TB Preventive Therapy in HIV Infected Patients

Preventive Therapy for Tuberculosis
in HIV-infected Patients

台大醫院內科部

愛滋病防治中心謝思民醫師

Rationale

the success of prophylaxis for PCP

effective in prevention of TB in pre-HIV era

<Adv Tuberc Res 1970>

serious complications

<AIDS 1997>

drug interaction with HAART

<Clin Infect Dis 1999>

increased mortality

<BMJ 1995>

<Am J Respir Crit Care Med 1995>

Preventive therapy:

	treatment of latent M. tuberculosis infection
	to prevent the development of clinically active TB
	CDC: 12-month INH prophylaxis in

(1) patients with TST > 5mm, or

(2) anergic patients with estimated risk > 10%

<MMWR 1990>

Who? Duration? Frequency? Regimen? Benefit? Applied in everywhere?

6 months or 12 months of daily INH?

In pre-HIV era

(1) 12-month regimen (93%) had better protection than 6-month regimen.

<IUAT trail. Bull WHO 1982>

(2) In Alaska, after 9 months, no additional benefit in decreased TB case rates

<Am Rev Respir Dis 1970>

In studies on HIV-infected patients

(1) no direct comparison

(2) similar reduction in incidence

<Pape et al. Lancet 1993>

<Whalen et al. N Engl J Med 1997>

	More than 6 months of daily INH is needed.
	Therapy for 9 months appears to be sufficient.
	Therapy for >12 months does not appear to provide additional protection.

<MMWR 1998>

Daily or twice-weekly?

	Trials that compare the same drugs administered daily versus intermittent have not conducted.
	70% reduction in incidence by 6-month twice-weekly INH

<Mwinga et al. AIDS 1998>

Twice-weekly INH with directly observed preventive therapy (DOPT) is useful in HIV-infected injecting-drug users.

<Arch Intern Med 1996>

Short-course multi-drug regimens

2-month daily RIF and PZA is similar to 12-month daily INH, but more likely to be completed.

<Gordin et al, Chicago, 1998>

6-month twice-weekly INH is equivalent to 2- or 3-month twice-weekly RIF and PZA.

<Halsey et al. Lancet 1998>

<Mwinga et al. AIDS 1998>

3-month daily INH + RIF, 3-month daily INH + RIF + PZA, 6-month daily INH are similar.

<Whalen et al. N Engl J Med 1997>

TB preventive therapy in HIV-infected patients

Preventive therapy has not been found to be useful in HIV-infected adults with a high risk of latent infection and a negative TST

Anergic

<Whalen et al. N Engl J Med 1997>

<Gordin et al. Chicago, 1998>

TST-negative

	Preventive therapy can reduce the risk of active TB in HIV-infected patients with positive TST.
	No significant effect of risk reduction in TST (-) patients, whether anergy is confirmed or not.
	No significant impact on survival.
	Long-term benefits remain to be unknown.
	The impacts between preventive therapy and drug resistance are also unknown.

Recommendation by CDC

	The recommendations are appropriate for isolates susceptible to INH and rifamycins.
	DOPT should be applied in twice-weekly dosing and 2-month regimens.
	9-month daily or twice-weekly INH, or 2-month daily RIF and PZA can be recommended.
	Rifampin should be replaced by rifabutin if protease inhibitors or NNRTIs are used. (no data)

In Taiwan: Standard of care?

Consider:

Interpretation of TST?

--- Nationwide BCG vaccination
--- High prevalence/incidence of TB
--- Abundant environmental mycobacteria

Efficacy of preventive therapy with INH?

--- High rate of INH resistance in AIDS patients?
--- Further increase the INH resistance rate?

Benefit in survival?

--- No worsened outcome in Taiwan

Adequate candidate?

--- negative TST is very common

More side effects?

--- evaluation for risk / benefit?

Who? How? Benefit? Cost?

　