Facts about SPARTAC
In this section you can some questions and answers about SPARTAC. If you want to find out more general information about HIV, please go to our 'Facts about HIV useful links' page.
- What is SPARTAC?
- How is HIV treated currently?
- What is CD4 count?
- What is acute/primary HIV infection?
- What is seroconversion?
- Why is SPARTAC important?
- Why was SPARTAC done in resource-limited countries?
- Who sponsored and funded the SPARTAC trial?
- Which drugs were used in SPARTAC and where did the drugs come from?
- Why did SPARTAC choose 12 and 48 weeks of treatment?
- How were participants recruited?
- Why did people decide to take part in SPARTAC?
- What was done for participants’ safety and welfare?
- How informed were community stakeholders about SPARTAC?
- What will happen to the study participants now SPARTAC has finished?
- Did SPARTAC have a group who received continuous long-term treatment?
- Did SPARTAC look at HIV transmission?
- What other clinical trials are looking at new ways of treating HIV?
- Is an AIDS vaccine still necessary?
- How can I find out more about SPARTAC?
What is SPARTAC?
SPARTAC (Short Pulse Anti Retroviral Therapy at HIV Seroconversion), is the largest randomised controlled trial ever undertaken in primary (recent) HIV infection. The study ran between 2003 and 2011 across eight countries.
SPARTAC examined whether treating people recently infected with HIV (within 6 months of infection) with anti-HIV drugs for a short period of time could slow down the damage caused by HIV to the immune system and consequently delay the need to start long-term treatment.
The SPARTAC team recruited enough participants to ensure that any differences between the study groups would be detectable, and that any findings from the study would not be due to chance: 366 adults – mainly heterosexual women and men who have sex with men (MSM) – took part from 35 sites in Australia, Brazil, Ireland, Italy, Spain, South Africa, Uganda, and the UK. SPARTAC participants were allocated into one of three treatment strategy groups randomly, like the roll of dice. The three groups were:
- a short-course of ART for 12 weeks (ART-12);
- a short-course of ART for 48 weeks (ART-48);
- no ART (the current standard of care (SOC) for people recently infected with HIV).
The SPARTAC team followed up participants for at least 3.5 years measuring when a participant’s CD4 count had fallen below 350 cells per mm3 blood (a measure of the strength of the immune system) and/or they started long-term treatment. The team are now working to compare how the 3 groups fared in terms of the measurements taken.
Trial design:
Where SPARTAC was being conducted and number of participants in each country:
How is HIV treated currently?
Anti-HIV treatments, called antiretroviral therapy (ART), can only slow the course of the disease; there is no known cure or vaccine. HIV destroys a person’s immune system which protects the body against illnesses. If HIV destroys too much of the immune system, the body can no longer protect itself against illnesses and the person can become very sick. This can take up to 10 years to happen. ART is usually only prescribed once blood test results (CD4 count) show that the immune system is failing. Once a person starts ART, it is long-term and has to be taken for life. ART is expensive, must be taken every single day and can have negative side effects.
Usually when people have recently become infected with HIV, even if they feel unwell for a couple of weeks, they are not sick, and are not treated with anti-HIV treatment. People who have recently become infected with HIV often don't even know that they have the virus, as symptoms are often few and non-specific. In rare cases, people recently infected with HIV can become sick straight away and need life-long treatment immediately; anyone who was judged to be in this group by their clinician was not eligible to join the SPARTAC study.
What is a CD4 count?
HIV destroys CD4 cells which are involved in the body’s immune system response. The CD4 count is a measure of how many immune cells there are in the blood and reflects the level of how well the body can fight infections. A normal CD4 count is 500 or more CD4 cells per mm3 blood. People living with HIV usually lose around 50-100 cells per year without treatment. Most National and International HIV treatment guidelines recommend starting lifelong anti-HIV treatment when the CD4 count falls below 350 cells/mm3 blood. However, this is not the case for all countries.
