Daily micronutrients of some benefit for HIV-positive patients receiving TB treatment

A simple micronutrient tablet reduced the rate of tuberculosis relapse in HIV-positive patients, according to a study published in Tanzania and published in the June 1^st edition of the Journal of Infectious Diseases (now online). Use of the micronutrient also reduced the risk of peripheral neuropathy, a condition that can be caused by both HIV infection and key medication used to treat tuberculosis.

None of the patients was taking antiretroviral therapy, and the use of micronutrients did not reduce the risk of death, nor was it associated with an improvement in CD4 cell count or a fall in viral load. However, the investigators did find that micronutrients reduced the risk of both extrapulmonary tuberculosis and genital ulcers in HIV-negative patients.

An editorial accompanying the study called its results “promising” and suggested that micronutrients could be “an important adjuvant therapy for patients with TB.”

Latest figures from the World Health Organization suggest that there were 1.7 million deaths from tuberculosis, and the infection is an important cause of death in patients with HIV in resource-limited countries, despite the availability of effective anti-tuberculosis therapy.

Patients with tuberculosis often have significant nutrient deficiencies, particularly low levels of vitamins A, B complex, C, as well as selenium. These nutrients are key to the health of the immune system and its ability to respond to serious infections like tuberculosis.

But there is contradictory evidence regarding the value of micronutrient therapy for patients receiving tuberculosis treatment. Therefore investigators designed a randomised, placebo controlled study involving 471 HIV-positive and 416 HIV-negative adults in Dar es Salaam, Tanzania, with sputum-positive pulmonary tuberculosis. The study ran between 2000 and 2005.

Patients were randomised to receive either a daily micronutrient tablet containing vitamin B complex, vitamin C, vitamin E, folic acid and selenium at doses of six to eight times the recommended daily allowance, or a placebo. All the patients received tuberculosis therapy consisting of rifampicin, isoniazid, pyrazinamide, and ethambutol by directly observed therapy for two months, and then self-administered isoniazid and ethambutol daily for a further six months.

The study outcomes included treatment failures after one month (defined as a failure to achieve smear-negative tuberculosis), relapse from smear-negative to smear-positive tuberculosis during the rest of treatment, death during two years after the completion of treatment, changes in immune system measures, including CD4 cell count, weight gain, and for, patients with HIV, alterations in viral load.

Over two-thirds (67%) of the patients were male, and the average age for patients with HIV was 34 years, and 30 years for HIV-negative individuals.

Tuberculosis therapy was less likely to fail after one month in HIV-positive patients who received the micronutrient tablet than those who were given the placebo (13% vs.17%; for all patients 15% vs. 21%), but these differences were not statistically significant.

However, amongst HIV-positive patients who responded to tuberculosis therapy, those who received the micronutrients were significantly less likely to experience a relapse and the reemergence of smear-positive tuberculosis during the next seven months of treatment than those who received the placebo (5% vs. 13%, p = 0.02).

Overall there were 155 deaths during the total follow-up period. Most of these deaths (140) were in patients infected with HIV. There was no difference in mortality between patients who received the micronutrient supplement and those treated with the placebo (74 deaths vs. 66 deaths). Nor was there any difference in the risk of progression to another AIDS-defining illness between the micronutrient arm and the placebo arm.

Amongst HIV-positive patients, CD3, CD4, and CD8 cell count and HIV viral load were comparable between those who received the micronutrient and those given the placebo during the eight months of tuberculosis therapy and during the extended follow-up period. But micronutrients were associated with CD8 cell counts (p = 0.02) and CD3 cell counts (p = 0.02) during tuberculosis treatment for HIV-negative patients. This group of patients also had a non-significant increase in CD4 cell count (p = 0.07), during longer follow-up.

Micronutrient supplementation was associated with a 57% reduction in the risk of peripheral neuropathy (41% vs. 69%, p < 0.001), irrespective of a patient’s HIV status. For HIV-negative patients, micronutrients reduced the risk of extrapulmonary tuberculosis (p = 0.01). There was also some evidence that micronutrients might help reduce the risk of infection with HIV for HIV-negative patients, as patients who received them were significantly less likely to be diagnosed with genital ulcers (p = 0.03).

There was no evidence that taking the micronutrient improved body weight or body composition in either HIV-positive or HIV-negative patients.

In their discussion, the investigators highlight their finding that “micronutrient supplements appeared to decrease the risk of early tuberculosis recurrences among HIV-positive patients”, as well as the “significantly decreased… incidence of peripheral neuropathy, regardless of HIV status.”

They note, however, that none of the patients in their study were taking antiretroviral therapy and conclude “the impact of micronutrient supplementation on TB-related outcomes needs to be ascertained among HIV-infected patients receiving antiretroviral therapy.”