Transcript Document

23 July 2013
Clinical Guidance
on Managing Coinfections
Dr Philippa Easterbrook
Outline
• Co-trimoxazole
• Key Co-infections
– Tuberculosis
– Cryptococcus
– Hepatitis B & C
Co-trimoxazole Recommendations (2006)
Planned revision early 2014
AGE
CRITERIA FOR INITIATION
Contraindications: severe sulfa allergy, severe liver
or renal disease and G6PD deficiency
CRITERIA FOR DISCONTINUATION
(Stevens-Johnson syndrome, severe liver
disease, anaemia, pancytopaenia or HIV -ve
status)
Until risk of HIV transmission ends HIV
excluded
HIV-EXPOSED
INFANTS
Universal, starting at 4–6 weeks after birth
<1 YEAR
Universal 1
Until 5 years of age regardless of CD4% or
clinical symptoms OR Never
1–5 YEARS
WHO clinical stages 2, 3 and 4 regardless of CD4 %
OR Any WHO stage and CD4 <25%
OR Universal 1
Never
≥5 YEARS,
INCLUDING
ADULTS
Any WHO stage and CD4 count <350 cells/mm3 2
OR
WHO 3 or 4 irrespective of CD4 level
OR
Universal 1
Never (A-IV) or when CD4 ≥350 cells/mm3
after 6 months of ART 3
OR
CD4 ≥200 cells/mm3 after 6 months of ART
1
Universal regardless of CD4 percentage or clinical stage in settings with high HIV prevalence, high infant
mortality due to infectious diseases and limited health infrastructure.
2 Some countries may choose to adopt a CD4 threshold of <200 cells/mm3.
3 In settings with high prevalence of bacterial infections or malaria.
TB in the 2013 Consolidated Guidelines
• Synthesis of existing recommendations
http://whqlibdoc.who.i
nt/publications/2011/9
789241500708_eng.pdf
http://whqlibdoc.who.i
nt/publications/2009/9
789241598323_eng.pdf
http://whqlibdoc.who.int
/publications/2012/9789
241503006_eng.pdf
The 3 I’s for TB/HIV
18/07/2015
6
TB Screening Algorithm in Adults
Adults and adolescents living with HIV should
be screened for TB with a clinical algorithm;
those who report any one of the symptoms of
current cough, fever, weight loss or night sweats
may have active TB and should be evaluated for
TB and other diseases
(strong recommendation, moderate-quality
evidence).
TB patients with known
positive HIV status and TB
patients living in HIVprevalent settings should
receive at least six months of
rifampicin treatment regimen
(strong recommendation, highquality evidence).
TB Screening in Children
Children living with HIV who have any of the
following symptoms of poor weight gain,
fever or current cough or contact history with
a TB case may have TB and should be
evaluated for TB and other conditions. If the
evaluation shows no TB, children should be
offered isoniazid preventive therapy
regardless of their age
(strong recommendation, low quality
evidence).
Isoniazid Preventive Therapy (IPT)
IPT reduces the incidence of TB in PLHIV
even if they are on ART
Offer IPT to all PLHIV who do not have TB even if they are on ART
Adult and adolescents and children living with HIV should be screened with
a clinical algorithm; those who do not report any one of the symptoms of
current cough, fever, weight loss or night sweats are unlikely to have active
TB and should be offered IPT
(strong recommendation, moderate-quality evidence).
