive
compared with HIV negative persons who
have a positive tuberculin test.
• Outbreaks of TB, including multi-drug
resistant disease, have highlighted the
speed with which HIV infected patients
progress to active TB after recent infection
with M. tuberculosis.
Double Trouble
HIV alters the pathogenesis and
clinical presentation of TB.
The frequency of extra pulmonary TB
increases with low Cd4 (70% with less
than 100 count)
The clinical and radiographic
presentation may be atypical.
TB and HIV
• HIV positive patients with TB have a
significantly higher mortality when
compared to HIV negative cases.
• Delays in the diagnosis of TB have been
associated with worse outcomes, so
initiation of treatment as soon as TB is
suspected is very important.
TB and HIV
• While initial studies emphasized the impact of
HIV on the natural progression of TB, recent
studies have demonstrated that TB may alter the
natural history of HIV disease.
• Viral load has been shown to increase in the
setting of active TB and decrease with
appropriate therapy. Furthermore, HIV patients
with TB have been shown to die sooner and
develop AIDS faster than HIV-1-infected controls
without TB.
When to Suspect
• All patients should be questioned regarding :
• close contact with a person who has MDR TB
• previous residence in a country where drugresistant TB is common;
• previous treatment for TB, especially if it was
• previous residence in an institution (e.g. prison,
homeless shelter) with documented
transmission of a drug-resistant strain of TB.
Mantoux Screening
• Tuberculin skin testing should be done
using the Mantoux method in all HIV
• A tuberculin reaction of > 5 mm of
indurations is classified as positive in
persons known to have or suspected of
having HIV infection.
Mantoux Screening
• Unfortunately, as the CD4 lymphocyte count
declines with progression of HIV , many patients
no longer react to delayed-type hypersensitivity
• More than 60% of persons with CD4 lymphocyte
counts of < 200 cells/µl may have skin test
reactions of < 5 mm.
• Thus, it is impossible to detect the presence of
tuberculosis infection in many HIV.
Anergy Testing
• In the past, anergy testing has been used to try
to distinguish false negative from true negative
tuberculin reactions.
• However, recent data have documented
limitations in the usefulness of anergy testing in
public health tuberculosis screening programs.
• Therefore, anergy testing in conjunction with
tuberculin skin testing is no longer
recommended for inclusion in screening
programs for M. tuberculosis infection among
HIV infected persons.
• All patients who have a positive tuberculin skin
test should have a chest radiograph performed
to rule out active disease.
• Patients should be asked about any symptoms
which suggest the presence of active TB.
• Persons who are found to have an abnormal
chest radiograph and/or are symptomatic should
be evaluated for the possibility of active disease
by sending three sputum specimens for AFB
smear and culture.
TB and HIV
• Patients with advanced HIV-1 disease are
more likely to have an extrapulmonary site
involved and atypical radiographic
presentation such as lower lobe
involvement and intrathoracic adenopathy.
It is important to note that HIV-1 infected
patients with pulmonary TB may have a
normal chest radiograph.
Large right paratracheal
Bilateral diffuse small nodules
Radiological Picture
Radiological Picture
Bilateral diffuse opacities with hilar
Post Primary disease
Treating TB
HIV infected patients with TB respond well to ATT, as
long as the regimen contains INH and rifampin.
• A 6-month regimen consisting of INH, rifampin,
pyrazinamide, and either ethambutol or streptomycin
given for 2 months followed by INH and rifampin for 4
months is the preferred treatment for drug-susceptible
• Pyrazinamide should be continued for the first 2 months
regardless of the results of drug-susceptibility testing,
whereas ethambutol can be stopped after drug
susceptibility test results indicate that M. tuberculosis is
sensitive to INH and rifampin.
Treatment of TB (Contd.)
• Because the effect of patient adherence
on the outcome is much more critical,
directly observed therapy (DOT) is
strongly recommended for persons with
HIV infection.
• ATT should be supplemented with
pyridoxine (B6).
• Patients should be monitored closely for
adverse reactions
• Ask HIV infected about antiretroviral
therapy use and specifically whether they
are currently taking protease inhibitors
(PIs) or non-nucleoside reverse
transcriptase inhibitors (NNRTIs).
• CD4 lymphocyte count and viral load
should be measured to assist with the
treatment of the underlying HIV infection.
Paradoxical Reaction
• Occasionally, patients with TB may
experience a temporary exacerbation of
symptoms after beginning TB treatment.
• This is known as a paradoxical reaction (or
immune reconstitution syndrome) These
reactions are often related to the
simultaneous administration of both ARV
and ATT’s.
Paradoxical reaction-diagnosis
• The diagnosis of a paradoxical reaction should
be made only after a thorough evaluation has
been made to exclude other etiologies.
