Antiretroviral roll-out results in major TB decline in South African study

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The roll out of antiretroviral treatment to cover 90% of eligible people has resulted in a significant decline in new cases of tuberculosis in a South African township, demonstrating for the first time the potential of antiretroviral treatment to make major inroads into the burden of TB in high prevalence countries.

New TB cases fell by 60% in HIV-positive people in just three years, contributing to a 20% decline in TB cases in the township between 2005 and 2008.

The findings were presented by Dr Keren Middelkoop of the Desmond Tutu HIV Centre at the University of Cape Town as a late breaker at the Fifth International AIDS Society conference in Cape Town.

Glossary

sputum

Material coughed up from the lungs, which can be examined to help with diagnosis and management of respiratory diseases.

sample

Studies aim to give information that will be applicable to a large group of people (e.g. adults with diagnosed HIV in the UK). Because it is impractical to conduct a study with such a large group, only a sub-group (a sample) takes part in a study. This isn’t a problem as long as the characteristics of the sample are similar to those of the wider group (e.g. in terms of age, gender, CD4 count and years since diagnosis).

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

active TB

Active disease caused by Mycobacterium tuberculosis, as evidenced by a confirmatory culture, or, in the absence of culture, suggestive clinical symptoms.

oral

Refers to the mouth, for example a medicine taken by mouth.

The study measured changes in TB prevalence in the population of a single township served by one health centre, in order to capture all cases of TB. The research group conducted cross-sectional studies in 2005 and 2008.

ART coverage in the community expanded from approximately 12% of the HIV-positive population on antiretroviral therapy in 2005 to 24% on treatment by 2007. Ninety per cent of those qualifying for antiretroviral treatment under South African guidelines (a CD4 count below 200 or active TB) were receiving it in the township by 2008.

A random sample of 762 individuals was included in the study in 2005 and 1251 in 2008. They each provided two sputum samples and completed a TB history questionnaire. All the individuals also had an anonymous, oral HIV test, the result of which was linked to their sputum samples.

Results of the anonymous HIV tests showed that 25% of the study participants were HIV-positive.

In 2005, 4% of HIV-positive individuals were receiving TB treatment compared to 1% of HIV-negative individuals. However, in 2008 approximately 1% of both HIV-positive and HIV-negative study participants were taking TB therapy.

Similarly, in 2005 there was a significantly higher prevalence of undiagnosed TB amongst HIV-positive patients than HIV-negative individuals (5.2% vs. 0.5%). In 2008, however, only 3.6% of HIV-positive individuals had undiagnosed TB compared to 1.1% of HIV-negative individuals.

Overall TB prevalence amongst patients with HIV fell from 9.2% in 2005 to 3.6% in 2008.

 

HIV Negative

HIV Positive

 2005 n=584

 2008 n=899

p-value

 2005

n=174

 2008 n=306

  p- value

Current Notified TB

0.7%

0.7%

0.97

4.0%

2.3%

0.24

Previously Undiagnosed TB

0.5%

0.4%

0.84

5.2%

1.3%

0.01

TOTAL

1.2%

1.1%

0.98

9.2%

3.6%

0.02

After adjusting for age, sex and HIV status, there was a significant fall in TB prevalence in 2008 compared to 2005 (p = 0.02). This decrease was driven by a fall in HIV prevalence amongst the patients with HIV, most notably the fall in the prevalence of undiagnosed TB.

When TB notifications were analysed according to antiretroviral treatment status, it became clear that virtually all of the decrease occurred in people receiving ART, in whom the notification rate fell from 8,000 cases per 100,000 to approximately 2,500 cases per 100,000, a reduction of almost 60%. In contrast the TB notification rate remained almost stable at around 6,500 cases per 100,000 in untreated people with HIV.

The investigators ruled out a higher death rate in people with HIV as the reason for the decline, since the decline occurred in people receiving antiretroviral treatment. Nor could the decline be explained by changes in local TB management or emigration out of the district, since neither changed during the study period.

At this point the authors cannot determine whether the effect of antiretroviral therapy on TB prevalence is a function of a lower rate of transmission (due to the lower population burden) or of a reduction in TB reactivation, and they plan further analyses to shed more light on the question.

Further information

A webcast of the conference session in which Keren Middelkoop presented is available on the IAS 2009 website.