Children and adults living with HIV who are contacts of TB patients should
be screened and evaluated for TB. Those without TB should be offered IPT
(strong recommendation, very low quality of evidence)
Recommendations for investigating contacts of persons with
infectious tuberculosis in low- and middle-income countries
http://www.who.int/iris/bitstream/10665/77741/1/9789241504492_eng.pdf
Diagnosis of TB in PLHIV
Xpert MTB/RIF should be used as the initial diagnostic
test in persons with HIV and suspected MDR-TB
(strong recommendation)
•
http://whqlibdoc.who.int/
publications/2011/978924
1501569_eng.pdf
Sputum smear microscopy has a very low
TB detection rate among PLHIV compared
with sputum culture and Xpert MTB/Rif
Xpert MTB/RIF
• Fully automated molecular test
• Suitable for use outside laboratory
• simultaneously detects TB disease and
rifampicin resistance within 2 hours
• Detects 92% of culture-positive TB
Infection Control
All facilities offering HIV services should implement TB
infection control policies
Administrative
 A triage system to identify TB suspects
 Separate patients with suspected or
confirmed TB
 Cough etiquette/ respiratory hygiene
 Rapid diagnostics with Xpert T
Environmental
 Ventilation (mechanical)
 Ventilation (natural)
 Upper room Ultraviolet Germicidal
Irradiation
Health workers and carers
 Surveillance and information
 Package of care for HIV positive workers
(ART and IPT)
 Protective equipment –( particulate
respirator masks which meet or exceed N95
standards)
 Relocation for HCWLHIV to lower risk area
Personal
 Spend as much time as possible outside
 Cough etiquette
 Sleep alone while smear positive
 Avoid congregate settings and public
transport while smear positive
(Strong recommendations, low / high quality of evidence)
TB Treatment and ART in PLHIV
• ART should be started in all TB patients living with HIV irrespective
of their CD4 counts
(strong recommendation, low quality of evidence)
• Start TB treatment first using a rifampicin containing regimen
• Start ART asap within the first 8 weeks of TB treatment
(strong recommendation, moderate quality of evidence)
• Patients with CD4< 50 cells/mm3 should receive ART immediately
with the first 2 weeks of initiating TB treatment
ART in PLHIV and TB
Adults, adolescents and children over 3 years
Preferred first-line ART regimen
Efavirenz is preferred NNRTI in patients starting ART (TDF + 3TC (or FTC) + EFV )
while on TB treatment
(strong recommendation, high-quality evidence)
Second-line ART regimen
Rifampicin reduces effective concentrations of PIs
If rifabutin available
use standard PI regimens
If rifabutin not available
provide double dose Lopinavir/ritonavir(LPV/r)
(800mg/200mg or 400mg/400mg twice daily)
Children and Infants Initiating TB
Treatment while Receiving ART
Interactions between rifampicin and LPV/r or NVP mean that TBHIV co-treatment
in children under three years is challenging
If on a standard NNRTI-based continue NVP (ensure dose is 200 mg/m2)
regimen (two NRTIs + EFV or
OR
NVP)
Triple NRTI (AZT + 3TC + ABC)
If on standard PI-based
regimen (two NRTIs + LPV/r)
Triple NRTI (AZT + 3TC + ABC)
OR
Substitute NVP for LPV/r (ensure dose is 200 mg/m2)
OR
Continue LPV/r (consider adding RTV to achieve the full
therapeutic dose)
Once TB therapy has been completed, this regimen should be stopped and the
original regimen should be restarted (strong recommendation, moderate-quality
evidence)
Implementation and Operational
Considerations
Provide ART in TB treatment settings
In settings with a high burden of HIV and TB, ART should be initiated for an
individual living with HIV in TB treatment settings, with linkage to ongoing HIV care
and ART
(strong recommendation, very-low-quality evidence)
Diagnose and Treat TB in HIV treatment settings
In settings with a high burden of HIV and TB, TB treatment may be provided for an
individual living with HIV in HIV care settings where TB diagnosis has also been
made
(strong recommendation, very-low-quality evidence)
Implementation considerations
o Collaboration across different programmes
o Implement TB infection control in all HIV and TB care settings
o Ensure continuity of care and linkage to chronic HIV care services
Implementation and Operational
Considerations
Trained non-physician staff can initiate, maintain and dispense ART
Trained non-physician clinicians, midwives and nurses can initiate first-line ART
(strong recommendation, moderate-quality evidence)
Trained non-physician clinicians, midwives and nurses can maintain ART
(strong recommendation, moderate-quality evidence)
Trained and supervised community health workers can dispense ART between regular
clinical visits
(strong recommendation, moderate-quality evidence)
Implementation considerations
o
o
o
Enabling policy/regulatory framework
Quality assurance, health workers ongoing professional education,
mentoring, supportive supervision,
Sustainability
Management of Cryptococcal Infection
• Common cause of adult meningitis
• Case fatality rate remains unacceptably
high at 30 -70%
• Accounts for up to 20% of all HIV-related
deaths, and major contributor to high
early mortality in ART programmes
http://www.who.int/hiv/pub/crypto
coccal_disease2011/en/index.html
Park AIDS 2009; Bicanic, CID 2007 & 2008; Lessells, SAMJ 2011; Kambugu, CID 2008
Prevention of Cryptococcal Meningitis
•
•
Routine serum or plasma CrAg screening (using LA or LFA with use of
pre-emptive fluconazole therapy if CrAg +ve* may be considered in
patients with a CD4 ≤ 100 cells and high prevalence of CrAg +ve (>3%).
