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hiv & aids treatment in practiceIsoniazid preventive therapy for TB in people with HIV: barriers to national implementation - 29/11/2007 The current outcome data for the Botswana IPT programme Getting the HIV programme, and health providers to ‘buy in’ to IPT Excluding active disease: is chest x-ray necessary? What about excluding smear negative (SNTB) and extrapulmonary disease (EPTB)? Staging implementation for the best candidates for IPT NAM publishes a wide range of publications on treatment for HIV. For details contact:NAM, Lincoln House, 1 Brixton Road, London, SW9 6BR, UKtel +44 20 7840 0050 The Stop TB Department of the World Health Organization kindly supported this issue. For more TB relatedresources please go to By Theo Smart
All in all, the studies discussed in part I of this article underscore that enough is known about IPT that itsrisks can be kept to a minimum in large programmes in resource-limited settings, and that it may markedlyreduce active TB and improve survival.
Theoretically, it might even reduce onward transmission, and the overall burden of TB.
So given these benefits, what is holding up national implementation? Part of the problem has been the tension between HIV/AIDS and TB programme areas that have debatedthe topic endlessly. In addition to the worries about safety — which one hopes some of the recent studieshave assuaged, IPT implementation is primarily being held up by the related fears that IPT may be given tosome cases of active TB missed during the screening process (how to exclude active disease), possiblyleading to INH resistance, which could in turn contribute to the growing multidrug resistance problem,especially as adherence to preventive medicine is notoriously low.   When it started, the programme in Botswana seemed to have all of these angles covered, which is part ofwhy its example is being watched so closely.
“In 1999/2000, there was nothing on the horizon to offer folks in Botswana who had HIV. And the only thingthat appeared to have any kind of benefit was IPT — as death from TB was the biggest issue they had withHIV at the time,” said Dr Charles Wells, who formerly provided support for CDC’s international TB/HIVresearch, including the IPT trial.
Indeed, once upon a time, Botswana was one of the rare countries in Sub-Saharan Africa where TB controlstrategies appeared to be working. But since the spread of HIV, the TB case rate has tripled to around 603cases per 100,000 (2005 figures). The estimated TB-HIV coinfection rate is over 80%, and an autopsy studyin 1998 suggested that at least 36% of the deaths in people with HIV were due to TB.
The same year, WHO and UNAIDS released recommendations to use preventive therapy for TB in peoplewith HIV. Botswana was quick to act.
The country went about setting up the programme in a very methodical, responsible way: by forming aworking group in 1999, and conducting a pilot study in three districts to determine the feasibility ofimplementing IPT country-wide.
The pilot study was quite successful. It screened over 1000 subjects, and ultimately put over 600 people on
IPT with a completion rate of 70% — much better than the adherence reported in other programmes.
Notably, at the time, this pilot IPT project also demonstrated that a simple symptom screen (cough, fever)
was nearly as sensitive as performing a chest radiograph to rule out active TB (more on this below)
(Mosimaneotsile).
On the basis of the feasibility study’s success, the Ministry of Health decided to proceed with a national IPT
programme for people with HIV and signed a cooperative agreement with the CDC/BOTUSA, which would
assist in developing an electronic recording and reporting system, and to help the country perform another
national anti-TB drug resistance survey to closely monitor isoniazid resistance trends.
In addition, they planned to launch a study to determine the optimal duration of IPT, and whether testing forlatent TB adds any benefit versus simply treating all people with HIV (as the current programme is designed).
This was all arranged toward the end of 2001.
NAM publishes a wide range of publications on treatment for HIV. For details contact:NAM, Lincoln House, 1 Brixton Road, London, SW9 6BR, UKtel +44 20 7840 0050 The IPT programme would be housed in the TB department at the national level, and staffed with onenational coordinator, two regional coordinators, three data officers and a data manager. Implementation,however, would occur in the district (there are 24 health districts in the country), with screening and deliveryof IPT by the doctors and nurses working at the country’s general clinic network. Support and supervision atthe district level were to be provided by district TB coordinators. At that point, the national TB programmewas relatively strong, though as anywhere else in sub-Saharan Africa, Botswana had far too few healthworkers for its needs.
The plan was great. And yet, according to Oaitse Motsamai, programme director: “Actually it has been verydifficult to implement this programme in the country.” The current outcome data for the Botswana IPT programme Over 350,000 people have tested HIV-positive in Botswana. At present, of 71,096 people with HIV have beenscreened for the programme, and 67,413 started on IPT. 18,121 (27%) are documented as completing theircourse, 6,779 (10%) are currently on IPT, and 42,513 (63%) are listed as non-completers. They havereasons for 24% and no reasons for 76%.
Of the 24% with recorded reasons for non-completion: ■ A few (less than 0.5%) have been due to severe side effects or terminal AIDS,■ 2% were reported to have developed active TB (whether they were adhering to IPT at the time is not ■ 10% were discontinued for one reason or another by their healthcare worker,■ 19% are listed as ‘other’ (it’s not clear how many, but for example some could be due to women ■ 69% are categorised as known to be lost to follow-up (LTFUs). They were only categorised as such when healthcare workers actually visited their homes and found them not to be available or to havemoved away.
