CASE PRESENTATION

DR F J MUGALA –MUKUNGU

PHYSICIAN KATUTURA STATE HOSPITAL

25-03-2017

ROOF OF AFRICA

CASE PRESENTATION

MR T.R

DOB 1983.03.20

AGE 33

DOA-1 29.07.16

DOD- 16.08.16

DOA-2 22.08.16

DOD- 6.09.16

CASE PRESENTATION

•New HIV Diagnosis at the time of

Admissions

•Complaining of Fever, dry Cough and

Shortness of Breath.

•He was started on Efavirenz /Tenofovir/

Emtricitabine (Teevir) and Purbac 960

Social History

-Single

-Employment –Available

-Alcohol Consumption - High

-Smoker

Examination

Critically ill

High Temperature 40 0C

High Respiratory rate 35/min

Saturation 94% on 5L oxygen

at weight 65.0 Kg

Oedema +++

oral Candida

Cheilosis

Examination

Respiratory System Clear

Clear

Abdomen

Distended

Hepatomegaly

CNS

well oriented Clear

Terminal neck Stiffness

LABORATORY RESULTS AVAILABLE

WCC was normal

CD4 15

HB 5.0

Platelet 220

Urea 10.8mmols/L

Creatinine 140µmoLs/L

CRP- 300mg/L

Liver Function : ALP is elevated 327

LABORATORY RESULTS AVAILABLE

GGT elevated 445 IU/L

ALT elevated 87 IU /L

AST elevated 241 IU /L

LDH – 727

Chest Xray taken on 23/07/2017

Normal

NORMAL

Question

What is the cause of Fever ?

What is the Cause of Anaemia?

What is the Cause of Abnormal Liver

Enzymes?

Question

What is the cause of Fever ?

1. Sepsis

2. IRIS

3. PCP,

4. TB

5. Lymphoma

Question

What is the cause of Fever ?

Question

What is the cause of Anemia ?

1. Blood Loss

2. Sepsis

3. Disseminated Infection –Bone marrow

infiltration

4. Medication AZT

Question

What is the cause of Anemia ?

1. Parvovirus Infection

2. TB,

3. Fungal –candida-malnutrition

4. Malabsorption of Vitamin B12

5. Vitamin deficiencies due to severe Alcohol use

Question

What is the cause of Abnormal Liver Enzymes ?

1. Ethanol Use

2. Hepatitis B

3. Disseminated Tuberculosis

4. Drug Induced: RHZE,NVP

5. TUMORS

6. Abscesses

What Test do you want to carry out?

•-VITB12 folate, ferritin

•Blood Cultures

•PCR CMV

•Lumbar puncture

•Crag

•Urine MCS

•Urine TB PCR

•Repeat cx12

•Sonar abdomen

Are you Happy with the ARV

regimen?

-No

-Nephrotoxic

-He has elevated Urea and

Creatinine

What do you want to Change it

to ??

What do you want to change it

to?

Answer

Efavirenz

Abacavir/ Lamivudine (Kivexa)

Would you Consider PCP as a

cause of Tachypnoea?

Answer

-Yes

-So he received high dose co-

trimoxazole

Repeat Chest X-ray-7 days later

Interstitial lung Pattern is present

What are the causes of Interstitial Lung Pattern in HIV Patients?

1. Tuberculosis

2. PCP

3. Lymphangitis Carcinomatosis

4. Pulmonary Oedema

5. CMV-Infection

6. Cryptococcus

7. Diffuse Interstitial Lymphocytosis-

Children

8. Castleman’s disease

How would you make a

diagnosis of Disseminated

Tuberculosis in this Patient??

1. Bone Marrow Biopsy and Aspirate

- TB Culture

- Histology of the Bone

- granulomas

2. Urine TB PCR

3. Liver Biopsy

Would you give Empiric PCP

Treatment?

What is the Dose of Cotrimoxazole for

PCP?

Answer 15-30mg/Kg/Day of TMX P.O/ IV divided

6-8 hourly

This Patients need 975mg TMX/3900

SMX

Total Dose 4.875G / 24hours

Each 15mls = 480G ≈ 150mls/24 hours

What is the size effects of this High

dose?

1. Bone Marrow Suppression on Aplastic anemia, Agranulocytosis, Thrombocytopenic Purpura

2. Drug Induced Liver Disease

3. Cutaneous Hypersensitivity reaction- sterens Johnson Syndrome TEN

4. Cardiovascular : QT Prolongation Leading to Ventricular Tachycardia and Torsades de Pointes

The Patient Developed Bone

Marrow

Suppression, He had severe Anemia

and low platelets with epistaxis

The platelet was low 31 x 109/L

White Cell count was 2.7

HB dropped from 10 post

transfusion to 7g/dl

How would you manage this

Complication?