• Some patients have required the use of
corticosteroids (in addition to TB treatment) to
treat these reactions.
• The decision to use corticosteroids must be
made on a case-by-case basis.
• Indications may include severe hypoxemia,
airway obstruction, neurologic impairment, or
possibly enlarged painful lymph nodes.
Monitoring Response to
• Because the margin of error for treatment
failure and relapse is probably less in HIV,
the 6-month regimen should be
considered the minimum duration of
Monitoring Response to
• Patients having a delayed response to
treatment should have treatment
prolonged from 6 to 9 months.
• Malabsorption of the ATT drugs should be
considered as a possible cause of
treatment failure or the acquisition of drug
resistance, particularly if gastrointestinal
symptoms or chronic diarrhea is present.
Treatment of TB in Patients with
CD-4 count<100/µL
• They should NOT be treated with once- or twiceweekly regimens.
• These patients should receive daily therapy
during the first 2 months, and then daily or threetimes weekly therapy during the next 4 months.
• This recommendation is based on a recent study
showing an increased rate of acquired rifamycin
resistance among patients who received twiceweekly therapy.
• All patients with advanced AIDS and TB should
be treated by DOT.
TB Treatment & Antiretroviral
• Potent antiretroviral agents are now available for the
treatment of HIV infection. These agents are classified
as nucleoside/nucleotide (NRTI/NtRTI) or nonnucleoside
reverse transcriptase inhibitors (NNRTI) , protease
inhibitors (PI)and Fusion inhibitors.
• The nucleoside agents do not have clinically significant
drug interactions with the standard antituberculosis
• However, the PIs and NNRTIs may inhibit or induce
cytochrome P-450 isoenzymes (CYP450) and thus,
these drugs may alter the serum concentration of the
• The rifamycins induce CYP450 and may
substantially decrease blood levels of the
antiretroviral drugs resulting in the potential
development of resistance to these important
• The potential benefit of the antiretroviral drugs
must be weighed against the importance of
rifamycins in treating HIV related tuberculosis.
• The loss of a rifamycin from the treatment
regimen is likely to delay sputum conversion,
prolong the duration of therapy, and possibly
result in a poorer outcome
• Previous guidelines specifically stated that
rifampin was contraindicated for patients
who were taking any PI or NNRTI.
• New data indicate that rifampin can be
used for the treatment of tuberculosis in
several situations
• Other issues in the guidelines to be aware of are:
• the rifabutin dose should be reduced to 150 mg two or
three times per week when given with ritonavir
• The dose of rifabutin should be increased to 450 mg or
600 mg daily or 600 mg two or three times per week
when rifabutin is used concurrently with efavirenz
• Rifabutin can be used with many protease inhibitors, but
doses of both the protease inhibitors and rifabutin may
need to be altered.
• In some patients, use of ATT regimens
containing no rifamycins may be
• For such patients, a 9-month, largely
intermittent, regimen consisting of
isoniazid, streptomycin, pyrazinamide and
ethambutol for 2 months then isoniazid,
streptomycin, and pyrazinamide for 7
months is an option.
Treatment of Latent TB Infection
• Treatment of latent tuberculosis infection (LTBI)
with isoniazid (INH) is very effective in
preventing persons infected with M. tuberculosis
from developing tuberculosis, regardless of
HIV.Rifampin and pyrazinamide is not
recommended for reasons of heptotoxicity
• Recent studies have also documented no
significant reduction in TB among anergic
individuals who took INH.
• HIV persons should be treated for LTBI if they
have a tuberculin skin test > 5 mm and have not
previously received treatment for LTBI.
Treatment of LTBI
• In certain cases, treatment of LTBI in persons
who are not tuberculin positive may also be
considered. Such therapy may be beneficial for:
• close contact to an infectious case
• persons with a history of prior untreated or
inadequately treated TB who have fibro nodular
opacities on a chest radiograph (if active TB is
ruled out)
• HIV infected adults who reside or work in
institutions and are continually and unavoidably
exposed to patients who have infectious TB
Treatment of LTBI
• The current CDC recommendations include several
options for treatment of LTBI in HIV-1-infected persons:
• INH (300 mg/day) for 9 months, either daily or twiceweekly (900 mg biw)
• Therapy should be supplemented with pyridoxine (25-50
mg a day) to help prevent peripheral neuropathy
• rifampin daily for 4 months. Rifabutin may be substituted
for rifampin
• When treatment is provided with isoniazid twice a week,
the therapy should be given under direct observation.
delavirdine cannot be given with either rifampin or
Thank You
Dr.Rakesh Bharti,MD,
[email protected]