In the name of GodIn the name of God

Fariba RezaeetalabFariba Rezaeetalab

Assistant ProfessorAssistant Professor

TB and HIVTB and HIV TB/HIV Pathogenesis Importance of Screening Clinical Presentations of HIV-related

TB Clinical Management of TB and HIV

Co-infection

TB/HIVTB/HIV

TwoTwo Diseases Diseases

OneOne Patient Patient

TB: A Growing Concern TB: A Growing Concern for PLWHAfor PLWHA

Approximately 1/3 of Approximately 1/3 of the world population the world population

is infected with TBis infected with TB

TB is one of the TB is one of the leading causes of leading causes of

death in people with death in people with HIV, particularly in HIV, particularly in

low-income low-income countriescountries

HIVHIV

TBTB

HIV & TBHIV & TB

The Effects of TB on HIV The Effects of TB on HIV ProgressionProgression

TB increases HIV progressionTB increases HIV progressionDually infected persons often have very Dually infected persons often have very

high HIV viral loadshigh HIV viral loadsImmuno-suppression progresses more Immuno-suppression progresses more

quickly, and survival may be shorter quickly, and survival may be shorter despite successful treatment of TBdespite successful treatment of TB

Persons who were co-infected have a Persons who were co-infected have a shorter survival period than persons shorter survival period than persons with HIV who never had TB diseasewith HIV who never had TB disease

The Effects of Immune The Effects of Immune Suppression on TB Suppression on TB

ProgressionProgressionHIV+ person has a greater risk of HIV+ person has a greater risk of

reactivation of latent TB infection (LTBI)reactivation of latent TB infection (LTBI)HIV+ person is more likely to progress HIV+ person is more likely to progress

to TB disease following infectionto TB disease following infectionHIV+ person has a high risk of HIV+ person has a high risk of

becoming sick again after treatmentbecoming sick again after treatmentHIV+ person with LTBI has a 5-15% HIV+ person with LTBI has a 5-15%

annual risk of developing active TB annual risk of developing active TB (versus 10% lifetime risk among HIV-(versus 10% lifetime risk among HIV-negative persons)negative persons)

The Effects of HAART The Effects of HAART on TB Progressionon TB Progression

Highly Active Anti-retroviral Therapy Highly Active Anti-retroviral Therapy (HAART) alone can reduce the risk of (HAART) alone can reduce the risk of latent TB infection progression to latent TB infection progression to active TB disease by as much as active TB disease by as much as 80%–92%80%–92%

In In areas with a high prevalence of HIV areas with a high prevalence of HIV infectioninfection in the general population where in the general population where tuberculosis and HIV infection are likely to tuberculosis and HIV infection are likely to co-exist, co-exist, HIV counseling and testing is HIV counseling and testing is indicated for all tuberculosis patientsindicated for all tuberculosis patients as part as part of their routine managementof their routine management . .

In areas with lower prevalence rates of HIV, In areas with lower prevalence rates of HIV, HIV counseling and testing is indicated for HIV counseling and testing is indicated for TB patients with symptoms and/or signs of TB patients with symptoms and/or signs of HIV-related conditions and in tuberculosis HIV-related conditions and in tuberculosis patients having a history suggestive of high patients having a history suggestive of high risk of HIV exposurerisk of HIV exposure . .

TB Screening (2)TB Screening (2)TB Screening QuestionnaireTB Screening Questionnaire

.1.1Has the patient had a cough for Has the patient had a cough for >>3 weeks3 weeks??

.2.2Has the patient had night sweats for Has the patient had night sweats for >>3 3 weeksweeks

.3.3Has the patient lost Has the patient lost >>3 kg in the past four 3 kg in the past four monthsmonths??

.4.4Has the patient had fever for Has the patient had fever for >>3 weeks3 weeks??

.5.5Has the patient had recent contact with Has the patient had recent contact with another person with active TBanother person with active TB ? ?

