Unit 12

1. TB and HIV
Co-Infection
Unit 12
HIV Care and ART: A Course for Pharmacists by
Salahadin M.Ali

2. TB & HIV Co-infection 2
Introductory Case
■ PF is a HIV + 33 y.o. female who comes in with her
boyfriend for follow-up and medication management.
She and her boyfriend have just been treated for
Chlamydia/ gonorrhea. Today, she has just been
diagnosed with pulmonary TB and is beginning therapy.
■ Her CD4 cell count from 3 months ago is 180.
■ Her current medications include: Cotrimoxazole DS
daily for PCP prophylaxis, Nevirapine 200 mg bid,
Zidovudine 300 mg bid and Lamivudine 150 mg bid

3. TB & HIV Co-infection 3
Introductory Case (2)
■ PF comes to the pharmacy with the following new
prescriptions for pulmonary TB:
■ Ethambutol 1 gm qd
■ Isoniazid 300 mg qd
■ Pyridoxine 40 mg qd
■ PZA 1750 mg qd
■ Rifampin 600 mg qd

4. TB & HIV Co-infection 4
Introductory Case Questions
Which of the following statements are true regarding the
drug interaction between this patient’s ART and TB regimens?
A. Rifampin does not lower nevirapine levels, therefore these 2
drugs can be used together at normal doses.
B. Ethambutol lowers nevirapine levels, therefore the patient
should be monitored for treatment failure.
C. Rifampin lowers nevirapine levels and should only be used
together when no other options are available .
D. Nevirapine reduces rifampin levels and should not be used in
combination.

5. TB & HIV Co-infection 5
Unit Learning Objectives
■ Describe the epidemiology of TB and TB-HIV
■ Describe clinical features of TB and TB-HIV among PLHIV
■ Discuss clinical features of TB and TB-HIV among PLHIV
■ Anticipate potential drug-drug interactions between anti-
tuberculosis and ART
■ Outline management principles of ARV and anti-TB drug-
drug interactions
■ Differentiate treatment of latent Vs active TB
■ Explain the overlapping toxicities of ARVs and anti-
tuberculosis drugs

6. Global TB estimates - 2007
Estimated
number of
cases
Estimated
number of
deaths
1.77 million
(27 per 100,000)
9.27 million
(139 per 100,000)
~150,000
511,000
All forms of TB
Greatest number of cases in Asia; greatest
rates per capita in Africa
Multidrug-resistant
TB (MDR-TB) 511,000
Extensively drug-
resistant TB (XDR-TB)
~50,000 ~30,000
HIV-associated TB 1.4 million (15%) 456,000

7. TB estimates, Africa - 2007
Estimated
number of
cases
Estimated
number of
deaths
734,891
(93 per 100,000)
2.90 million
(363 per 100,000)
???
511,000
All forms of TB
Greatest number of cases in Asia; greatest
rates per capita in Africa
Multidrug-resistant
TB (MDR-TB) 8772
Extensively drug-
resistant TB (XDR-TB)
~535 ???
HIV-associated TB 1,08 million 377,535

8. High TB/HIV co-infection....50% regional average
(2006 & 2007)

9. TB & HIV Co-infection 9
Problems of Managing TB/HIV
Co-Infection
■ High incidence of
adverse drug reactions
■ Atypical
presentation/EPTB more
common
■ High pill burden
■ Adherence
■ Resistance to anti-TB
drugs
■ Resistance to one or more
of the first line drugs in
Ethiopia seen in
15% - 33%
■ Drug interactions
■ Immune reconstitution
syndrome

10. TB & HIV Co-infection 10
Epidemiology
■ The risk of TB disease is greatly increased among persons with
HIV infection
■ 10% lifetime risk of active TB among non-immune suppressed individuals
■ 10% risk per year of active TB among HIV+ individuals
■ HIV+ persons are at increased risk of developing active TB when
newly infected with TB
■ Co-infected patients with active TB often have very high viral
loads and immunosuppression progresses more quickly
■ Impact on survival

