Why is the world's largest IPT programme not even bigger?

As Professor van der Walt said in an interview with me at the South African TB conference, there is a push to get South Africa to provide continuous isoniazid preventive therapy (IPT) to people with HIV without symptoms of TB.

In his plenary talk at the conference, Professor Gavin Churchyard stressed the one silver lining in the Thibela TB study of IPT in the mines: IPT reduced TB by two thirds in people known to have HIV who qualified for it. But it only worked as long as they were taking it. This was in line with the findings from the BOTUSA study comparing six months to 36 months of IPT in people living with HIV. In that study, people started developing TB again shortly after discontinuing treatment (roughly 6 months to a year afterwards).

Notably, final data from that study presented as a late breaker at CROI this year, showed that the same thing happened to the tuberculin skin test positive cases in the 36 month IPT arm: cumulative TB incidence increased by 90% after IPT was discontinued.

The implication seems clear, continuous IPT is indicated for people at risk of active TB in settings with a high burden of HIV and TB.

But if that is so, why was there not a single mention of isoniazid preventive therapy (IPT) in the “Transforming the HIV/TB response: Defining the next 10 years” activist pre-meeting to the 3^rd South African TB Conference held last month in Durban? It suggests that, as TB interventions go, IPT doesn’t rate very highly on the agenda of the South African HIV-TB activists who organised the meeting in South Africa.

South Africa revised its IPT strategy in 2010 closely matching the WHO’s ICF/IPT guidelines. These guidelines emphasise the use of WHO’s 4 TB symptom screening tool to rule out TB in PLHIV every single time a person with HIV had contact with the health system, and recommend 6 or 36 months of IPT for everyone who doesn’t have TB symptoms in settings with a high HIV prevalence (unless there is some contraindication that would make IPT dangerous such as heavy alcohol use) for either 6 months or 36 months (essentially continuously). Of course, South Africa is just such a setting, but this detail wasn’t given much attention at the time. Tuberculin skin testing was no longer required, making implementation much easier. So South Africa moved ahead with rolling out the six-month course

How well it has done is a matter of perspective. South Africa now has the largest IPT programme anywhere in the world, having provided IPT to 124,049 people, according to WHO data for 2011.¹ But that’s out of roughly 5.6 million PLHIV in the country according to 2009 data, of which, a couple of million have had some contact with the country’s HIV care and treatment programmes, and 1.5 million are on ART. Since over 213,006 were people living with HIV were being treated for active TB as well, that would suggest that less than 10% of the people living with HIV who are accessing services received IPT. So why so few? There are clearly opportunities for screening that are being missed, but the data show that the HIV programme screened 758,837 HIV-positive people for TB.

Why did only one in six get IPT? Surely the other five out of six weren’t all alcoholics?

Some of the problem could be the non-specific nature of the symptom screen, which essentially screens out anyone who isn’t feeling well to make sure that they receive diagnosis and treatment for whatever ails them. After that, they should qualify for and be put on IPT according to the guidelines. But it sounds as though they simply get lost to the IPT process.

According to reports from some HIV clinics, at any point in time, half of the people with HIV will screen positive on the TB symptom screen.

But the figures weren’t so high in a study presented at the South African TB conference by US CDC’s Dr Joel Chehab, who presented findings from a cross-sectional study assessing levels of TB/HIV integration in 49 health facilities in 9 provinces in South Africa.²

Out of 2512 people newly diagnosed in February 2011, about 76% received a TB symptom screen. About 8% had TB, for 23% the data were missing or not recorded, which ended the process (these could have been the remaining symptomatic patients who tend to wander into black holes). 70% had no TB symptoms, which is higher than what other clinics have reported, but these arepeople who have just been diagnosed, and tend to be healthier than people attending an ART clinic. But only 46% of the eligible patients started IPT.

In part this was because 29% of the facilities were not providing IPT, though they provided all the other key TB services. Having the 2010 guidelines on hand at the clinic had an impact on whether or not patients received IPT: guidelines were available in 84% of the facilities which offered IPT, but were avialble in only29% of facilities which did not (p= 0.006), suggesting a fundamental lack of information represents a primary barrier for IPT provision.

Dr Chehab also pointed out that in some provinces, IPT provision was very low, due to problems in the health sector in Mpumulanga and Limpopo. Meanwhile the Western Cape Province had not yet accepted the IPT policy (it has since with some caveats described below).

