tb and hiv a deadly combination

TB and HIV

A Deadly Combination

Dr D Rowen. Dept GU/HIV Medicine Royal

South Hants Hospital

TB and HIV

• 14% of all TB cases in adults are attributable to

HIV infection

• Up to 500,000 die each year from HIV

associated TB

• ~80% of co-infections are found in Africa



Diagnosis of TB in the Face of

HIV Infection

• Presentation and radiologic features often

atypical

• More likely to have a normal CXR

• More likely to be smear negative but culture

positive

• Using liquid media cultures often posive within

7-28 days



Clinical Presentation

• Reactivation of latent disease is common

especially with low CD4 counts

• Primary infection may be at different site to

reactivation site

• Reactivation can develop years after primary

infection

• Progression may be rapid



Diagnosis of TB in the Face of

HIV Infection:

• Culture and sensitivity remains Gold Standard

• Liquid based culture systems preferable

• Tuberculin Skin Tests

• Can Identify latent infection

• Sensitivity low in patients with low CD4 counts

• Prior BCG vaccination may give false positive

result



Diagnosis of TB in the Face

of HIV Infection:

• Interferon Tests

• May not perform well at very low CD4 counts but

probably better than Tuberculin Skin Tests

• Detect latent infection

• Not affected by BCG

• Not affected by previous infection with atypical

TB, with exception of M kansasii



Diagnosis of TB in the Face of HIV

Infection:

• Molecular Methods

• Sensitivity and specificity of NAATs highly variable

• Molecular probes for Rifampicin resistance are

useful. 90%+ of isolates that are Rifampicin

resistant are INH resistant



Treatment of TB in Face of

HIV Infection

• 2 Phase Approach

• Initial phase for 2 months

INH, Rifampicin, Pyrazinamide, Ethambutol.

• Continuation Phase for minimum of 4 months

INH and Rifampicin

• If MAI suspected Azithromycin or Clarithromycin

is added to above regimens



Treatment of TB in Face of

HIV Infection • Prolonged Duration of Treatment:

• Continuation phase prolonged in cavitating

disease where patient remains culture positive

at 2/12

• Where Pyrazinamide is not used in Initial phase

• CNS disease

• Optimal duration of treatment in co-infected

patients not defined



Treatment Interruptions

• Common due to poor adherence and side

effects

• Can resume treatment with no added doses if

interruption <14 days in initial phase or <3

months in continuation phase

• Can continue unless ALT or other

transaminase >x3 ULN



Treatment

• Initiation of ART should not be delayed if

possible.

• Better outcome if started early

• Toxicities may prevent early initiation and are

common

• May see worsening of symptoms (IRIS) with

very early initiation



Drug-Drug Interactions

• NNRTIs and PIs metabolized via CYP3A4

• Rifa drugs induce CYP3A4

Rifampicin>Rifabutin

• Absorption and distribution of PIs mediated

through PgP an intestinal drug transporter

• Activity of PgP increased by Rifampicin

• Rifabutin metabolized via CYP A4 but not

Rifampicin



Drug –Drug Interactions

• PIs may inhibit CYP3A4

• Efavfirenz induces CYP3A4

• Interactions are complex



Drug Interactions

• Rifampicin and Nevirapine both relatively

inexpensive therefore use in resource poor

countries is an attractive option

But

• Both hepatotoxic, therefore should not be

used concomitantly



Drug Interactions: Potential

solutions • Rifabutin commonly used in 3 days a week

regimen in combination with PI

• Dose adjustment of Efavirenz when Rifa drug

used

• Aminoglycosides eg Amikacin can be used but

long term toxicity common and monitoring

required



tb and hiv a deadly combination

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