11. TB & HIV Co-infection 11
Clinical Features
■ CD4 < 200 cells/mm3
■ Fever, weight loss, cough
■ Chest radiograph atypical
■ Lower lobe or other
atypical infiltrates
■ Cavitation uncommon
■ Sputum smears often
negative
■ CD4 > 200 cells/mm3
■ Cough, fever, weight loss
(classic presentation of TB
symptoms)
■ Chest radiograph typical
■ Upper lobe infiltrates
■ Pulmonary cavities
■ Sputum smears often positive

12. TB & HIV Co-infection 12
Clinical Features (cont.)
■ Among co-infected patients, extrapulmonary TB is
present in up to half: this rate increases as CD4 cell
count diminishes
■ Common extrapulmonary sites include:
■ Blood, lymph nodes, CNS, genitourinary tract and pleura

13. TB & HIV Co-infection 13
Diagnosis: Latent TB
■ Ethiopians commonly receive BCG vaccine & previous
exposure to TB is common  tuberculin skin tests
(PPD or TST) are NOT recommended
■ Latent TB is highly prevalent in Ethiopia (~80%) and
therefore, is not treated. PPD is not regularly
administered. There is no prophylactic program. It is
currently being piloted.
■ HIV+ pts with a known TB exposure should be
assumed to be TB infected regardless of their current
PPD results.

14. TB & HIV Co-infection 14
Diagnosis: Latent vs. Active TB
■ Obtain 3 sputum smears for AFB if pt fulfills the
criteria of “TB Suspect” for National TB Control
program
■Cough > 3 weeks
■Other constitutional symptoms
■Chest X-Ray suggestive of pulmonary TB

15. TB & HIV Co-infection 15
Diagnosis: Active TB
■ Clinical Diagnosis: Cough > 3 wks, fever, weight loss
■ Chest radiograph
■ Positive culture for M. tuberculosis from
■ Sputum x 3
■ Bronchoscopy (if can’t get sputum)
■ Blood
■ Drug susceptibility testing
■ Reporting

16. TB & HIV Co-infection 16
Abnormal Chest X-Ray in a Patient
with Pulmonary TB
Cavitary Lesion
Normal Lobe

17. TB & HIV Co-infection 17
TB in the ART Era
■ TB treatment is the priority in co-infected patients
■ When to begin ART depends on CD4/TLC and level of
immune-suppression
■ Improved immune response to TB during ART era
■ Reduction in case rates of TB during ART era
■ ART could reduce risk of TB primary infection, relapse
and re-infection

18. TB & HIV Co-infection 18
Antiretroviral Therapy and TB
■ Treatment of active TB is a priority in co-infected pts
■ ART is recommended for HIV patients
■ with CD4 <200 cells/mm3 OR TLC < 1,200/mm3 OR
■ Extrapulmonary disease (WHO)
■ Patients already on ART may develop TB, requiring
addition of TB medications
■ Consider potential drug interactions and adjust dose of rifampin or
antiretrovirals as needed. If pts ART regimen includes an ARV that
is contraindicated with Rifampin, a change in the ART regimen may
be required.

19. TB & HIV Co-infection 19
Immediate vs Delayed Therapy (1)
■ Arguments to withhold ART until TB is treated (at
least initial 2-month phase)
■ HIV is a chronic disease & ART is not Emergency
■ Adherence may be compromised
■ Toxicity management is more complex
■ Complex drug interactions
■ Immune reconstitution syndrome
■ Acceptance of both diseases

20. TB & HIV Co-infection 20
Immediate vs Delayed Therapy (2)
■ Arguments to initiate ART at the onset of TB:
■ TB is associated with immune activation, increased
HIV replication, and HIV disease progression
■ HAART can reduce viral load, improve immune
function and slow HIV disease progression
■ HAART reduces risk of developing opportunistic
infections
■Including CMV or cryptosporidiosis for which prophylaxis is
neither routinely used nor available

21. TB & HIV Co-infection 21
Immediate Vs Delayed Therapy (3)
■ Arguments to initiate ART at the onset of TB:
■ British observational study of 188 HIV+ TB patients at London
HIV centers 1996-99
■ 8.5% died prior to completing TB therapy
– Mostly not on HAART
■ Fewer further OIs in TB patients on HAART
– 4% on HAART developed OIs Vs 24% not on HAART
– 66% of those who developed OIs had CD4 count < 100
Source: Dean G, AIDS 2002;16:75

