HIV-positive patients who have tuberculosis (TB) as their first AIDS-defining illness are no more more likely to experience accelerated disease progression than other patients, according to a large multi-centre study published in the June 1st edition of the Journal of Acquired Immune Deficiency Syndromes.
The role of TB on HIV disease progression is controversial. Studies conducted in industrialised and resource limited settings have produced contradictory results, although laboratory studies suggest that active TB increase cytokine production, which enhances HIV replication. The situation is complicated further by recent studies suggesting that increases in HIV viral load precedes the development of TB.
Investigators involved in the CASCADE Study (Concerted Action on Seroconversion to AIDS and Death in Europe) compared HIV disease progression between patients with TB and those without it, taking into account time since HIV seroconversion. Although details of TB therapy were not gathered by the investigators, they assumed that all patients had access to adequate treatment.
The study involved patients from ten cohorts in Europe and Australia for whom approximate dates of HIV seroconversion were known. Patients who had had an AIDS-defining illness were divided into one of five categories. TB; Kaposi's sarcoma (KS); esophageal candidiasis (OC) and the pneumonia PCP; other opportunistic infection; and non-Hodgkin lymphoma (NHL) and invasive cervical carcinoma.
Of the 4,398 patients in the study, 1,294 (29%) developed AIDS. TB was the first AIDS-defining illness in 72 patients (5.6%). The average time from seroconversion to AIDS was a little over ten and a half years, although patients with TB, KS, OC and PCP tended to develop AIDS-defining illnesses sooner than people with other opportunistic infections or cancer.
Average CD4 cell count in patients with TB was 125 cells/mm3 compared to 130 cells/mm3 in patients with KS, 77 cells/mm3 in patients with OC and PCP, 68 cells/mm3 in patients with other opportunistic infections and 228 cells/mm3 for patients with AIDS-defining cancers.
Compared with patients who did not develop AIDS, the risk of death from seroconversion was no higher for patients who developed TB as their first AIDS-defining illness (HR=23.23, 95% CI 14.60-36.96), than those who were diagnosed with KS (HR=23.47, 95% CI 16.66-33.05), PCP or OC (HR 30.97, 95% CI 24.38-39.34) and was significantly lower than those patients who experienced other opportunistic infections (HR=46.83 95% CI 37.86-47.94) and cancers (HR 92.71, 95% CI 60.83-141.3).
This result remained the same even when CD4 cell count was controlled for.
The investigators note “HIV progression was not inherently faster in subjects who developed TB compared with other individuals with AIDS who had been infected with HIV for the same length of time in countries where TB treatment is widely available.”
However, patients with TB had an increased risk of death compared to those who remained AIDS-free, although “this does not necessarily mean that TB or any other” AIDS-defining illness “is the cause of HIV disease progression but [is] rather the consequence of HIV-related immunosupression.”
In settings such as sub-Saharan Africa where healthcare is poor and TB treatment suboptimal, the laboratory findings that TB accelerates HIV progression, could, the investigators suggest, be valid.
They conclude however, “in a setting where TB control is adequate...the onset of TB does not accelerate HIV disease progression when compared with that of other individuals with AIDS who have been infected with HIV for the same length of time.”
Further information on this website
Tuberculosis - overview
Tuberculosis - factsheet
Report on NAM forum on TB - January 2003
CASCADE Collaboration. Impact of tuberculosis on HIV disease progression in persons with well-documented time of HIV seroconversion JAIDS 33: 184 - 190, 2003.