Source: Gasana M, et al. Int J Tuberc Lung Dis. 2008; 12(3):S39-S43

TB Screening (3)TB Screening (3)

All patients suspected or known to be All patients suspected or known to be HIV-seropositive and those who have HIV-seropositive and those who have AIDS should be examined for TB, AIDS should be examined for TB, particularly when there is a coughparticularly when there is a cough

Clinical Presentation of Clinical Presentation of HIV-related TBHIV-related TB

CD4 counts >350CD4 counts >350•Disease usually limited to the lungsDisease usually limited to the lungs

•Often presents like TB in HIV-Often presents like TB in HIV-uninfected personsuninfected persons

•““typical” chest X-ray findings with typical” chest X-ray findings with upper lobe infiltrates with or without upper lobe infiltrates with or without cavitiescavities

Clinical Presentation ofClinical Presentation ofHIV-related TB (2)HIV-related TB (2)

CD4 counts <50-100CD4 counts <50-100•Extrapulmonary disease is commonExtrapulmonary disease is common

•Disseminated disease with high fevers Disseminated disease with high fevers and rapid progression is seenand rapid progression is seen

•Chest X-ray findings often look like Chest X-ray findings often look like “primary TB” with adenopathy, “primary TB” with adenopathy, effusions, interstitial or miliaryeffusions, interstitial or miliary

Pulmonary TB in Early and Late HIV Infection

Features of pulmonary TB

Early Stage HIV infection

Late Stage HIV infection

Clinical picture often resembles post-primary PTB

often resembles primary PTB

Sputum smear result

often positive more likely to be negative

Chest X-ray appearance

upper lobe infiltrates with or without cavitation

infiltrates any lung zone, no cavitation; miliary; normal

Smear-negative Smear-negative Pulmonary TBPulmonary TB

TB sputum culture is the gold TB sputum culture is the gold standard for TB diagnosisstandard for TB diagnosis

If sputum smears are negativeIf sputum smears are negative::•Obtain sputum culture if availableObtain sputum culture if available

•Culture will improve the quality of care Culture will improve the quality of care and assist the confirmation of the and assist the confirmation of the diagnosisdiagnosis

•A CXR can help with earlier diagnosis, A CXR can help with earlier diagnosis, i.e., if findings show intrathoracic i.e., if findings show intrathoracic adenopathy, miliary changes, or upper adenopathy, miliary changes, or upper lobe infiltrateslobe infiltrates

Diagnosing TB in Diagnosing TB in Persons with HIVPersons with HIV

In HIV-positive or suspect patientsIn HIV-positive or suspect patients::•33 sputum samples for microscopy are sputum samples for microscopy are

indicated for any symptoms of TB indicated for any symptoms of TB regardless of duration or sputum regardless of duration or sputum characteristicscharacteristics

•Fever and weight loss can be important Fever and weight loss can be important symptomssymptoms

•If sputum smear is +, a chest X-ray is not If sputum smear is +, a chest X-ray is not required to confirm the diagnosis PTBrequired to confirm the diagnosis PTB

Post - Primary Post - Primary TuberculosisTuberculosis

Air space consolidationAir space consolidation

Cavitation, cavitary noduleCavitation, cavitary nodule

Upper lung zone distributionUpper lung zone distribution

Endobronchial pattern of spreadEndobronchial pattern of spread

Post – Primary TB : Cavitation

Post – Primary TB : Consolidation

Primary Pulmonary Primary Pulmonary TuberculosisTuberculosis

Distribution :Distribution : Slight upper lobe Slight upper lobe predominance but any lobe can be predominance but any lobe can be involvedinvolved

Intrathoracic adenopathy, hilar and Intrathoracic adenopathy, hilar and paratrachealparatracheal

Cavitation is uncommon (<10%)Cavitation is uncommon (<10%)

Miliary patternMiliary pattern

HIV & TB : Adenitis

HIV & TB : Adenitis

1 TB : Adenitis

Understand the Differential Understand the Differential Diagnosis of Smear-Diagnosis of Smear-Negative PTB in HIV Negative PTB in HIV

PatientsPatientsAlways reassess the patient for conditions Always reassess the patient for conditions

that may be mistaken for PTB, including that may be mistaken for PTB, including non-infectious conditionsnon-infectious conditions

Acute bacterial pneumonia is common in Acute bacterial pneumonia is common in HIV patients (short symptom history usually HIV patients (short symptom history usually differentiates pneumonia from PTB)differentiates pneumonia from PTB)

Consider PCPConsider PCP::•In a seriously ill patient with dry cough, severe In a seriously ill patient with dry cough, severe

dyspnoea and bilateral diffuse infiltratesdyspnoea and bilateral diffuse infiltrates

•Concomitant treatment of TB and PCP may be Concomitant treatment of TB and PCP may be lifesavinglifesaving

•PCP almost never produces a pleural effusionPCP almost never produces a pleural effusion

Extra-pulmonary TBExtra-pulmonary TBMore strongly HIV-related than PTBMore strongly HIV-related than PTB