22. TB & HIV Co-infection 22
Immune Reconstitution
Syndrome
■ The worsening of signs and symptoms due to known
infections, or the development of disease due to occult
infections, that results from improvement in immune
function after the initiation of anti-retroviral therapy
■ May occur in other OIs
■ MAC, PML, CMV vitritis, mild herpes zoster, cryptococcal
meningitis

23. TB & HIV Co-infection 23
Immune Reconstitution Syndrome
(IRS) in TB and HIV Co-infection
■ Can occur with any ART regimen
■ IRS is NOT indicative of treatment failure or med S/Es
■ More common when CD4 Cell Count < 50
■ Mean onset of symptoms: 2 weeks
■ Mean duration of symptoms: 3 weeks
■ Most common symptoms include fever, cervical
lymphadenopathy, intrathoracic lymphadenopathy
■ Associated with restoration of TB reactivity

24. TB & HIV Co-infection 24
Immune Reconstitution
Syndrome: Management
■Management
■Continue anti-tuberculosis and anti-retroviral
therapy
■Symptomatic management:
■NSAIDS or Aspirin
■For severe symptoms: steroids (40 to 80 mg/d
for 5 to 14 weeks
Source: Furrer, Am J Med, 1999])

25. TB & HIV Co-infection 26
Treatment of Pulmonary TB
■ Four drug therapy preferred for active TB (for the first 2 months
only)
■ INH 5mg/kg (maximum 300 mg) qd (with pyridoxine 40 mg qd) +
■ Ethambutol 15-25 mg/kg (maximum 1.6 gm) qd +
■ (streptomycin used in place of Ethambutol for HIV negative patients)
■ PZA 15-30 mg/kg (maximum 2 gm) qd +
■ Rifampin 10-20mg/kg (maximum 600 mg) qd
■ Followed by maintenance phase for 6-9 months (or 3-6 months
after cultures are consistently negative, whichever is longer)
■ INH + Ethambutol (doses as above)

26. TB & HIV Co-infection 27
Adverse Effects of Anti-tubercular
Medications
■ Ethambutol (EMB)
■ Dose related ocular toxicity, GI intolerance
■ Pyrazinamide (PZA)
■ Hepatotoxicity, hyperuricemia, GI intolerance
■ Isoniazid (INH)
■ Hepatotoxicity, peripheral neuropathy, GI intolerance
■ Rifampin (RIF)
■ Orange-brown discoloration, hepatotoxicity
■ Streptomycin (SM)
■ Ototoxicity, vestibular dysfunction, rash, renal damage

27. TB & HIV Co-infection 28
Monitoring TB Therapy
■ Baseline: ALT/AST, sputum, visual acuity & color discrimination
■ Clinical Monitoring - monthly
■ Symptoms of hepatitis: nausea, vomiting, dark urine, malaise,
fever > 3 days, abdominal pain, decreased appetite
■ Eye exam: Visual acuity and Color discrimination
■ Laboratory
■ ALT with symptoms of hepatitis
■ If ALT/AST > 5XULN, discontinue INH, RIF + PZA and give alternative
■ In Ethiopia, no alternative available  patient is ‘untreatable’
■ Repeat sputum smear at 2 & 7 months and culture until negative
■ Chest X-Ray at 2 months and end of therapy

28. TB & HIV Co-infection 29
DOT (Directly Observed Therapy)
■ DOT is always preferred
■ DOT was introduced in 1995
■ At the end of 2001, about 34% of health facilities were
using DOT
■ About 55% of Ethiopians have access to (within 10 km)
general health services, DOT expansion may be very
difficult

29. TB & HIV Co-infection 30
Complexity of Management of
Co-infected Patients
■ Immune reconstitution syndrome
■ Toxicity
■ Drug-interactions
■ High pill burden
■ Adherence
■ Resistance

30. TB & HIV Co-infection 31
Drug Interactions
Between ART and TB Therapy
■ Clinically significant drug interactions exist
between rifampin and PI/ NNRTI therapy
■ Certain combinations are contraindicated, others can
be used safely together with dosage adjustments
■ Rifabutin based regimens are preferred to rifampin, if
available
■ No interaction between rifampin and NRTI class