(Conditional recommendation, moderate quality of evidence)
Routine fluconazole prophylaxis in all patients with a CD4 count ≤ 100
cells, and CrAg negative or CrAg status unknown is not recommended,
unless prolonged delay in ART initiation likely.
(Strong recommendation, high quality of evidence)
* LP and CSF CrAg to exclude active meningitis in patients with symptoms/signs of
crypto meningitis.
Timing of ART Initiation
•
•
Immediate ART initiation is not recommended in patients with CM due
to high risk of IRIS, which may be life-threatening.
(Conditional recommendation, low quality of evidence)
Defer ART initiation until evidence of a sustained clinical response to
anti-fungal therapy AND after:
Induction regimen
Meningitis
Non-meningeal
Amphotericin
2-4 weeks
2 weeks
Fluconazole
4-6 weeks
4 weeks
(Conditional recommendation, low quality of evidence)
Discontinuation of Anti-fungal
Maintenance
Discontinuation of maintenance treatment based on following
criteria:
• > 1 year stable and adherent to ART and anti-fungal
maintenance, and CD4 ≥200 cells
(Strong recommendation, low quality of evidence)
• > 1 year stable and adherent to ART and anti-fungal
maintenance, and CD4 ≥100 cells if viral load suppressed.
(Conditional recommendation, low quality of evidence)
HIV-Hepatitis B Coinfection
•
•
•
•
•
Liver disease emerged as a leading cause of death in PLHIV and HBV
higher rates of chronicity / less spontaneous HBV clearance
accelerated liver fibrosis progression, cirrhosis and hepatocellular carcinoma
higher liver-related mortality
decreased ARV response
Initiate in all individuals with CD4 ≤500 cells/mm3
AND
regardless of CD4 cell count in presence of severe chronic liver disease*
(strong recommendation, low-quality evidence)
Insufficient evidence to support ART initiation in all HBV infected above 500
*Severe chronic liver disease includes cirrhosis and end-stage liver disease and is categorized into compensated and
decompensated stages. Decompensated cirrhosis is defined by the development of clinically evident complications of
portal hypertension (ascites, variceal haemorrhage and hepatic encephalopathy) or liver insufficiency (jaundice).
HIV-Hepatitis C Coinfection
• Accelerates HCV related
progression of liver fibrosis
• Higher rate of end-stage
liver disease and mortality
Initiating ART should follow the same general principles
as for all PLHIV
WHO hepatitis C management guidelines (for publication end 2013)
will provide guidance on HCV screening, care and treatment
WHO guidance 2013:
HIV–related Skin and oral conditions
in adults and children
•
•
•
•
•
•
•
•
•
•
Kaposis sarcoma
Seborrhoic dermatitis
Molluscum contagiosum
Eosinophilic folliculitis
Papular pruritic eruption
Tinea
Oral candida
Scabies
Varicella
Severe drug reactions