TUBERCULOSIS-HIV

COINFECTION
 OVERVIEW
• DIAGNOSIS

• IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME(IRIS)

• DRUG INTERACTIONS

• DRUG REACTIONS

• ISONIAZID PROPHYLAXIS

• MDR/XDR TB

• INFECTION CONTROL
TB-HIV COINFECTION
• TB is the commonest opportunistic infection in HIV infected adults
and the commonest cause of death.
• HIV negative TB patients have a 10% lifetime chance of getting Tb
whilst HIV+ have 10%/year chance of getting TB again.
• Sputum + patients, HIV + patients, XDR AND MDR TB are considered
to be the drivers of the Tb epidermic
• Tb accelerates the progression of HIV and vice versa, and despite
adequate tb therapy, both morbidity and mortality are increased in
HIV seronegative patients
• Tb is prevalent at any stage regardless of CD4 cell count
 Diagnosis
• Culture (growing) of the bacteria is the gold standard –
distinguishes M.tb from other AAFBs/Mycobacteria
• Alternatively show the bacteria
• Smear microscopy
• Histopathological diagnosis
• Nucleic amplification tests on clinical specimens, including sputum
• Radiographic methods
• Phage-based detection methodology
• Sputums only 60% of HIV + patients will be HIV positive
• Smear positive case-if one acid fast bacillus seen in at least one sputum
sample
• Smear negative case-At least 2 sputum specimens are negative for AAFBs
and
 Pulmonary tuberculosis
• Sputums only 60% of HIV + patients will be AAFB positive
• Only 25% culture positive in milliary TB)
• Smear positive case-if one acid fast bacillus seen in at least one sputum sample
• Smear negative case-
• at least 2 sputum specimens are negative for AAFBs and
• radiological abnormalities are consistent with active Tb and
• there is laboratory confirmation of HIV or
• strong clinical evidence of HIV infection;
• Decision by clinician to treat with full course of antituberculosis chemotherapy
Improving the diagnosis of smear-negative TB
• Step 1
• Send a third sputum specimen for AFB/ culture
• Step 2
• Supply client with 7/7 broad spectrum antibiotic (amoxil 500mg po tds)
• Step 3
• CXR
* Induced sputa/Bronchoscopy may be used in those with no sputum production.
 Smear negative pulmonary tuberculosis

• Chest radiograph is an essential Ix in all smear negative suspects

• Radiological findings depend on CD4 count
• Tb pleural effusion can be diagnosed in adults younger than 45
years if the fluid is not purulent and is clinically an exudate(straw
coloured that forms clot on standing)
• In adults over 45 , blood fluid total protein ratio of >0.5 suggest
exudate/cytology-neutrophils-Para pneumonic
effusion/lymphocytes –tb/atypical cells –malignancy
• Alternatives available include nucleic acid amplification assay
which is specific for M.tb and is 80% sensitive.
• In milliary tb alternative specimens e.g. blood cultures 60%
sensitive.
 DIAGNOSIS
• TUBERCULIN SKIN TEST-Also known as purified protein derivative
test/Mantoux test indicates an immunological memory of previous/ ongoing
contact with M.tb. Also positive in BCG vaccinated and those who had contact
with atypical mycobacteria
• Usually gives false negative results in patients with CD4< 200/µl

• Recently INTERFERON GAMMA RELEASE ASSAYS have been introduced for

diagnosis of TB. They detect secretion of IFN γ by peripheral blood mononuclear
cells induced by specific MTB peptides. More specific and sensitive than TST for
diagnosis in immunosuppressed patients.
 Treatment

• Lesotho 2007 guidelines

• Tuberculosis is a stage 3( pulmonary)/stage 4(extra pulmonary)
disease thus patients are eligible for HAART regardless of CD4
count
• It is essential to rule out tb in all patients for ART initiation and
treat tb as soon as diagnosis is made.
• Children can be given Ethambutol in view of high resistance
rates(3%) rates in Lesotho
Cd4 count When to initiate ART
<200 2 to 8 weeks after initiating ATT
201 - 350 After 8 weeks of ATT
>350 Re evaluate after completing ATT
 The Breastfeeding mother and TB
A breastfeeding mother who has TB should receive full course of
ATT. Timely and efficient Tb therapy is the most effective way to
prevent transmission to the baby.
• Mom and baby should continue to stay together and the
breastfeeding should be continued.
• After active TB in the baby is ruled out, the baby should receive
Isoniazid prophylaxis at 5 mg/kg for 6 months after which BCG is
given.
• Pyrazinamide is recommended for all breastfeeding and pregnant
mothers
• Streptomycin is contraindicated in pregnancy.
Immune Reconstitution inflammatory Syndrome

