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APACC Capacity Building Session 3:

Online Clinical Management Tools

Jonathan Schapiro

Saye Khoo

Tavitiya Sudjaritruk

•iOS App •Android App

www.druginteractions.orgOur Mission

“To provide clinically useful, reliable, comprehensive, up-to-date,

evidence-based drug-drug interactions resources,

freely available to healthcare workers, patients and researchers

worldwide”

www.hiv-druginteractions.org www.hep-druginteractions.org www.cancer-druginteractions.org

http://www.druginteractions.org/

http://www.hiv-druginteractions.org/

http://www.hep-druginteractions.org/

http://www.hiv-druginteractions.org/

www.druginteractions.org

1. Select HIV Drugs 2. Select Comedications

1. Select HIV Drugs 2. Select Comedications


Case study #1Tavitiya Sudjaritruk, MD, ScM, PhD

Division of Infectious Diseases, Department of Pediatrics

Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

Email: [email protected]

Identification data

•An 8-year-old boy with perinatally acquired

HIV infection

•Address: Lamphun province, Thailand

•Date of admission: September 2008

Medical History

At age 3 years – first presentation at the local

hospital

• Presentation:

• Oral candidiasis

• Recurrent pneumonia

• Wasting syndrome (weight and height <3rd percentiles)

• Lab investigations:

• Anti HIV test: positive

• CD4 0% (2 cells/mm3)

• Plasma HIV RNA 318,156 copies/ml

Medical History

At age 3 years – first presentation at the local

hospital

• Management:

• Started the first-line cART regimen: zidovudine,

lamivudine, nevirapine (according to the Thai national

HIV treatment guidelines at that time)

• Progression:

• Clinical status was improved

• Opportunistic infections were subsided

• Weight gained 3 kg/year

• Height gained 10 cm/year

Progression

At age 5 years – followed up at the local hospital

• Presentation: anemia suspected from zidovudine


• Hemoglobin 2.5 g/dL

• Hematocrit 7%

• CD4 12.8% (202 cells/mm3)

• Plasma HIV RNA – not done

• Management:

• Blood transfusion

• Switched zidovudine to stavudine (plus lamivudine and

nevirapine)

• Progression: anemia was improved

Progression


• Presentation: poor adherence to antiretroviral medications


• CD4 8% (142 cells/mm3)

• Plasma HIV RNA 78,727 copies/mL

• HIV drug resistance mutations:

• NRTI: K65R, K70KT, M184V

• NNRTI: V108I, Y181C, H221Y

Discussion #1

What is the second-line cART regimen

will you choose for this patient?

Stanford HIV Drug Resistance Database

https://hivdb.stanford.edu/

https://hivdb.stanford.edu/

Discussion #1

What is the second-line cART regimen

will you choose for this patient?

Progression


• Presentation: poor adherence to antiretroviral medications


• CD4 8% (142 cells/mm3)

• plasma HIV RNA 78,727 copies/mL

• HIV drug resistance mutations:

• NRTI: K65R, K70KT, M184V

• NNRTI: V108I, Y181C, H221Y

• Management:

• Switch cART to the second-line regimen

• Stavudine (2 MKDay), lamivudine (10 MKDay),

lopinavir/ritonavir (LPV 185 mg/m2 + RTV 45 mg/m2 every

12 hours)

Present illness


• Presentation:

• Prolong fever for 2 weeks

• Chronic cough for 1 month

• Weight loss (2 kg during the past month)

• Multiple neck mass with spontaneous ruptured for 2 months

• Additional history: his grandmother was diagnosed with

drug susceptible pulmonary TB (sputum AFB 2+) 4 months

ago, and was currently on anti-TB treatment

• He was referred to our hospital

Present illness

• Physical exam:

• Temp 38.0-38.5°C

• Respiratory rate 24 /min

• Mild pale conjunctivae

• Multiple cervical

lymphadenopathies (2-3

cm in diameter) with

spontaneous ruptured

• Lungs: clear

• Hepatomegaly (liver 5 cm

below right costal margin)

• No splenomegaly

The photographs were consented by the patient

Work up


• CBC: hemoglobin 8.8 g/dL; hematocrit 26.2%, platelet

295,000 /mm3

• LFT: albumin 2.4 g/dL, globulin 6.8 g/dL, AST/ALT

35/13 U/L, TB/DB 0.46/0.24 mg/dL

Work up

• Chest X-ray:

Findings: coarse reticulonodular densities on the right upper and middle lung fields with right pleural thickening

Work up

• Lymph node excisional biopsy:

• Pus – AFB staining 1+, but no Mycobacterium

tuberculosis growth in 8 weeks

• Pathology: caseous and suppurative granulomatous

inflammation

• Sputum AFB for 3 days: not found

• Sputum culture: Mycobacterium tuberculosis grown

• Drug susceptibility test: sensitive to isoniazid,

rifampicin, streptomycin

• Hemoculture for Mycobacterium spp: no growth

in 8 weeks

Diagnosis

Drug susceptible, smear positive,

pulmonary TB with TB lymphadenitis

Management

• Started anti-TB drugs

• Isoniazid (10 MKDay)

• Rifampicin (18 MKDay)

• Pyrazinamide (30 MKDay)

• Ethambutol (15 MKday)

• Continued cART regimen:

• Stavudine (2 MKDay),

• Lamivudine (10 MKDay)

• Increased dose of lopinavir/ritonavir to LPV 270 mg/m2

+ RTV 70 mg/m2 every 12 hours

Discussion #2

What issues should be concerned in this

patient?

Progression

• Concern about drug-drug interaction: rifampicin and lopinavir/ritonavir

• Measured drug level (trough level) for lopinavirand ritonavir

• Impression: Drug-drug interaction

Day of anti-TB

treatment

Lopinavir

(ng/mL)

Ritonavir

(ng/mL)

Day 0 20,021 857

Day 7 <50 undetectable

Discussion #2

What should we do next?

Progression

• Management: Anti-TB regimen modification

• Taken off rifampicin

• Added ofloxacin (15 MKDay)

• New anti-TB regimen: HZEQ

• Continue cART regimen:

• Stavudine (2 MKDay),

• Lamivudine (10 MKDay)

• Lopinavir/ritonavir (LPV 270 mg/m2 + RTV 70 mg/m2

every 12 hours)

Progression

• Measured drug level (trough level) for lopinavir

and ritonavir again after anti-TB modification

• Management: continue anti-TB for 14 months

(4HZEQ + 10HEQ)

• Clinical status was improved

Day of anti-TB

treatment

Lopinavir

(ng/mL)

Ritonavir

(ng/mL)

Day 0 20,021 857

Day 7 <50 undetectable

Day 14

(Day 7 after off RF)

15,625 738

Lesson learned

• Poor adherence to antiretroviral medication is one of the major concerns during the course of HIV treatment

• HIV drug resistance testing can guide us to select the appropriate treatment regimen for the patients

• Tuberculosis is the most common co-infection in HIV-infected patients

• Drug-drug interaction between anti-TB and antiretroviral medications should be considered when concomitantly provide treatment for both diseases

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