But for the overall cohort, they aren’t sure what happened to about 49% of the people started on IPT. Andthey have little data on what happened to the TB suspects identified in the screening process (deemedineligible for IPT) —such as whether they went through the diagnostic process or had active TB.
It’s important to reiterate that this is the first time any country has ever tried to run this type of public healthintervention, so some problems, and if necessary, course corrections, are to be expected.
“Botswana’s the first place globally that’s ever tried to deliver this service as an active part of the programmeon a large scale,” said Dr Wells. “My biggest worry is that people are going to throw the baby out with thebath water, and not look at this as a learning situation.” Indeed, but it may be possible to draw a number of lessons from Botswana’s experience, even though someof the challenges were unique to the time and place. There were a number of factors involved in whatunfolded.
 “Unfortunately, the IPT office was not established until late 2003,’ said Motsomai. “I came into the officealmost two years after the inception when there was just somebody picked from NTP to oversee the roll-out.
Just one person. And then when the office came up, we started with three persons, me and two data clerks -after two years. My feeling is that the office should have been established first, protocols, making everythingvery clear —reporting, monitoring, evaluation, search indicators or whatever.” It’s important to remember what else was going on in Botswana at the time. In early 2002, the Governmentof Botswana took the bold step of launching Africa's first national antiretroviral programme — which overnight NAM publishes a wide range of publications on treatment for HIV. For details contact:NAM, Lincoln House, 1 Brixton Road, London, SW9 6BR, UKtel +44 20 7840 0050 became the country’s number one priority. The country launched four ART sites within the year, and beganpreparations to rollout ART to all the district hospitals. And in the years since, unlike most other countries,Botswana believes that it has actually put around 85% of its people in immediate need of treatment on ART.
“This was the right thing to do, but there were opportunity costs for doing it,” said Dr Wells. “And oneprogramme in particular that suffered was the TB programme, because before the HIV programme waslaunched, there was a TB coordinator in every district (except for three). One person dedicated to solelymaking sure that TB services were delivered and that things run smoothly and that drugs were where theyneeded to be, smears were being done, and all those things. Well, that model changed with the advent andthe launch of the antiretroviral programme. they went from one person who does everything for TB in 21 ofthe 24 districts, to one public health nurse responsible for six different major programmes, including TB.” “So the IPT service was being implemented and delivered at a time when there was a huge transition to HIVservice delivery at the cost of the rest of the health services.
And also too, to defend the HIV people in terms of taking something like IPT on or making sure it was part oftheir package — they were told to get antiretrovirals out, and that anything else was background noise. Andthat’s understandable,” he said.
But this massive change in Botswana’s public health system impacted heavily on efforts to try to roll-out IPT,which at times must have seemed like a competing vertical programme to the healthcare workers in theclinics.
So it was in this context, in the end of 2003, that Motsamai and just two data clerks began trying to roll theIPT programme across the country, training trainers and healthcare workers — until IPT was launched inevery district by June 2004. Other staff would be hired to the programme.But the IPT programme found itselfdistracted by trying to solve the staff shortage in the wider national TB programme.
“At the national level, the IPT programme belongs to the TB programme and the TB programme has beenshort staffed for many years now. And when we came into the programme, we were looking at all the nationalTB control strategies and on that endeavour we ended up losing track of our core business that was IPT,”said Motsamai.
But some of this was probably unavoidable, as having a functioning national TB programme was essential toaspects of IPT’s success.
“We had people like community health nurses and other health carers who were tasked with theresponsibility of taking care of the TB programme, but we have found that most times they put maybe lessthan 10% of their effort on TB control activities and that is why we decided to come up with designated TBcoordinators, and also this has helped us because we have actually improved on our records,” she said.
But there has also been a high turnover in district health workers, including TB coordinators, so the IPT teamhas found that they have to train and retrain.
Every HIV programme experiences losses to follow-up among people who test positive for HIV, even amongthose who qualify for ART. But the rates in the IPT programme seem particularly high.
Motsamai listed a number of reasons why clients were getting lost.
Some patients received inadequate counselling and did not know that they had to retrun regularly forcheck-ups.
NAM publishes a wide range of publications on treatment for HIV. For details contact:NAM, Lincoln House, 1 Brixton Road, London, SW9 6BR, UKtel +44 20 7840 0050 Other reasons were more typical such as transport problems, particularly in the districts, wrong addressesgiven by clients, and high mobility of clients (in Botswana, it is very common for people to work in the city ormines part of the year, and return to their ancestral village the rest of the year).
But in contrast to ART programmes that tell patients to come back every three or even every six monthswhile they have high CD4 cells, participants in the IPT had to visit the clinic every month. And this is during aperiod when ART sites in Botswana were packed to capacity, and where doctors and nurses were strugglingto put people on ART.
“Sometimes clients are registered and given the first or second doses, then they just disappear. You don’tknow what happened to them and nobody bothers to find out where they are. Follow up is very limited andthis is what we are trying to push, that all the clients that have been on IPT should be followed up,” she said.