31. TB & HIV Co-infection 32
Rifamycin Drug Interactions
■ Rifampin induces CYP3A4
■ Reduces serum levels of PIs and NNRTIs
■ Inadequate ARV drug levels
■ Failure of and resistance to ART (monitor closely)
■ PI or NNRTI may require dose adjustment, may need to avoid
use
■ Rifabutin less potent inducer of CYP3A4
■ Rifabutin requires dose adjustment when administered with
PIs or NNRTIs
■ PI or NNRTI may require dose adjustment

32. TB & HIV Co-infection 33
Drug Interactions with ART and TB Agents-Non boosted PIs
Rifabutin (RFB) Rifampin (RFP)
Antiretroviral ARV
Dose
RFB dose Details
Atazanavir
(ATV)
400mg
QD
150mg QOD
Contraindicated
ATV ↑ RFB conc.
Limited data with RFP
Amprenavir
(APV)
1200mg
BID
150mg QD or
300mg 3 times
a week
APV ↑ RFB by 204%
RFB ↓ APV by 15%
RFP ↓ APV by 82%
Indinavir
(IDV)
1000-
1200mg
Q8H
150mg QD
IDV ↑ RFB by 60%
IDV ↑ RFP by 73%
RFB ↓ IDV by 32%
RFP ↓ IDV by 89%
Nelfinavir
(NFV)
1250mg
BID
150mg QD
NFV ↑ RFB by 200%
RFB ↓ NFV by 32%
RFP ↓ NFV by 82%

33. TB & HIV Co-infection 34
Drug Interactions with ART and TB Agents-NNRTIs
Rifabutin (RFB) Rifampin (RFP)
Antiretroviral ARV
Dose
RFB dose
ARV
Dose
RFP
Dose
Details
Efavirenz
(EFV)
600mg
QD
450mg QD
or
600mg 3
times a
week
800mg
QD
600mg
QD
EFV ↓ RFB by 32%
RFB no effect on EFV
RFP ↓ EFV by 26%
Nevirapine
(NVP)
200mg
BID
300mg
QD
200mg
BID
600mg
QD
No relevant interaction
with RFB/NVP
RFP ↓ NVP by 31-58%
Use cautiously. Higher
dose NVP has not been
evaluated.

34. TB & HIV Co-infection 35
Introductory Case Answers
■ The statement, B): Ethambutol lowers nevirapine levels,
therefore the patient should be monitored for treatment
failure, is false. There is no drug interaction between
ethambutol and nevirapine.

35. TB & HIV Co-infection 36
Introductory Case
Answers (cont.)
■ The statement D): Nevirapine reduces rifampin levels
and should not be used in combination, is false.
Rifampin lowers nevirapine levels significantly.
Nevirapine has no effect on rifampin levels.

36. TB & HIV Co-infection 37
Drug Interactions with ART & TB Agents-Boosted PIs
Rifabutin (RFB) Rifampin (RFP)
Anti-
retroviral
ARV Dose RFB dose ARV Dose
RFP
dose
Details
LPV/r
400mg/100mg
BID
150mg QOD or
3 times a week
(TIW)
400mg/400mg
800mg/200mg
(both BID)
600mg
QD
LPV/r ↑ RFB
RFB no effect on LPV/r
RFP ↓ LPV/r by 75%
SQV/
RTV
400mg/400mg
BID
150mg QOD or
TIW Contraindicated
RFB ↓ SQV by 40%
RFP ↓ SQV by 84%
High risk of heaptotoxicity
with SQV/RTV + RFP
IDV/RTV
800mg/100mg
800mg/200mg
(both BID)
150mg QOD or
TIW
Contraindicated
No data on IDV/RTV with
RFB. RTV may overcome
induction by RFB.
ATV/RTV 300mg/100mg QD
150mg QOD or
TIW
No Data No formal studies with
ATV/RTV + RFB or RFP
APV/RTV
600mg/100mg
BID or
1200mg/200mg QD
150mg QOD or
TIW
No Data No Data with RFP

