13 December 2012
Risk of TB among HIV-positive people in high-income countries
The widespread availability of potent combination anti-HIV therapy (commonly called ART or HAART) has greatly reduced deaths from many AIDS-related infections in Canada and other high-income countries. ART does this by suppressing the production of HIV, which in turn allows the immune system to begin to repair itself. The beneficial effects of ART are so profound that researchers increasingly expect that a young HIV-positive adult who starts therapy today should have a near-normal life span, provided that they are engaged with their care and treatment and have minimal pre-existing health conditions.
Unfortunately, ART does not cure HIV infection and the restoration of the immune system remains incomplete. Indeed, HIV-positive people, particularly those who are co-infected with cancer-causing viruses—including hepatitis B and C viruses, human papillomavirus and some members of the herpes virus family such as human herpes virus 8 and Epstein-Barr virus—remain at elevated risk for several cancers despite prolonged use of ART. Furthermore, although ART does reduce the risk of illness due to AIDS-related infections, research suggests that HIV-positive people continue to have an elevated risk for developing tuberculosis (TB) compared to healthy HIV-negative people.
Starting ART before the immune system is severely weakened and getting tested for latent infection with TB are important steps to reduce the risk of developing disease caused by TB.
Researchers in Canada, Australia and Western Europe have collaborated by sharing health-related data collected from people whose dates of becoming HIV positive were known. Some of these people later developed TB.
In an analysis of nearly 20,000 participants, the researchers found that the risk for developing TB increased once a person became HIV positive. Moreover, the longer an HIV-positive person remained untreated with ART, the greater the risk for developing TB. Once a person initiated ART, their risk of developing TB decreased gradually.
Researchers pooled health-related data collected over several decades. The study team grouped participants into two time periods, as follows:
Pre-HAART era – 1982 to 1996
- 9,175 participants
- 243 participants developed TB
- CD4+ count at time of TB diagnosis – 125 cells
HAART era – 1996 to 2009
- 11,178 participants
- 120 participants developed TB
- CD4+ count at time of TB diagnosis – 195 cells
The risk of developing TB doubled over the first decade of HIV-infection.
Rates of TB increased in the first two months following initiation of ART, particularly in participants who had less than 50 CD4+ cells. This finding is explored later in our report.
Researchers found that participants whose CD4+ counts were relatively high and whose viral loads were low at the initiation of ART were at significantly reduced risk for developing TB.
According to the researchers, when compared to HIV-positive men who had sex with men, HIV-positive people who injected street drugs were at increased risk for TB once they began to take ART. The reasons for this were not explored in the study but may be due to the following addiction-related issues:
- having a poor diet, which leads to a weakened immune system
- living in crowded or substandard housing
- the negative effect of street drugs on the immune system
- sharing equipment for injecting drugs with people who have TB
The risk of developing TB increases with the duration of untreated HIV infection. Thus, HIV-positive people, particularly those at high risk for TB, would benefit from early initiation of ART and screening for TB.
The researchers suggest that the elevated risk of TB shortly after initiation of ART seen in their study may have arisen for a number of reasons, such as the following:
- incomplete recovery of the immune system
- increased exposure to TB-causing bacteria because of frequent visits to clinics or hospitals
- the possibility that a large proportion of study participants were drug users and/or were recent immigrants from countries where TB is relatively common
A note on HAART
In addition to restoring CD4+ cell counts, the research team notes that by reducing the production of HIV in the body, HAART is able to restore different defence mechanisms that the immune system has against TB. The researchers stress that lowering the amount of HIV produced in the body appears to be very important for controlling latent TB infection.
For the future
To help reduce the burden of TB in high-income countries, the researchers recommend “more stringent diagnosis and treatment of latent TB in early HIV infection.”
Moreover, because the risk of developing TB is greater among HIV-positive people who have not started HAART, the researchers add that “access to [HAART] and implementation of effective TB treatment is essential to reducing the TB risk in high-income countries.”
—Sean R. Hosein
- Raviglione MC, O’Brien RJ. Chapter 165. Tuberculosis. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012.
- Lodi S, Del Amo J, d’Arminio Monforte A, et al. Risk of tuberculosis following HIV seroconversion in high-income countries. Thorax. 2012; in press.
- Caylà JA, García de Olalla P, Galdós-Tangüis H, et al. The influence of intravenous drug use and HIV infection in the transmission of tuberculosis. AIDS. 1996 Jan;10(1):95-100.
- Rodrigo T, Caylà JA, García de Olalla P, et al. Characteristics of tuberculosis patients who generate secondary cases. International Journal of Tuberculosis and Lung Disease. 1997 Aug;1(4):352-7.