HIV

1
????????????? ?? HIV ???? ??????????????
2
Clinical manifestations of active TBin early
versus late HIV infection a
For practical purposes , early and late may be
defined as CD4cell counts gt 300 cells/mm³ and lt
200 cells/mm³.
3
Radiographic Pictures of TB/HIV

• CD4 gt 300
• - patchy or nodular infiltration
• - location in apical or subapicoposterior
  segment of upper lobe or superior segment of
  right lower lobe
• - dry, thick wall cavitation (50), air-fluid
  level is uncommon
• - lymphadenopathy is unusual
• - pleural effusion could be found

Typical radiographic pattern of PTB
4
Radiographic Pictures of TB/HIV

• CD4 lt 200
• - alveolar infiltration, diffuse interstitial
  infiltration, or mixed infiltration
• - location in any segments or lobes
• - common enlarged lymphadenopathy
• - normal CXR (14-20) in very advanced AIDS
  (CD4lt50)

Non-specific radiographic pattern
5
Tuberculosis in AIDS.Clinical manifestations

• Prolonged fever 114 (100)
• Chronic weight loss 84 (74)
• Cough 37 (32)
• Dyspnea 6 (5)
• Chronic diarrhea 32 (28)
• Hematochezia 4 (3.5 )
• Gut obstruction 3 (2.6)
• Meningitis 14 (12)
• Tbc-BIDH-1993

6
(No Transcript)
7
Treatment of TB/HIV

• Treatment of TB remains central priority,
  following the DOTs
• Specific considerations
• - pill burden
• - adherence
• - duration of treatment
• - drug toxicity
• - drug interaction
• - immune reconstitution syndrome (IRS)

8
??????????????????????????? HIV

• ????????????????? HIV neg ??????
• H-Rifapentine, once weekly continuation phase
• HR or H-Rifabutin, twice weekly, CD4 lt100
• ?????????????????????? 1stline drug
• 2HRZE/4HR
• ??????????????????????? (culture pos at M2)
• 2HRZE/7HR

American Journal of Respiratory and Critical Care
Medicine 2003167(4)603-662 Recommendations and
Reports June 20, 2003 / 52(RR11)1-77
Treatment of Tuberculosis. American Thoracic
Society, CDC, and Infectious Diseases Society of
America
9
???????????????????????????? HIV pos

• ????????????? HIV neg, response ?????????
• ????????? Thiacetazone, ??? E
• ??????????? S
• Case fatality
• HIV pos ?????????? HIV neg ???
• 12 ????? ?????????? 6 ?????
• SA ?????????? DOT
• Relapse
• ????????????? R ???? ???????????????????
• ?????????????? HE HIV pos relapse ??????? HIV
  neg
• ??????? HIV pos relapse ??????? HIV neg

10
??????????????????????????? HIV

• DOT ????????????
  ????????????????????????????
• ????????????? drug interaction ??????? ARV ???
  R
• Malabsorption
• Paradoxical reactions

American Journal of Respiratory and Critical Care
Medicine 2003167(4)603-662 Recommendations and
Reports June 20, 2003 / 52(RR11)1-77
Treatment of Tuberculosis. American Thoracic
Society, CDC, and Infectious Diseases Society of
America
11
????????????????????????????? HIV
12
????????????????????????????? HIV
13
????????????????????????????? HIV
14
????????????????????????????? HIV
15
HAART ???????????????????????????????????????????
??????????? HIV ??????????????????????????????????
????

• ??????? 1 d4T 3TC NVP (GPO-vir)
• ??????? 2 d4T 3TC EFV
• ??????? 3 d4T 3TC IDV RTV

??????????????????????????????????????????????????
??????????????????????????????????????????????
???????????????????? ?.?. 2546.
???????????? ????????????????
16
Anti-retroviral Therapy (ARV)

• 4 classes
• Nucleoside Reverse Transcriptase Inhibitors
  (NRTIs)
• zidovudine (ZDV, AZT), didanosine (ddI),
  zalcitabine (ddC), stavudine (d4T), lamivudine
  (3TC), abacavir (ABC)
• Nucleotide Reverse Transcriptase Inhibitors
  (NtRTIs)
• Non- Nucleoside Reverse Transcriptase Inhibitors
  (NNRTIs)
• nevirapine (NVP), delavirdine (DLV), Efavirenz
  (EFV)
• Protease Inhibitors (PIs)
• indinavir (IDV), nelfinavir (NFV), ritonavir
  (RTV), saquinavir (SQV), amprenavir (AP),
  lopinavir (LPV)

17
???????????????? ARV ??? Rifampicin

• ??????? ??????? ARV
• NRTIs ZDV, d4T, ddI
• NNRTIs NVP 37, EFV 25
• PIs IDV 89, SQV 84
• NFV 82, LPV 75
• RTV 35

??????????????????????????????????????????????????
???? ????????????????????????????.?. 2547
(???????????????????? 8) ????????????????
????????????? 1 ??????? 2546.
18
?????????????????????????????????????

