Isoniazid preventive therapy (IPT) has been recommended as part of the routine package of care for people living with HIV since 1998 . Despite substantial evidence that IPT reduces incidence of tuberculosis (TB) in HIV-infected individuals [2,3], implementation has been limited. In 2007, only 0.1% of people living with HIV worldwide had been started on IPT . Few studies have addressed why this policy has failed to become practice.
The study setting was the Aurum Institute, a not-for-profit donor funded organization in South Africa. Aurum delivers an HIV care programme providing antiretroviral therapy (ART) and prophylaxis, including IPT free of charge to those with limited financial resources. It is implemented by local private healthcare providers, but Aurum is responsible for treatment guidelines and staff training, along with pharmacy and data management systems.
Aurum provides all clinic staff with written HIV care guidelines, which recommend IPT for all patients unless contraindicated; regular free topic-specific training, including HIV/TB management; 6-monthly refresher workshops, featuring interactive sessions and debate, which always include IPT and which are well attended; and regular performance reports that include IPT coverage. Despite this, implementation remains poor at most sites.
Our study aim was to describe the barriers to IPT delivery and uptake from provider and user perspectives. Objectives were to determine operational barriers to IPT delivery, and to evaluate attitudes of clinic staff and patients to IPT.
We conducted a qualitative study using in-depth interviews with clinic staff and patients, and a focus group discussion. Interviews were conducted at a purposive sample of 10 clinics, selected based on accessibility and likely willingness to participate. Aurum's database was used to identify five clinics defined as ‘routine’ and ‘low’ IPT implementers (defined arbitrarily as above or below 5% of HIV-positive patients taking IPT, respectively, as a way of including IPT prescribers and nonprescribers in interviews). At each site, fieldworkers aimed to interview all doctors, professional nurses and lay counsellors. Patients attending for ART programme appointments were selected by key clinic workers based on likely willingness to participate. Interviews were tape-recorded, unless consent for recording was refused, in which case detailed notes were taken. The focus group discussion was carried out during an HIV training workshop organized by Aurum.
Thematic analysis of transcripts was conducted by coding the data line by line. Themes focusing on reasons for low IPT prescription and methods of improvement were analysed in greater depth.
The study was approved by the Research Ethics Committees of the University of Witwatersrand, Johannesburg and the London School of Hygiene and Tropical Medicine. All participants gave written informed consent.
Interviews were conducted with 42 participants (Table 1). Among 22 staff and 20 patients invited to participate, there were no refusals to participate. The focus group discussion included nine doctors and two nurses. There being no thematic differences between staff from routine and low IPT use clinics, data were combined for analysis.
Staff prescribed IPT according to inconsistent criteria and only one site was prescribing according to Aurum guidelines. Two sites were using IPT in patients with CD4 cell count less than 200 and one site thought IPT should only be used in patients taking ART. None of the patients interviewed had heard of IPT and, therefore, the main focus of the analysis was the staff interviews.
Four themes influencing IPT delivery and uptake emerged, which are outlined below.
Knowledge and experience
Although all doctors had heard of IPT, several were either unaware of its efficacy in preventing TB or believed that the evidence was equivocal:
‘If one was convinced that it works, one would have made means, but I'm honestly not convinced it works'– doctor, low usage
‘….I attended several meetings and some authorities were saying it's really not an established fact that INH will definitely protect ….’ - doctor, routine usage
Interviews with doctors revealed that IPT was not part of routine practice. Doctors were, therefore, unfamiliar with IPT and less willing to prescribe.
‘From our facility, since I started I've never had a patient who has had it. Had I had one at least I'd be able to judge.’- doctor, low IPT usage
‘I was thinking why am I now in the school of not using IPT, and I've never been thinking of it as routine like Bactrim [co-trimoxazole]. I'm going to be honest with you and say I don't have enough experience’– doctor, low IPT usage
Perceived operational barriers
Staff cited a number of practical issues that they believed were prohibitive to the use of IPT. A particular concern was the belief that isoniazid monotherapy would induce drug resistance, particularly in the South African context of high prevalence of multi-drug-resistant (MDR) and extensively drug-resistant (XDR) TB.
