Case history id forum tb & hiv

POSTGRADUATE COURSE IN INFECTIOUS DISEASES, June 2002

This week is the web begins to feature the various lectures/exercises that were presented at a recent scientific meeting organized by the College of Physicians and Academy of Medicine of Malaysia.Infection covers all disciplines of medicine, and despite our earlier optimism that we got infection “licked”, it is very clear with the new millennium infection is going to be with us for a long time. Therefore all doctors must keep pace with new developments in infection in order to provide the best possible care to his patients.I hope these series of lectures/exercise will help you in that direction.I wish to thank all my colleagues who have kindly consented to have their lectures featured in my website.

CASE PRESENTATION – HIV/AIDS“Managing Opportunistic Infections”

“The Twins” – TB and HIVThe Headaches that Won’t Go Away“Doctor, I Can See the Two of You”Fever, Dyspnea and Cough

Professor Adeeba KamarulzamanDr Christopher LeeDr Norliza AriffinDr Suresh Kumar

The TwinsTB & HIVTB & HIV

Case History LSHLSH 27 yr old chinese male27 yr old chinese male Sales executiveSales executive Married, wife positive, Married, wife positive, 1 child 4 years old - negative1 child 4 years old - negative History unprotected sex with CSW before marriageHistory unprotected sex with CSW before marriage 1995 – CD4 223/mm31995 – CD4 223/mm3 Defaulted follow up and came back again 1997 with Defaulted follow up and came back again 1997 with

complaints of recurrent fever and mouth ulcers complaints of recurrent fever and mouth ulcers

CD4 – 17/mm3CD4 – 17/mm3 Started on Started on

Zidovudine(AZT) and Zidovudine(AZT) and Didanosine (ddI) and on Didanosine (ddI) and on T BactrimT Bactrim

4 /98 – CD4 – 85/mm34 /98 – CD4 – 85/mm3 8/98 – CD4 – 14/mm38/98 – CD4 – 14/mm3 11/98 – CD4 – 9/mm311/98 – CD4 – 9/mm3 12/98 Changed to AZT 12/98 Changed to AZT

+ Lamivudine (3TC)+ Lamivudine (3TC)

17

85

14

911

0

10

20

30

40

50

60

70

80

90

Dec-97

Jan-98

Feb-98

Mar-98

Apr-98

May-98

Jun-98

Jul-98

Aug-98

Sep-98

Oct-98

Nov-98

Dec-98

Jan-99

Feb-99

Mar-99

AZ

T+

3TC

AZ

T+

ddI

Mar/99 – CD4 – 11/mm3Mar/99 – CD4 – 11/mm3 June/99 – CD4 – 8/mm3June/99 – CD4 – 8/mm3 Apr/00 – CD4 – 16/mm3Apr/00 – CD4 – 16/mm3 Sept/00 – CD4 – 6/mm3 Sept/00 – CD4 – 6/mm3

Started on Started on Stavudine (d4T) 30mg bdStavudine (d4T) 30mg bd Lamivudine(3TC) 150mg bdLamivudine(3TC) 150mg bd Nevirapine 200mg dailyNevirapine 200mg daily

1 week later developed pruritic 1 week later developed pruritic eythematous rash. eythematous rash.

The rash was generalized The rash was generalized maculopapular with no systemic maculopapular with no systemic symptoms and mucosal involvement symptoms and mucosal involvement

64kg

17

85

14

911

8

16

6

00

10

20

30

40

50

60

70

80

90

AZ

T+

3TC

AZ

T+

ddI

d4T

+3T

C+

Nev

What is the next step ?What is the next step ?