37. TB & HIV Co-infection 38
ART for TB Co-Infected Patients
Clinical
Situation
Recommendation Note
On NVP Change to EFV Exceptions: intolerance to EFV or
risk of pregnancy. If NVP must be
used, monitor ALT q month
Not on ART
CD4 < 200 or
TLC < 1200
Start TB treatment. Start ART as
soon as TB treatment tolerated
(between 2 weeks to 2 months)
EFV containing is preferred with
monthly ALT monitoring
Not on ART
CD4 200-350
TLC >1200
Start TB treatment. Re-evaluate
patient for ART indications after
completion of intensive phase (end
of 2 months) and end of TB therapy.
Start ART therapy if there are
indications,i.e.,. patient is severely ill.
Start ART therapy according to the
recommendations for other non-TB
HIV patients
CD4 > 350 Start TB treatment Defer ART
CD4 not
available
Start TB treatment Consider ART

38. TB & HIV Co-infection 39
Introductory Case
Answers (cont.)
■ The true statement is C): Rifampin lowers nevirapine
levels by 31-58% and should only be used together
when no other options are available. This combination
also increases the risk of hepatotoxicity. If used
together, monitor closely.
■ If a patient is on ART and is to begin therapy for TB, the
NNRTI of choice is efavirenz with an adjusted dose of
800 mg qhs while the patient is on rifampin and for 2
weeks afterwards to account for enzyme induction.

39. TB & HIV Co-infection 40
Possible Regimens for
Administration of Rifampin with ART
■ NNRTI based regimen
■ D4T 40 mg bid (or ZDV 300 mg bid) + 3TC 150 mg bid + EFV-800 mg qhs
■ Use NVP with caution when no other options exist. Monitor closely
■ PI based regimen
■ (D4T 40 mg bid or ZDV 300 mg bid +3TC 150 mg bid) + LPV/r 400
mg/400 mg bid or 800mg/200mg bid
■ PI or NNRTI sparing regimen
■ D4T 40 mg bid ( or ZDV 300 mg bid) + 3TC 150 mg bid + ABC 300 mg bid
■ For women of childbearing age (without effective contraception)
or pregnant women
■ D4T 40 mg bid (or ZDV 300 mg bid)+ 3TC 150 mg bid + ABC 300 mg bid

40. TB & HIV Co-infection 41
Introductory Case
Answers (cont.)
■ The statement A): Rifampin does not lower efavirenz
levels, therefore both medications can be used together
at normal doses is false.
■ Rifampin reduces efavirenz levels by 26%. These
medications can be used together safely (except
among pregnant women) if efavirenz dose is increased
to 800mg QHS. Rifampin dose does not need to be
adjusted.

41. TB & HIV Co-infection 42
Challenges to Adherence with TB
and ART Therapy Co-administered
■ Involves a large number of pills
(Three drugs for HIV + Four drugs for TB for first the 2
months)
■ Poor tolerability
■ Toxicity management is more complex
■ Cost
■ Immune reconstitution syndrome
■ Acceptance of both diseases

42. TB & HIV Co-infection 43
Overlapping Toxicities of ART
and TB Therapy
Side
Effect
Nausea Hepatitis Peripheral
neuropathy
Rash
ARV
therapy
ZDV,DDI, RTV,
SQV, LPV/r
NVP, EFV,
PIs
DDI, D4T NVP, EFV
TB
therapy
Pyrazinamide,
INH,
Ethambutol
Rifampin,
INH,
Pyrizinamide
INH Rifampin,
INH,
Pyrazinamide

43. Drug Resistant TB
TB & HIV Co-infection 44

44. Classification of drug- resistant TB
■ Primary resistance: TB infection with resistant
strain.
■ Comment: If DST done before the start of patient’s first anti-
tuberculosis treatment, any resistance documented is primary
resistance
■ Secondary or acquired resistance: TB infection with
susceptible strain which became resistant due to
inadequate treatment.
■ Comment: If new resistance is found when DST is later
repeated and genetic testing confirms that it is the same strain,
only then can it be concluded that the strain has acquired
resistance

45. Limitations of primary and secondary
classification
■ “Primary” and secondary or “acquired”
resistance terminology has not been used in the
WHO drug-resistant tuberculosis guidelines
because most TB programmes may not
distinguish between the two:
■ If patient omits to mention history of previous TB, he /
she may be misdiagnosed
■ If resistance is diagnosed after re-treatment or failure,
it does not mean resistance is acquired; it could have
been there when TB was first diagnosed

