Unprecedented focus on TB at HIV Implementers' Meeting

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“There’s been a lot on tuberculosis at this meeting, and I think it is pretty exciting,” said Dr Bess Miller, Associate Director for TB/HIV Prevention and Care for the US Centers for Disease Control (CDC). “Not only in several designated sessions on TB, but also in many of the HIV treatment sessions, TB has been front and centre in terms of mortality, morbidity and the delivery of services.”

In the opening plenary address, Dr Kevin De Cock of WHO’s HIV Department highlighted the importance of tuberculosis as the leading cause of death of people with HIV. Immediately following his address, Zahedul Islam, of the HIV/AIDS Alliance described conditions in the Ukraine, where 65% of the reported HIV deaths are caused by TB. Then, during one of the first HIV treatment sessions of the conference, Turate et al reported that 30% of people dying on ART in Rwanda have concomitant TB.1

There were also three dedicated TB sessions that focused on improving monitoring and evaluation (M&E) of TB/HIV collaborative activities, the Three I’s (intensified case finding (ICF), isoniazid preventive therapy (IPT) and infection control (IC)), and improving the clinical management of TB in people with HIV — as well as an informal session which was devoted mostly to discussion.

Improving monitoring and evaluation

In the session on monitoring and evaluation, Dr Christian Gunneberg of WHO introduced the revised and harmonised WHO / PEPFAR / UNAIDS indicators for TB/HIV collaborative activities that should help countries and funding partners to better understand the burden of TB/HIV, plan accordingly and measure the implementation and impact of their interventions (see this report).2 The guidelines can be downloaded at the WHO website here.

Glossary

infection control

Infection prevention and control (IPC) aims to prevent or stop the spread of infections in healthcare settings. Standard precautions include hand hygiene, using personal protective equipment, safe handling and disposal of sharp objects (relevant for HIV and other blood-borne viruses), safe handling and disposal of waste, and spillage management.

capacity

In discussions of consent for medical treatment, the ability of a person to make a decision for themselves and understand its implications. Young children, people who are unconscious and some people with mental health problems may lack capacity. In the context of health services, the staff and resources that are available for patient care.

isoniazid

An antibiotic that works by stopping the growth of bacteria. It is used with other medications to treat active tuberculosis (TB) infections, and on its own to prevent active TB in people who may be infected with the bacteria without showing any symptoms (latent TB). 

multidrug-resistant tuberculosis (MDR-TB)

A specific form of drug-resistant TB, due to bacilli resistant to at least isoniazid and rifampicin, the two most powerful anti-TB drugs. MDR-TB usually occurs when treatment is interrupted, thus allowing organisms in which mutations for drug resistance have occurred to proliferate.

culture

In a bacteria culture test, a sample of urine, blood, sputum or another substance is taken from the patient. The cells are put in a specific environment in a laboratory to encourage cell growth and to allow the specific type of bacteria to be identified. Culture can be used to identify the TB bacteria, but is a more complex, slow and expensive method than others.

WHO has also produced “Three Interlinked Patient Monitoring Systems for HIV care/ART, MCH/PMTCT and TB/HIV” with TB indicators integrated into tools, materials and registers that countries can adapt to support patient tracking, and improve the quality of data collecting for cohort analysis and quality improvement at the facility levels (this is available online here).

Presentations from Ethiopia and Malawi illustrated how TB/HIV monitoring can be integrated into registers and reporting systems.3 4

“Integrating TB/HIV will enable us to reach the ambitious targets of halving the prevalence of TB and TB deaths by 2015. A reliable and timely monitoring and evaluation system is vital for the effective management of TB and HIV programmes,” said Mrs Mtemwa Nyangulu, a clinical officer working for the MOH in Malawi.

Recently, WHO has published a monograph, documenting the best practice of TB/HIV M&E in Malawi and that shows how an integrated TB/HIV M&E system can function, has also recently been made available.

Integrating these TB/HIV indicators into the registers and the patient management system can improve the uptake of collaborative activities. Even so, simply adapting these tools doesn’t guarantee uptake, or that staff will record, report or compile the data – which in turn makes it difficult to analyse or interpret the data.

“It can be difficult to distinguish whether missing data means that the activity was not done or whether there was a problem with recording,” said Dr Wafaa El-Sadr of the International Center for AIDS Care and Treatment Programs.5

So at the same time that new M&E systems are introduced, “supportive supervision and training of healthcare workers on M&E must be intensified,” said Dr Endris Mohammed of WHO in Ethiopia.