1.1. Stop all the ARVTStop all the ARVT

2.2. Stop one of the drugs - d4T/ Stop one of the drugs - d4T/ 3TC / Nevirapine3TC / Nevirapine

3.3. Ask him to scratch on and Ask him to scratch on and increase Nevirapine to 200mg increase Nevirapine to 200mg bd after 1 weekbd after 1 week

Treated with antihistamines and steroid Treated with antihistamines and steroid creams. ARVT continuedcreams. ARVT continued

Rashes subsided Rashes subsided Nevirapine increased to 200mg bd after 2 Nevirapine increased to 200mg bd after 2

weeks with no increase in rashweeks with no increase in rash

64kg

61kg

Management of Nevirapine rash 50% of antiretroviral hypersensitivity will resolve 50% of antiretroviral hypersensitivity will resolve

spontaneously despite continuation of therapyspontaneously despite continuation of therapy Therapy should be stopped if there isTherapy should be stopped if there is

Mucosal involvementMucosal involvement Blistering / ExfoliationBlistering / Exfoliation Significant hepatic dysfunctionSignificant hepatic dysfunction Fever >38 CFever >38 C Intolerable pruritusIntolerable pruritus

Lancet 2000;356:1425

18.Oct 00: developed jaundice18.Oct 00: developed jaundice LFT resultLFT result

Protein 71 g/dl ; Albumin 41 g/dlProtein 71 g/dl ; Albumin 41 g/dl Bilirubin 208umol/lBilirubin 208umol/l ALP 867 U/l ; ALT 166 U/lALP 867 U/l ; ALT 166 U/l

Will youWill you

1.1. Stop all ARVTStop all ARVT

2.2. Stop one of the drugs – d4T / 3TC / NevirapineStop one of the drugs – d4T / 3TC / Nevirapine

3.3. Continue the present treatmentContinue the present treatment

4.4. Give JeteparGive Jetepar

What further investigations need to be carried What further investigations need to be carried out ?out ?

1.1. Ultrasound LiverUltrasound Liver2.2. Liver biopsyLiver biopsy3.3. Head to toe CT scanHead to toe CT scan4.4. Hepatitis ScreenHepatitis Screen5.5. Don’t do any investigation – just sit tightDon’t do any investigation – just sit tight

All ARVT withheld on 25.10.00All ARVT withheld on 25.10.00 Ultrasound LiverUltrasound Liver

NormalNormal Hepatitis ScreenHepatitis Screen

Negative for Hepatitis A, B and CNegative for Hepatitis A, B and C Patient managed conservatively with LFT Patient managed conservatively with LFT

monitoring weeklymonitoring weekly

LFT 18.10.00 21.12.00 Prot 71 78g/l Alb 41 39g/l Bilirubin 208 22umol/l ALP 867 402U/l ALT 166 78U/l

Appetite improved, No fever or abd pain d4T, 3TC and Nevirapine along with

T.Bactrim restarted on 11 Jan 01

61kg

58kg

Severe or life threatening hepatotoxicity, including fatal fulminant hepatitis has occurred in patients with Nevirapine. It should be interrupted in patients experiencing moderate to severe liver function abnormalities until these return to baseline values. Nevirapine should be permanently discontinued if liver function abnormalities recur upon re-administration

Source:Product insert - Viramune

Feb 2001Feb 2001 Admitted with intermittent fever, nausea, Admitted with intermittent fever, nausea,

vomiting and itchy maculopapular rashvomiting and itchy maculopapular rash No headache, No diarrhoea, No cough No headache, No diarrhoea, No cough Variable appetite, Loss of weight +Variable appetite, Loss of weight + Poor compliance to ARVT especially Poor compliance to ARVT especially

Nevirapine, because of these symptomsNevirapine, because of these symptoms In the ward intermittent fever, scattered In the ward intermittent fever, scattered

erythematous itchy papular rashes, erythematous itchy papular rashes, hepatomegaly 3cm. No lymphadenopathy hepatomegaly 3cm. No lymphadenopathy or spleenomegaly. or spleenomegaly.

58kg

55kg

Hb 10.3g/dlHb 10.3g/dl WBC 4,000c/cmm WBC 4,000c/cmm PLT 240,000PLT 240,000 Renal Profile NormalRenal Profile Normal Blood C&S ; Urine C&S No GrowthBlood C&S ; Urine C&S No Growth Chest X-rayChest X-ray

Comment on the X-Ray

2 months ago now

What is the possible diagnosis ?What is the possible diagnosis ?

