The danger Numero Uno

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The danger Numero Uno
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Thats how it reaches you

• Unprotected sexual intercourse
• Intravenous drug abuse and shared needles
• From a HIV positive mother to her infant during
  breastfeeding

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No ,Not this way
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I am no less

• World Population is six billion
• Two billion have me
• The Tubercle Bacilli.

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(No Transcript)
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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.

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• 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.

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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.
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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.

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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.

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When to Suspect

• All patients should be questioned regarding
• close contact with a person who has MDR TB
• previous residence in a country where
  drug-resistant TB is common
• previous treatment for TB, especially if it was
  incomplete
• previous residence in an institution (e.g.
  prison, homeless shelter) with documented
  transmission of a drug-resistant strain of TB.

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Mantoux Screening

• Tuberculin skin testing should be done using the
  Mantoux method in all HIV patients.
• A tuberculin reaction of gt 5 mm of indurations
  is classified as positive in persons known to
  have or suspected of having HIV infection.

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Mantoux Screening

• Unfortunately, as the CD4 lymphocyte count
  declines with progression of HIV , many patients
  no longer react to delayed-type hypersensitivity
  testing.
• More than 60 of persons with CD4 lymphocyte
  counts of lt 200 cells/µl may have skin test
  reactions of lt 5 mm.
• Thus, it is impossible to detect the presence of
  tuberculosis infection in many HIV.

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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.

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Evaluation

• 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.

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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.

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Lymphadenopathy
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Large right paratracheal lymphadenopathy
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Bilateral diffuse small nodules
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Radiological Picture
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Radiological Picture
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Bilateral diffuse opacities with hilar adenopathy
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Post Primary disease
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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 organisms.
• 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.

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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

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ARV and ATT

• 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.

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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 ATTs.

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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.

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Monitoring Response to Treatment

• 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 treatment.

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Monitoring Response to Treatment

• 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.

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Treatment of TB in Patients with CD-4
countlt100/µL

• They should NOT be treated with once- or
  twice-weekly regimens.
• These patients should receive daily therapy
  during the first 2 months, and then daily or
  three-times 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
  twice-weekly therapy.
• All patients with advanced AIDS and TB should be
  treated by DOT.

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TB Treatment Antiretroviral Treatment

• 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 medications.
• 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 rifamycins.

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ATT and ARV

• The rifamycins induce CYP450 and may
  substantially decrease blood levels of the
  antiretroviral drugs resulting in the potential
  development of resistance to these important
  agents.
• 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

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ATT and ARV

• 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

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ATT and ARV

• 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.

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ATT and ARV

• In some patients, use of ATT regimens containing
  no rifamycins may be considered.
• 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.

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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 gt 5 mm and have not
  previously received treatment for LTBI.

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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

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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
  twice-weekly (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 rifabutin.

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Thank You

• Dr.Rakesh Bharti,MD,
• rakeshbharti1_at_rediffmail.com