• ????? rifampicin ??? ARVs
• NRTIs ???????
• NNRTIs ????? EFV gt NVP
• PIs ????? ARV ????????????

??????????????????????????????????????????????????
???? ????????????????????????????.?. 2547
(???????????????????? 8) ????????????????
????????????? 1 ??????? 2546.
19
??????? HAART

• ????????????????
• ??????? 1 d4T 3TC NVP (GPO-vir) 1200
• ??????? 2 d4T 3TC EFV 3000
• ??????? 3 d4T 3TC IDV RTV 6000

?????? ?????? 1 ??????? 2 ??????-??????? 2546
20
Survival rate between HIV-infected TB patients
who received and did not receive ART, October
2004-March 2006
On ART
No ART
Sanguanwongse et al., Manuscript in process of
submission
21
?????? ARV???????? R

• ???????? ARV ?????????????????????????????????
• ???????? R ????????????????????? ARV
• ???????????? R -gt delayed sputum conversion
  
  
• -gt prolong Rx duration, poorer
  outcome
• ???????????????????????????????????????????
• ?????????, ?????????????????
• ????? overlap ???, ???????????????????????

American Journal of Respiratory and Critical Care
Medicine 2003167(4)603-662 Recommendations and
Reports June 20, 2003 / 52(RR11)1-77
Treatment of Tuberculosis. American Thoracic
Society, CDC, and Infectious Diseases Society of
America
22
?????????????????? ... ??????? ARV

• ???????? ARV ????
• ???????????????????????????????????????????????
• ????????????????????????????????
• ?????? ARV ??????????????????????????? 4-8
  ???????
• ??????????????????????????????????
• ??????????????? paradoxical reaction
• ????????????????????????????????
• ??????????? ???????
• ????????????????????????
• ??????????????????
• ??????? ARV

American Journal of Respiratory and Critical Care
Medicine 2003167(4)603-662 Recommendations and
Reports June 20, 2003 / 52(RR11)1-77
Treatment of Tuberculosis. American Thoracic
Society, CDC, and Infectious Diseases Society of
America
23
(No Transcript)
24
??????????????????????????????????????????????????
???? ????????????????????????????.?. 2547
(???????????????????? 8) ????
179 ???????????????? ????????????? 1 ??????? 2546.
25
(No Transcript)
26
???????????????? ARV
27
???????????????? ARV
28
???????????????? ARV
29
(No Transcript)
30
Immune Reconstitution Syndrome

• Many words immune reconstitution syndrome,
  immune restoration syndrome (IRS), immune
  reconstitution inflammatory syndrome, immune
  restoration inflammatory syndrome, immune
  inflammatory recovery syndrome (IRIS), immune
  reconstitution disease (IRD), and paradoxical
  reaction (PR)
• Mechanisms
• - increases CD4 cells especially memory cell
  phenotype
• - dysregulation of immune process
• Usually occur during 1-4 months after initiation
  of HAART

31
MTB IRS

• 36 of patients with combined MTB HIV
  infections after initiation of HAART developed
  paradoxical clinical deterioration
• Prolong fever (gt101.5F)
• Increasing respiratory symptoms
• Increasing lymphadenopathy
• Cutaneous lesions
• Ascites
• CXR worsening (?lymph node, consolidation,
  effusion)
• Tuberculoma

Woraphot Tantisiriwat, MD,MPH
32
Immune Reconstitution Syndrome
Start TB Therapy
Start ARV Therapy
Paradoxical Reaction
onset within days to weeks (Mean 15 11 days)
Duration 1-4 Mo
Furrer H.Am J Med 1999106 371-2
Burman WJ.Am J Respir Crit Care Med 2001 164
7-12
Narita M. Am J Respir Crit Care Med 1998 158
157-161
33
Paradoxical reaction of TB/HIV

• Incidence in HAART era 30
• Risk
• - miliary/disseminated TB
• - baseline CD4lt50 (Ag ???, OI)
• - HAART started within the
• first 2 months of TB treatment
• Clinical manifestations
• - fever, worsening pulmonary lesions,
• new/increased inflammatory lymphadenopathy
  (possible to spontaneously rupture),
• pleural/pericardial effusions, ascites, psoas
  abscess and new/expanding CNS symptoms

34
Paradoxical reaction of TB

• Differential diagnosis
• - Non-compliance
• - treatment failure
• - drug hypersensitivity
• - other common infections
• Diagnosis
• - to rule out other causes
• Treatment
• - prednisolone or methylprednisolone 1-1.5
  mg/kg and gradually reduced after 1-2 weeks
• - NSAIDs tend not to be helpful
• - recurrent needle aspiration of
  tense/inflammed nodes or abscesses can prevent
  spontaneous rupturea
• (a lead to long-term sinus formation,
  necrosis and persist discharge)

35
Immune Reconstitution Syndrome after
Antiretroviral Therapy

• Key points
• HAART should be delayed in patient with active OI
  in order to prevent IRS, however, benefit must be
  weighed against the risks (develop other
  life-threatening conditions) in advanced AIDS
  (CD4 lt 50)
• HAART should not be interrupted once IRS is
  happened, however, interruption of therapy might
  be considered for severe, life-threatening
  complications of IRS (such as fulminant
  hepatitis)
• Corticosteroid must be considered if indicated
  despite pathogen-specific treatment, however,
  other hidden infections should be rule out before
  initiating steroid.