1.1. LymphomaLymphoma

2.2. Bacterial PneumoniaBacterial Pneumonia

3.3. Pulmonary TuberculosisPulmonary Tuberculosis

4.4. Bronchogenic carcinomaBronchogenic carcinoma

5.5. Metastatic Lung cancerMetastatic Lung cancer

What is the next investigation that you What is the next investigation that you will like to perform ?will like to perform ?

1.1. CT ThoraxCT Thorax

2.2. BronchoscopyBronchoscopy

3.3. Bone marrow for HPEBone marrow for HPE

4.4. Open lung biopsyOpen lung biopsy

5.5. No further investigation needed – No further investigation needed – refer to Hematologist / refer to Hematologist / OncologistOncologist

CT ThoraxCT Thorax Soft tissue mass Soft tissue mass

posterior to the posterior to the SVC; Enlarged SVC; Enlarged right paratracheal right paratracheal lymphnode. No lymphnode. No focal lesion in the focal lesion in the lung parenchymalung parenchyma

BronchoscopyBronchoscopy Right main bronchus inflammed. Right main bronchus inflammed.

? Endobronchial ? Endobronchial TBTB

Bronchial washing – no growth; AFB Bronchial washing – no growth; AFB negative.negative.

Started on antituberculous medications Started on antituberculous medications – EHRZ– EHRZ

55kg

53kg

TB in HIV vs Non HIV Patients

HIV+TBHIV+TB TB onlyTB only

Pulmonary disease alonePulmonary disease alone 40%40% 72%72%

Extrapulmonary diseaseExtrapulmonary disease 34%34% 16%16%

BothBoth 26%26% 12%12%

Sputum positive in Pulmonary Sputum positive in Pulmonary disease only patientsdisease only patients 57%57% 76%76%

Rates of diagnosis by sputum culture were similarRates of diagnosis by sputum culture were similar

Study in ZambiaStudy in Zambia 182 patients with HIV+TB vs 67 with TB only182 patients with HIV+TB vs 67 with TB only

J Trop Med Hyg 1993; 96:1-11

PTB in early vs late HIV infection

Features of PTBFeatures of PTB Stage of HIV infectionStage of HIV infection

EarlyEarly LateLate

Clinical PictureClinical PictureOften resembles post Often resembles post primary PTBprimary PTB

Often resembles Often resembles primary PTBprimary PTB

Sputum SmearSputum Smear Often positiveOften positive Often NegativeOften Negative

CXRCXR Often CavitiesOften CavitiesOften infiltrates with Often infiltrates with no cavitiesno cavities

PTB treatment in HIV patients

Among patients treated for TB, early Among patients treated for TB, early clinical response to therapy and the clinical response to therapy and the time in which M. tuberculosis sputum time in which M. tuberculosis sputum cultures convert from positive to cultures convert from positive to negative appear to be similar for those negative appear to be similar for those with HIV infection and those without with HIV infection and those without HIV infection HIV infection

However, the data are less clear about However, the data are less clear about whether rates of TB relapse whether rates of TB relapse (recurrence of TB following successful (recurrence of TB following successful completion of treatment) differ among completion of treatment) differ among patients with or without HIV infectionpatients with or without HIV infection

MMWR October 30, 1998 / Vol. 47 / No. RR-20

MMWR 1998 / Vol. 47 / No. RR-20

What will you do with his ARVT ?What will you do with his ARVT ? Stop ARVTStop ARVT Continue ARVTContinue ARVT Continue ARVT but change his drugsContinue ARVT but change his drugs