Dr Taraz Samandari of BOTUSA thinks that: “The statistics that Motsamai gave are actually pretty much theworst case scenario because there are many people who got five months of bottles of pills but they just didn’tcome back for the 6th month to say, ‘Okay, I’m done.’” In other words, if the data were re-analysed looking at subjects who finished five months, Dr Samandaribelieves the losses to follow-up would be much lower.
Even so, the goal should be to retain people in care. So IPT programmes could benefit by being closelylinked into community-based mechanisms of adherence support that the more successful ART programmesuse (see HATIP # 90 and 92).
But huge numbers of the non-completers could simply be miscategorised because of poor record keepingand reporting.
The programme started out using a paper-based register and reporting system — separate from the TBregister, and from the ART/pre-ART registers — while the electronic database for the programme wasn’trolled out until November 2005. But by then more than 20,000 people had already been put on IPT.
And in the beginning, even with the paper registers, “out of the 24 districts, maybe sometimes six districtswould report, sometimes ten but it was very inconsistent,” Motsamai said. “We have a lack of timelyreporting. I’ve actually been doing some supervisory visits recently only to find there’s a good number withinthe registers that have completed the 6-month visit. But somebody just failed to pick that up and post this tooutcomes.” But again, part of this may be due to competing priorities for the health worker’s time.
Motsamai described a typical exchange: “We have a feeling that there are some attitude problems within thehealth workers themselves because they will complain, ‘Oh, workload!’ There are too many documents torecord and so many initiatives at the same time that they have to take care of. And at the end of the day youcome across a situation where somebody has been on IPT, and there aren’t clear records/adherence. Andthen you ask, ‘Where is this patient? And they say, ‘He has completed treatment.’ ‘But then, what about the(records)?’ ‘I know, I’m very sure that they are completed?’ they will answer. But there is nothing on record.” Getting the HIV programme, and health providers to ‘buy in’ to IPT Taken together, the entire episode illustrates a larger problem about the need to sensitise people working inHIV not only about how IPT can save lives, but why the manner in which it is distributed is extremelyimportant, for the safety of the patient and for TB control in general. There are, after all, dangers related tonot investigating TB suspects identified by these programmes, and in releasing large quantities of animportant TB drug within the community without properly educating people on how to use it.
NAM publishes a wide range of publications on treatment for HIV. For details contact:NAM, Lincoln House, 1 Brixton Road, London, SW9 6BR, UKtel +44 20 7840 0050 The HIV programme bears some responsibility for this. Of course, TB and HIV coordination has been slow inmost countries.  As a result IPT wasn’t emphasised as part of the ART roll-out. A TB/HIV Advisory body wasonly established a year ago.
Getting people in HIV care to buy-in to IPT has been a problem in many other countries as well.
For instance, one study from the THRio project, identified major differences in IPT usage from clinic to clinic,and then found that the doctors were to blame.
“Doctors’ lack of knowledge about the TB prevention protocol in HIV patients was an important reason fordifferent performance among the units,” said Dr Betina Durovni during one presentation at the conference.
“So after almost two years of implementing this strategy, we are actually revising our strategy and developingnew communication strategies for physicians.” In 2001, it was difficult to predict that the TB programme would be decimated by worker turn over and otherhealth system changes, but it's clear that the scale-up of programmes such as IPT, whether housed in TB orHIV departments, has to go hand in hand with strengthening TB control.
And recently, the Botswana TB programme has been bolstered considerably by recreation of the position ofDistrict TB Coordinator, trained to strengthen TB control strategies at the local level.  “Now that we have designated TB coordinators we do have control over them. We do monitor them. We docall them to table more frequently and can see a big difference from the effect. We can see a big differencein the uptake, the monitoring and even the outcomes of the programme”. Recently reporting has improvedsubstantially — at least with the paper-based records. “The average is about 94% on paper-based reportingon a monthly basis which is very good. But we are still only getting five to ten out of the districts to file anelectronic report.” Even so, she said the quality of the data that comes out of the programme should start improving soon.
“I’m just coming from a particular district where they were performing very badly and now they haveimproved a lot. So the outcomes are coming,” she added.
A formal review of the programme is slated for next year.
Even though most of the problems in the Botswana IPT programme had more to do with the unique time inhistory in which it was rolled out (and with a health system trying to do so many things at once), the reporthas launched a debate between those in favour of IPT and some who think there should be a more cautiousapproach to scaling it up.