36
(No Transcript)
37
(No Transcript)
38
(No Transcript)
39
(No Transcript)
40
Immune Restoration Syndrome

• ??????????????????????????????????
  ????????????????????? ????????????
• ???????????????????????????? CD4 ???? CD8 ??????
• ??????????????????
• ??????????????????????? prednisolone ???
  ???????????????????

??????????????????????????????????????????????????
???? ????????????????????????????.?. 2545
(???????????????????? 7) ????????????????
????????????? 1 ????????? 2545.
41
IRS ????????????

• CD4 ???
• ?? pathogen ???? pathologic Ag ???
• ???????????????????????????
  (Immune dysregulation)
• Price P, et al Hum Immunol 157-64, 2001
• French M, et al HIV Med 107-15, 2000
• French M, et al WEST PAC Conference, Perth, 2002
• Shelburne SA, et al Medicine 213-27,2002
• Chien J, et al Chest 933-6, 1998

Woraphot Tantisiriwat, MD,MPH
42
???????????

• IRS ??????
• CD4 ?????? (lt50)
• ?? OIs ???????? ?????????? HAART
• ?????????? OIs ????????? HAART ??????????
• ?????? IRS ??????? OIs ????? 3 ????? ?????????
  HAART
• ???????? Steroid ?????????????

43
MTB IRS

• 36 ??????????????????????????? HIV ???? ??????
  IRS ????????? HAART
• ???????? (gt101.5F)
• ????????????????? ?????????
• ??????????????????? ?????????
• ????????????????
• Ascites
• CXR ????? (?lymph node, consolidation, effusion)
• Tuberculoma

Woraphot Tantisiriwat, MD,MPH
44
MTB IRS

• ???????? ?????
• ??????????????????? ?????? ??????????????
• CD4 lt 50 ????????? HAART
• ????? HAART ????????????????? ??????? 2 ?????
  (??????????????? 3-4 ?????)

45
???????? ??????? HAART 4 ???????
Woraphot Tantisiriwat, MD,MPH
46
???????? IRS

• Prednisolone 0.5-1 mg/kg 1-2 ??????? ?????
  ???????????? ????????????????
• NSAIDs ????????????????????????
• drainage ???????????? ??????????????????????????

47
??????????????????? ARV ??????????????

• ??????????????
• ?????????????????
• IRIS

48
?????????????????????????????????TB/HIV
Collaboration
49
????????????
?????????????
?????????????????? 30-60
????????HIV???????? 10-20
50

• Impact of TB on HIV
• leading AIDS-related OI
• can infected in any stage of HIV
• enhance HIV replication ? accelerate the
  progression of HIV infection
• drug interaction between RMP vs. ARV
• Impact of HIV on TB
• high rate of primary TB and reactivation
• increase incidence of extrapulmonary/disseminated
  TB
• increase incidence of paradoxical reaction
• might need longer treatment course
• more adverse drug reactions
• increase incidence of MDR-TB
• high mortality rate

51
?????????????????????????????????

• ??????????????
• ??????????
• ????????????
• ???????????? ?????????
• ??????????????????????, nosocomial transmission
• ??????????????
• ????? ??????????? stigma ???????????

??????????????? ?????????????????? ???????????? ?
????????????
52
?????????????????????????????????

• ????? case load ?????????????????????????? HIV
• ????????????? HIV related immunosuppression
• ????????????-??????????????????????????????? HIV
• ??????????????????????????????????????????? HIV
• ????????????????????????????

53
ICF
IPT
IC
VCT -gt DCT
CPT
ART
D. Others
54
1. ?????????????????????????????????

• ??????????????????????????????
  (Intensified Case Finding,
  ICF)
• ??????????????????
  
  (Isoniazid Preventive Therapy, IPT)
• ??????????????????????????????????????????????????
  ????????????????????????
  (Tuberculosis
  Infection Control, IC)

55
ICF
56
IPT
57
Tomans Tuberculosis Case Detection, Treatment,
and Monitoring. Questions and Answers. 2nd
Edition World Health Organization. 2004.
WHO/HTM/TB/2004.334 p.227
58
2. ?????????????????????????????

• ???????????????????? HIV
  (Provider Initiated
  Counselling Testing, PICT)
• ?????????????????? HIV
• ??? co-trimoxazole ???????
  
  (Co-trimoxazole Preventive Therapy, CPT)
• ???????????????????????? HIV/AIDS
• ?????????????? (Antiretroviral Therapy, ART)

12
13
59
(No Transcript)
60
??????
HIV/AIDS
??????? REFER

• DOTS ???????????

Pv Care ???????????
DCT
ICF
HIV pos
HIV neg
TB case
TB infected
CPT, ART
IPT
DOT
Pv
61
(No Transcript)
62
HIV LIFE TB CURED
63
(No Transcript)
64
(No Transcript)