This document discusses the interaction between HIV and tuberculosis (TB). It outlines how the two infections exacerbate each other through interference with immune responses and increased viral replication. Clinical presentation of TB depends on CD4 count and includes pulmonary and extra-pulmonary manifestations. Diagnosis is challenging due to high rates of smear-negative disease in HIV patients. Treatment principles involve combination drug therapy, directly observed treatment, and managing drug interactions with antiretroviral therapy.

1. HIV/TB INTERACTION.
DR.AGABA WILFRED

2. Outline
1. Recap
2. HIV-TB Pathogenesis
3. Immune Aberrations in HIV/TB co-infection
4. Clinical Presentation
5. Diagnosis
6. Treatment

3. Recap

4. HIV TB Pathogenesis. ( Esaki et al,2014)
TB and HIV infection interfere and impact the pathogenesis phenomena of each other.
How does HIV contribute to exacerbation of TB infection?
HIV related dysfunction of immune responses reduces the ability of granuloma to wall off TB
infection leading to dissemination of bacilli hence severe pathology.
There is increased HIV replication within the activated CD4+ T cells at the site of M tuberculosis
infection affecting granuloma integrity.
The functionality of the immune cells is altered in co-infected individuals.

5. HIV TB Pathogenesis
How does tuberculosis exacerbate HIV-1 infection?
Co-infection with TB negatively impacts HIV immune responses and this is demonstrated by
higher incidences of new AIDS defining OIs in HIV/TB coinfected individuals.
HIV uses receptor CXCR4 for disease progression. Mycobacterium tuberculosis creates an
environment accommodating expression of CXCR4 in alveolar macrophages hence increased
progression of HIV.
M.tuberculosis infected macrophages containing LAM produce increased levels of TNF-α, IL-1, IL-
6 leading to enhanced viral replication.

6. Immune Aberrations In HIV/TB Co-
infection.
HIV/TB coinfected macrophages release lower levels of TNF-α, induce less TNF-dependent
apoptosis.
IL-10 is higher in co-infected individuals portraying decreased cell-mediated immunity.
LAM increases IL-12 secretion causing expansion of CD4+Th1 cells.
There is lower IFN-γ and IL-2 production and proliferation by M.tuberculosis specific T cells in
HIV infected individuals.
There is higher Macrophage Inflammatory Protein-1β(MIP-1β) production.
HIV preferentially infects and depletes IL-2 producing CD4+ Tcells and is partially inhibited from
depleting MIP-1β producing CD4+ Tcells.

7. Immune Aberrations Cont…
HIV promotes secretion of indoleamine 2,3 dioxygenase (IDO), a tryptophan catabolizing enzyme
required for T cell suppression.
HIV induces expression of immune activation markers such as CD38,CD70,HLA-DR which weaken
T cell responses

8. Clinical Presentation (Sedhain A et
al,2012)
At CD4 count< 200/mm³.
Most have TB lymph node(36%) then Disseminated TB(19%), PTB(15%), TB pleural effusion(11%) and military
TB(8%) are common.
CXR usually shows mid-zone involvement, military pattern, lower zone involvement, pleural effusion.
CD4 count 201-350/mm³
Most patients have PTB(53%) followed by TB lymphnode (21%). A few may have disseminated TB and TB pleural
effusion.
CXR mostly shows upper zone involvement(59%), then hilar involvement(17%), Tb pleural effusion(17%),
cavitation(7%)
CD4 count> 350/mm³
Pulmonary tuberculosis (60%) followed by disseminated TB and TB pleural effusion.
CXR mostly shows upper zone involvement and pleural effusion (30%)

9. Clinical Picture of TB Associated with HIV
(influenced by degree of immunodeficiency )
Early disease
 Clinical features resemble those seen in HIV negative pts with PTB
 Often sputum smear positive
Progressive disease
 Atypical PTB, E-PTB and disseminated TB become more common
 Often sputum smear negative
FACTORS UNDERLYING FAILURE TO RAPIDLY DX AND EFFECTIVELY TREAT TB
• Rapid progression from infection to active disease in co-infected persons.
• Stigmatization of persons living with HIV/TB hence reluctance to seek medical care.
• Limited health care provision in resource poor countries, poor access to TX.
• Lack of a sensitive, specific, rapid point of care diagnostic test.

10. Diagnosis
Dx of TB in HIV
Protocol for dx of TB follows the same principle irrespective of the pt.'s HIV status
But
The timely Dx of TB in HIV+ persons is more difficult :
 Increased rates of sputum AFB smear negative disease(PTB or E- PTB )
 Increased atypical radiographic manifestations and paucibacillary disease
Evaluation of person suspected of TB disease
1. Medical HX, physical examination
2. Test for TB infection (mantoux tuberculin skin test or TB blood test )
3. Chest Radiograph (CXR or CT scan)
4. Diagnostic Microbiology(acid fast microscopy and culture)
5. Drug resistance test
Other DX tests include Nucleic acid amplification tests (MTD), and Xpert MTB/RIF(PCR) and Urinary lipoarabinomannan (LAM) in rapid dx of active TB

11. Diagnosis cont.
INVESTIGATIONS
1)CXR
Helps with dx when negative sputum smear in a patient who continues to cough despite a full course
of antibiotics
Common CXR findings in TB/HIV
 Cavitation's in the upper lobes
 Focal infiltrates in upper and hilar regions
 Hilar adenopathy
 Pleural or pericardial effusions
 Miliary TB

12. Treatment
Principles of TB treatment
 Use multiple drugs in combination
 Pt’s must be DOT (directly observed treatment) supported
 Use standardised TX regimens
 Cure pt.'s the 1St time round
 Give the correct drugs for the correct period of time(6mths short course)
 No trial of therapy should be given
 NTBCP protocols must be followed.
TB & ARV’s the challenges
1. Complex drug-drug interactions
2. Increased pill burden and compliance
3. Shared toxicity
4. Paradoxical deterioration of TB due to
immune reconstitutions

13. Treatment cont.
Common shared toxicity of HAART
and anti-TB drugs.
Toxicity TB DRUG/S ART
Peripheral
neuropathy
INH
Ethambutol
Stavudine(d4T)
Didanosine(ddI)
Rash RIF,
INH,
PZA
NNRTI’s
Nausea PZA Didanosine(ddI)
Zidovudine(AZT)
Protease inhibitors
Hepatitis RIF,
INH,
PZA
NNRTI’s

14. Treatment cont…
Drug interactions
• Rifampicin is a powerful enzyme inducer
-enhanced metabolism of PI’s (except Ritonavir and Lopinovir)and to
a lesser extent NNRTI’s
• RIF levels are not significantly affected by HAART
• ART drugs can be used concomitantly with RIF

15. Treatment
Successful treatment for drug-sensitive TB generally requires 6 months of therapy.
first 2 months (intensive phase) use of 4 drugs--rifampin (or other rifamycin), INH, pyrazinamide, and
ethambutol
4 months(continuation phase) rifampin and INH alone
Treatment duration is extended to 9 months for patients with cavitary
disease at baseline, those with a positive culture after 2 months of treatment, CNS TB and those who
did not receive pyrazinamide during the first 2 months. Patients with evidence of drug resistance
require a modified regimen and, often, a more-lengthy course of treatment
HIV-infected patients with TB generally respond well to anti-TB therapy (if with RIF & INH)

16. Thank you.