In addition to the traditional worries: how to exclude active disease, prevent INH resistance, and how toensure adherence, there are operational concerns, including who should really be in charge of running theprogramme (the TB or HIV department, and how should the data from the programme be recorded andcross-linked between TB and HIV programmes? Excluding active disease: is chest x-ray necessary? In a recent TB/HIV newsletter from the TB/HIV Working Group of the Stop TB Partnership, Dr Yibeltal Assefaof the National HIV/AIDS Prevention and Control Office, Ethiopia, said that he is worried that there are noclear guidelines that show how to confidently exclude active pulmonary TB without a chest x-rays. In hissetting:  "we don’t have the infrastructure capacity to confidently rule out active TB in facilities where manyPLHIV are seen. I would like to see some well designed studies. and. a locally applicable protocol toexclude active TB that takes the infrastructure development of the country into consideration. More NAM publishes a wide range of publications on treatment for HIV. For details contact:NAM, Lincoln House, 1 Brixton Road, London, SW9 6BR, UKtel +44 20 7840 0050 contextual and locally-oriented operational research is needed to scale-up IPT as a practical public healthintervention in Ethiopia.” But chest x-rays aren’t required in Botswana’s programme. So just how safe was the practice? Results from the IPT study in Botswana presented earlier this year at CROI suggested that Botswana’scurrent algorithm without x-rays misses more cases of active pulmonary disease than originally anticipated.
Out of a total of 4328 adults screened, 2608 patients who were asymptomatic (and thus may have qualifiedfor IPT) had a chest X-ray. 12% (305 subjects) of these had an abnormal chest radiograph as compared to4% reported in the earlier pilot study, 31 (10%) of those were found to have active TB, and so overall, 1.2%of all the asymptomatic subjects could actually have active pulmonary disease (Samandari). However, thatleaves out 38% of the people with abnormal chest x-rays who never came back in for further evaluation andwho were lost to follow-up. So 31 out of 190 (17%) of those with abnormal chest x-rays who did come backin were diagnosed with TB, and the number of active cases missed could have been higher.
Notably in the IPT programme, 2% of the non-completers with a known cause were due to breakthrough ofactive TB.
Although the percentage seems small, the public health consequences of under-treating this small butpossibly significant proportion of active TB cases are unclear at present. Notably, in the CDC study, 72 ofthose with abnormal chest x-rays were known to have initiated a 6-month course of IPT. Four of thesedeveloped active TB, one of whom had an INH mono-resistant TB isolate.
Including chest x-rays at sites where they are available would decrease the chances of sub-optimally treatingactive disease. They are certainly included in the CREATE study project algorithms.
But requiring chest x-rays as part of the screening algorithm for active disease for each patient wouldincrease the cost of these programmes substantially — and make it logistically impossible in more peripheralsettings.
“Chest x-ray is not accessible to most HIV-infected people who could benefit from IPT in sub-Saharan Africa,so having radiography as an obligatory part of the algorithm will deny people access to an interventionpreventing disease and possibly death" said Dr. Kevin De Cock, Director of WHO HIV/AIDS Department.
At least one study at the World Lung Health conference suggested performing chest-x rays makes IPT lesscost-effective than intensified case finding (where cases can often be diagnosed by smear microscopy alone)(Sutton) and one speaker pointed out that what can be detected on x-ray is really in the eye of the beholder:clinicians who know that the patient has TB symptoms are more likely to see (or perceive) evidence of TB onthe x-ray than an observer who is off-site (Tamhane).
On the other hand, perhaps we should be thinking outside the box and trying to improve access to chestx-ray at more peripheral levels of the health system in Africa? If money can be found to upgrade laboratoryfacilities, why not chest x-ray? Small low cost devices have been developed, and nurses could be trained atleast to tell the difference between a normal chest x-ray versus an abnormal one. People with a normal chestx-ray could be put onto IPT while the others are referred for more intensive investigations. This would havethe added benefit of leading to more TB diagnoses.
But Dr Tony Harries in Malawi isn’t sure that it would work.
“I am not convinced about this approach. It is expensive and without maintenance these low cost x-raymachines have the potential to be discarded to the corner of some room, never to be used again oncesomething minor goes wrong,” he says.
“With the normal full size chest x-rays and relatively competent clinicians one gets wide variations ininterpretation - we tested this many years ago in Malawi! Nurses are not generally used to reading chest NAM publishes a wide range of publications on treatment for HIV. For details contact:NAM, Lincoln House, 1 Brixton Road, London, SW9 6BR, UKtel +44 20 7840 0050 x-rays, so I would expect interpretation variation to be quite high with this cadre. Finally, it is well known thata proportion of HIV-infected, immunosuppressed patients with culture-proven TB have completely normalchest x-rays - up to 20%. Thus, having a normal chest x-ray does not rule out active TB!” What about excluding smear negative (SNTB) and extrapulmonary disease (EPTB)? But these screening assays mostly focus on typical pulmonary disease, while many people with HIV developless easy to diagnose forms of the disease that may not always be screened out by a pulmonary diseasesymptom assessment. In fact, isoniazid treatment in such cases could actually delay diagnosis by partiallysuppressing the infection. “My view is that the messages should be simple — only WELL patients should get IPT. Any ill patient (recentweight loss, constitutional symptoms, any impairment of daily function) should not get IPT. Rather defer andinvestigate and/or monitor for TB in such patients — hopefully this would avoid SNTB and EPTB patientsgetting IPT,” said Dr Graeme Meintjes of GF Jooste Hospital in Cape Town.