CD4 Count – 6 cells/cmm

CD4 Count – 6 cells/cmm

Viral L

oad – 66,100copies/ml

Viral L

oad – 66,100copies/ml

17

85

14

911

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16

6

0

10

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Dec-97

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Apr-98

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Aug-98

Oct-98

Dec-98

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Apr-99

Jun-99

Aug-99

Oct-99

Dec-99

Feb-00

Apr-00

Jun-00

Aug-00

AZ

T+

3TC

AZ

T+

ddI

d4T

+3T

C+

Nev

Interactions between rifampicin and antiretroviral therapy

IndinavirIndinavir Indinavir levels decrease by 89%Indinavir levels decrease by 89%

RitonavirRitonavir Ritonavir levels decrease by 35%Ritonavir levels decrease by 35%

Saquinavir Saquinavir (Invirase)(Invirase)

Saquinavir levels decrease by 84%; if Saquinavir levels decrease by 84%; if using with ritonavir-use rifampicin using with ritonavir-use rifampicin 600mgdly or 2-3 times/week600mgdly or 2-3 times/week

NevirapineNevirapine Nevirapine levels decrease by 37%Nevirapine levels decrease by 37%

EfavirenzEfavirenz Efavirenz levels decrease by 25%Efavirenz levels decrease by 25%

ARVT withheld in March 01ARVT withheld in March 01 Seen 2 months later Seen 2 months later

Wt gainWt gain No feverNo fever Good appetiteGood appetite

Changed to biweekly treatment – HRChanged to biweekly treatment – HR CD 4 Count – 0 cells/cmmCD 4 Count – 0 cells/cmm

59kg

53kg

What to do next ?What to do next ?

1.1. Complete 6 months of HR and then Complete 6 months of HR and then start ARVTstart ARVT

2.2. Restart ARVT now – if yes which Restart ARVT now – if yes which regimeregime

In Jun 01- changed to HEZ; Planned to give In Jun 01- changed to HEZ; Planned to give it for 6 monthsit for 6 months

Started on Started on Indinavir 800mgbdIndinavir 800mgbd Ritonavir 100mgbdRitonavir 100mgbd Efavirenz 600mgONEfavirenz 600mgON

2 months later2 months later AsymtomaticAsymtomatic CD4 Count 144cells/cmmCD4 Count 144cells/cmm

In Dec 01In Dec 01 Completed antituberculosis treatmentCompleted antituberculosis treatment CD4 Count 216cells/cmmCD4 Count 216cells/cmm Viral load < 50copies/mlViral load < 50copies/ml

62kg

59kg

Treatment Options HIV positive patient who is not on HIV positive patient who is not on

antiretroviral therapyantiretroviral therapy 2 months of EHRZ 2 months of EHRZ 4 months of biweekly HR4 months of biweekly HR Can be extended to 9 months in patients with Can be extended to 9 months in patients with

poor responsepoor response If antiretroviral treatment is required after this – If antiretroviral treatment is required after this –

give wash out period of 3 weeks after finishing give wash out period of 3 weeks after finishing anti-TB therapyanti-TB therapy

If patient requires antiretroviral therapy (very If patient requires antiretroviral therapy (very low CD4 count and high viral load)low CD4 count and high viral load) Efavirenz based regime (800mg/day) along Efavirenz based regime (800mg/day) along

with 2EHRZ/4HR(2)with 2EHRZ/4HR(2) If Efavirenz cannot be used – withhold ARVT If Efavirenz cannot be used – withhold ARVT

for 2 months and give 2EHRZ and then give 6 for 2 months and give 2EHRZ and then give 6 months of non-rifampicin based regime with months of non-rifampicin based regime with ARVT e.g.,6SHZ biweekly or dailyARVT e.g.,6SHZ biweekly or daily

Treatment Options

And he lived happily ever after…..

On last reviewOn last review AsymptomaticAsymptomatic Viral load still < 50copies/mlViral load still < 50copies/ml CD4 Count 373cells/cmmCD4 Count 373cells/cmm Bactrim stoppedBactrim stopped

71kg

62kg

7

85

149 11 8 166 0

144

373

0

50

100

150

200

250

300

350

400

AZ

T+

3TC

AZ

T+

ddI

d4T

+3T

C+

Nev

Cri

x+N

or+

Efa