Improving the management of TB in people with HIV

Another session addressed the clinical management of TB — which includes screening for HIV and offering care and treatment including ART to people who are coinfected. The need to aggressively diagnose HIV and improve its management was underscored by a study from Uganda, which found that people with HIV were significantly more likely to default on treatment (Lwanga) and a study from Namibia, that found that HIV-infected TB patients were more likely to die on treatment —because of late presentation, delays in diagnosis and delays in starting ART (Zvavamwe).6 7

Fortunately, “there’s been a remarkable scale up of HIV testing of TB patients in Africa, so much so, it appears that scale up to testing all TB patients is possible,” said Dr Gunneberg.8

Likewise in Asia “the rapid expansion of provider-initiated testing and counselling in TB clinics is feasible,” said Dr Nguyen Viet Nhung of Vietnam’s National TB programme. However, he continued “low rates of successful referrals, CD4 testing and ART suggest that improvement of collaboration, between TB and HIV programmes at all levels, is urgently needed in parallel with testing.” 9

 “We will probably win the battle against HIV but it is not certain that we will win the one on TB unless there is more integration of HIV and TB programmes at all levels,” said Dr Reynold Grand Pierre of GHESKIO (the Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic Infections).10

In particular, he noted that laboratory and X-ray equipment capacity would have to be improved throughout the country. However, with the assistance of Partners in Health and PEPFAR, a multidrug resistant (MDR) TB care centre has been established to improve the quality of care and diagnosis for HIV/TB, and MDR-TB (about 3% of the TB cases are believed to be multidrug resistant). Because of the new centre (and the capacity to screen for MDR-TB), Haiti now qualifies for assistance from the Green Light Committee to obtain drugs for MDR-TB treatment. 

During the informal session, Dr Haileyesus Getahun of WHO’s Stop TB Department reported that there will also be some changes this year in WHO policy regarding the treatment of TB. One change regards the recommended first line of treatment: The WHO will now recommend that all new TB cases (pulmonary and extrapulmonary) should be treated with two months of isoniazid, rifampicin, pyrazinamide and ethambutol (2HRZE), and then with a four month continuation phase of isoniazid/rifampicin (HE). Note that this will require putting in place adherence support mechanisms to cover the entire course of TB treatment. An alternate regimen (with 2HRZE induction, followed by 6 months isoniazid and ethambutol should be phased out. Optimal dosing is daily, throughout the course.

During the discussion, some meeting participants raised concerns about phasing out the six-month continuation phase of HE regimen, given that the main reason for it had been to offer an option for settings that could not provide four months of directly observed therapy (since it is a rifampicin-containing regimen). But Dr Getahun said that with updated patient-centred methods of adherence support, this shouldn’t be an issue.

“Since the Stop TB Strategy, we are no longer aiming at or promoting the policing type of supervision. It has to be patient-centred treatment support, not really supervised treatment. This is clearly stated in the policy,” he said. “But I know the implementation of this policy in some countries will present problems so whenever we get the opportunity in country reviews or in country missions, we try to pass along the message that treatment has to be supported, and it has to be supported in the interest of the patient, with a patient-centred adherence strategy.”

However, in areas with high isoniazid resistance, it will be recommended to add ethambutol to the continuation phase. In addition, “culture and DST needs to be expanded (particularly for patients who were previously treated), and whenever there is a likelihood of a patient having drug-resistant TB, we should consider using an empiric MDR regimen depending on the national guidelines.” said Dr Getahun.

Also last year, WHO added rifabutin 150 mg to the essential medicines list as TB treatment in HIV-infected patients who are taking a ritonavir-boosted protease inhibitor (PI)-containing ART regimen. Since it has little effect on PI serum concentrations, rifabutin can be substituted for rifampicin — and even though rifabutin is considerably more expensive, when used in combination with standard doses of boosted-PIs, it turns out to be cost-effective.

The Three I's

Several studies and posters described the growing uptake of the 3I’s to reduce the burden of TB in people with HIV, especially intensified case finding.11 12

“In terms of intensified case finding, it’s very encouraging that we see many activities happening in many countries. HIV implementers now seem to have embraced this activity. We are still lagging behind what we need to do, but we are on the right track.” said Dr Getahun.