“The other message is that there is never an urgency to start IPT. if the patient could have TB but you can’tbe sure, rather wait and investigate. If they do have TB this will show itself in the next three months in anHIV-infected person with a low CD4 count, and then they should get TB treatment and not IPT.”   “I am nervous that if we don’t get these messages out clearly then in operational settings patients withunrecognised active TB will get IPT with adverse consequences for the patient and the programme,” he said.
Others are also concerned about resistance, especially in light of the MDR/XDR crisis.
“In an analysis of an MDR cohort in our situation, six out of 140 patients had previous IPT. All six of thosepatients developed MDR-TB within one year of incomplete treatment with IPT,” said Dr Alistair Calver, who iswith AngloGold Ashanti Health (associated with the mining industry in South Africa) during the question andanswer session after Motsamai’s talk. “So I am concerned about Botswana’s figures of high drop out ratesfrom their IPT - that may well be fueling the MDR epidemic.” But Dr Alison Grant, who is working with miners as well in the Thibela TB project, believes that this could becircumstantial evidence, because the miners might have been newly infected with an MDR strain.
HIV programmes should not be too dismissive of the risk of resistance, and its potential consequences —but at the same time, the roll out of IPT should not be paralysed by this argument either.
Botswana is very much on top of this issue. The country has performed four surveys since 1996, when INHresistance among new patients was 1.6%. That went up to 4.4% in 1999 and remained stable (at 4.5%) in2002 (it actually decreased in re-treatment cases). MDR resistance in 2002 was 0.8% among new patients.
The current review will be finished by March, 2008.
“They have actually put in the appropriate monitoring practices to see how this programme is impactingresistance in the country,” said Dr. Wells.
Adherence
The 27% completion rate in Botswana is a long way from the 70% completion rate reported in the pilotstudies. It is more in line with the abysmal adherence seen in ProTest, an initiative that linked anIPT-containing package of care to HIV counselling and testing, in South Africa, Zambia and Malawi, whichranged from 24% to 59% across the project.
But as previously noted, the large simple trial of IPT in Botswana has had very high completion rates of 94%(of those 1893 who were not discontinued for other reasons) (Chengeta). According to pill count data, 90% ofthe study participants took 80% or more of their pills. One thing that seemed to encourage them — they gave NAM publishes a wide range of publications on treatment for HIV. For details contact:NAM, Lincoln House, 1 Brixton Road, London, SW9 6BR, UKtel +44 20 7840 0050 participants little prizes, like coffee mugs with dancing zebras, when they successfully completed their IPTcourse.
After conducting focus group discussions to discuss appropriate incentives, the Thibela TB project adoptedthis strategy as well, by offering various items of small value such as t-shirts, caps, water bottles and keyrings  (Coetzee). In addition, the project is conducting targeted participant education, individual and peergroup support.
“I think there is grassroots resistance and concerns about inducing MDR but I think this can be overcome,”said Dr Venter in South Africa. “We recently analysed our cohort in central Johannesburg, and 94% of themwho started ART were on cotrimoxazole. So getting healthcare workers to give prophylaxis is possible, withsufficient training.” “One of our major problems is the failure of the retention in care of those with good CD4s – the muchvaunted wellness [patient education] programmes are empty of content in most cases, and patients feel theyget little benefit (which is largely true). We need these fixed, so that TB screening and regular stagingactually happens. Paradoxically, providing isoniazid may make these patients more likely to remain in care,as they actually receive treatment beyond a non-evidence based health lecture after sitting in a long primaryhealth queue,” he said.
This naturally raises the issue about where IPT programmes should be housed. In the recent TB/HIVnewsletter, Dr Mario Raviglione, Director of Stop TB Department of WHO Geneva, Switzerland, argued forputting it in the HIV/AIDS Department. “I am fully convinced that IPT will never be scaled up and accessibleto those who need it unless it is taken up by those services handling PLHIV: from VCTs and ARV clinics togeneral primary care services. Hence, the paramount key strategic move must consist in getting thosecomponents of the health sector delivering HIV and primary care services fully engaged in theimplementation of IPT.” “It just seems to me - as an HIV physician, that this fits completely naturally into HIV care and that’s I thinkhow we should be doing it,” said Dr Grant. “Obviously there are clearly problems where TB ControlProgrammes are not happy to release isoniazid for this purpose. I think that’s clearly something that has tobe addressed on a higher level to try to encourage people and reassure them that this is not going to causea disaster for their TB Control Programme. I think this is part of HIV care and this is how we should be doingit because we are perfectly placed. We’ve got people coming to be screened for TB and if they don’t haveTB, they’re in a perfect position to go onto IPT. It’s a natural synergy - if you like.” However, Dr Halima Dawood of Edendale Hospital in KwaZulu Natal worries about the capacity forprogrammes to support so many “well” patients.
“First, I think that we need to get our cure rates and interruption rates at a more respectable level before weuse IPT, though this intervention has certainly been beneficial in settings in South Africa. But I worry aboutthe follow-up that IPT requires, as the current ARV programmes are saturated and there are some thoughtsabout extending follow-up intervals already. I am unsure if these programmes can be supported by doctors inthe future. We need to start thinking laterally and including communities in the management of HIV/AIDS/TBeven more,” she said.