‘There's such a fear of inducing INH resistance. We are taught for HIV and for TB that this is why we use several drugs. Why should this be any different? That's the first leg of active drug resistance’– doctor, low IPT usage
The high prevalence of TB meant some prescribers believed that starting empirical courses of full treatment for TB was safer and offered greater benefit than prophylaxis.
‘This is South Africa, the world headquarters of TB. Every other patient has TB. In the developed world, maybe INH has a place, but here, in this setting, it's the treatment we need. Just treat for TB– what are you going to lose?’– doctor, low IPT usage
The need to screen for and rule out active TB prior to commencing IPT was a concern for all nine doctors. They believed that false-negative sputum tests and chest radiography, as well as atypical presentations among those infected with HIV, made TB screening difficult.
‘Testing for TB is difficult– it's paucibacillary, extrapulmonary. Standard pulmonary TB is not more than 30% of our patients. Sputum, abscesses, lymph nodes, X-rays are very often negative. I would never use INH on my patients, for this reason alone’– doctor, low IPT usage
Actual operational barriers
Only one clinic had onsite chest radiography and none could test sputum onsite. Most investigations for TB screening were, therefore, performed offsite and clinic staff frequently cited lack of co-ordination between TB and HIV activities as a barrier to starting patients on IPT.
‘I think the problem there is the length of time you have to wait.… because the patient has to go to another clinic so there's a chance they might not go and you know all sorts of things might happen along the way.’– doctor, routine IPT usage.
‘I have been trying to get in contact with the lab. You can't assume that ‘oh we've not heard anything’ so it is negative. The problem is from their side, they can't contact or communicate. And they lose specimens’– nurse, low IPT usage
‘We ask the sister to give them the results either by mouth or by hard copy. But that has not been so simple. It's a real struggle to find out if they have TB or not.’ – counsellor, routine IPT usage
The majority of doctors were not concerned with patient opposition to IPT, believing that problems of adherence were minor.
‘They take what we give them, they want to have their lives saved’– doctor, low IPT usage
Counsellors and nurses were concerned about perceived patient-derived barriers such as lack of money for transport to clinic and pill burden as potential problems:
‘The clients complain at first. They feel they've got too many tablets. They keep asking when their 6 months is coming up. But they do take it. They like to count it down’ counsellor, routine usage
‘Some people they say like, I forgot or I didn't have time to come and collect my next supply, or work they didn't allow me, but it's not really very common, it's a drop in the ocean’– nurse, routine IPT use site
None of the patients interviewed had heard of IPT, but when it was explained to them, they felt it did not raise significant issues. When questioned directly about pill burden or socioeconomic problems, most felt these barriers could be overcome.
‘I am taking so many tablets anyway. One more doesn't make any difference. It would not be an issue for me. It would not be an issue.’– patient, low IPT use site
Barriers to IPT use in this setting are predominantly derived from healthcare workers, whose uncertainty over the benefits and risks of IPT and poor knowledge of guidelines, along with operational obstacles to screening for TB, have resulted in low overall usage, despite a readily-available and cost-free drug supply.
Previous work has shown that the existence of guidelines is insufficient to influence prescribing practice, and perceived patient preferences and peer influences are important . In contrast to previous literature, which focuses on patient adherence , in this setting it appears that prescription rather than uptake of IPT is the major barrier.
The lack of familiarity and confidence in IPT prescribing was evidenced not only by variable and inconsistent prescribing practices, but by healthcare workers' own admission that they were unclear about its benefits. In a programme that has promoted IPT since its inception in 1999, this is even more remarkable, and policy clarification and dissemination of accurate information is required. However, our study highlights that the promotion of IPT guidelines does not guarantee that policy will translate into practice, mirroring findings from other areas of medicine . The influence of peers and leaders is important in determining whether guidelines are adopted ; some senior clinicians in South Africa have publicly opposed IPT, and this is likely to have increased the reluctance of staff to prescribe IPT. The lack of familiarity with IPT expressed by staff suggests that if well chosen local opinion leaders acted as ‘IPT champions’ and set an example by prescribing IPT, other health workers might follow . Supervision with provision of feedback concerning IPT delivery might also improve implementation .
