Taking antiretroviral drugs at the same time as TB treatment halved the death rate when compared with delaying HIV treatment until after TB treatment was completed, a major South African study has found.
Trial investigators announced on September 17th that they have terminated an arm of the study in which patients waited until they had completed TB treatment before starting antiretroviral therapy, because patients in this arm had a significantly higher risk of death.
The finding could have important implications for how HIV is treated in TB patients, the investigators say.
Up until now, many clinicians have preferred to wait until after the completion of TB therapy before initiating HIV treatment in a patient diagnosed with TB, citing concerns about immune reconstitution, drug interactions and drug toxicity.
The SAPIT study (Starting Antiretroviral therapy at three Points In Tuberculosis therapy) is a randomised open-label trial which recruited 645 adults diagnosed with smear-positive tuberculosis in South Africa. The trial is designed to identify the optimal time to start HIV treatment in TB patients.
Participants were randomised to receive a once-daily antiretroviral regimen of ddI/3TC and efavirenz at one of three time points during their course of TB therapy:
- Early integrated treatment: antiretroviral treatment started as soon as possible after TB treatment (within two months)
- Later integrated treatment: antiretroviral treatment started after the two-month intensive phase of TB treatment is completed, generally in months three or four of TB treatment.
- Sequential treatment: antiretroviral treatment started after TB treatment is completed, generally six to eight months after starting TB treatment.
The trial Safety Monitoring Committee decided to terminate the sequential treatment arm after an interim safety analysis showed that patients in the two integrated treatment arms had a 55% lower death rate than the sequential treatment arm (p = 0.0049). There were no significant differences in characteristics of participants in the two groups.
This analysis covers about 60% of the follow-up time that would be expected to accrue by the end of the trial. Twenty-six patients in the sequential treatment arm died (mortality rate of 11.6 per 100 person years) compared to 24 patients in the combined integrated arms (mortality rate of 5.1 per 100 person-years). This reduction in mortality in the integrated treatment arms was statistically significant both in patients with CD4 counts below 200 and patients with CD4 counts from 200 to 500.
The Safety Monitoring Committee has recommended that all patients in the sequential treatment arm should be counselled to start antiretroviral therapy as soon as possible.
The two integrated treatment arms will continue until 2010 to determine whether there is any difference between the two `integrated treatment` strategies.
In a press release issued this week, the trial’s organiser, the Centre for the AIDS Programme of Research in South Africa (CAPRISA) said: “The SAPIT trial findings provide strong evidence for the integration of TB and AIDS care and treatment. To achieve this, all newly diagnosed TB patients in South Africa need to be offered an HIV test; those who are HIV positive need to be offered a CD4 count and those with a CD4 count below 500 offered ART [antiretroviral treatment] in conjunction to their TB treatment. This public health and clinical care approach to the joint TB and HIV epidemics has the potential to save lives.”
“A rough estimate is that implementation of integrated TB and HIV treatment in South Africa could lead to an additional 100,000 to 150,000 patients (with TB and CD4 < 500) being initiated with ART and thereby prevent about 10,000 deaths each year by the earlier initiation of ART.”
Translating these findings into public health practice could take time, and will require funders such as the President’s Emergency Plan for AIDS Relief and the Global Fund to Fight AIDS, TB and Malaria to start monitoring what proportion of TB patients diagnosed with HIV start to receive antiretroviral therapy while still on TB treatment. It will also require much more thought about how to integrate HIV treatment into TB services (see the HIV & AIDS Treatment in Practice report on this subject from July 2008).