Rx Leucovorin

Doses very according to severity

and response

Tablets are 15mg in Namibia

He received 15mg 6 Hourly P.O

The Urine TB PCR was Positive

He was sensitive to Rifampicin

What is the Treatment of

Choice?

-He developed Drug Induced Hepatitis

to RHZE

-His eye became yellow 2 weeks after

starting RHZE

-He had Tender enlarged Liver

-He was Nauseous

-

RHZE INDUCED LIVER DISEASE

Bilirubin had been normal and now it

was 83.2 ALP Phosphatase rose to 629

IU/L.

-The GGT rose to 1641 IU/L

-Liver Biopsy confirmed Inflammation

and necrosis in the portal tracts but no

granulomas

What is the New Treatment

option?

Answer

Levofloxacin

Streptomycin

Ethambutol

Could His have been due to

Abacavir?

Answer

- NO

He was Tested for the Genotype

HLAB5701 which is associated

with Abacavir Hypersensitivity

and it was negative

What about Cryptoccosis?

Was this infection Possible

?

Answer

- Yes, CRAG was negative

on the blood

CMV Infection: was

this Possible?

Answer

Yes, CMV PCR was elevated;

he did well on IV Ganciclovir

for 5 days

Current Status

He has returned to work

He is on his TB Treatment, Low

Dose Cotrimoxazole and ARV

WHO recommendations for the

management of Advanced HIV Disease

Dr Nathan Ford PhD FRCPE

WHO Treatment and care team

Background and rationale

• A significant proportion of patients continue to

present with advanced HIV disease

• People starting ART with advanced HIV disease have

high mortality particularly in first six months

following ART initiation

• Major causes of death include co-infections such as

TB, severe bacterial infections, cryptococcal

meningitis

• WHO guidelines include individual

recommendations for diagnosis, prophylaxis and

treatment

• Recent studies have assessed the potential for an

enhanced package of interventions to reduce

mortality/morbidity

For adults and adolescents, and children older than five

years, advanced HIV disease is defined as CD4 cell

count <200cells/mm3 or WHO stage 3 or 4 event.

Includes both ART naïve individuals and those who interrupt

treatment and return to care

All children younger than five years old with HIV are

considered as having advanced HIV disease.

WHO definition of advanced HIV

disease

IeDEA-COHERE: Results based on 951 855 adults from 55 countries after imputation of missing data

Does not include re-starters after interruption

In 2015 37% of people

starting ART did so at

CD4 cell count <200

cells/mm3

The public health response to HIVDR Guidelines meeting: 20-21 March 2017

Causes of mortality

Ford et al, Lancet HIV 2016

Packaged interventions for reducing mortality

among patients with advanced HIV disease

Key study

characteristics

REALITY (enhanced prophylaxis)

REMSTART (enhanced OI screening &

adherence)

Study countries Kenya, Malawi, Uganda, Zimbabwe Tanzania, Zambia

Sample size and design study 1805 individuals (open label) 1999 individuals (open label)

Eligibility criteria and population CD < PLHIV ≥ yrs old) CD < PLHIV ≥ 18 yrs old)

Main outcome Mortality reduction at 6 and 12 mo Mortality reduction at 12 mo

Rapid ART initiation

CrAg screening test

Adherence support visits x 4 weeks

CTX/isoniazid/B6 daily x 12 weeks

Fluconazole 100mg daily x 12 weeks

Azithromycin 500 mg daily x 5 days

Albendazole 400 mg x single dose

Costing analysis

Cost effectiveness analysis

1 TB screening with GenXpert at baseline included in both arms of the study , re-screening at 6 weeks in intervention arm :TB cases only asssessed in interventiongroup

2 ART intensification (RAL) x 4 weeks and food supplementation x 12 weeks, not included a s part of the PICO question but assessed in the factorial analysis and

discounted.

Outcomes

• 28% reduced death

• Improved adherence

at 6 months

• 27% reduced death

• Reductions in

incident morbidity

• Reductions in

hospitalization

BE

NE

FIT

S &

HA

RM

S

BENEFITS HARMS

• Reduced all-cause mortality • Potential for antimicrobial resistance

-azithromycin

• Reduced incident morbidity

• New TB disease

• New cryptococcal disease

• Potential for antifungal resistance -

fluconazole 100mg

• Reduced (or unchanged) new

hospitalisations

• Potential increased absolute cost to

health services

• Simplified package consistent with

public health approach

• Simplified package may reduce

attention to other important

comorbidities/co-infections

• Promotes increased attention to

advanced disease

A package of interventions including screening,

treatment and/or prophylaxis for major

opportunistic infections, rapid ART initiation*

and intensified adherence support

interventions should be offered to everyone

presenting with advanced HIV disease.