He reported that currently WHO and the CDC are working on a meta-analysis of primary data for TB screening (including twelve data sets and over 30,000 people). The primary question: What is the most sensitive clinical algorithm to screen for culture-confirmed pulmonary TB in people living with HIV? The objective is to develop a standardized evidence-based approach and guidelines for TB screening and prevention (IPT) among PLHIV.

The guideline will contain an algorithm that identifies an individual as a TB suspect, who should then be referred for diagnosis.  If they are not a suspect, they should be put on a course of IPT. WHO plans to finalise this analysis in the next two or three weeks at a meeting in Geneva.

One issue raised by several speakers is that scaling up intensified case finding cannot be done successfully without also scaling up TB laboratory capacity.

According to Dr Bernard Langat of the Division of Leprosy TB and Lung Disease in Kenya, to support ICF, his country needs to expand diagnostic capacity (especially fast liquid culture to diagnose smear-negative TB in patients with HIV). “We need to decentralise and it costs money”, he said. Plus there are issues of workload. “For every patient found with active TB, ten are screened with very good screening tools. So the number of smears will be going up and human resources in the lab are definitely an issue.”

Dr El-Sadr agreed that if programmes begin using screening tools that are highly sensitive, but with low specificity, “The amount of work-up that will need to be done on all of our suspects will increase tremendously. We need to think about how we are going to balance using highly sensitive but not specific tools with laboratory capacity to diagnose.”

PEPFAR is willing to provide assistance with laboratory scale-up, according to Dr Amy Bloom of USAID: “ICF is very high up on our radar — then looking at laboratory services to support it.”

Another option might be to simply offer TB treatment to suspects with advanced disease and symptoms of TB.  Dr El-Sadr described a study that is in development that would randomise people with advanced HIV disease entering care with very low CD4 cell counts at the time of initiating ART to immediate empiric TB treatment, versus the standard approach of work-up and diagnosis of TB, then followed by treatment. The outcome will be mortality.

But Dr Francois Venter of Johannesburg Hospital stressed that finding TB suspects is not enough, “It’s what you do with them after you’ve found them. We spend a huge amount in South Africa, diagnosing people with TB and then not retaining them in care or rapidly initiating them on therapy. At Baragwanath Hospital in Johannesburg, 50% of the hospitalised patients diagnosed with TB don’t make it to a TB clinic. These are diagnosed patients with fully susceptible TB and they still can’t get to the clinic. The system is failing these patients.”

He complained about all the money being invested in expensive diagnostics and new drugs, saying that there are fairly simple cost effective solutions to these problems.

“Asking for new drugs and new diagnostics is useless. If instead, we had somebody phoning these patients, or actually escorting them to the TB clinics, I bet we would save a hell of a lot more lives,” he said.

The uptake of IPT is still limited (and discussed in a related article in this edition of HATIP); but “of all the Three I’s, infection control still seems to be the most neglected,” said Dr Getahun.

“We’re all well aware of how far behind we are,” said Dr Bess Miller, who is also the chair of the Infection Control subgroup of the TB/HIV Working Group of the STOP TB Partnership.

Dr Miller noted that the WHO is also in the process of finalising TB Infection Control Policy for Health Facilities (a draft copy was finally available for distribution at the meeting). She also said the working group has put together a work plan to address a number of areas.

“The area we’ve been most successful in is training, and human resource development. Between TB CAB and WHO, there have been numerous trainings in every region of the world to train people at the national level in TB infection control.  In addition to that, we are developing training materials for health care workers. We also need to have some M&E tools — surveillance of TB among workers in facilities is part of that.  Another area we are working on (ICAP has taken some of the lead on this) is developing facility-level materials. We are in the process of developing a manual.”

Dr Miller believes that the responsibility for infection control will ultimately fall on nurses.

“We have hired an infection control nurse, and want to work with the International Confederation of Nurses, and the Association of Practitioners of Infection Control to try to work on nurse behaviours, on an ongoing basis, to monitor infection control.” While the complete package is in development, Miller shared a tool with a basic checklist for nurses to use to monitor basic infection control practices at a facility.

Dr Venter is sceptical this approach will work.

“You try to tell a nurse in Johannesburg that she has to work with open windows in the winter. Even in Africa, it does get cold. Their opposition is rational, because it is an unpleasant place to work in. And they keep telling me that I have to move coughing patients to another area. Seventy per cent of the admissions in my hospital are there for respiratory infections. My sense is that we should just build another hospital for the patients who aren’t coughing. I have yet to visit a hospital in Southern Africa where coughing patients are put in another place. I think we need to take three steps back and think about what is going to work in this situation.”