What is acute/primary HIV infection?
The first few months following infection with HIV are known as primary, or acute, HIV infection. This is the period between when HIV first enters the body and the time that HIV antibodies, produced by the immune system to try and get rid of HIV, can be detected in the blood. Definitions as to the length of time this takes vary. In SPARTAC primary, or recent, HIV infection was defined as within six months of becoming infected with HIV.
What is seroconversion?
Seroconversion is the time when the immune system starts to produce antibodies to get rid of HIV in the body (the individual changes from being sero-negative to being sero-positive).
Why is SPARTAC important?
SPARTAC is important for three main reasons:
1. Improve current HIV treatment
Scientists and doctors specialising in HIV are always looking for better ways to treat people living with HIV. HIV affects a person’s immune system by killing the cells that protect the body against illnesses. Upon infection, HIV starts to spread quickly but it usually takes a few years for the virus to destroy enough cells for the immune system to fail. According to current standards of care, anti-HIV treatment, called anti-retroviral therapy (ART), is usually prescribed once biological tests show that the immune system is failing. Once a person starts ART it is a long-term commitment for life. ART is expensive, must be taken every single day and can have negative side effects.
The aim of SPARTAC was to see if giving ART over a short period when a person has recently been infected could delay damage to the immune system (CD4 count) and consequently the need to start long-term ART enough to significantly shorten the time on long-term ART.
2. Treating recent infection
A number of studies carried out before SPARTAC suggested that giving ART to people recently infected with HIV, even for a short period of time, could limit the damage to their immune system (CD4 count) and delay their need to begin long-term ART. However, these studies were either on too few individuals or had not been randomised, and were therefore were unable to produce the scientific evidence needed to determine if immediate treatment is beneficial to the individual.
3. Inform treatment guidelines
Current national and international HIV treatment guidelines therefore lack the evidence on which to base recommendations on how to manage and whether to treat people known to have recently been infected with HIV.
Why was SPARTAC done in resource-limited countries?
It is important to test new strategies of treating HIV in all settings in which HIV is present to ensure that the new strategies are generalisable, safe and acceptable in as many relevant populations as possible.
Who sponsored and funded the SPARTAC trial?
The study was funded by the Wellcome Trust and was part of an international collaboration led by the Chief Investigator, Professor Jonathan Weber, at the sponsor, Imperial College London, together with the University of Oxford, the Medical Research Council Clinical Trials Unit (MRC CTU), and participating clinical Partners in Australia, Brazil, Italy, Spain, South Africa, Uganda, and the UK and Ireland. Abbott Laboratories donated the anti-HIV drug Kaletra to resource-limited SPARTAC clinical sites.
Which drugs were used in SPARTAC and where did the drugs come from?
The SPARTAC study looked at evaluating anti-HIV treatment strategies rather than any specific drugs. The drugs used in SPARTAC were standard anti-HIV drugs with a known safety toxicity profile, i.e. drugs which are known to have minimal side effects (mostly two NRTIs and a boosted PI). These anti-HIV drugs are all currently being used for the long-term treatment of people with later-stage, symptomatic HIV. SPARTAC did not use any new drugs during the trial.
The drugs used in Brazil, South Africa and Uganda, were donated by Abbott Laboratories and not taken from hospitals treating those most in need of HIV treatment. Clinical resources used in resource-limited settings and all other anti-HIV drugs used in SPARTAC were funded by the Wellcome Trust and did not impact on diverting health care resources in resource-limited settings.
Why did SPARTAC choose 12 and 48 weeks of treatment?
The length of the short courses of treatment were based on previous pilot studies which suggested that using 12 weeks of treatment might significantly reduce the amount of HIV in the blood. It was anticipated that 48 weeks of treatment would mean participants in this group would experience a period when HIV levels were so low, they were undetectable.
How were participants recruited?
