1. Clinical Guidance on Managing Co-infections
23 July 2013
Clinical Guidance on Managing Co-infections
Dr Philippa Easterbrook

2. Outline
Co-trimoxazole
Key Co-infections
Tuberculosis
Cryptococcus
Hepatitis B & C

3. Co-trimoxazole Recommendations (2006) Planned revision early 2014
AGE
CRITERIA FOR INITIATION
Contraindications: severe sulfa allergy, severe liver or renal disease and G6PD deficiency
HIV-EXPOSED INFANTS
Universal, starting at 4–6 weeks after birth
<1 YEAR
Universal 1
1–5 YEARS
WHO clinical stages 2, 3 and 4 regardless of CD4 %
OR Any WHO stage and CD4 <25%
OR Universal 1
≥5 YEARS, INCLUDING ADULTS
Any WHO stage and CD4 count <350 cells/mm3 2 OR
WHO 3 or 4 irrespective of CD4 level
CRITERIA FOR DISCONTINUATION
(Stevens-Johnson syndrome, severe liver disease, anaemia, pancytopaenia or HIV -ve status)
Until risk of HIV transmission ends HIV excluded
Until 5 years of age regardless of CD4% or clinical symptoms OR Never
Never
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.

4. TB in the 2013 Consolidated Guidelines
Synthesis of existing recommendations

5. The 3 I’s for TB/HIV
12/11/2018

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 HIV-prevalent settings should receive at least six months of rifampicin treatment regimen
(strong recommendation, high-quality evidence).

7. 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).

8. 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

9. 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)
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

10. 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
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
Environmental
Ventilation (mechanical)
Ventilation (natural)
Upper room Ultraviolet Germicidal Irradiation
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)

11. 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

12. 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)

13. 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 regimen (two NRTIs + EFV or NVP)
continue NVP (ensure dose is 200 mg/m2) OR
Triple NRTI (AZT + 3TC + ABC)
If on standard PI-based regimen (two NRTIs + LPV/r)
Substitute NVP for LPV/r (ensure dose is 200 mg/m2)
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)

14. 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
Implementation considerations
Collaboration across different programmes
Implement TB infection control in all HIV and TB care settings
Ensure continuity of care and linkage to chronic HIV care services

15. 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
Implementation considerations
Enabling policy/regulatory framework
Quality assurance, health workers ongoing professional education,
mentoring, supportive supervision,
Sustainability

16. Management of Cryptococcal Infection
Common cause of adult meningitis
Case fatality rate remains unacceptably high at %
Accounts for up to 20% of all HIV-related deaths, and major contributor to high early mortality in ART programmes
Park AIDS 2009; Bicanic, CID 2007 & 2008; Lessells, SAMJ 2011; Kambugu, CID 2008

17. 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.

18. 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)

19. 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)

20. 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).

21. 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

22. 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