“New AIDS prevention pill could cut infection rates in IV drug users by 50%,” the Mail Online reports, as the US Centers for Disease Control and Prevention (CDC) is set to approve the medication for injecting drug users.
The drug proved its worth in a large, well-conducted randomised control trial in Thailand. In this study, over 2,000 injecting drug users were given either placebo tablets or the ‘new’ drug tenofovir – which has been used to treat HIV since 2006.
The participants also attended monthly clinics to have blood tests to check for HIV infection, assess adverse events and to give them risk-reduction counselling. They were followed, on average, for four years to see if they contracted HIV.
The trial found that daily oral tenofovir reduced the drug users’ risk of catching HIV during the trial by about half: seven to eight per 1,000 would develop HIV per year without taking tenofovir, reducing to three to four per 1,000 per year if they did take tenofovir. Side effects for tenofovir were tolerable.
These are promising results though there are many other factors that would need to be considered before implementing an effective strategy on a wider scale outside of the context of a clinical trial.
While the obvious message in terms of HIV prevention is to stop injecting drugs, this type of pragmatic harm reduction approach could save many lives.
Where did the story come from?
The study was carried out by researchers from Bangkok Tenofovir Study Group, Bangkok, Thailand, and additional researchers from Centers for Disease Control and Prevention (CDC), Atlanta, and Johns Hopkins University, Baltimore, in the US. Funding was provided by the US CDC and Bangkok Metropolitan Administration.
The study was published in the peer-reviewed medical journal The Lancet.
The Mail Online's reporting of the study is accurate. However, there are additional issues that may need to be considered before the drug is licensed for this use, which the Mail does not describe.
What kind of research was this?
This was a randomised controlled trial that aimed to assess whether daily use of the antiretroviral (anti-HIV) drug, tenofovir, could reduce HIV transmission in injecting drug users.
Injecting drug users are at high risk of getting HIV due to needle sharing. Tenofovir is currently licensed for the treatment of people who have HIV infection, usually taken in combination with other antiretrovirals.
The researchers suggest that use of antiretrovirals to prevent HIV infection could be ‘a promising new strategy to end the HIV/AIDS epidemic’. Previous studies in animals and humans have suggested the drugs can prevent transmission of the virus. They are currently used to reduce the risk of mother-to-child transmission of HIV, and to reduce risk among healthcare workers who may have been exposed to HIV (for example, through a ‘needlestick’ injury).
The current study is a phase III trial, meaning the research has already progressed through the earlier stages of clinical trials. This study investigated tenofovir's effects and safety compared with inactive placebo in a large sample of injecting drug users.
What did the research involve?
The trial assessed whether giving tenofovir to injecting drug users reduced their chances of getting HIV over an average of four years.
It enrolled 2,413 injecting drug users from 17 drug-treatment clinics in Bangkok, Thailand. The clinics offer a wider range of services including HIV counselling and testing, risk-reduction counselling, social services, medical care, methadone treatment, condoms, and materials to clean injecting equipment (clinics cannot provide fresh needles under Thai law).
Participants were eligible if they were aged between 20 and 60 years, were HIV-negative, and reported injecting drugs during the previous year. The researchers excluded those positive for hepatitis B, and pregnant or breastfeeding women.
Participants were given contraception and hepatitis B vaccine, and were randomised to receive either daily oral tenofovir 300mg or identical placebo pills. Participants could choose either to be observed daily taking their treatment (this ensures the participants do actually take their pills), or could just attend the monthly visits. All participants attended monthly clinic visits where they received HIV blood testing, were assessed for adverse effects, and were counselled on risk-reduction and adherence to treatment.
Risk behaviour was assessed in more depth every three months.
The trial was long term, and lasted up to seven years. The average duration of follow-up was four years. The researchers assessed the number who remained in treatment each year.
What were the basic results?
Of the 2,413 randomised participants, 80% were men, 43% were in their 20s, 38% were in their 30s, and the remainder were older. The majority (63%) had injected drugs within the past three months.
Drugs used included heroin (22%), methamphetamine (33%), midazolam – a sedative which can give feelings of euphoria if injected at high doses (23%), and 22% were currently in a methadone programme.
For the first year, the proportion of participants retained in the trial was high (88% of the tenofovir group and 89% of the placebo group). However, this gradually declined each year up to seven years.
Overall, 34% of both groups withdrew from the study during the course of the seven years. Dropout during the course of the trial was for various reasons including loss to follow-up, death, pregnancy and contracting HIV. Participants took the drugs for an average 84% of treatment days, with no difference in adherence between the groups. Overall, 8% of participants reported sharing their drugs in some way.
HIV was acquired by 50 people during the trial:
- 17 in the tenofovir group – an incidence of 3.5 cases per 1,000 person-years of follow-up (if 1,000 people were followed for one year, three to four would develop HIV while taking tenofovir)
- 33 in the placebo group – an incidence of 6.8 per 1,000 person-years of follow-up (if 1,000 people who were not taking preventative treatment were followed for one year, six to eight would develop HIV)
This meant that taking tenofovir cut the risk of contracting HIV by about half (48.9% reduction, 95% confidence interval [CI] 9.6 to 72.2%).
There was no significant difference in the risk of any adverse events between groups. The most frequent adverse events were:
- abdominal pain
- weight loss
Between 5% and 20% of people in both groups experienced these events. The only event that was significantly more common with tenofovir was nausea and vomiting, which affected 8% of the tenofovir group and 5% of the placebo group.
How did the researchers interpret the results?
The researchers concluded that daily oral tenofovir reduced the risk of HIV infection in people who inject drugs. They suggest that preventative treatment with tenofovir ‘can now be considered for use as part of an HIV prevention package for people who inject drugs’.
This was a well-conducted trial which has many strengths, including its very large sample size, long duration of follow-up, and regular and thorough assessments of HIV outcomes, adherence to treatment, adverse effects and risk counselling.
It found that daily oral tenofovir, when taken by injecting drug users, causes an almost 50% reduction in their relative risk of contracting HIV. It found that about seven to eight per 1,000 would develop HIV per year without taking tenofovir, reducing to three to four per 1,000 per year if they did take tenofovir.
Although the drug has been demonstrated to be effective, it is not yet licensed by drug regulators for this use. They will need to review a submission from the manufacturer on the evidence of efficacy and safety of the drug in injecting drug users before this can be granted. If tenofovir is licensed for this use, when considering whether it should be widely offered for this purpose, there are many factors to be taken into account. This includes the number of people that would need to be treated and duration of treatment, and the cost of this treatment.
For injecting drug users there are other important considerations. This includes that injecting drug–users’ often chaotic lives mean that they can find it difficult to access health services and may only be in contact with health professionals sporadically. This trial included only those who were currently attending drug treatment clinics. However, there are likely to be many other vulnerable groups of injecting drug users in the community who are not attending clinics, or who attend but then are lost to follow-up. Therefore, ensuring that all drug users are able to access care, and receive continued care and treatment may be issues that would need to be considered.
Another potential concern, is that preventative HIV treatment could possibly give false reassurance that the person is fully protected and would not be harmed by practices such as sharing needles or other injecting equipment, or having unprotected sex. It would still be important to ensure that people receive full information and guidance on the risks of blood borne infections (and other sexually transmitted infections), and the need to follow safe practices such as using single use needles and equipment and using condoms.