Only people with a confirmed recent HIV infection were eligible to participate in the SPARTAC trial. Repeat HIV testing is the only way to detect recent HIV infection (also known as primary HIV infection). Seroconversion between two HIV tests (i.e. the first test is negative and second positive) indicate that a person has recently become infected with HIV.
People were not enrolled if there were any indications that their participation might not be in their best interest. Reasons for ineligibility included: being sick at the time of recent HIV infection, needing immediate lifelong treatment, pregnancy, any other clinical reasons, financial or social reasons, drug or alcohol abuse or if the participant showed signs that they may have difficulty with treatment adherence.
All eligible participants were fully informed before joining that SPARTAC was a research study and not an anti-HIV treatment access program. All participants had to satisfy staff that they understood the trial and its potential effects on them and provide formal agreement to take part. This is called informed consent and is an International agreement (Helsinki agreement) that is used to recruit participants into any clinical study and ensures that the participation is entirely voluntary and that the person has a full understanding of what the study is about and what will happen to them whilst in the study.
Throughout the trial, updates were given to participants about the study and they could withdraw at any time and join an anti-HIV treatment access programme instead. Participants received ongoing counselling throughout the trial, as well as support from field workers and SPARTAC trial staff with regard to any concerns about taking part in SPARTAC.
Participant meetings and treatment literacy workshops were organised by Partner institutions in Africa with the involvement of Treatment Action Campaign (TAC).
The low withdrawal rate is testament to participants being fully informed and satisfied with the way the trial was conducted. The SPARTAC team is grateful to the contribution participants have made to furthering progress in HIV treatment by taking part in this clinical trial.
Why did people decide to take part in SPARTAC?
SPARTAC participants gave various reasons for taking part in the trial. For example, in the UK most participants stated that that they wanted to do something to feel in control of the virus; participants wanted to be involved in case there was a chance that the treatment they received through SPARTAC could be beneficial to them. Altruistic reasons were also an important motivation; study participants were willing to take part if they felt anything important could be learned from their experience that could help others in the future. In resource-limited settings many participants valued the opportunity to receive a more intensive and personalised care programme than would be available through national treatment centres, which can be over-subscribed and where it is often costly and time consuming to wait for an appointment.
What was done for participants’ safety and welfare?
Before the trial started in 2003, the study design received ethics approval from the Multicentre Research Ethics Committees (MREC) and the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. Each participating site also received individual ethics committee approvals in each of the countries participating. These independent bodies made sure that the trial was ethically sound and that participants would be well monitored. Subsequent amendments to the trial protocol were also approved by MREC, MHRA and all local ethics committees.
SPARTAC’s progress was monitored by a data and safety monitoring committee (DSMC); an independent committee composed of clinical research experts and statisticians that provided additional oversight of the clinical study. As with the DSMC of any trial, they had access to all the information about trial participants throughout the study and if data suggested there were any safety problems or that one group was clearly doing much better than the others before the scheduled trial end date, they would recommend stopping the study early. The DSMC regularly reviewed the SPARTAC data throughout the trial to ensure both that the safety of the participants was independently monitored and that any benefits shown in the study would be made available to all participants. SPARTAC’s DSMC met annually for the duration of SPARTAC. On each occasion, the DSMC reported no safety concerns with the data and recommended that the SPARTAC trial proceed as planned according to the trial protocol.
All participants had access to treatment according to national treatment guidelines should they become ill or need to start long-term treatment and received HIV-related care (information on safe sex practices, free condoms, treatment for sexually transmitted infections, frequent evaluation and treatment for any complications related to HIV infection, and ongoing counselling). Participants in South Africa and Uganda received additional clinical care through SPARTAC according to national treatment guidelines (such as antibiotic provision and tuberculosis treatment), referrals to local Wellness Centres for support and clinical care before participants became eligible for long-term treatment and referrals after SPARTAC follow-up finished to local treatment centres for when participants became eligible for long-term treatment under national guidelines. This was done to ensure participants in all settings received optimal care.
