Preliminary results from the first programme to integrate directly observed therapy (DOT) TB treatment with methadone treatment for people who inject heroin in Africa show that it “is feasible and the patients found it quite acceptable despite stigma-related to TB/HIV treatments,” said Dr Robert Bruce of Yale University, speaking during the TB-HIV Late Breaker Session of the 44th Union World Conference on Lung Health, held from the October 31-Novermber 3rd, 2013 in Paris.
Dr Bruce was describing a preliminary report on a small open label study involving 51 participants, who were all willing to receive their TB and HIV medications from the window where methadone was being dispensed.
“The study has demonstrated treatment successes and low rates of mortality and treatment default — only three patients so far have defaulted. The treatment completion rates approach the WHO global standard but in a high risk and traditionally non-adherent population,” he said.
Drugs and HIV in Africa
Heroin has been coming into East Africa through Mombasa, throughout Kenya as well as through Zanzibar into Dar es Salaam for the last two decades.
In 2011 The United Nations Office on Drugs and Crime (UNODC) estimated in 2011 that there were 1,736,000 heroin users in Africa with approximately 533,000 residing in East-Africa. In 2005, an estimated 200,000 to 250,000 heroin users were in Dar es Salaam alone – most of whom were smoking heroin while approximately twenty to forty thousand people who were injecting heroin.
According to Dr Bruce, these tend to be individuals (the majority are male) with a median age of 34 (between 25 to 49) who live on the street. Most of them have a history of incarceration.
The HIV prevalence in Tanzania is 5.6%, and in Dar es Salaam it is approximately 9.5%. However among residence from Dar es Salaam who inject heroin, an estimated 42% are living with HIV. And as has been observed in Eastern Europe, Russia and in many other places in the world, injection drug use leads to HIV and HIV-infected drug users are at a great elevated for tuberculosis.
The Methadone Clinic at Muhimibili Hospital
One evidence-based method to reduce these risks is methadone. Methadone is a synthetic opioid helps treat heroin dependence by controlling withdrawal symptoms. It’s administered once daily in structured settings — and people who are seeking to reduce dependence on street heroin may be highly motivated to come to the clinic for their daily treatment.
Methadone also has demonstrated HIV-preventive effects since it can lead to a reduction of unsafe injecting practices that spread HIV among people who inject heroin.
So, in an effort to help address the epidemic of HIV among people who inject heroin, the first publically available methadone clinic in sub-Sahara Africa was established in Dar es Salaam at Muhimibili Hospital.
“It took a lot of effort to sell the country that methadone was not enslaving people to a medication that caused harm. But as individual patients, and as physicians began to see the added benefits of the treatment, it has become very in demand,” said Dr Bruce. “Most recently what is helped is that President Jakaya Kikwete had an individual that he was quite close to obtain methadone maintenance. It was very helpful to that person’s life and since then the president did a photo op at the methadone clinic and has been encouraging the ministry of health to expand evidence-based treatment for heroin addition throughout the country.”
Addressing Tuberculosis among people who use Drugs
There is also a high rate of tuberculosis in this key population in Tanzania. According to the WHO Global TB Report for 2013, the rate of TB in the general population in Tanzania is 177 per 100,000. But Dr Bruce’s group has looked at the rate of TB in the methadone population and found it to be around 4,000 per 100,000. Aside from the greater associated with a high HIV burden, people who inject drugs are placed at greater risk of TB because they congregate during the day in intimate settings to use drugs, and many of them have previously been incarcerated — and the risk of contracting Mycobacterium TB in many of the prisons in Africa is extremely high.
However, it can be difficult for people who inject heroin to adhere to TB (or HIV) treatment when they are threatened by withdrawal symptoms — finding the next hit of heroin to prevent withdrawal can become one’s overriding concern.
The Methadone Clinic at Muhimibili Hospital
“The National TB programme has a very warranted concern about non-adherence in this TB population who are heroin injectors,” said Dr Bruce. “We wanted to use methadone, which is administered, once daily under observation, as an avenue to address adherence by integrating the TB treatment with the methadone maintenance.”
“Methadone is a very powerful incentive for adherence. When patients come to the clinic every day and take their methadone they feel normal, functional; they can go get a job and participate in life. If you don’t get your methadone you become quite ill. And so you’re very incentivised to attend the clinic,” Dr Bruce said, adding, “and the methadone is free,” (while heroin is not).
A pharmacist dispenses methadone through a dispensary window at the clinic, seven days a week. TB medications (or HIV medications for that matter) can be dispensed at the same time, and adherence directly observed.
For the purposes of this evaluation, a retrospective chart review was performed of all the people attending the methadone clinic at the Muhimibili National Hospital as of July 2013 — a total of 638 patients — looking for those who had received first-line anti-TB treatment with their methadone from the start of the clinic, which was February 2011. (The TB diagnoses had been made using standard microbiological and/or clinical criteria).
