People living with HIV who have a history of
active tuberculosis (TB) have a significant risk of the recurrence of the
disease, investigators report in the online edition of Clinical Infectious Diseases.
The risk of developing active TB was
three times higher for individuals with previous active TB compared to people
with no history of active disease.
“We found that the hazard of future
tuberculosis was increased 3-fold among those with a history of prior active
tuberculosis,” write the authors. “This enhanced hazard of future tuberculosis
among subjects with prior tuberculosis was robust and consistent across
multivariable analyses adjusted for several key clinical factors.”
The authors believe their findings have
important and immediate clinical implications and suggest that TB prevention
measures for people with HIV should be targeted at those with a previous
history of active disease.
TB is the single most important cause of
serious illness and death in people living with HIV worldwide. It has long been
known that HIV-negative people with a prior history of active TB have a high
risk of experiencing recurrence of active disease.
However, it was unclear if this is also the
case in people with HIV.
The DarDar TB vaccine trial provided an
opportunity to explore this question. Conducted in Tanzania, the seven-year
placebo-controlled trial examined the efficacy of a TB booster vaccine in
adults living with HIV.
A total of 979 people were recruited to
the trial and 8% had a history of previous active TB. All had a CD4 cell count
above 200 cells/mm2 and a BCG vaccine scar. People with a reactive
tuberculin skin test were provided with a course of isoniazid preventive
therapy lasting six months.
Study participants were checked at regular intervals
during follow-up for active TB disease. All cases were evaluated by a panel of
three doctors who designated participants as having either definite or probable TB.
Baseline characteristics did not differ
significantly between people with and without a history of active TB.
During follow-up, 9% of participants were
diagnosed with definite or probable TB, of whom 5% were classified as definite TB (two positive sputum cultures or smears, or one positive sputum culture of >10 CFU or one positive blood or other non-sputum culture).
Participants who developed active TB had lower
CD4 cell counts (p < 0.001), higher viral load (p = 0.001), were less likely
to be taking antiretroviral therapy (0% vs 4%, p < 0.001), and were more
likely to have a history of active TB (p < 0.001) than individuals who did
not develop TB.
Definite TB was diagnosed in 14% of
people with previous active TB (4.57 cases per 100 person years), compared
with 5% of people without prior active TB (1.43 cases per 100 person years).
Definite or probable TB was diagnosed in 21% of those with a previous history of active
disease (7.42 cases per 100 person years). This compared to 8% of people with
no history of active TB (2.14 cases per 100 person years).
The investigators adjusted their findings
to take into account factors associated with an increased risk of TB, such as
CD4 cell count, age and treatment with isoniazid preventive therapy. People
with a previous history of active TB had a more than three-fold increase in
their risk of being diagnosed with definite active TB (HR = 3.69; 95% CI,
1.79-7.63, p < 0.001). The risk of definite or probable disease was also
increased significantly (HR = 2.78; 95% CI, 1.58-4.87, p < 0.001).
“Among immunocompromised patients living
where tuberculosis is highly endemic, failure to contain tuberculosis infection
once is associated with substantial risk of future active tuberculosis
disease,” comment the investigators. “We recommend that both isoniazid
preventative therapy and ART be provided to HIV-infected adults on the basis of
a clinical history of active tuberculosis.”