And there are other problems implementing the IPT policy within the health system.

At some sites, healthcare worker perception of IPT also continues to be a barrier to implementation.  One poster described health worker attitudes towards IPT at 8 facilities in and around the city of Potchefstroom in the Northwest Province from April 2009-March 2011. During that period, only about 9% of eligible patients received IPT during the study period. In a survey to find out why, only 41.1% of the nurses had received HIV/AIDS training within 12 months of the survey. Notably, this was the same percentage who said they felt competent initiating IPT treatment. 17% of them felt that IPT initiation was “a waste of time.”

Clearly, there hasn’t been adequate training support for the IPT rollout. Other critical support was lacking, according to another presentation.

“IPT has been implemented without monitoring tools being provided and that created a challenge to follow up clients and to evaluate the outcomes,” said Tumi Mbengo of the University Research Corp (URC). Consequently, the USAID TB Project developed and implemented an IPT follow-up register in some districts supported by URC in October 2010. She presented an analysis of the data recorded in these registers from the 17 health facilities in the Sedibeng district during 2011. Use of the registers led to improved rates of IPT initiation and improved follow-up.  They show that breakthrough TB became much rarer over time, due to improved symptom screening. They also showed dips in IPT initiation due to isoniazid stock outs in the district in the third and forth quarters.

But she stressed that “the most significant finding was the high and stable level of unknown outcomes due either to early treatment interruptions or to weak data recording by the health staff.

“Advocacy at all levels needs to be addressed so as to improve adherence,” she said, including patient and community education about IPT and development of community based mechanisms to track down people who default on IPT treatment.

But getting community buy-in and support may be difficult, given the low interest that many of the leading activists in the country have in the IPT programme as it is currently structured. The reasons are quite clearly illustrated by the following excerpt from the first edition of the NSP Review: Engaging with South Africa’s National Strategic Plan for HIV, STIs and TB, which is being produced by the Treatment Action Campaign and Section 27 to monitor the progress of the country achieving the targets set out in the strategic plan.

“Isoniazid preventative therapy (IPT) is now available in public health facilities for people living with HIV. IPT can reduce a person’s risk of developing active TB. However, concerns were raised that IPT is being implemented in South Africa without the condition that it only be offered to patients who are tuberculin skin test-positive (TST-positive). There is abundant evidence that IPT only benefits such patients. Moreover, it is potentially harmful to give IPT to TST-negative patients. As there are conflicting views on the use of IPT, there needs to be further consultation involving clinicians and people living with HIV on its use and roll-out,” the unnamed author writes.

They are of course right. The data pretty consistently show that only TS- positive people get any significant benefit from IPT, and for them that benefit is profound. IPT doesn’t seem to do much for people without signs of an immune response to TB however.

These data were considered during the ICF/IPT guideline policy setting consultations convened by WHO, which included leading experts and community representatives. Nevertheless, they concluded that the “Tuberculin Skin Test (TST) is not a requirement for initiating IPT for people living with HIV. However, in some settings where it is feasible, it can help to identify those who would most benefit from IPT.”

Their chief concern about requiring TST was that the operational challenges to providing IPT in resource-constrained settings represented a barrier to IPT access. “The challenges include staff training in the administration and accurate reading of the test, the need for the patient to attend the clinic at least twice over 48-72 hours with associated inconvenience and cost. Additionally, there is a limited supply of tuberculin world wide, it is costly to ship and requires an adequate cold chain to ensure test performance.”

A number of studies have shown that large numbers of people don’t come back in to get their TST’s read — but strategies such as doing home visits to read the TST could address that problem. Community-based methods of providing TST have not been adequately considered.  Problems with tuberculin supply and providing cold chain storage may be more intractable.

And yet, now, as leading TB experts are calling for people to be put on continuous IPT, the community may insist that these challenges be dealt with before they endorse such a strategy.

Notably in the Western Cape, the decision to provide IPT to PLHIV has finally been reached — even continuous IPT — however, they will be providing TST for people so that they can know whether IPT will offer them benefit, before they go on it.

References

[1] Uwimana J.  TB/HIV Integration Conference. 3^rd South African TB Conference, Durban, South Africa, 2012.

[2] Chehab JC. Vilakazi-Nhlapo K, Peters A et al. Integration of TB and HIV Services in South Africa, 2011. 3^rd South African TB Conference, Durban, South Africa, 2012

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