Tuberculosis (TB) was the leading cause of AIDS-related death in a large Brazilian cohort between 1996 and 2005, according to a July 1st article in the International Journal of Tuberculosis and Lung Disease. The findings lend weight to growing calls for better management of tuberculosis and HIV coinfection in developing countries.
Treatment activists and public health professionals are seeking to galvanize a more cohesive global and country-level response to TB/HIV coinfection. Their concern is that even if coinfected people have access to antiretroviral therapy, they may still face a high risk of dying from TB.
About one-third of HIV-positive people globally are thought to be infected with TB, which is caused by the mycobacterium tuberculosis (M.Tb) bacteria. Because of their weakened immune systems, HIV/TB-coinfected people are much more likely their HIV-negative counterparts to develop active TB disease. TB can be easily overlooked in resource-limited settings, and is sometimes not recognised until the disease has reached a dangerously advanced stage. TB is the leading cause of death in HIV-positive people worldwide.
TB actually is a highly curable disease when the right drugs are available and are used appropriately. The low-cost drug isoniazid is the treatment prescribed most widely for latent TB, and a standard six-month course of treatment is known as isoniazid preventive therapy.
More complex regimens are required for active TB. These regimens, while not easy to undergo, are fairly straightforward from a medical standpoint except in cases of multidrug-resistant TB (MDR-TB). Often MDR-TB is much harder to cure, since it requires a longer course of treatment with more toxic medicines.
TB is currently thought to be largely under control in the developed world, but resource constraints have undermined TB prevention and treatment efforts in many developing countries, especially those with high HIV prevalence.
The Brazilian study retrospectively analysed information from standard death records for Rio de Janeiro City. The physicians who completed those records had indicated a primary cause of death in accordance with the International Classification of Diseases.
Between 1996 and 2005, physicians reported 8601 AIDS-related deaths in Rio de Janeiro City. They named TB as the primary cause of death in 9% of those cases, and pneumocystiis jiroveci pneumonia (PCP) in 4.7%. Another 54.3% of cases were attributed to infectious diseases other than TB or PCP.
People who died from TB were more likely to be under age 35 than people who died from other causes (38.7% vs. 32.4%, p < 0.001), and to be non-white (63.7% vs. 46.1%, p < 0.0001). They were also less educated (60.8% vs. 52.7%, schooling less than eight years, p < 0.0001).
The Brazilian government has made potent combination antiretroviral therapy regimens available to all citizens for free since 1997. Antiretroviral therapy is only available through the public sector, and thus the study’s authors were able to obtain information about antiretroviral usage by residents of Rio de Janeiro City from a comprehensive source. They linked the local antiretroviral drug database to their mortality database in order to examine antiretroviral usage in the cohort under investigation.
The analysis showed that 27.3% of people whose deaths were attributed to TB had received antiretroviral therapy (median 18 months), and that 20.1% of those whose deaths were attributed to PCP had done so (median 20 months).
The paper concludes, “The high burden of TB can reduce survival among people living with HIV despite free access to care and [antiretroviral] drugs.” The authors emphasise the need to reduce overall infectious disease-related mortality in HIV-positive people in Rio de Janeiro City, calling for “strategies that lead to earlier diagnosis of HIV in the general population, to wider prescription of those preventive treatments available and to the appropriate timing of starting [antiretroviral therapy].”
CD4 and viral load information was not available for the Rio de Janeiro City cohort, nor was there any means for investigators to assess isoniazid preventive therapy usage in people who later died of TB.
Brazil has national guidelines calling for the prescription of isoniazid preventive therapy to HIV-positive people with latent TB. However, it is not known to what extent the guidelines are followed, and the overall prescription of isoniazid preventive therapy is thought to be low.
Globally, there is increasing recognition of the importance of isoniazid preventive therapy for HIV-positive people. Isoniazid preventive therapy is one of the “Three I’s,” a set of essential activities that the World Health Organization (WHO) says HIV programs should be doing to protect HIV-positive people from tuberculosis. The other two activities are intensified case finding and infection control.
WHO and other stakeholders, including policy makers, programme managers and civil society representatives met in April 2008 to discuss how to address challenges in scaling up implementation of the Three I’s. According to a WHO representative at the meeting, only 82 countries have IPT policies, and those policies do not appear to be widely implemented.
Saraceni V et al. Tuberculosis as primary cause of death among AIDS cases in Rio de Janeiro, Brazil. Int J Tuberc Lung Dis 12: 769 – 772, 2008.