The requirement to rule out active TB prior to commencing IPT was perceived as a critical barrier by the majority of clinic staff. This is particularly critical barrier in South Africa, which has one of the highest caseloads of HIV/TB co-infection worldwide. In the longer term, this highlights the need for point-of-care tests for active TB. In the shorter term, clearer guidelines are needed on how to exclude active TB prior to IPT; clarification that chest radiography is not mandatory if the patient is asymptomatic could mean many more patients receive IPT. Prescribers should be made aware of the consensus from current literature that IPT does not promote isoniazid resistance .
Inadequate HIV/TB service integration was an operational barrier mentioned by all clinic staff. Although South Africa now has a large number of individuals accessing ART, it is only in recent years that there has been emphasis on TB/HIV service integration. As well as being historically separated from HIV services, TB care has often proved a secondary priority. Considerable political will and financial commitment will be required if improved service collaboration is to be achieved in line with WHO targets.
Limitations of this study arise mainly from the relatively small number of staff and clinics included; this and the purposive sampling strategy means that we cannot assume that the results are widely generalizable. However, the results provide valuable insights into barriers to policy implementation and highlight the value of qualitative research in this area.
A significant amount of effort is likely to be needed to achieve widespread IPT roll-out. Overcoming operational barriers is necessary, but will be insufficient without a parallel focus on changing the perceptions of healthcare workers, which could be addressed via the influence of local clinical opinion leaders.
The authors are grateful to the staff and patients at Aurum clinics for their collaboration in the work.
The authors declare that there were no conflicts of interest in the work.
The present study was funded by the London School of Hygiene and Tropical Medicine trust funds, and the Aurum Institute.
1. WHO. Policy statement on preventive therapy against tuberculosis
in people living with HIV; 1998. http://whqlibdoc.who.int/hq/1998/WHO_TB_98.255.pdf
. [Accessed 12 September 2010].
2. Woldehanna S, Volmink J. Treatment of latent tuberculosis infection in HIV infected persons.Cochrane Database Syst Rev
3. Grant AD, Charalambous S, Fielding KL, Jay KH, Corbett EL, Chaisson RE, et al
. Effect of routine isoniazid preventive therapy on tuberculosis
incidence among HIV-infected men in South Africa: a novel randomized incremental recruitment study. JAMA 2005; 293:2719–2725.
4. WHO. Three I's meeting. Report of a Joint WHO HIV/AIDS and TB Department Meeting. http://who.int/hiv/pub/meetingreports/WHO_3Is_meeting_report.pdf
. [Accessed 12 September 2010].
5. Chandler CIR, Jones C, Boniface G, Juma K, Reyburn H, Whitty CJ. Guidelines and mindlines: why do clinical staff over-diagnose malaria in Tanzania? A qualitative study. Malar J 2008; 2:53.
6. Rowe KA, Makhubele B, Hargreaves JR, Porter JD, Hausler HP, Pronyk PM. Adherence to TB preventive therapy for HIV-positive patients in rural South Africa: implications for antiretroviral delivery in resource poor settings? Int J Tuberc Lung Dis 2005; 9:263–269.
7. Grimshaw JM, Thomas RE, MacLennan G, Fraser C, Ramsay CR, Vale L, et al
. Effectiveness and efficiency of guideline dissemination and implementation strategies. Health Technol Assess 2004; 8:1–72.
8. Greenhalgh T, Robert G, Macfarlane F, Bate P, Kyriakidou O. Diffusion of innovations in service organizations: systematic review and recommendations. Milbank Q 2004; 82:581–629.
9. Locock L, Dopson S, Chambers D, Gabbay J. Understanding the role of opinion leaders in improving clinical effectiveness. Soc Sci Med 2001; 53:745–757.
10. World Health Organisation 2009. Medicines use in primary care in developing and transitional countries. Fact Book summarizing results from studies reported between 1990 and 2006. WHO/EMP/MAR/2009.3.
11. Balcells ME, Thomas SL, Godfrey-Faussett P, Grant AD. Isoniazid preventive therapy and risk for resistant tuberculosis.Emerg Infect Dis