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