Any changes to international and national HIV treatment guidelines that could impact the SPARTAC participants were discussed with the SPARTAC Principal Investigators and clinicians.
Participants were regularly monitored throughout the trial for any adverse effects of the 12 or 48 weeks of treatment received outside the standard of care. Any cases of serious adverse events, adverse events and AIDS events were monitored by the Trial Physician and reported to the regulatory authorities.
All participants attended regular clinic visits and were monitored for drug induced resistance. Resistance usually occurs when the level of drug in the blood system falls below a certain critical level which then allows virus to start growing again. This can happen if there is any interruption in the adherence to anti-HIV treatment, i.e. the drugs are not taken regularly and consistently or the drugs are not absorbed properly. Resistance means that the drugs will no longer work against HIV and the patient has to use a different anti-HIV drug. Drug resistant strains of HIV can also be passed on from one person to their sexual partners.
Participants given 12 and 48 weeks of anti-HIV treatment received resistance tests during and 4 weeks after stopping the short courses of treatment. Resistance tests were carried out on any participant who came into a SPARTAC clinic with signs of drug resistance. If any participant was found to have become resistant to their prescribed first line drug regimen, the regimen could be altered to a second line drug regimen that the HIV did respond to. Support and advice was available from the Trial Physician to all participating sites.
How informed were community stakeholders about SPARTAC?
A representative of communities at risk of HIV infection sat on the SPARTAC Trial Steering Committee and regular community stakeholder meetings were held in each of the South African sites prior to the trial commencing, and then at quarterly intervals. At these meetings, the community stakeholders were informed of the trial design, expectations and status of the trial as it progressed.
What will happen to the study participants now SPARTAC has finished?
In the resource rich settings (including Brazil) in which SPARTAC took place, participants will either continue to be seen at the same clinical centre for their ongoing clinical care or will be referred to a local treatment centre.
In Africa, where long-term anti-HIV treatment cannot be provided by the clinical trial centres, intensive work with the participants has been ongoing throughout the trial to reinforce the need for participants to take up anti-HIV treatment within the public sector to receive their ongoing clinical care and anti-HIV treatment. This has included referrals, enrolment, orientation and supported visits to participants’ local service providers for long-term anti-HIV treatment, ongoing counselling to wean participants off the dependency of the trial site and referrals to local service providers for contraception, tuberculosis (TB) treatment and other services provided by trial sites during SPARTAC.
At the end of the trial, each participant received an individualised summary of their medical history and clinical issues requiring follow up as needed for subsequent care in the public sector.
SPARTAC trial centre staff will stay in touch with participants to ensure long-term clinical care and anti-HIV treatment is taken up. SPARTAC is also proposing further work to follow up participants in all countries to see if the 12 and 48 weeks of treatment given to two of the participant groups have had any long-term effects.
Participant meetings will also be held to inform participants and community stakeholders in all countries of the SPARTAC result and to enable participants to ask questions.
Did SPARTAC have a group who received continuous long-term treatment?
Since 2003, when SPARTAC was initially designed, opinions on treating recent HIV infection have evolved and a number of studies have started to point towards treating people with HIV with long-term anti-HIV treatment as soon as possible (continuous treatment). There was no evidence to suggest this at the time of the SPARTAC trial design, and hence it was not included.
Did SPARTAC look at HIV transmission?
Although SPARTAC did not look at whether giving a short course of 12 or 48 weeks treatment to people recently infected with HIV has an effect on HIV transmission it may be able to show that it is possible to regularly test people for HIV in a diverse range of settings.
Recent HIV infection is estimated to be responsible for up to four out of ten new HIV transmissions within a given population. People who have recently become infected with HIV often don't know they have HIV as most people have few and often non-specific symptoms. At this stage of infection, people also tend to have very high levels of the virus in their blood, making them especially high risk to pass on the virus to their partners. By identifying people recently infected with HIV it may be possible to change a person’s behaviour and stop the spread of the virus. The tests we have for HIV at the moment cannot tell how long the person who carries the virus has been infected. The only way to find out if a person has been recently infected with HIV is through regular testing, i.e. a negative test on one occasion is followed by a positive test the next.