Ironically, there was no HIV programme when the IPT programme in Botswana was conceived. Of course, itis only the administration that is housed in TB in Botswana. The delivery is through general care. But wouldmoving it into the HIV programme area increase its uptake? Dr Wells believes it is actually more appropriate in the TB programme in Botswana: “I think ironically it was the right decision to have nested it within the TB programme because since that time— especially with the advent of XDR and all of that — there’s been a lot more focus put back on the TBprogramme and people realising to do it all they can’t just do one without the other. In retrospect it was thewiser move because it only served to link the programmes better.” NAM publishes a wide range of publications on treatment for HIV. For details contact:NAM, Lincoln House, 1 Brixton Road, London, SW9 6BR, UKtel +44 20 7840 0050 Dr Annalies Van Rie thinks that there could be problems putting IPT in either programme area: “If you houseit in the TB programme or the HIV/ART programme, it will always be a programme of secondary objective.
For the TB programme, TB treatment is the main mission, and for the HIV/ART clinics, getting people onART and keeping them on ART is the most important task.” Given capacity problems in some HIV programmes, there may not be any one right or wrong answer sincedifferent models might work differently in different countries.
For example, in Cambodia’s IPT project, they actually attach one or two TB programme officers to HIV clinicsthat want to do IPT, according to Dr Phalkun Chheng. This actually strengthens linkages between the twoprogrammes, and increases the capacity at the clinic to perform intensified case finding or manage patientson IPT.
“Each country has to look at its own situation and then make that determination,” said Dr Riita Dlodlo ofZimbabwe. “Obviously not a separate vertical programme but otherwise, it needs to be negotiated betweenNTP and NACP.” The focus should be the need of the community and the person with HIV to prevent TB — rather than on theprogrammes themselves. TB and HIV programmes need to work together to figure out how to deliver IPT ina way that makes sense for the patient and community and then work out the programmatic logistics.
“IPT is currently aimed at those people living with HIV who are well and do not need ART. These are exactlythe people who fall out of the boat. They are told they have HIV, are well and asked to come back later. Theyare probably often perceived as a burden to the system, as they take up time and space of those who reallyneed care,” said Dr Van Rie. “We should advocate for better care for those living with HIV but not in need ofART. These individuals need counselling on prevention and how to stay healthy. IPT (and cotrimoxazole) fitsinto this setting, possibly in general outpatient primary health care clinics.” Staging implementation for the best candidates for IPT By targeting only the well, as suggested by Dr. Meintjes or people with higher CD4 cell counts, the risk oftreating subclinical TB would also be much lower. But another school of thought is that this approach mightdeny IPT to those patients who would benefit the most (people with a lower CD4 cell count who are at higherrisk of TB). Still, either way, it might be possible to stage implementation of IPT by targeting one population ata time.
"Some physicians suggest that probably we should give IPT only to people with high CD4 counts,” said adoctor from Kampala, Uganda, following Motsamai’s presentation. “But another view is to give it in those withlow CD4 counts, give IPT when we give them ARV’s. That way, if they are on ARVs and IPT they are closelyfollowed up so if they get active TB it’s more likely to be picked up, as opposed to people who are fairlyhealthy and given treatment and don’t complete it and who are more likely to miss having the diagnosis ofactive TB made because of poor follow up." “In Malawi, we are wondering about combining IPT with ART but that needs careful thought, especially asmany of our patients with unexplained fever and weight loss may have undiagnosed TB,” said Dr TonyHarries, but he added, “we have plans to try scaling up IPT within the context of PMTCT where mostHIV-infected women will be WHO Stage 1 and therefore the fear of placing subclinical TB patients onmonotherapy is reduced considerably.” Pregnant women are often excluded from IPT programmes, a suggests thatpregnant women could have a huge unaddressed need for TB preventive therapy and we have to rethinkhow to handle pregnancy/pregnant women in these programmes.
Children with HIV must also be considered. “For children, you must have the ability to diagnose childhoodTB,” said Dr Mark Cotton of Tygerberg Hospital. Exclusion of active disease is even more challenging inchildren HATIP #32 ).
NAM publishes a wide range of publications on treatment for HIV. For details contact:NAM, Lincoln House, 1 Brixton Road, London, SW9 6BR, UKtel +44 20 7840 0050 But Dr Cotton sees IPT as offering a chance to improve mother-child care overall. “It can be used as anopportunity to improve diagnosis of TB as a preparatory exercise. It should go hand in hand with early HIVdiagnosis, access to early HAART and screening pregnant women for TB.” Finally, given the problems in record keeping, wouldn’t it have made more sense just to combine the IPTregister with either the TB or the pre-ART/ART register?  Dr Wells isn’t sure whether it would have mademuch difference in Botswana, because of the poor quality of data reporting when it came to TB data overall.
“It’s really, really critical to have it linked to the TB case register because what you want to know is: howmany cases of TB are we seeing among people who’ve received IPT?” he added.
