CMTO5210: INTERNAL

MEDICINE
SESSION 15: TB and HIV Co-
Infection
 Learning Objectives
By the end of this session, students are expected to be able to:
• Describe relationship between HIV and TB
• Describe clinical presentation of TB in TB/HIV co-infected patients
• Explain TB/HIV collaborative activities
• To describe strategies for reducing TB burden in PLHIV and HIV in TB patients
• Explain diagnostic approaches for TB/HIV co-infection
• Outline management of TB/HIV co-infected patients
• Describe measure to prevent TB/HIV co-infection
TB is the most common opportunistic infection and the major cause of
deaths among HIV and AIDS patients.
TB and HIV have been declared global emergencies demanding global
attention.
HIV increases the risk of TB reactivation and progression from TB
infection to active disease.
TB Management in HIV and AIDS Patients
Pattern of HIV-related TB
o As HIV infection progresses, CD4+ T-Lymphocytes that play an important role in
the body’s defence against tubercle bacilli declines in number and function.
o Thus, the immune system fails to prevent the growth and local spread of M.
tuberculosis.
o There are two types of TB: Pulmonary and Extra pulmonary TB (EPTB).
o The most common type of TB in HIV is extra pulmonary TB.
 Pulmonary TB
 Pulmonary tuberculosis is defined as one sputum smear examination positive
for acid-fast bacilli (AFB).
 AFB Smear-negative pulmonary tuberculosis is defined as the presence of at
least two sputum specimens negative for AFB but radiographical
abnormalities consistent with active tuberculosis.
 Pulmonary TB is also indicated when a clinician decides to treat with a full
course of anti-tuberculosis chemotherapy OR when a patient has AFB smear-
negative sputum which is culture-positive for Mycobacterium tuberculosis.
 Extra-pulmonary tuberculosis (EPTB)

 EPTB is defined as tuberculosis in organs other than the lungs proven by one
specimen from an extra-pulmonary site culture-positive for Mycobacterium
tuberculosis or smear-positive for AFB; or histological or strong clinical evidence
consistent with active extra-pulmonary tuberculosis.
 The most common forms of EPTB are pleural effusion, lymphadenopathy, pericardial
disease, milliary disease, meningitis, spinal TB (Pott’s disease) and disseminated TB.
 Other sites of the body which may be affected by TB include bones other than spine,
peripheral joints, adrenal glands, skin, genito-urinary tract, intestines, peritoneal
membrane and upper respiratory tract.
 Tuberculosis diagnostic approaches

 There are 2 approaches for TB diagnosis: Clinical and laboratory.

o Clinical diagnosis
o Clinical diagnosis of TB involves:
o A careful and extensive history-taking, which includes asking the patient relating to:
 Classical symptoms suggestive of TB disease among adults: cough for two weeks or more,
night sweats, fever, and weight loss.
 If coughing, the sputum colour and quantity.
 History of TB disease and the outcome of treatment.
 The presence of other medical conditions such as HIV and AIDS and diabetes mellitus.
  History of TB contact(s).
 Tobacco-smoking, including amount and duration of smoking.
 History of substance abuse (drugs and alcohol).
 Alcohol ingestion, including amount and duration.
 Occupational history that may suggest exposure to silica dust, especially among miners.
Physical examination. Although no physical sign is sensitive or specific
enough for TB, it is critical to
Note:
Nearly a quarter of all TB patients may not have the classical symptoms of
TB, including cough, and the diagnosis is based on an abnormal chest X-
ray suggestive of TB.
 Laboratory diagnosis

 Early identification and effective treatment of TB cases is important in TB care and control. Diagnosis
of PTB depends on the identification of tubercle bacilli either by sputum microscopy, or culture and
identification of bacterial DNA using molecular techniques (Gene X pert).
o Sputum smear microscopy
o Sputum smear examination is the cornerstone of TB diagnosis. The test is relatively quick, easy to perform, and
inexpensive. The purpose of sputum microscopy is to:
 Diagnose people with active TB.
 Monitor the progress of treatment.
 Confirm whether cure has been achieved.
o Sputum culture
o Culture is a more sensitive method for detecting Mycobacterium than AFB microscopy and can detect as low as 10
bacilli/ml of sputum. However, culture methods are slow and expensive.
 New technologies
GeneXpert® MTB/RIF assay
o This is a highly sensitive and specific rapid automated molecular test for the combined detection of TB and rifampicin resistance. WHO recommends the use of GeneXpert test as the
initial test for PLHIV.
o However, due to the limited number of GeneXpert machines and cartridges available in Tanzania it is an initial test in only health facilities where GeneXpert machines are available.
o In health facilities without GeneXpert machines, it is used as a follow-up test for smear-negative HIV-positive, TB suspects.
 Drug Susceptibility Testing (DST)
o In Tanzania, DST is done primarily for routine surveillance of drug resistance, through the Proportion Method using solid media.
o The drugs for which DST is carried out include the first-line drugs Isoniazid (H), Rifampicin (R), Streptomycin (S), and Ethambutol (E), and the second-line drugs Ofloxacin and
Kanamycin.
 Other New technologies adopted by the country for TB case detection and DST:
o Liquid culture using the Mycobacterium Growth Indicator Tube (MGIT): It allows rapid growth and detection of M. Tuberculosis.
o Polymerase chain reaction using strip technology in Line Probe Assay (LPA) for DST. LPA is used for rapid detection of Rifampicin and Isoniazid resistance, which can occur within
two days, hence facilitating early initiation of correct treatment or appropriate measures to prevent transmission of MDR TB.
 Other relevant investigations for tuberculosis in adults
o Chest X-ray
o Histological examination
Presumptive TB treatment for severely ill patients

