Risk factors for immune reaction to HAART in TB patients studied by French

An increase in CD4 percentage and in the ratio of CD4 to CD8 cells after commencing antiretroviral therapy are associated with the development of immune reconstitution inflammatory syndrome in HIV-positive patients who initiate HAART shortly after starting anti-tuberculosis therapy, according to a French study published in the December 1^st issue of Clinical Infectious Diseases.

It is well known that starting HAART shortly after commencing anti-tuberculosis treatment can cause an immune reconstitution inflammatory syndrome. However, the factors associated with the development of the syndrome in HIV-positive tuberculosis patients are not known.

Accordingly, French investigators conducted a retrospective review of the medical records of 37 HIV-positive patients with tuberculosis who started HAART within six months of commencing tuberculosis treatment between 1996 and 2001.

Patients had a median age of 35 years, 81% were men, heterosexual sex was the main HIV-risk activity (68%), and 41% were migrants from sub-Saharan Africa. At the time of their tuberculosis diagnosis, 74% of individuals were unaware that they were HIV-positive, and 14% of patients had had a previous AIDS-defining illness.

Tuberculosis was disseminated in 29 (78%) patients, with the median number of organs involved being three. At the time when anti-tuberculosis treatment was started, the patients had a median CD4 cell count of 100 cells/mm³ and median viral load was a little under 400,000 copies/ml.

HAART was initiated a median of 30 days after the commencement of tuberculosis therapy. In total 16 (43%) patients had an immune reconstitution reaction, the syndrome developing within a median of 48 days of starting tuberculosis treatment and twelve days after starting HAART.

In univariate analysis, individuals developing immune reconstitution syndrome were significantly more likely to have disseminated tuberculosis (p = 0.01), and have a higher HIV viral load (p = 0.03) when their tuberculosis was first diagnosed. After a month of HAART, patients developing an immune reconstitution syndrome were significantly more likely to have had a higher increase in their CD4 cell percentage (p = 0.04), and a higher increase in their ratio of CD4 to CD8 cells (p < 0.001). In multivariate analysis, which adjusted for baseline CD4 cell count, both an increase in CD4 cell percentage and the ratio of CD4 to CD8 cells after starting HAART remained significantly associated with immune reconstitution syndrome. Disseminated tuberculosis at baseline and viral load ceased to be significant.

“These results have implications for a better understanding of immune reconstitution inflammatory syndrome” write the investigators, adding, “the recognition of these markers can improve the accuracy of the diagnosis of immune reconstitution inflammatory syndrome.”