He cited the TB infection control projects that MSF has pioneered, “but it takes the dedicated passion of a large group of people to implement them in just one area in South Africa, if we have to demand this from the system across the board, it is very difficult.”

Dr Venter believes that an emergency response that includes teams with infection control engineers are needed to make site visits to get facility managers on board, and enforce infection control.

“I agree that infection control is important, but the leadership behind it has been lacking. Recently, 30 healthcare workers died in one year in a hospital north of Tugela Ferry, of MDR TB. If they all died in car accidents we would make compulsory driving lessons for healthcare staff. It just happened quietly and was swept under the carpet. So where is the action? Where is the emergency that WHO declared a few years ago?”

Dr El-Sadr noted that infection control issues do go beyond the scope of the HIV programme. “Facilities have to buy into infection control (even though there are some activities that fall square on the HIV department, like ICF and IPT), but without advocacy and buy-in at the facility level, it is going to be hard for the HIV programme to push a specific agenda.”

Nevertheless, as is so often the case if the HIV programme does not push for infection control, it isn’t clear who will. 

Overall, Dr Venter voiced frustration with the implementation of the Three I’s.

“We have to scale beyond the believers. We wouldn’t come to a PEPFAR Implementers' meeting and talk about how we put 120 patients on antiretrovirals and these are the lessons learned. We’d be laughed out of the room. But we do this for TB quite often but that’s not scale, that’s a joke,” he said. “We need more research on operational interventions to make these programmes work, rather than biological or treatment approaches.”

Dr El-Sadr was more upbeat however:

“I always feel like [after] meetings on TB/HIV, that we walk out feeling depressed, but I want to fight this. We’ve really achieved a lot. A few years ago, nobody was being tested for HIV in TB clinics, now in some countries, all the people are being tested and linked to HIV care. I think that even starting to think about screening for TB routinely is great, and the efforts being put into place to improve laboratory capacity, and talking about TB in kids and trying to do IPT in kids [too]. We really should walk out of here encouraged,” she said.

References

[1] Turate, I. et al. Mortality rates and causes of death in Rwandan patients on HAART: recommendations to improve patient care. 2009 HIV Implementers' Meeting, Windhoek, Namibia, abstract 1793.

[2] Gunneberg C. Newly revised global estimates of HIV related to TB: M&E implications for HIV implementers. 2009 HIV Implementers' Meeting, Windhoek, Namibia.

[3] Chimbwandira F et al. The Malawi experience of HIV and TB monitoring and evaluation system. 2009 HIV Implementers' Meeting, Windhoek, Namibia.

[4] Mohammed E. Ethiopian experience of TB/HIV monitoring and evaluation in HIV care settings. 2009 HIV Implementers' Meeting, Windhoek, Namibia.

[5] El-Sadr W. Experience from the field: success and challenges of capturing TB/HIV collaborative activity data in HIV care settings. 2009 HIV Implementers' Meeting, Windhoek, Namibia.

[6] Lwanga I et al. Examining drug default for treatment of tuberculosis in an urban HIV clinic in Uganda. 2009 HIV Implementers' Meeting, Windhoek Namibia, abstract 117.

[7] Zvavamwe C et al. TB/HIV co-Infection: proximate determinants of mortality among TB patients in the Omaheke region of Namibia. 2009 HIV Implementers' Meeting, Windhoek, Namibia, abstract 1101.

[8] Gunneberg C. HIV Testing for TB patients in the African region. 2009 HIV Implementers' Meeting, Windhoek, Namibia, abstract 1090.

[9] Viet Nhung N et al. Expansion of provider-initiated HIV testing and counseling for TB patients to 14 provinces in Vietnam, 2007-2008. 2009 HIV Implementers Meeting, Windhoek, Namibia, abstract 706.

[10] Grand’Pierre, R. et al Capacity building at rural sanatorium in Haiti to diagnose HIV/TB and MDRTB. 2009 HIV Implementers Meeting, Windhoek Namibia, Abstract: 217.

[11] Odawo P et al. Integrating screening and diagnosis for tuberculosis (TB) into HIV clinics in a Nairobi slum, 2001-2008. 2009 HIV Implementers' Meeting, Windhoek, Namibia, abstract 894.

[12] Fernandes R et al. Use of a TB screening tool at ART facilities improves TB case finding and management of co-Infected patients. 2009 HIV Implementers' Meeting, Windhoek, Namibia, abstract 1708.