This document summarizes guidelines for treating HIV-TB coinfection. It notes that India accounts for 10% of the global HIV-TB burden. HIV increases the risk of active TB through depletion of immune cells and reactivation of latent TB. ART reduces this risk but drug interactions with TB treatment can cause toxicity. A key approach is the "3 I's": intensified case finding for TB, isoniazid preventive therapy (IPT) for latent TB, and airborne infection control. IPT for 6 months is recommended to prevent progression to active TB in HIV-positive individuals with no signs of active disease. Managing drug interactions and immune reconstitution inflammatory syndrome (IRIS) is also discussed.

2. Sources

RNTCP guidelines Sep 2016

3. Index

The burden of HIV TB

Interactions between TB & HIV

Treatment of TB & HIV in HIV-TB

Impact of ART
− Drug interactions & toxicity
− IRIS

3 ‘I’s approach

4. The burden of HIV - TB

2.1 million PLHIV in
India

10% global burden of
HIV+TB

0.27% prevalence in
population

6-8% prevalence :
PLHIV visiting ART
centre

Incidence relatively
high despite ART

5% of TB : HIV + : >1
lakh/year

TB : 25% deaths in
PLHIV

5. HIV : Effects on TB

Risk increases after seroconversion : 2x within
the first year (rapid depletion of TB-specific T
helper cells) & increases with time.

Latent to active TB : 12-20 x

Risk of new TB : 5-10% / year : 8x risk

Rapid progression : outbreaks of MDR,XDR

Recurrence after successful treatment : Usually
exogenous re infection

6. HIV : Effects on TB

Atypical presentation

Extra pulmonary : 4x

Smear negative

Normal CXR 20%

Lower lobe
involvement

8. TB : Effect on HIV

Increases risk of progression to AIDS or death

TB infection : significantly increased plasma
HIV viremia

Generalized immune activation due to TB :
increased CD4 : targets for HIV

Increased expression of HIV coreceptors CCR5
& CXCR4 in TB-HIV

9. Rx of TB in HIV -TB

Cat,Rx, followup & testing as for HIV neg

Check for DST before initiation

Drug sensitive TB & second line ART
− Rifabutin 300mg x 3/7 or 150mg OD
− Rifampicin suppresses bio availability of Ritonavir
boosted Atazanavir/Lopinavir/Darunavir

ART 2w-8w +

CPT to prevent OI

10. Rx of HIV in HIV-TB

First line : TLE as per NACP

Second line :
− T/L/Pi
− Z/L/Pi
− St/L/Pi
− Ab/L/Pi

11. Impact of ART

Reduces the risk of developing TB

Relative risk remains high

Reduces mortality & morbidity

12. Impact of ART

Drug interactions

Shared toxicity

High pill burden

Paradoxical IRIS

13. Drug interactions & toxicity

Rifampicin decreases [Efavirenz] concn : Use
600mg/day ( 800mg in >50kg)

OCP decrease [Efavirenz],[Rifampicin]

Hepatotoxicity of both
− INH,RIF,PZA,MOX,PAS
− NVP ( Fatal hepatic necrosis), PI

14. TB associated IRIS

Paradoxical worsening after ART

Biphasic : 3-6 m CD4 memory, exp of naive
CD4 from thymus, total CD8 initially inc,
memory CD8 later declines

Inc markers of immune activation, pathogen sp
delayed hypersensitivity, almost 3x inducible
lymphocyte proliferation ( Ifn y, TNF a, CRP, IL-
2,6 & 7)

15. TB associated IRIS

33% HIV/TB

5d – 3m on ART especially CD4<50/uL

Fever, worsening of LN/resp disease,stridor

Self limited usually

16. Criteria & treatment

Criteria
− Low CD4 (<100) exception TB
− + virological & immunological response
− R/O DR infection, bacterial super infection, allergy,
non compliance, reduced drug levels, abacavir
hypersensitivity
− Temporal association
− Inflammatory response

Predn (1.0 mg/kg, max 80mg/d) or dexa 8-16
mg/d divided in twice daily doses; tapered/1-2m
adjunct to AKT & CART

17. Single Window approach & 3 ‘I’s

Intensified TB case finding

Isoniazid Preventive Therapy

Airborne Infection Control

18. Intensified case finding
Adult :
1)Current cough
2)Fever
3)Weight loss
4)Night sweats
Children :
1)Current cough
2)Fever
3)Lack of weight gain
4)Contact with a TB
case4-S screening
(a) 85% sens
(b) 98% NPV
(c) Meta analysis of 12 studies & 8,148 PLHIV

19. Approach to presumptive TB

Priority CBNAAT ( 84% sens comp to 53%
smear)

Daily FDCs ( switch to daily if prev. on 3/w)
− 2HRZE + 4HRE
− 2HRZES + IHRZE + 5HRE ( previously treated)

20. LTBI

Infection without signs/ symptoms/
radiographic/bacteriological evidence

Endemic : TST / IgRA

6m INH/ 9m INH/ 3m Rifp + hi dose INH / week
are equivalent

IPT 6m recommended

21. IPT

Indications
1) 4S neg
2)LTBI in adult & children ( +TST unnecessary)
3)Children post Rx
4)Previously / Recently Rx TB

With ART : safe

Pregnancy & lactation : safe

22. IPT

CI
− Active TB/hepatitis
− PN
− Poor adherence to Septran preventive therapy
− Contact with MDR TB
− Completed DRTB therapy

23. IPT

Dose
− Adult H 300 + B6 50mg
− Children > 12m : H 10/kg + B6 25mg

Duration : 6m

Less chance of H res in LTBI

24. IPT Spl Sit

Children born to Micr.
+ TB : IPT if active TB

TB during IPT : DST
& if S
− Cat I ( if IPT < 1m &
Rx naive), else II

IPT LFU/toxicity :
restart if gap <3m;
else don’t

25. Thank you