ARV and TB drugs taken together halve deaths

Combining antiretroviral (ARV) therapy with treatment for tuberculosis (TB) could more than halve the current mortality rate among patients co-infected with HIV and TB, saving an estimated 10,000 lives a year in South Africa.

These are the findings of a clinical trial by the Centre for the AIDS Programme of Research in South Africa (CAPRISA) in Durban, which compared mortality rates in three groups of co-infected patients who began ARV treatment at different stages of their TB therapy.

One group started taking ARVs in the first two months of TB treatment; a second group started taking them soon after completing their first two months on TB drugs; and a third group of patients did not begin ARV treatment until they had completed their six- to eight-month course of TB medication.

This third arm of the trial reflects the current practice in South Africa, which is based on the theory that taking ARV and TB drugs simultaneously can result in harmful interactions and reduce the effectiveness of both types of medications.

It is a theory that has never before been clinically tested. A recommendation by the World Health Organisation (WHO) that only patients with a CD4 count (which measures the strength of the immune system) below 50 should take TB and ARV treatment together, is based on doctors' observations.

A safety monitoring committee recommended closing down the third arm of the CAPRISA trial earlier this month, after the death rate in that group was found to be 55 percent higher than in the two groups on integrated ARV and TB treatment.

The study found that even patients with CD4 counts of between 200 and 500 were more likely to die if ARV treatment was delayed until they had finished their TB therapy. The American Association for Clinical Chemistry puts the normal CD4 count in adults from 500 to 1,500 cells per cubic millimetre of blood.

We should urgently evaluate our practice

Reacting to the findings, Dr Francois Venter, head of the Southern African HIV Clinicians Society noted that few clinicians would be surprised by the results for patients with CD4 counts below 200.

"However, the striking mortality difference above 200 will force us to re-look at the way we treat these patients, which has traditionally been to complete the full TB course before starting antiretrovirals," he said. "Using this approach means that many patients will die, and we should urgently evaluate our practice."

According to the WHO, up to 30 percent of co-infected patients in sub-Saharan Africa die before finishing their TB treatment; in South Africa, more than 60 percent of patients with TB also have HIV.

Results from the two remaining arms of the trial regarding the optimal time to start integrating ARV treatment with TB treatment are not expected until 2010. In the meantime, trial researchers said the findings "provide strong evidence for the integration of TB and AIDS care and treatment".

In a statement released this week, they recommended that all newly diagnosed TB patients be offered an HIV test, and that those who test positive and have CD4 counts below 500 be given ARV treatment in addition to TB treatment. In South Africa only patients with a CD4 count below 200 qualify for ARV treatment.

HIV specialists have urged the health department to revise its treatment guidelines in response to evidence that patients who start ARV treatment earlier respond better to treatment and are less likely to develop AIDS-related illnesses like TB, but the department has yet to do so.

Venter noted that the CAPRISA study answered one of the most important questions in the field of HIV. "We need to act on this data quickly," he said.

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