However, others think that having too many registers may inevitably lead to problems.
“Registers are like mushrooms, you have to stomp them out,” said Dr Reuben Granich of WHO. “Feasibilityis key and must be kept in mind - every new register you implement is a potential recipe for disaster.” “There is no time to fill in separate registers in sub-Saharan African countries that have one tenth or so oftheir required health care workers!” said Dr Dlodlo. “Integrate it into pre-ART and ART registers. And to quoteDr. Antony Harries, keep it simple, simple, simple!” Indeed, keeping it simple is clearly the point of the Core Group of the TB/HIV Working Group of the Stop TBPartnership.
“Accelerating implementation of IPT is one of the major initiatives of the HIV/TB Working Group of the STOPTB partnership,” said Dr Diane Havlir, who serves as chair of the group. “Putting the brakes on IPT, anintervention that prevents the leading cause of mortality in persons living with HIV based on the Botswanareport is not justified, and certainly not in the best interests of the individual or the public health. Just likeART, IPT has challenges that are surmountable and that will be addressed by ongoing programmaticexperience and operational research.”   "One of the things that we all need to work on is to make sure we can create systems that are capable ofruling out active TB, of diagnosing active TB so that people can receive appropriate treatment. If people inhigh HIV burden regions who are HIV-positive don’t have active TB, then they are candidates for IPT andthey should be given the chance to take it - it can save their lives and prevent them from getting TB," saidMark Harrington, executive director for the Treatment Action Group. "It’s a call to arms. and that’s going tobe a message we are putting out along with the Stop TB working group." Knowing what we now know about rolling out large successful public health interventions to people with HIVin resource limited countries, it should be possible for programmes to take the model that Botswanadeveloped, take the bits that worked well, and improve upon it substantially.
“It is doable. IPT is no more complex than many other programmes we’ve rolled out successfully,” said DrGranich.
The technical and logistical challenges can be worked out, but HIV and TB programmes have to get onboard together to figure out how to make it happen.
“WHO is really behind this as well and we really want to work with the scientific and programmatic ways todeliver IPT to people with HIV,” said Dr Granich.
"My feeling is that widespread use of IPT can only happen through close collaboration between AIDS and TBprogrammes," said Paul Nunn, Coordinator, TB/HIV and Drug Resistance for the Stop TB Department ofWHO.
NAM publishes a wide range of publications on treatment for HIV. For details contact:NAM, Lincoln House, 1 Brixton Road, London, SW9 6BR, UKtel +44 20 7840 0050 "My vision is that the best place to start would be in ART clinics, because there you have the infrastructurefor identifying those who really need it and for following them up. Then as ART clinics disseminate to theperiphery, IPT can go with them. By creatively packaging services together, it should be possible to retainmore people in care and on IPT, keep on top of safety and drug resistance issues, and reduce the overallburden of TB disease among people with HIV and their families." At the policy level, it is essential to ensure the access of HIV stakeholders and service providers to isoniazidthrough existing systems such as the Global Drug Facility, and also through national level consultationbetween the two programmes. In most countries, national TB programmes have full control of the purchaseand distribution of isoniazid which could prevent its accessibility to HIV service providers.
This would be in the best interest of people with HIV who are more likely to die of TB than anything else.
In the meantime, perhaps programmes should think about a staged roll-out — either beginning first in thehealthier people with higher CD4 cell counts before moving into subjects with more advanced disease inwhom it may be more difficult to exclude active disease — or perhaps starting first in people on ART in whomit may be easier to ensure closer follow-up. Either way, this would allow programmes to work out some of thelogistical issues first, gain experience and then work out how to provide the service to the other populationsmore effectively.
But we don’t have to settle for high losses-to-follow-up or risk potentially misusing an important drug. Today,we should be able to do better than that.
There are successful community-based models that can achieve high-levels of treatment literacy, andprovide adherence support that can keep patients in care. IPT should be packaged with something that givespeople additional incentive to stay on treatment, perhaps by book-ending IPT between other services thatpeople with HIV and their communities actually want. Of course, that will require the engagement of peoplewith HIV and their communities in the design of these programmes.  But by creatively packaging services together, it should be possible to retain more people in care and on IPT,keep on top of safety and drug resistance issues, saving even more lives, and reducing the overall burden ofTB disease among people with HIV and their families.
Motsamai OI. Isoniazid preventive therapy (IPT): Botswana experience. Stop TB Symposium, Cape Town,2007.
International Union Against Tuberculosis Committee on Prophylaxis. Efficacy of various durations of isoniazidpreventive therapy for tuberculosis: five years of follow-up in the IUAT trial. Bulletin of the World HealthOrganization. 60: (4) 555-564, 1982.
Woldehanna S, Volmink J. Treatment of latent tuberculosis infection in HIV infected persons. CochraneDatabase Syst Rev. (1): CD000171, 2004.
Churchyard GJ et al.  Efficacy of secondary isoniazid preventive therapy (IPT) among HIV-infected SouthernAfricans: time to change policy? AIDS 17: 2063-2070, 2003.