•If combined extra-pulmonary TB If combined extra-pulmonary TB (EPTB) and PTB, HIV infection is (EPTB) and PTB, HIV infection is

even more likelyeven more likely

In HIV, EPTB is WHO Clinical Stage In HIV, EPTB is WHO Clinical Stage 44

Patients with HIV and EPTB are at Patients with HIV and EPTB are at risk for disseminated disease and risk for disseminated disease and

rapid clinical deteriorationrapid clinical deterioration

Extra-pulmonary TB Extra-pulmonary TB (2)(2)

If a patient has EPTB, look also for If a patient has EPTB, look also for PTB with sputum smears - many PTB with sputum smears - many patients with EPTB, however, do not patients with EPTB, however, do not have coexisting PTBhave coexisting PTB

Forms of EPTB commonly seen in patients Forms of EPTB commonly seen in patients with HIV-associated TB includewith HIV-associated TB include : :

–LymphadenopathyLymphadenopathy–Pleural effusionPleural effusion

–AbdominalAbdominal–PericardialPericardial–Miliary TBMiliary TB –MeningitisMeningitis

Extra-pulmonary TB Extra-pulmonary TB (3)(3)

PresentationPresentation•Constitutional symptoms (fever, night sweats, Constitutional symptoms (fever, night sweats,

weight loss)weight loss)•Local features related to the site of the diseaseLocal features related to the site of the disease

Diagnostic toolsDiagnostic tools•X-rays, ultrasound, biopsyX-rays, ultrasound, biopsy

Diagnosis may be presumptive provided Diagnosis may be presumptive provided other conditions are excludedother conditions are excluded

Note: Note: disseminated TB may have no disseminated TB may have no localizing signs, may present with anemia, localizing signs, may present with anemia, or low plateletsor low platelets

TB TreatmentTB Treatment

Anti-TB regimens in an HIV-positive Anti-TB regimens in an HIV-positive patient follow the same principles as in patient follow the same principles as in HIV-negative patientsHIV-negative patients

TB Treatment (2)TB Treatment (2)CautionsCautions::

•Extensive diseaseExtensive disease•Culture positive at 2 monthsCulture positive at 2 months

•Daily during initial phase then thrice Daily during initial phase then thrice weekly or dailyweekly or daily

All patients with tuberculosis and HIV All patients with tuberculosis and HIV infection should be evaluated to infection should be evaluated to determine if antiretroviral therapy determine if antiretroviral therapy (ART) is indicated during the course of (ART) is indicated during the course of treatment for tuberculosistreatment for tuberculosis

Appropriate arrangements for access Appropriate arrangements for access to antiretroviral drugs should be made to antiretroviral drugs should be made for patients who meet indications for for patients who meet indications for treatmenttreatment

Given the complexity of co-administration Given the complexity of co-administration of antituberculosis treatment and ART, of antituberculosis treatment and ART,

consultation with a physician who is consultation with a physician who is expert in this area is recommended expert in this area is recommended

before initiation of concurrent treatment before initiation of concurrent treatment for TB and HIV infection, regardless of for TB and HIV infection, regardless of

which disease appeared firstwhich disease appeared firstHowever, However, initiation of treatment for initiation of treatment for

TB should not be delayedTB should not be delayedPatients with TB and HIV infection Patients with TB and HIV infection

should also receive cotrimoxazoleshould also receive cotrimoxazole as as prophylaxis for other infectionsprophylaxis for other infections

SummarySummaryTB increases HIV progressionTB increases HIV progressionHIV increases TB progressionHIV increases TB progression

Standard TB treatment usually cures TB in Standard TB treatment usually cures TB in TB/HIVTB/HIV

Despite successful TB treatment, mortality Despite successful TB treatment, mortality among TB/HIV patients remains highamong TB/HIV patients remains high

All HIV/TB patients qualify for All HIV/TB patients qualify for cotrimoxazole prophylaxis and it improves cotrimoxazole prophylaxis and it improves survivalsurvival

Summary (2)Summary (2)

HAART for eligible patients greatly HAART for eligible patients greatly improves survivalimproves survival

Different HAART regimens may be Different HAART regimens may be required because of drug interactions required because of drug interactions with rifampicinwith rifampicin

Programmatic synergy between the TB Programmatic synergy between the TB and HIV programs is needed to and HIV programs is needed to improve treatment of both conditions improve treatment of both conditions and will reduce disease and deathand will reduce disease and death

Thank youThank you