Timing of ART initiation during TB treatment may not have significant impact on risk of death

This article is more than 12 years old. Click here for more recent articles on this topic

There was no significant difference in the risk of death if antiretroviral (ARV) treatment was initiated within two months of beginning TB treatment or more after two months after beginning TB treatment, according to results of a South African cohort study presented earlier this month at the South African TB Conference in Durban.

Nor was there any difference in rates of toxicity-related treatment modifications, loss to follow up, hepatic toxicity, or poor immunologic and virologic response.

However baseline CD4 cell count, body mass index (BMI) and haemoglobin level at the time of ARV initiation were the significant risk factors for mortality regardless of the time period of ARV initiation.


inter-quartile range

The spread of values, from the smallest to the largest. The inter-quartile range (IQR) only includes the middle 50% of values and measures the degree of spread of the most common values.

body mass index (BMI)

Body mass index, or BMI, is a measure of body size. It combines a person's weight with their height. The BMI gives an idea of whether a person has the correct weight for their height. Below 18.5 is considered underweight; between 18.5 and 25 is normal; between 25 and 30 is overweight; and over 30 is obese. Many BMI calculators can be found on the internet.

loss to follow up

In a research study, participants who drop out before the end of the study. In routine clinical care, patients who do not attend medical appointments and who cannot be contacted.

haemoglobin (HB)

Red-coloured, oxygen-carrying chemical in red blood cells.



The prospective cohort study examined and compared clinical outcomes occurring within different groups of HIV/TB co-infected patients initiating ART after different durations of TB treatment, and was presented by Dr Simbarashe Takuva of the Clinical Research Unit at the University of Witwatersand

An ongoing randomised clinical trial, SAPIT, is examining whether there is any difference in outcomes according to whether antiretroviral treatment is initiated quickly after starting TB treatment – within two weeks – or delayed for two months in order to overcome potential problems of drug toxicity, drug interactions and immune reconstitution inflammatory syndrome (IRIS).

One arm of the SAPIT study, in which patients were randomised to receive antiretroviral treatment after they had completed their course of TB treatment, was halted after an interim analysis showed that patients in this arm were more likely to die than those who started ART during their course of TB treatment.

This prospective cohort provides an interim indication that the condition of the patient in the early weeks of TB treatment is probably more important than the interval between starting TB treatment and starting ART in predicting the likely outcome for the patient.

A total of 1612 ARV-naïve patients receiving TB treatment were included in the study from the Themba Lethu Clinic, the outpatient ARV clinic of Helen Joseph Hospital in Johannesburg where over 15,000 patients have been initiated on ART to date. Patients were followed for 12 months after ARV initiation, with the primary outcome examined being all-cause mortality.

A total of 165 (10.2%) of the patients died, 84 (50.9%) of which were in the group who initiated ARVs within two months of starting TB treatment and 81 (49.1) in the group who initiated ARVs at least two months after TB treatment initiation. No statistically significant difference was found between the mortality rates of the two groups.

The median time to ARV initiation after beginning TB treatment was 60 days (IQR 32 – 98 days). For those who began ARVs less than 2 months after TB treatment, the median time was 32 days (IQR 21 – 47 days) whereas for those who began ART after 2 months, the median was 98 days (IQR 75 – 131 days).

The median time on concurrent treatment was 135 days (IQR 85 to 190 days). No patients in this study cohort deferred ARVs until after completing TB treatment; indeed this was one of the exclusion criteria, as the recent SAPIT trial by Dr Abdool Karim showed a lower mortality in those that initiated ARVs during TB treatment compared with ARV initiation after completing TB treatment.

According to the multivariate analysis for mortality, patients with a baseline CD4 count of less than 100 cells/mm3 were 3.16 times more likely to die compared to those with a CD 4 count above 100 cells/mm3 (p=0.002).

Those with a haemoglobin level of less than 10 g/dl at baseline were also found to be 2.52 times as likely to die in comparison to those with higher haemoglobin levels (p<0.001).

Patients with a BMI of less than 18.5 kg/m were twice as likely to die than those with a higher BMI (p=0.002).

184 (6.7%) of the patients were lost to follow up, of whom 98 (53.3%) were in the early ARV initiation group and 86 (46.7%) were in the delayed ARV-initiation groups. There was no significant difference between the two groups’ loss to follow up.

Failure to achieve maximal viral suppression at six months was found in 108 (6.7%) of patients, with 49 (45.4%) in the early ARV initiation group and 59 (54.6%) in the delayed ARV-initiation group. Again, no significant differences between the two groups were found.

Poor immune response at six months (CD4 response less than 50 cells/mm3 from baseline CD4) was found in 622 patients, 277 (44.5%) from the early ARV initiation group and 345 (55.5%) from the delayed-initiation group.

Progression to AIDS, according to WHO criteria, within the first 12 months of ARV initiation was found in 84 (5.2%) of all patients, with 38 (45.2%) in the early initiation group and 46 (54.8%) in the delayed-initiation group, for which the difference was not found to be significant.

The results support recent recommendations for ART initiation in patients with TB while still taking TB treatment, say the authors.


Tavuka S. Survival experiences in South African cohort on TB treatment according to time of HAART initiation. 2nd South African TB Conference, Durban, 1-4 June 2010, abstract no. 154

Karim A et al. Starting ARV therapy at three points in TB therapy. N Engl J Med 2010; 362:697-706