 Presumptive TB case among PLHIV is defined as individuals suspected of having

TB according to TB screening tool (Annex 6) or with any of the following danger
signs: Respiratory Rate >30 per minute, Temperature >39 degree Celsius, Heart
Rate > 120 per minute and unable to walk unaided.
 Presumptive TB treatment is based on expert opinion where expedited diagnosis
of TB is not possible or feasible due to patient or health system limitations, but TB
investigations should be done even after presumptive TB diagnosis is made.
 Treatment should be stopped only upon having proof of a negative TB test or
strong evidence of an alternative diagnosis.
Standard TB Treatment Regimens for adults

 There are two phases of TB treatment: initial (intensive) and continuation.

 During the intensive phase, there is a rapid killing of the TB bacilli.
 Most patients with smear-positive TB become non-infectious after about 2 weeks of effective treatment.
 During the continuation phase, the drugs kill the remaining bacteria, and prevent relapse after completion of
treatment.
o New adult TB patients should receive a six-month regimen containing rifampicin: 2RHZE/4RH. The regimen requires direct
observed treatment by a health care worker or treatment supporter throughout the six months.
o Standard regimen for previously treated adults other than MDR TB: All previously treated TB patients should provide a
specimen for rapid molecular testing (GeneXpert® MTB/ RIF), and where available, culture and DST.
o All patients who are Rifampicin resistant should receive MDR TB treatment in a designated health facility.
 Patients with no Rifampicin resistance should be treated with a first-line retreatment regimen containing all five
drugs (2SRHZE/1HRZE/5RHE) while waiting for DST
 In the absence of GeneXpert®, all previously treated patients should submit a specimen for culture and DST.
 Previously treated patients with treatment failure will be initiated MDR TB treatment immediately, while waiting for
DST results.
 Previously treated patients who are relapses and return after loss to follow-up (defaulters) will be initiated on an interim
first-line retreatment regimen containing all five drugs (2SRHZE/1HRZE/5RHE) while waiting for DST results.
 Once DST results are available, treatment should be modified accordingly.
 Patients who are resistant to Rifampicin alone or Rifampicin and Isoniazid (MDR TB) will change to an MDR TB
treatment regimen.
 Those who are not MDR TB will continue with the first-line retreatment regimen and resistance will be monitored for
three to five months.
 Other previously treated patients (others) will be treated with a first-line retreatment regimen (2SRHZE/1HRZE/5RHE)
while waiting for culture and DST results.
 Tuberculosis associated Immune Reconstitution Syndrome

 HIV positive patients may experience an occurrence of features of active TB or a temporary

exacerbation of signs and symptoms of TB with or without an aggravated radiographic
manifestation after the initiation of ART.
 This paradoxical reaction in HIV infected TB patients is a result of immune reconstitution.
 Signs and symptoms include fever, lymphadenopathy, central nervous system lesions and
worsening of the chest X-ray appearance.
 This syndrome is known as the Immune Inflammatory Reconstitution Syndrome (IRIS).
 In such cases, it is crucial that TB treatment failure is excluded before diagnosing IRIS.
 The management includes continuation of both ART and anti-TB therapies, and if severe,
 Intensified TB case-finding

 Intensified TB case finding involves screening for symptoms and signs of TB in settings
where HIV-infected people are concentrated using standardized TB screening tools
(available for both children and adults)
 TB screening promotes early identification of TB among PLHIV and thus increases access
to TB treatment, improves survival and quality of life and reduces transmission of TB in
the community.
 People with presumptive TB should undergo diagnostic follow up using the TB diagnostic
algorithm available for children older than 6 years and adults
 Furthermore, the diagnosis of childhood TB may be done clinically in the absence of
bacteriological confirmation by using the score chart.
 Isoniazid Preventive Therapy (IPT)

 Isoniazid Preventive Therapy (IPT) is an intervention that should be part of the package of care for PLHIV.
 IPT involves giving Isoniazid (INH) tablets to eligible individuals in order to prevent progression of active TB
disease.
 In individuals with HIV, IPT reduces the risk of developing tuberculosis for about 60% and prolongs survival.
 The protective effect is expected to last for about 18 months from the last dose of Isoniazid28 .
 Exclusion of active TB is critically important before this preventive therapy is started.
 Isoniazid is given daily for six to nine months and should be given only once in a life time.
 This therapy requires consideration of several steps, including identification of HIV-positive clients, screening
in order to exclude active TB, assessing eligibility for IPT and monitoring of treatment adherence.
Eligibility for IPT among adults and adolescents