A recent study separate to SPARTAC called HPTN 052 has looked at HIV transmission.
What other clinical trials are looking at new ways of treating HIV?
Since SPARTAC started, opinions on treating HIV have evolved and a number of new studies are pointing towards starting people with HIV on life-long treatment earlier than previously recommended. There have also been other studies looking at interrupting treatment or giving short-courses of treatment. A few of these studies are described below:
HPTN STUDY 052
This study looked into whether giving anti-HIV treatment to people with chronic, late-stage, HIV before their immune cell count fell to 350 cells per mm3 blood (referred to as ‘early treatment’) protected their uninfected long-term sexual partners from HIV infection. It showed that early HIV treatment reduced HIV transmission between couples by 96%.
SMART: A Comparison of Two Ways to Manage Anti-HIV Treatment
This study aimed to look at better ways of using anti-HIV treatment resources by seeing if people with late stage, chronic HIV who were doing well on long-term treatment could have a ‘break’ in their treatment. It showed it is unsafe to stop long-term treatment given during chronic HIV infection, the main risk being heart attacks.
START: Strategic Timing of Anti-Retroviral Treatment
This study is evaluating whether it is better for people infected with HIV to start long-term treatment earlier when they are well and their immune system is still functioning, rather than when they are ill or their immune system has early signs of immune damage (CD4 count is less than 350 cells/mm3 blood) as is currently recommended. START differs to SPARTAC as it is looking at giving participants with strong immune systems who may have been infected for many years long-term treatment, rather than giving people recently infected with HIV a short course of treatment (12 or 48 weeks), as in SPARTAC. The trial is still recruiting participants and is due to report its findings in 2015.
ACTG 5217, the SETPOINT study
This study compared the effect of giving 36-weeks anti-HIV treatment to people recently infected with HIV versus no treatment (unless needed because of HIV disease progression and according to standard of care). The study was testing if a short course of anti-HIV treatment would lower the amount of virus in the blood (viral load) when measured 36 weeks after stopping treatment (the ‘viral set point’ chosen for this study). Following a Data and Safety Monitoring Board review in June, 2009, the study was stopped because participants were starting long-term treatment before they had reached the viral set point (i.e. 36 weeks after stopping treatment). However, when comparing the time to starting long-term treatment the data showed that giving a short course of 36 weeks treatment to people recently infected with HIV delayed starting long term treatment by 18 weeks over a 60 weeks period.
Test and treat
The test and treat approach to HIV prevention comprises a number of strategies aimed at identifying a very large proportion of those infected with HIV, linking them to care and starting anti-HIV treatment as soon as possible regardless of their CD4 count. The approach relies on effective treatment reducing the amount of HIV in the blood (viral load) to levels where the infected person is no longer infectious i.e. reducing transmission.
Is an AIDS vaccine still necessary?
HIV clinicians and scientists are working to find a vaccine against HIV and therefore AIDS, a disease developed as a result of HIV. Current anti-HIV treatment delays disease progression but has side effects, is expensive and has to be taken every day. A successful vaccine to prevent new HIV infections would be a much safer way to control the epidemic. An HIV vaccine would work like a ‘flu vaccine and prepare the body’s immune system to fight the virus. If a person becomes infected, the immune system is ready to fight the virus thereby preventing the virus spreading and the person becoming ill and passing on HIV. If a vaccine is found, national and international treatment guidelines would be changed accordingly.
How can I find out more about SPARTAC?
We will regularly update the SPARTAC website but if you have any specific inquiries please email us at spartac@imperial.ac.uk.
If you are a participant and have any concerns about your involvement in SPARTAC, please contact your SPARTAC clinician or counsellor.