Golub JE et al. The impact of antiretroviral therapy and isoniazid preventive therapy on tuberculosisincidence in HIV-infected patients in Rio de Janeiro, Brazil. AIDS 21: 1441–1448, 2007.
Cobelens FG et al. Tuberculin skin testing in patients with HIV infection: limited benefit of reduced cutoffvalues. Clinical Infectious Diseases. 43: 634-639, 2006.
Quigley MA et al. Long-term effect of preventive therapy for tuberculosis in a cohort of HIV-infected Zambianadults.AIDS 15(2): 215-222, 2001.
Johnson JL, et al. Duration of efficacy of treatment of latent tuberculosis infection in HIV-infected adults.
AIDS 15: 2137-2147, 2001.
NAM publishes a wide range of publications on treatment for HIV. For details contact:NAM, Lincoln House, 1 Brixton Road, London, SW9 6BR, UKtel +44 20 7840 0050 Riska N. Hepatitis cases in Isoniazid treated groups and in a control group. Bulletin of the International UnionAgainst Tuberculosis, 51:203-207, 1976.
American Thoracic Society and Centers for Disease Control and Prevention.Targeted tuberculin testing andtreatment of latent tuberculosis infection. Am J Respir Crit Care Med 161 :S221–S247, 2000.
Nolan CM, Goldberg SV, Buskin SE. Hepatotoxicity associated with isoniazid preventive therapy: a sevenyear survey from a public health clinic. JAMA 281: 1014–1018, 1999.
Eldred L et al.  Lack of hepatotoxicity in patients on isoniazid preventive therapy (IPT) and antiretroviraltherapy (ART). 38th World Lung Health Conference, Cape Town, abstract TS-71788-10, 2007.
Mngadi K et al. Adverse event experience in workplace settings with widespread isoniazid preventativetherapy. 38th World Lung Health Conference, Cape Town, abstract PS-71835-10, 2007.
Nyirenda S et al. Isoniazid-associated hepatitis in people living with HIV (PLWH) during TB prophylactictherapy (IPT) – Botswana. 38th World Lung Health Conference, Cape Town, abstract PS-72134-11, 2007.
Popane F et al. Reasons for ineligibility for a community-wide isoniazid preventative therapy study. 38thWorld Lung Health Conference, Cape Town, abstract PS-72071-11, 2007.
Grant AD et al. Effect of routine isoniazid preventive therapy on tuberculosis incidence among HIV-infectedmen in South Africa: a novel randomized incremental recruitment study. JAMA  293: 2719-2725, 2005.
Coetzee L et al. Interpreting good clinical practice for a community study. 38th World Lung HealthConference, Cape Town, abstract PS-71930-11, 2007.
Durovni B. Implementing isoniazid preventive therapy for people living with HIV: overcoming the barriers —perspective of the HIV programme. Stop TB Symposium, Cape Town, 2007.
Sutton BS et al. Cost-effectiveness of treatment for isoniazid preventive therapy among HIV-infected patientsin Battambang, Cambodia. 38th World Lung Health Conference, Cape Town, abstract PS-71480-10, 2007.
Tamhane A et al. Inter-reader agreement for chest X-ray readings in HIV-infected pulmonary tuberculosissuspects, Battambang, Cambodia. 38th World Lung Health Conference, Cape Town, abstract PS-71464-11,2007.
Mosimaneotsile B et al. Value of chest radiography in a tuberculosis prevention programme for HIV-infectedpeople, Botswana. Lancet 362: 1551-1552, 2003.
Mtei L et al. High rates of clinical and subclinical tuberculosis among HIV-infected am-bulatory subjects inTanzania. Clinical Infectious Diseases 40(10): 1500-1507, 2005.
Chengeta B et al. Adherence to isoniazid TB preventive therapy (IPT) among people living with HIV (PLWH),Botswana, 2004-2006. 38th World Lung Health Conference, Cape Town abstract PS-72129-11, 2007.
WHO global tuberculosis programme/UNAIDS. Policy statement on preventive therapy against tuberculosis
in people living with HIV. Report of a meeting held in Geneva, 18-20 February 1998. Weekly Epidemiological
Record, 74(46): 385-400, 1999.
Getahun H, Van Gorkom J, Harries A, Harrington M, Nunn P, Perriens J, et al. Interim policy on collaborativeTB/HIV activities. Geneva, Switzerland. Stop TB Department and Department of HIV/AIDS. World HealthOrganization 2004.
*The Global TB/HIV Working Group is one of the seven Working Groups of the Stop TB Partnershipestablished in 2001 to coordinate the global response to the dual TB and HIV epidemic. The Core Group isthe decision making body which sets the strategic directions of the Working Group and makesrecommendations on the global response to the TB and HIV co-infection epidemic.
NAM publishes a wide range of publications on treatment for HIV. For details contact:NAM, Lincoln House, 1 Brixton Road, London, SW9 6BR, UKtel +44 20 7840 0050

Source: http://www.tbpreventiontoolkit.org/sites/tbpreventiontoolkit.org/files/references/ipt-overview/Nam_IPT%20Part2.pdf