High incidence of TB after ART started, MSF reports

Medecins Sans Frontieres’ treatment programmes in resource-limited countries are seeing high rates of tuberculosis (TB) in people after they begin taking antiretroviral therapy (ART), according to a presentation from the group at last week’s 36^th Union World Conference on Lung Health in Paris.

A diagnosis of TB in a person taking anti-HIV therapy, or just about to start it, makes treatment of both diseases much more complicated. Current guidelines recommend that wherever possible the first two months of TB therapy should be accomplished without antiretroviral therapy, in order to avoid interaction between rifampicin and nevirapine, and in order to reduce the risk of an immune reconstitution syndrome that affects many people with a prior history of TB. As the immune system begins to recover with the aid of antiretroviral therapy, it responds aggressively to mycobacterial fragments, leading to TB-like symptoms such as swollen lymph nodes, fever and pleural effusion. Some deaths have been reported due to the syndrome.

However, a bigger concern is the possibility that ART treatment may begin without diagnosing TB. Diagnosis is more difficult in HIV-positive people because they are more likely to have smear-negative TB or extrapulmonary TB.

A survey of 3151 patients receiving antiretroviral therapy through MSF programmes in Kenya, Malawi, Cameroon, Cambodia and Thailand shows an incidence rate of between 4.8 and 17.6 cases of pulmonary TB per 100 person years of follow-up, with the majority of cases appearing during the first three months of treatment.

Incidence of extrapulmonary TB varied from 12.7 cases per 100 patient years of follow-up in Cambodia to none in Cameroon.

The median follow-up ranged from 3.7 months in Kenya to 11.1 months in Cameroon.

Although patients in Thailand and Cambodia had much more advanced HIV disease (over two-thirds had CD4 cell counts below 50 and around half had WHO stage 4 disease when they began treatment, compared with less than one third in African programmes), the incidence of TB was no greater in these patients. There was also no substantial difference between countries in the time to onset of TB in people beginning antiretroviral therapy, suggesting that local environmental factors are not having a significant influence.

MSF says that the main problem is the lack of a rapid testing that can be used to determine TB infection status before starting people on treatment. Its physicians believe that the vast majority of early TB cases on ART occur in people whose TB was not spotted, either because diagnostic tests failed to pick it up, or because symptoms were not obvious enough.

They say that programmes dependent on nevirapine for HIV treatment and rifampicin for TB treatment need access to more expensive alternative drugs in order to manage this problem, and that as numbers of the treated grow, it will become more problematic. Patients are having to interrupt antiretroviral therapy in order to treat TB successfully, and MSF complains that randomised clinical trial data that would allow confident prescription of nevirapine and rifampicin together are still lacking.