Strong recommendation, moderate-quality evidence

WHO Recommendation

* linked recommendation

• The role of presumptive treatment in managing TB,

Pneumocystis jirovecii pneumonia, severe bacterial infections

and cryptococcal disease should be considered in settings in

which access to diagnostic tests is limited and people present

with typical signs and symptoms (especially when

accompanied by clinical signs indicating severe illness)

• The WHO algorithm for managing people with HIV who are

suspected of having TB and are seriously ill incorporates

presumptive treatment of TB, bacterial infections and

Pneumocystis jirovecii pneumonia into the care pathway

Considerations

Guideline Development Group

Co-chairs: Alexandra Calmy (Hôpitaux Universitaires de Genève, Switzerland) and Graeme Meintjes (University of Cape

Town, South Africa).

Eduardo Arathoon (Asociacion de Salud Integral, Guatemala), Patricia Asero (International Community of Women Living

with HIV, Kenya), Rosa Bologna (Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Argentina), Mohamed Chakroun

(Fattouma Bourguiba Teaching Hospital, Tunisia), Lucia Chambal (Ministry of Health, Mozambique), Tom Chiller (Mycotic

Disease Branch, United States Centers for Disease Control and Prevention, USA), Francesca Conradie (University of the

Witwatersrand, South Africa), Serge Eholie Centre Hospitalier Universitaire de Treichville, Côte d’Ivoire , Lisa Frigati

(Tygerberg Hospital and Stellenbosch University, South Africa), Diana Gibb (Medical Research Council, United Kingdom),

Eric Goemaere (Médecins Sans Frontières, South Africa), Nelesh Govender (University of the Witwatersrand and National

Institute for Communicable Diseases, South Africa), Alison Grant (London School of Hygiene and Tropical Medicine, United

Kingdom), Nagalingeswaran Kumarasamy (YRGCARE, India), David Lalloo (Liverpool School of Tropical Medicine, United

Kingdom), Thuy Le (Oxford University Clinical Research Unit, Viet Nam), Emilio Letang (Barcelona Institute for Global

Health and Ifakara Health Institute, Spain), Dorothy Mbori-Ngacha (UNICEF, Kenya), Sayoki Mfinanga (Muhimbili Medical

Research Centre, National Institute for Medical Research, United Republic of Tanzania), Mathieu Nacher (Université de

Guyane, French Guiana), Muhayimpundu Ribakare (Rwanda Biomedical Centre, Rwanda), Kenly Sikwese (African

Community Advisory Board, Zambia), Nini Tun (Medical Action Myanmar, Myanmar), Jose E. Vidal (Instituto de

Infectologia Emílio Ribas and Universidade de São Paulo, Brazil)

External Review Group

Xavier Anglaret (Inserm – French National Institute of Health and Medical Research, France), Moherndran Archary (King

Edward VIII Hospital, South Africa) Moses Bateganya (United States Centers for Disease Control and Prevention, USA),

David Boulware (University of Minnesota, Uganda), Sergio Carmona (National Health Laboratory Services, South Africa)

Marcelo Freitas (ICAP, Mozambique), Beatriz Grinstejn (Fundação Oswaldo Cruz, Brazil), Joseph Jarvis (London School of

Hygiene and Tropical Medicine, United Kingdom and Botswana Harvard AIDS Institute Partnership, Botswana), David Meya

(Makerere University, Kampala, Uganda), Eyerusalem Negussie (Ministry of Health, Ethiopia), Daniel O’Brien (Barwon

Health, Australia), Heather Paulin (United States Centers for Disease Control and Prevention, USA), Andy Prendergast

(Queen Mary University of London, United Kingdom), George Siberry (Office for the US Global AIDS Coordinator, USA), and

Evy Yunihastuti (Faculty of Medicine, Universitas Indonesia, Indonesia)

WHO

Nathan Ford and Marco Vitoria (HIV Department, WHO) coordinated the overall guideline development process with

support from Chantal Migone (HIV Department, WHO), under the leadership of Meg Doherty and Gottfried Hirnschall

(HIV Department, WHO). Helen Bygrave (independent consultant, United Kingdom) wrote the guideline document with

Nathan Ford

Acknowledgements

THANK YOU