46. Preferred classification
■Resistance in new tuberculosis patients
(those never treated or treated for less
than one month)
Resistance in previously treated patients
(those previously treated with anti-TB
drugs for more than one month)

47. Working definitions
■ Mono resistance: resistance to single anti-TB medicine
■ Poly-resistance: resistance to more than one anti-TB medicine
other than Rifampicin and Isoniazid together
■ Multi-Drug Resistance (MDR): resistance to at least Isoniazid
and Rifampicin
■ Extensive drug resistance: MDR plus Resistance to:
■ A fluoroquinolone : Ciprofloxacin,Ofloxacin, Levofloxacin,
Moxifloxacin, Gatifloxacin, etc
■ One or more of the following injectable agents: Kanamycin, Amikacin,
Capreomycin

48. ■ Standardized or individualized
■ All patients - at least 4 effective drugs
■ Adequate use of injectable agent (at least 6 months.,
usually 6 months. past conversion)
■ Adequate duration of treatment (no less than 18
months. past conversion, usually 24 months. total)
Appropriate treatment regimens

49. 1st-line agents
•INH
•RIF
•PZA
•EMB
Injectable agents
•SM
•KM
•AMK
•CM
Fluoroquinolones
•Cipro
•Oflox
•Levo
•Moxi
•Gati
2nd-line Oral agents
"3rd-line" agents
•ETA/PTA
•PASA
•CYS
Not routinely recommended,
efficacy unknown, e.g.,
amoxacillin/clavulanic acid,
clarithromycin, clofazamine,
Classification of drugs into 5 groups based
on hierarchy of efficacy and safety including
2nd-line drugs

50. 1. Oral first line drugs
2. Injectable drugs
3. Quinolones
4. Oral 2nd-line drugs
5. Third line dugs
As many as possible
One from each group
As many as needed (to
get ≥ 4 effective)
In desperate cases (< 4
effective drugs)
Clear guidelines for designing regimens
should result in rational, consistent
treatment

51. TB & HIV Co-infection 52
CASE STUDIES

52. TB & HIV Co-infection 53
Case 1
■ SM is a 21 year old male who comes to Black Lion Hospital
coughing up blood, complaining of breathlessness and chest
pain. He has had an increase in his temperature in the evenings,
which subsides in the mornings. His weight has gone down
by 5 kg.
■ Physical exam reveals swollen lymph nodes in the neck and
groin area
■ Chest X-Ray
■ Upper lobe infiltrates
■ Pulmonary cavitary lesions
■ Sputum smear for Acid Fast Bacilli (AFB) is positive
■ TLC 1,100
■ Current Medication: none

53. TB & HIV Co-infection 54
Case 1 Questions
■ SM is started on four drug therapy for his advanced TB.
He is tearful and asks you if he should also take
antiretroviral therapy to help his immune system.
■ Is it appropriate for him to begin on antiretroviral
therapy today?
■ How would you counsel him?
■ What are the indications for ART in a co-infected
patient?

54. TB & HIV Co-infection 55
Case 2
■ A 40-year-old man presented 2 ½ months ago with 4
weeks of fever, cough with blood-tinged sputum, night
sweats, and had lost 7 kg of weight. He also had pain
and numbness in the soles of both feet.
■ A chest x-ray showed a right lower lobe infiltrate. He
was diagnosed with smear-positive pulmonary
tuberculosis. His HIV test was positive, and his CD4
cell count was 180cells/mm3.
■ He improved during his first two months of treatment
with INH, rifampin, ethambutol, and PZA, along with
vitamin B6 (pyridoxine). His fever, cough, & night
sweats have stopped and he is gaining weight.

55. TB & HIV Co-infection 56
Case 2 (cont.)
■ He also has been taking Cotrimoxazole for PCP
prophylaxis.
■ Following 2 months of 4-drug treatment, he has
changed to the continuation phase of treatment with
isoniazid and ethambutol, continuing vitamin B6. He
also started first line antiretroviral treatment with
zidovudine (because of the peripheral neuropathy),
lamivudine and efavirenz 600 mg qhs.
■ After two weeks on ART he developed fevers, cough,
and night sweats once again.

