Advanced HIV and seriously ill: challenges in low … · Advanced HIV and seriously ill: challenges...

Advanced HIV and seriously ill:challenges in low resource settings

Rosie Burton,Southern African Medical Unit, MSF

Mozambique

Mozambique

Mozambique

Mozambique

Preventing mortality

MSF hospital, Kinshasa, DRC: 130 % bed occupancy

MSF Hospital: KinshasaInpatient study, 2015-2017

• Over 2,000 patients

• Median CD4 count: 84

(IQR 26-244)

Inpatient mortality:

• 26% per admission

• Over 1/3 of patients had more than

one admission

• 36.6% patient mortality per patient

David Maman, Rapport Hospitalisation CHK 2015/2017, Epicentre, 2017

31%

34%

17%

18%

Time of death from hospital admission

< 48 hours

> 48 hours < 1 week

> 1 week < 2 weeks

> 2 weeks

56%

8%

12%

9%

7%

5%

Causes of mortality: % of total mortality

TBCryptococcal meningitis

Toxoplasmosis

PJP

non TB pneumonia

Malaria

other

0

10

20

30

40

50

60

<25 25-49 50-99 100-199 200-349 >350

% mortality by CD4 count

CD4 count: major predictor of mortality

0

10

20

30

40

50

60

<25 25-49 50-99 100-199 200-349 >350

% mortality by CD4 count

CD4 count: major predictor of mortality

CD4 on admission:• CD4 < 100: 53% • CD4 < 200: 70%

29%

25%

46%

ART status

ART naïve

ART < 6 months

ART > 6 months

ART > 6 months: median 3.6 years (IQR 1.7 – 6.7)

Homa Bay,

Kenya

Mortality IPD plus post-hospitalisation:

• CD4 < 100: 55%• WHO stage 3 or 4: 65%

Median time of death post discharge: 35 days (IQR 14-91)

Advanced HIV:CD4 < 200 or new stage 3 or 4 disease

Advanced HIV:CD4 < 200 or new stage 3 or 4 disease

Retention in

careART Clinic

Undetectable

Viral load

ART naive

‘Late presenters’

Advanced HIV:CD4 < 200 or new stage 3 or 4 disease

Retention in

careART Clinic

Undetectable

Viral load

ART naive

Return to care

after interruption

Advanced HIV:CD4 < 200 or new stage 3 or 4 disease

Retention in

careART Clinic

Undetectable

Viral load

ART naive

Return to care

after interruption

Treatment

Failure

Identify patients at highest risk of mortality needing hospital care

Danger signs

Identify patients at highest risk of mortality needing hospital care

Danger signs

Advanced HIVAmbulatory

no

Identify patients at highest risk of mortality needing hospital care

Danger signs

Advanced HIVSeriously ill

Advanced HIVAmbulatory

no yes

Identify patients at highest risk of mortality needing hospital care

Seriously ill:

1 or more danger signs

• Respiratory rate > 30/min• Saturation < 90%• Temperature > 39°C• Heart rate > 120/min• Systolic BP < 90 mmHg• Severe dehydration

• Incapable of walking unaided

• Confusion or other altered mental state • Any other new abnormal neurology, includingfocal neurological abnormalities, seizures

Seriously ill:

1 or more danger signs

• Respiratory rate > 30/min• Saturation < 90%• Temperature > 39°C• Heart rate > 120/min• Systolic BP < 90 mmHg• Severe dehydration

• Incapable of walking unaided

• Confusion or other altered mental state • Any other new abnormal neurology, includingfocal neurological abnormalities, seizures

Seriously ill:

1 or more danger signs

• Respiratory rate > 30/min• Saturation < 90%• Temperature > 39°C• Heart rate > 120/min• Systolic BP < 90 mmHg• Severe dehydration

• Incapable of walking unaided

• Confusion or other altered mental state • Any other new abnormal neurology, including

focal neurological abnormalities, seizures

• WHO• MSF additions

Primary care:• Point of care tests• Initiate

management• Resource

dependent: do what is feasible

Hospital admission:• Rapid investigation and

management

Primary care:• Point of care tests• Initiate

management• Resource

dependent: do what is feasible

Hospital admission:• Rapid investigation and

management

Primary care:• Point of care tests• Initiate

management• Resource

dependent: do what is feasible

HIV/TB Rapid

Assessment Unit

Active link to

primary care

HIV/TB experienced

clinicians and nurses

24 hour facility

with beds

Point of care tests

BasicLaboratoryplatform

Rapid Assessment Unit

Rapid assessment :

25 to 35 % mortality within

48 hours

Advanced HIV and seriously ill; preventing mortality

Public Health Approach

• Focusing on most common causes of mortality

• Point of care investigations, 24/7

• Empiric treatment

• Decision making and treatment initiation within hours – not days

• Effective ART

Major causes of mortality

Disseminated TB

Major causes of mortality

Neurological disease – ‘big 3’:

• CNS TB

• Cryptococcal meningitis

• Toxoplasmosis

Disseminated TB

Major causes of mortality

Neurological disease – ‘big 3’:

• CNS TB

• Cryptococcal meningitis

• Toxoplasmosis

Respiratory Disease – ‘big 3’:• Pneumocystis pneumonia• Pulmonary TB• Bacterial pneumonia

Disseminated TB

Major causes of mortality

Neurological disease – ‘big 3’:

• CNS TB

• Cryptococcal meningitis

• Toxoplasmosis

Other infections:

• Malaria

• Bacterial meningitis

• Other bacterial infections

• Parasite diarrhoea

Respiratory Disease – ‘big 3’:• Pneumocystis pneumonia• Pulmonary TB• Bacterial pneumonia

Disseminated TB

Major causes of mortality

Neurological disease – ‘big 3’:

• CNS TB

• Cryptococcal meningitis

• Toxoplasmosis

Other infections:

• Malaria

• Bacterial meningitis

• Other bacterial infections

• Parasite diarrhoea

Respiratory Disease – ‘big 3’:• Pneumocystis pneumonia• Pulmonary TB• Bacterial pneumonia

Non-infectious causes:• Hypoglycaemia• Renal disease• Electrolyte abnormalities• Liver disease• Drug side effects

Disseminated TB

Point of Care investigations: available 24/7

CD4 LAM CrAg Hbmalaria Glucose Creatinine

Syphilis

HepatitisB

Semi –quant CD4 LFA

TB –LAM

CRAG

Laboratory investigations: rapid turnaround time essential

Electrolytes CSF analysis

ALT, bilirubin

XpertMTB/RIF

Xpert VL

Radiology

Advanced HIV and seriously ill: high suspicion for TB

TB LAM on admission

Advanced HIV and seriously ill: high suspicion for TB

TB LAM on admissionPositive: Start TB treatment immediately

Advanced HIV and seriously ill: high suspicion for TB

TB LAM on admissionPositive: Start TB treatment immediately

Negative:Negative does not exclude TB:

Clinical decision to treatStart empiric treatment

immediately if high suspicion of TB

Advanced HIV and seriously ill: high suspicion for TB

TB LAM on admissionPositive: Start TB treatment immediately

Negative:Negative does not exclude TB:

Clinical decision to treatStart empiric treatment

immediately if high suspicion of TB

Xpert MTB/RIF:in parallel with TB treatment Negative does not exclude TB

Advanced HIV and seriously ill: high suspicion for TB

TB LAM on admissionPositive: Start TB treatment immediately

Negative:Negative does not exclude TB:

Clinical decision to treatStart empiric treatment

immediately if high suspicion of TB

Xpert MTB/RIF:in parallel with TB treatment Negative does not exclude TB

Xpert MTB/RIF:

• Sputum• Urine• CSF• Lymph node aspirate• Pleural effusion• Ascites

WHO: Advanced HIV

TB Diagnosis

TB symptoms present:• Xpert MTB RIF as first

test• LAM may be used if

CD4 < 100 or seriously ill at any CD4 count

WHO: Advanced HIV

TB Diagnosis

TB symptoms present:• Xpert MTB RIF as first

test• LAM may be used if

CD4 < 100 or seriously ill at any CD4 count

WHO: Advanced HIV

TB Diagnosis

TB symptoms present:• Xpert MTB RIF as first

test• LAM may be used if

CD4 < 100 or seriously ill at any CD4 count

Investigations positive for TB• Start TB treatment

WHO: Advanced HIV

TB Diagnosis

TB symptoms present:• Xpert MTB RIF as first

test• LAM may be used if

CD4 < 100 or seriously ill at any CD4 count

Investigations positive for TB• Start TB treatment

Investigations negative for TB• Consider other diagnoses• Consider presumptive TB

treatment in patients who are seriously ill even if TB test is negative or result unavailable

TB diagnosis: high diagnostic yield from urine

Cape Town, unselected HIV pts needing acute admission - within first 24 hours:

• Sputum samples from 37% of patients (nurse assisted):

• Urine samples from 99.5%

TB diagnosis: high diagnostic yield from urine

Cape Town, unselected HIV pts needing acute admission - within first 24 hours:

• Sputum samples from 37% of patients (nurse assisted):

• Urine samples from 99.5%

Xpert MTB/RIF - increased diagnostic yield in urine compared to sputum

CD4 < 100: n = 74

All:n=139

Lawn et al. BMC Medicine (2015) 13:192

TB bacteraemia: urine based testing identified 88% of patients,

sputum based testing identified 19.5%

Sputum microscopy and Xperthad identical diagnostic yield

Kerkhoff et al. Scientific Reports (2017) 7: 1093

Neurological Disease

‘Big 3’:• Cryptococcal

meningitis• CNS TB• Toxoplasmosis

Neurological Disease

‘Big 3’:• Cryptococcal

meningitis• CNS TB• Toxoplasmosis

Other CNS infections:• Bacterial meningitis• Cerebral malaria• Neurospyhilis

Neurological Disease: Point of care CrAg

CrAg negative neurological disease:

empiric treatment

Treat for toxoplasmosis:

• CD4 < 200 and neurological symptoms/signs

• No access to serology

Treat for CNS TB:

• Neurological symptoms and signs and cannot exclude TB

• LP suggestive of TB meningitis, or other evidence of TB stronglysupports the diagnosis

Look for and correct reversible metabolic causes

Respiratory Disease:Danger signs – empiric treatment

RR > 30 / min or SpO2 < 90%:

Immediate empirictreatment:

• Pneumocystis pneumonia• Bacterial pneumonia• TB

First line ART failure

• Turnaround time days (Xpert VL): switch on basis of this VL• Turnaround time weeks/months (centralised VL): clinical decision

ART > 6 months and new stage 4 disease; urgent switch to second line Current guidelines do not address these patients

Non-judgemental approach to patients with poor adherence or returning to care

after treatment interruptions:

‘welcome back’ clinics

Evidence Gaps

• Empiric TB treatment all seriously ill patients requiring hospital admission

• Xpert MTB/RIF: non sputum samples

• Characterising CNS disease

• Rapid initiation/switching of ART – ‘within 2 weeks’ too long?

• Steroids to prevent IRIS in seriously ill patients

• Dolutegravir for first and second line

Resources: Advanced HIV

www.samumsf.orgwww.msf.org.za

www.who.org

Acknowledgements

All staff at MSF supported inpatient sites

Eric Goemaere and other SAMU colleagues