Evaluation of ESAT-6 and CFP-10 as markers for response to TB treatment in HIV/TB coinfected patients
Simon Collins, HIV i-Base
Monitoring efficacy of TB treatment is essential for individual patient care and public health reasons, but laboratory facilities are often limited in countries with the highest prevalence.
ESAT-6 and CFP-10 are immunogenic secreted antigens of M. tuberculosis and may provide an easier surrogate marker for treatment response, although data in HIV/TB coinfected populations is limited.
Markova and colleagues from the National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria, measured ESAT-6- and CFP-10-specific IFN-gamma producing T cells using immunospot (T SPOT-TB) and ELISA (QuantiFeron-TB Gold, QFTG) assays, during TB treatment of ten HIV/TB coinfected patients. 
All patients had positive results at diagnosis. After three months treatment, response to ESAT-6 and CFP-10 remained positive in the two patients who either confirmed microbiological isolates or lack of clinical improvement.
A second study, from Seshadni and colleagues from Duke University Medical Center, Durham, USA, looking at ESAT-6 and CFP-10 was much less encouraging, when comparing the same ELISA test (QFGT) in 29 HIV-positive and 54 HIV-negative individuals. 
QFGT produced indeterminate results in 13/28 (46%) and 10/53 (19%) in HIV-positive and HIV-negative patients respectively (p<0.001).
Among patients with smear-positive TB, TST was positive in 7/13 HIV-positive compared to 40/40 HIV-negative individuals (p<0.003), and QFGT was positive in 3/13 (23%) HIV-positive individuals compared to 28/40 (70%) of HIV-negative subjects (p<0.001).
The study concluded that QFGT was less sensitive than TST in detecting patients with smear-positive pulmonary TB among both HIV-positive (p<0.001) and HIV-negative patients (p=0.008) and had a high rate of indeterminate results, as well as a lack of sensitivity, with limited use, unless benefit is clearly demonstrated in coinfection in larger trials.
These studies looked at alternative methods of diagnosing and monitoring TB. Traditionally the diagnosis of TB is based on signs and symptoms suggestive of TB together with appropriate chest x-ray changes and demonstration of mycobacteria in the sputum (smear-positive TB) and positive cultures for TB. In order to get a positive smear, numerous TB organisms need to be present in sputum. TB cultures are often slow and laborious and many labs may not have the appropriate facilities. A TB skin test is often used as an adjunctive to smears and cultures in helping establish a diagnosis of TB in patients with relevant symptoms and x-ray changes.
Over the recent years there has been an increasing interest in looking at blood markers to establish the diagnosis of TB. Two commercially available preparations have been used in the above studies TSPOT-TB and QuantiFeronTB-Gold. Both of these tests essentially detect T-cells in blood that react with antigens specific to mycobacterium tuberculosis.
However, since these tests look at T-cell reactivity and HIV-induced immune suppression affects T-cell function, then as shown by the study from Sheshadni and colleagues, carried out in Tanzania, these tests may not be as sensitive in HIV-positive patients when compared to HIV-negative patients with TB. A recent study in South African children with a high prevalence of HIV these tests performed better than the TST (Liebeschuetz S et al). One of the areas of interest currently is the T-cell reactivity in specific body compartments in the diagnosis of TB, for example sputum or bronco-alveolar lavage in patients with pulmonary TB.
The study by Markowa and colleagues shows that in those with reactive tests, these tests may have a role to play in monitoring the treatment response to TB.
- Markova R et al. Evaluation of ESAT-6 and CFP-10 specific T lymphocytes in coinfected HIV-1 and M. tuberculosis Bulgarian patients during specific anti-tuberculosis therapy. 3rd IAS Conference on HIV Pathogenesis and Treatment, Rio de Janiero, July 2005.Abstract TuPe7.1C02.
- Seshadri et al. Evaluation of an ESAT-6 and CFP-10 based whole blood IFN-gamma assay (QuantiFeron TB Gold) for the diagnosis of Tuberculosis among Tanzanian patients coinfected with HIV. 3rd IAS Conference on HIV Pathogenesis and Treatment, Rio de Janiero, July 2005.Abstract TuPe1C09.