56. TB & HIV Co-infection 57
Case 2 (cont.)
■ He and his treatment partner report excellent
adherence with both the TB and HIV treatment. Three
sputum smears were negative for acid-fast bacilli.
■ A chest x-ray showed a worsening right lower lobe
infiltrate, a new right-sided pleural effusion, and
enlargement of bilateral hilar lymph nodes. His ALT is
still normal.

57. TB & HIV Co-infection 58
Case 2 Questions
■ What do you think is happening?
■ Should he change his tuberculosis therapy, and
if so, how?
■ Should he change his antiretroviral therapy, and
if so, how?
■ Should he modify his treatment in any other
way?

58. TB & HIV Co-infection 59
Case 3
■ KH, an HIV+ 40 year old male was first seen in clinic 10
months ago because of chronic cough and chest pain. At
that time, his CD4 count was 300. A chest x-ray showed left
upper lobe infiltrates.
■ He did not improve on antibiotics, and the infiltrate on chest
x-ray worsened. Three sputum smears were negative. He
was treated empirically for pulmonary tuberculosis and
improved.
■ He completed 2 months of TB treatment. At his two month
TB visit, his CD4 count had fallen to 190. He is to continue
on Ethambutol and Isoniazid for 4-7 months

59. TB & HIV Co-infection 60
Case 3 Questions
■ Does he fulfill the criteria for antiretroviral
therapy?
■ If so, what else would you want to know before
recommending an antiretroviral regimen?
■ What would you recommend?
■ Does he require any additional therapy at this
time?

60. TB & HIV Co-infection 61
Case 4
■ A 35-year-old HIV-infected woman with a CD4 count of
300 cells/mm3 and an undetectable viral load presents
for routine follow-up. She is currently asymptomatic and
is taking ART (Efavirenz 600mg QHS, D4T 40mg BID,
3TC 150mg BID). She claims to use a reliable form of
birth control.
■ She states that her sister was recently diagnosed with
active pulmonary tuberculosis (TB) and is currently
receiving treatment.

61. TB & HIV Co-infection 62
Case 4 Question
■ Regarding the exposure to her sister, which of the
following 2 statements describes appropriate
subsequent management of this 35-year-old HIV-
infected woman? Explain why.
A. If she is diagnosed to have active TB, she should continue her
ART and begin an appropriate 4-drug TB regimen.
B. She should stop her ART and start on four-drug TB treatment.
C. She should be tested for latent TB infection with a tuberculin
skin test If, 50 hours later, she has 0 mm of induration for the
test, she does not require further TB treatment
D. If active TB is ruled out in this patient, she does not require
further treatment.

62. TB & HIV Co-infection 63
Case 5
■ A 37-year-old male is newly diagnosed with both HIV infection
and pulmonary tuberculosis.
■ His laboratory studies show a CD4 count of 6 cells/mm3 and an
HIV RNA greater than 500,000 copies/ml.
■ He is started on four-drug therapy for tuberculosis that consists
of isoniazid, ethambutol, rifampin, and pyrazinamide.
■ The plan is to start antiretroviral therapy after one month of anti-
tuberculosis therapy.
■ The antiretroviral therapy regimen that is suggested: zidovudine
plus lamivudine plus lopinavir/ritonavir

63. TB & HIV Co-infection 64
Case 5 - Question
■ Which of the following is true regarding a
potential drug-drug interaction?
A) Isoniazid can decrease lopinavir/r levels
B) Rifampin can significantly lower zidovudine levels
C) Rifampin can significantly lower lopinavir/r levels
D) Ethambutol will lower lopinavir/r levels by at least
50%.

64. TB & HIV Co-infection 65
Key Points
■ TB is the leading killer of patients with HIV/AIDS in
developing countries
■ TB is the most common opportunistic infection in
Ethiopia, and the incidence of TB due to HIV is
expected to increase
■ The risk of active TB disease is greatly increased
among persons with TB/HIV infections
■ Among co-infected patients, extrapulmonary TB is
present in up to 50% (this rate increases as CD4 cell
count diminishes)

65. TB & HIV Co-infection 66
Key Points (2)
■ The treatment of active TB is a priority in co-infected
patients.
■ Starting ART and TB therapy together is not always the
optimal choice.
■ Patients with TB merit special consideration because
co- management of HIV and TB is complicated by drug
interactions, high pill burden, adherence issues,
immune reconstitution syndrome, resistance, and drug
toxicity.