 For patients with no history of TB treatment:

o All HIV positive individuals with no signs or symptoms suggestive of active TB are eligible for IPT.
o A tuberculin skin test should be performed to all HIV infected individuals wherever possible.
o However, tuberculin test may be negative in severely immunocompromised clients due to cutaneous anergy and should not be used as exclusion
criteria for IPT.
 For patients with history of TB treatment:
o Patients who had active tuberculosis within 2 years ago should not be considered for IPT
o Patients who were treated for tuberculosis more than for the past 2 years ago should be considered for IPT because they may have already been re-
infected with TB.
 Other exclusion criteria for IPT include:
o Alcohol abuse
o Non-adherence to long term treatment
o Current / past history of hepatitis
o Medical contra-indication to INH
 IPT should only be offered in the following situations:
o Where quality supportive counselling is available
o After effective screening for active TB
o Where there is capacity for follow-up and monitoring of patients to encourage adherence to
preventive therapy.
o Where there is capacity to manage side effects and exclude active TB during IPT.
 Dosage:
o Isoniazid: 300 mg daily for 6 months to complete one cycle of IPT
o IPT should only be given in one cycle in life time and no repeat cycle is needed
Note: In case of neuropathy due to INH, Pyridoxine should be used for
treatment of neuropathy.
IPT in pregnancy
o IPT is not contraindicated in pregnancy.
o However, is should be avoided during the first trimester of pregnancy as there is no
enough evidence on safety of INH during the first trimester.
 ART in HIV and TB Co infected individuals

 ART has been reported to reduce TB rates by up to 90% at the individual level, and 60% at the population level,
and also reduces TB recurrence rates by 50%29,30,31 .
 Initiation of ART for all those with HIV and TB co-infection, if accompanied by high levels of coverage and ART
adherence, reduces the number of TB cases, TB mortality rates and TB transmission at the population level.
 For TBHIV co-infected individuals who are not on ART at TB diagnosis, TB treatment should be started first,
followed by ART as soon as possible, within the first 2 weeks after starting TB treatment.
 For PLHIV who are already on ART at TB diagnosis, TB treatment should be started immediately and ART
continued as instructed below.
 Rifampicin and Nevirapine should not be used concurrently due to drug interactions.
 PLHIV diagnosed with TB while on Nevirapine containing regimens should be switched to efavirenz based
regimens
 In individuals who need TB treatment and who require an ART regimen containing a boosted protease
inhibitor (PI), it is recommended to use LPV/r double dose (i.e. LPV/r 800mg/200mg twice a day) or with
an adjusted, super-boosted dose of RTV (i.e. LPV/r 400mg/ 400mg twice a day) but this is frequently
associated with high levels of toxicity and requires clinical and laboratory monitoring.
 NOTE: Consideration 1: When TB is diagnosed in patients already receiving ART, TB treatment should
be started immediately.
 There are two issues to consider in such cases: whether ART needs to be modified because of drug–drug
interactions to reduce the potential for overlapping toxicities, and whether the presentation of active TB in
a patient on ART constitutes ART failure that requires a change on the ART regimen.
 Consideration 2: When TB is diagnosed in PLHIV who are already on ART and Medically Assisted
Therapy using Methadone, Rifampicin decreases Methadone level by 33% to 68% and hence the
Methadone dose increase may be required32
TB Infection in health-care facilities and congregate settings

TB infection control should be implemented in health care facilities and

congregate settings where people with TB and HIV are frequently
confined.
 Measures to reduce TB transmission include administrative,
environmental, and personal protection measures, which are generally
aimed at reducing exposure to M. tuberculosis among health care workers,
prison staff, police and their clients, and other persons in the congregate
settings.
 Key Points

• TB incidence is on the rise due to HIV.

• When TB and HIV interact, they make each other worse.
• TB/HIV co-infection leads to several challenges in the areas of prevention, diagnosis, and treatment.
• With severe HIV disease, TB is more likely to present as extrapulmonary disease.
• Multidrug therapy is recommended when treating TB in HIV positive patient just as in HIV negative
patients.
• Monitoring patients for side effects if treating HIV and TB is very important
• TB/HIV co-infection requires a coordinated response which includes establishing mechanisms for
collaboration.
 Evaluation
• What are the challenges of HIV/TB treatment?
• Describe the importance of TB/HIV collaborative activities.
• Which measures should be taken to prevent TB in HIV patients?
• Outline the management of TBHIV co-infected patient based on CD4
levels.
 References

• Cumming, A.D. (2006). Davidson’s Principles and Practice of

Medicine.Oxford
• Kumar, P. & Clark, M. (2007). Clinical Medicine. Edinburgh:
Elsevier Saunders,
• Standard treatment guidelines by MOHCDGEC