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TB and HIV: A Deadly Combinaton

March 26, 2014
Researchers are finding a better way to screen for TB in HIV-infected patients

“Tuberculosis is a major HIV co-infection that, frankly kills many of our patients,” says Maj. Julie Ake, M.D., Associate Director for Vaccine Research and African Cohort Study Protocol Chair. “The TB and HIV epidemics together are really a perfect storm for causing morbidity and mortality in individuals who are affected by HIV. Historically, limitations in TB diagnostics have been challenging in terms of identifying cases within our HIV populations.” 
According to UNAIDS, tuberculosis remains the leading cause of death among people living with HIV. In 2012, people living with HIV accounted for 1.1 million (13%) of the estimated 8.7 million people globally who developed tuberculosis and Africa is home to 75% of all people living with tuberculosis and HIV. 
In 2013 MHRP began a study called the African Cohort Study (AFRICOS). This study in sub-Saharan Africa is examining current national treatment regimens and long-term outcomes such as time to progression to AIDS and mortality at its research sites in Kenya, Nigeria, Tanzania and Uganda. Researchers are collecting information about co-morbidities and using diagnostic techniques that are more rigorous than many cohort or other observational studies in Africa have employed. 
A critical component of the study is the collection of data regarding co-infections such as malaria and tuberculosis. TB/HIV co-infection rates are especially high in Kenya and Tanzania, two countries where MHRP conducts research with local partners, and both countries are among the 22 designated high burden countries for TB and high HIV burden countries.  
According to Ake, one of the strengths of AFRICOS is that researchers prospectively screen participants for co-morbidities and co-infections—including TB—over time regardless of symptoms. With TB, says Ake, as many as one-third of individuals with active TB who are co-infected with HIV may not have classic symptoms of TB and would fail a symptomatic screen. However, if they were to be tested for pulmonary TB, would actually have a positive culture showing they had active TB. 
In the AFRICOS study researchers are collecting sputum samples on at least an annual basis from all HIV-infected study participants. However, TB can be difficult to diagnose in the context of HIV as typical tools are insensitive. To overcome this, researchers are making use of the GeneXpert® platform that is being rolled out for TB diagnosis in resource-limited settings. It is a rapid nucleic acid amplification technology that can detect TB in hours instead of weeks with far greater accuracy than smear microscopy. “I think this will be important programmatically, and will provide additional data that does not exist in the setting where we’re working,” noted Ake.
With Non-HIV infected participants, researchers use basic questions on symptoms such as cough, weight loss, fever and night sweats to screen for potential TB, then follow-up with diagnostic tests including chest x-rays and culture. Because these screening questions don’t work as well with HIV-infected patients, researchers hope to develop a better algorithm for how and when to use the GeneXpert® technology. After screening all HIV-infected participants using GeneXpert®, researchers hope to then use that data, compared with symptom and clinical data, to better understand how to better identify TB suspects and how and when to use GeneXpert® in the context of limited resources. 
AFRICOS has already enrolled more than 550 people and is slated to follow participants for 15 years. The study is funded by the U.S. President’s Emergency Plan for AIDS Relief and MHRP.