51 patients who met these criteria were identified, 40 men, 11 women — which reflects the general demographics of the methadone clinic.
Of those 51, thirty have finished TB treatment, and thirteen (25%) are still on continuing on treatment.
Only three of the fifty-one patients default from treatment, and five have died, all of whom had HIV and were on HIV therapy.
“As you can imagine, patients attending the methadone clinic as heroin injectors are often coming in to process late in their disease,” said Dr Bruce. “In fact, the first patient died in the clinic before being able to be started on any treatment, patient no. 7, died of overwhelming TB infection.”
Thirty-eight of the fifty-one were HIV co-infected and thirty-two of these were on HIV therapy.
“We would all like to see one hundred per cent of co-infected patients with HIV therapy, but it is not a small task for us to convince the HIV department at the hospital to treat drug users,” he said. “We also had to vouch for the adherence of the HIV component as well, providing in some cases HIV, TB and methadone simultaneously from the methadone-dispensing window.”
Dr Bruce’s work highlights that heroin injecting is not just an issue in Eastern Europe and Asia but is an emerging issue in sub-Saharan Africa. In fact, there’s a very large population of heroin users in Africa who have high rates of HIV and TB — a population that receives too little in sub-Saharan Africa.
Furthermore, while the study is small, and needs to be confirmed in a larger number of patients and at other sites, it does suggest that an integrated methadone and TB-HIV treatment programme is feasible in an urban African setting — and achieves results similar to global standard for TB treatment.
“Prior to this programme, this population remained largely untreated. The general parlance in the environment was that these individuals were untreatable due to their heroin addiction,” said Dr Bruce. “This work highlights the importance of methadone as an essential component of TB treatment success among heroin injectors and stresses the need to expand access to methadone treatment.”
Next steps and future research:
The challenge of meeting the need should not be underestimated — as Dr Bruce noted, there are an estimated 200,000 people who use heroin in Dar es Salaam alone.
Future work in this area includes epidemiological research on the extent, severity and consequences for HIV and TB co-infection control among heroin users throughout the community and throughout Africa. Ongoing pharmacokinetic research is needed for TB/HIV interactions as well as methadone interactions. For instance, streptomycin, efavirenz and nevirapine all induce the metabolism of methadone.
According to Dr Bruce, this was a significant issue for the programme. “We budgeted for an average of 100 mg a day of methadone and in some cases patients run 200 mg a day due to induction from either nevirapine, azithromycin or nevirapine/efavirenz-based regimens. So we were giving people more methadone.”
Dr Bruce added that “additional operational and implementation science research is needed to expand this interventional strategy to other settings.”
One, not so far away, is Zanzibar, which is a conservative Muslim autonomous region of Tanzania that has been harder to sell on harm reduction. For instance, programmes working with people who inject drugs in Zanzibar have not been able to offer syringe exchange services.
“From an HIV prevention perspective the cheapest most effective thing to do is large-scale syringe exchange, for injection drug users,” said Dr Bruce. “But syringe exchange is fraught with multiple problems due to funding limitations and the misbelief that the exchange of syringes promotes drug use – and I will stress, ‘the misbelief’ — there is not evidence that shows that syringe exchange promotes drug use, it prevents HIV and saves lives. A lot of countries don’t like to do it, and Zanzibar is one of those places.”
Similarly, efforts have been underway since 2008 to roll out methadone in Zanzibar — it was supposed to start there before the programme in Dar es Salaam, but progress has been very slow.
“Part of it is that Zanzibar is a very Muslim part of Tanzania and so has different beliefs on being maintained on medication – we’ve been working closely with colleagues in Muslim countries who have methadone maintenance notably Malaysia, Iran to try and encourage our Zanzibar colleagues on the acceptability of methadone maintenance therapy in the population. But I think we’ll have methadone in Zanzibar maybe by this year or next year.
The audience of the presentation suggested a couple of other ideas for research in this setting. One was to study the use of this for isoniazid preventive therapy in people living with HIV on methadone maintenance therapy. Another issue, raised by doctor from the Ukraine was that TB is sometimes diagnosed late in people on methadone — because opioids can suppress cough — and extra care.
Dr Bruce agreed and noted that he had listened closely to a presentation by Dr Stephen Lawn (to be covered here shortly), which focused on the diagnosis of TB using urine as a specimen — “because in methadone clinics, we collect a lot of urine,” he said.
Bruce, R. Preliminary Report on the First TB-DOT Programme Integrated into Methadone Treatment for Heroin Injectors with TB in Sub-Saharan Africa. 44th Union World Conference on Lung Health, 2013, Late Breaker abstract.