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: Kinshasa Inpatient 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
Time of death from hospital admission 18% 31% < 48 hours 17% > 48 hours < 1 week > 1 week < 2 weeks 34% > 2 weeks
Causes of mortality: % of total 5% mortality 7% TB Cryptococcal meningitis 9% Toxoplasmosis 12% 56% PJP non TB pneumonia 8% Malaria other
% mortality by CD4 count 60 50 40 30 20 10 0 <25 25-49 50-99 100-199 200-349 >350 CD4 count: major predictor of mortality
% mortality by CD4 count 60 50 CD4 on admission: CD4 < 100: 53% CD4 < 200: 70% 40 30 20 10 0 <25 25-49 50-99 100-199 200-349 >350 CD4 count: major predictor of mortality
ART status 29% 46% ART naïve ART < 6 months ART > 6 months 25% 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 ART naive Late presenters ART Clinic Retention in care Undetectable Viral load
Advanced HIV: CD4 < 200 or new stage 3 or 4 disease Return to care after interruption ART naive ART Clinic Retention in care Undetectable Viral load
Advanced HIV: CD4 < 200 or new stage 3 or 4 disease Return to care after interruption ART naive ART Clinic Retention in care Undetectable Viral load Treatment Failure
Identify patients at highest risk of mortality needing hospital care
Identify patients at highest risk of mortality needing hospital care Danger signs
Identify patients at highest risk of mortality needing hospital care Danger signs no Advanced HIV Ambulatory
Identify patients at highest risk of mortality needing hospital care Danger signs no yes Advanced HIV Ambulatory Advanced HIV Seriously ill
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
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
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 WHO MSF additions Incapable of walking unaided Confusion or other altered mental state Any other new abnormal neurology, including focal neurological abnormalities, seizures
Primary care: Point of care tests Initiate management Resource dependent: do what is feasible
Primary care: Point of care tests Initiate management Resource dependent: do what is feasible Hospital admission: Rapid investigation and management
24 hour facility with beds Point of care tests Primary care: Point of care tests Initiate management Resource dependent: do what is feasible Hospital admission: Rapid investigation and management HIV/TB experienced clinicians and nurses HIV/TB Rapid Assessment Unit Active link to primary care Basic Laboratory platform
Rapid Assessment Unit Rapid assessment : 25 to 35 % mortality within 48 hours
Advanced HIV and seriously ill; Public Health Approach preventing mortality 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 Disseminated TB Respiratory Disease big 3 : Pneumocystis pneumonia Pulmonary TB Bacterial pneumonia
Major causes of mortality Neurological disease big 3 : CNS TB Cryptococcal meningitis Toxoplasmosis Other infections: Malaria Bacterial meningitis Other bacterial infections Parasite diarrhoea Disseminated TB Respiratory Disease big 3 : Pneumocystis pneumonia Pulmonary TB Bacterial pneumonia
Major causes of mortality Neurological disease big 3 : CNS TB Cryptococcal meningitis Toxoplasmosis Other infections: Malaria Bacterial meningitis Other bacterial infections Parasite diarrhoea Disseminated TB Respiratory Disease big 3 : Pneumocystis pneumonia Pulmonary TB Bacterial pneumonia Non-infectious causes: Hypoglycaemia Renal disease Electrolyte abnormalities Liver disease Drug side effects
Point of Care investigations: available 24/7 Semi quant CD4 LFA TB LAM CRAG CD4 LAM CrAg Hb malaria Glucose Creatinine Syphilis Hepatitis B
Laboratory investigations: rapid turnaround time essential Electrolytes CSF analysis ALT, bilirubin Xpert MTB/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 admission Positive: Start TB treatment immediately
Advanced HIV and seriously ill: high suspicion for TB TB LAM on admission Positive: Start TB treatment immediately Negative: Negative does not exclude TB: Clinical decision to treat Start empiric treatment immediately if high suspicion of TB
Advanced HIV and seriously ill: high suspicion for TB TB LAM on admission Positive: Start TB treatment immediately Negative: Negative does not exclude TB: Clinical decision to treat Start 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 admission Xpert MTB/RIF: Sputum Urine CSF Lymph node aspirate Pleural effusion Ascites Positive: Start TB treatment immediately Negative: Negative does not exclude TB: Clinical decision to treat Start empiric treatment immediately if high suspicion of TB Xpert MTB/RIF: in parallel with TB treatment Negative does not exclude TB
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
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 All: n=139 CD4 < 100: n = 74 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 Xpert had 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 strongly supports the diagnosis Look for and correct reversible metabolic causes
Respiratory Disease: Danger signs empiric treatment RR > 30 / min or SpO2 < 90%: Immediate empiric treatment: Pneumocystis pneumonia Bacterial pneumonia TB
First line ART failure ART > 6 months and new stage 4 disease; urgent switch to second line Current guidelines do not address these patients Turnaround time days (Xpert VL): switch on basis of this VL Turnaround time weeks/months (centralised VL): clinical decision
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.who.org www.samumsf.org www.msf.org.za
Acknowledgements All staff at MSF supported inpatient sites Eric Goemaere and other SAMU colleagues