• IRIS results from a pathological inflammatory response driven by the

recovering immune system after ART is started causing clinical
deterioration. May be
• Unmasking
• ARVs first and then TB presents
• Paradoxical
• TB treatment ARVs and then worsening of symptoms
• Paradoxical TB IRIS occurs in 8 -43% of pt started on ART whilst on TB
treatment, typically 1-4 weeks after initiating ART.
• It is generally advised that ART be continued and effective treatment of the
condition be started, in severe cases corticosteroids may be considered in
consultation with a specialist.
• Where the reaction is life threatening and not responding to steroids, it may
be necessary to interrupt ART.
 Drug interactions
• HIV-Tb co-infected patients are often on multiple drugs for the 2
conditions apart from medications for comorbidities, nutritional
supplements and alternative therapies hence great potential for drug
interactions. Furthermore there is potential for shared toxicities,
• Below are a few to look out for -
• Rifampicin decreases levels of Kaletra-increase dose of Ritonavir by 75%
• Avoid Nevirapine with Rifampicin.Possible hepatotoxicity + NVP levels
reduced. Use Efavirenz instead/Rifabutin.
• Fluconazole levels are reduced by Rifampicin and Nevirapine levels
increase by 100% - possible hepatotoxicity
• Avoid Phenytoin, Carbamazepine and Phenobarbitone with
Nevirapine.All reduce NVP levels.
• Oral contraceptives to be avoided with PIs and NNRTIs.With Rifampicin
use high dose estrogen pills/alternative contraceptive
 DRUG REACTIONS
Aetiology of jaundice in patient newly started on TB
treatment
Differentiate by baseline ALT/AST;
• TB liver
If N = S/E
• Other infection
If AbN = probable TB liver.
• Hepatitis B/C/A
• CMV hepatitis BUT should investigate further to confirm TB
involvement of liver
• Systemic bacterial infection

• S/E of drugs
• PZA
• INH
• Rifampicin
 day 1 INH 50 mg
•Management
Management
of drug-induced hepatitis 2 to TB drugs
o

• Stop TB treatment if ALT/AST day 2 INH 100 mg

≥5×ULN
day 3 INH 300 mg
• Monitor LFT;
• Start liver friendly TB regimen day 4-6 Daily ALT monitoring
• Ethambutol and streptomycin in
standard doses. Ofloxacin 800 day 7 Rifampicin 75 mg
mg daily day 8 Rifampicin 150 mg
• When bilirubin and transaminases
are approaching normal, day 9 Rifampicin 300 mg
rechallenge
• Do not reintroduce PZA day 10 Rifampicin full dose
day 11-13 Daily then weekly
ALT monitoring
 Management of skin reactions
2o to TB drugs

• Management day 1 INH 100 mg

• Stop TB treatment
• Start “liver friendly TB day 7 INH 300 mg
regimen” day 14 Rifampicin 300 mg
• Ethambutol and streptomycin in
standard doses. Ofloxacin 800 day 21 Rifampicin full dose
mg daily
• When skin reaction subsided Day 28 PZA full dose
rechallenge but at much
longer intervals vs hepatitis

• Listen to your patient!!!

 ISONIAZID PROPHYLAXIS THERAPY
• IPT has been found to be beneficial in certain settings in preventing morbidity and
mortality from TB. However due to difficulty of ruling out active TB in HIV patients and risk
of treating TB with a single agent, it is recommended that IPT be instituted at national
scale only if active TB can be excluded.
•Does IPT work?
• Early studies showed that
• IPT prevented TB amongst contacts of TB patients
• IPT prevented TB amongst people with CXR evidence of latent TB
infection
• In HIV positive patients showed that IPT prevented TB up to 2
years after giving 6 months IPT.
• Combined analysis of all trials revealed
• Effect of IPT varies with the baseline (community) risk of acquiring TB
• High prevalence TB settings
• IPT treatment of 24 people will prevent 1 case of TB disease
 Isoniazid prophylaxis therapy
• IPT should be given to
• HIV positive patients who have POSITIVE TUBERCULIN SKIN TEST with no
active TB
• =“5mm” of induration 48-72 hours after injection of 5iu of ppd
• INH 300mg daily x 6 months
• Assess at each visit signs and symptoms of illness

• Isoniazid 5mg/kg × 6 months with

• Pyridoxine 12.5mg if < 3years
• Pyridoxine 25mg if >3 years
• Health care workers who are HIV positive should be offered IPT.
 MDR/XDR TB
• MDR TB-resistant to rifampicin and Isoniazid
• XDR TB-resistant to resistant to rifampicin, isoniazid,
fluoroquinolones and to at least one injectable drug i.e. capreomycin,
amikacin and kanamycin.
• Suspect MDR TB if;
• Retreatment patient who remains sputum positive after 3 months intensive
phase
• Treatment failure and interruption cases
• Close contacts of MDR TB cases
• Chronic cases
• Treatment is with at least 5 drugs that are in vitro active against
causative strains should be administered for 4 month intensive phase
and at least 12 of continuation phase, based on culture conversion
 Infection control
Administrative tools- triage procedures, segregation of patients, measures
to rapidly identify patients
Environmental factors- enclosed congregate waiting areas compromise
health and safety
• Well ventilated waiting areas for clients OPEN THE WINDOWS!!!!
• Maintenance of good air circulation by opening windows and use of fans in
waiting areas and consultation rooms
• Use of ultraviolet germicidal radiation
Personal protection-Strategies to reduce the inhalation of infectious TB particles by
staff and clients present in health care facilities (personal protection)
• Use of N95 masks to prevent inhalation of TB
• Encouraging clients and staff to know their HIV status, and to take INH
prophylaxis if appropriate
• Training in infection control strategies
 N95 mask
• N95 masks will NOT work if
• They are not properly fitted
• If the wearer has facial hair (beard) preventing a proper fit
• They are damaged or crushed
• They are saturated (reused until the filter capacity has been exceeded)
• They get wet (even if they dry again) or oily
• Reusing masks
• Each staff member should reuse the same mask (it is helpful to write the
staff member’s name on the mask)
• Keep the mask dry, clean.
• Replace if undamaged or if two weeks old.
 THANK
YOU
REFERENCES
LESOTHO NATIONAL TB CONTROL MANUAL
Oxford handbook of HIV medicine
HIV 2010
National Antiretroviral treatment guidelines
Medical Management of HIV infection South Africa edition
Reproduction Health & HIV Research Unit Course handbook

Dr Tsitsi Vimbayi Chatora