Time to scale up IPT in South Africa

Most people who inhale the tuberculosis (TB) bug never get sick with TB because their bodies are able to contain the bug successfully. When the body controls TB infection like this, the infection is referred to as latent TB. In healthy individuals with latent TB the probability of developing active TB disease during their lifetime is only 5-10 percent1. By contrast, in HIV-positive people with latent TB the probability of developing active TB rises dramatically by up to 30 percent because their immune systems are compromised and unable to contain the infection. This risk is likely to be even higher for people with lower CD4 counts.

More than a third of the world population is estimated to be infected with latent TB. In South Africa, although the exact number of people with latent TB is not known because of difficulties in diagnosis, it is believed our burden is the highest in the world. These millions of people with latent infection function as a reservoir for the TB bacterium. Furthermore, TB is the biggest killer of HIV-infected people and accounts for more than a third of the deaths in HIV-positive people. It seems unlikely that we will ever see the end of TB if we do not reduce this high number of latent infections.

Good news
The good news is that latent TB infection can be cured with Isoniazid Preventive Therapy (IPT). Isoniazid is also part of the standard first-line treatment for active TB, but can be used as a single drug (single pill once a day) for the treatment of latent TB. Current guidelines in South Africa indicate that HIV-positive people must receive IPT for periods of 6, 12 or 36 months depending on their CD4 count, ART (antiretroviral therapy) status and TST (Tuberculin Skin Test) status in order to reduce the probability of developing active TB. This recommendation is in line with the current World Health Organisation guidelines for IPT.

While the likely public health benefit from IPT seems significant, it is essential to also consider the best interests of individual patients receiving IPT. In the recently concluded TEMPRANO trial, 27 people out of 1 030 who received IPT became sick with TB – much lower than the 58 people out of 1 021 in the non-IPT group. This builds on evidence from a clinical trial done in Khayelitsha that found a 32 percent reduced chance of active TB developing in HIV-positive patients who took 6 or 12 months of IPT combined with ART, as compared to ART alone. Another study from Botswana reported a 43 percent reduced chance of TB developing and up to 50 percent decrease in death, in patients who were on combined ART and IPT. Epidemiological models suggest that IPT rollout could play a significant part in turning around the TB epidemic, with evidence that it is only by treating both active and latent TB that the goal of eliminating TB could be achieved globally.

It is a concern, however, that despite good guidelines, the number of patients who are initiated onto IPT remains very low in this country. The most up-to-date data we could find from the Department of Health’s IPT Policy Review shows that, as of 2013, South Africa had only just over 300 000 HIV-positive people receiving IPT. One reason why IPT uptake has been low is that IPT used only to be recommended for HIV-positive people who tested positive for latent TB. The test for latent TB (TST) added significant complexity to the management of HIV-positive patients. However, more recent guidelines have removed this barrier by recommending that HIV-positive people should be started on IPT if TST results are not available. In addition, while there were some concerns over the safety and potential side effects of taking IPT, significant evidence has now accumulated to show that IPT is safe for periods up to one year.

While the increased rollout of IPT to HIV-positive people in South Africa must clearly be a priority, it is important to ensure that IPT is not given to people with active TB. Isoniazid alone will not cure active TB and giving IPT to people with active TB will put those people at risk of developing isoniazid resistance and ultimately, drug-resistant TB – in addition to not curing them.

Unanswered questions
Some important unanswered questions remain about IPT. For example, some studies have shown that, especially in high TB prevalence settings, the protective effect of IPT wanes quite quickly in the months after someone stops taking IPT. The latest evidence shows that IPT protection last only for a year at the most. In other words, someone might be protected while on IPT, but may fall ill with TB a few months after they stop taking IPT. To counter this problem, we need trials that assess the safety and efficacy of keeping HIV-positive people on IPT for longer periods – potentially for even longer than 36 months. But unanswered questions and caveats aside, the available evidence suggests that providing IPT to more HIV-positive people right now will save lives. We have good guidelines in place. It is time we insist on implementation.