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DART trial finds HIV therapy could be given safely without routine laboratory tests to save more lives in Africa

21 July 2009

The largest clinical trial of anti-retroviral therapy (ART) for people with HIV infection ever run in Africa has found that regular laboratory tests offer little additional clinical benefit to populations when compared to careful clinical monitoring.

The results suggest that many more people with HIV in Africa could be treated for the same amount of money as is currently spent if lab tests are not routinely used to monitor the effects of ART.

The evidence from the Development of Anti-Retroviral Therapy in Africa (DART) clinical trial will be of value to low income or resource poor countries that are prioritising ART access over investment in expensive laboratory facilities.

The DART trial aimed to find out whether the lab-based strategies used to deliver ART to people with HIV infection in resource rich countries were essential in Africa, where around 4 million people still need ART urgently and resources are limited.

The DART team believes governments and policymakers, as well as people living with HIV/AIDS, can now be confident that ART can be delivered safely and effectively by trained and supervised health workers in remote communities where routine laboratory services are not available.

In all, 3,316 people who had not previously had ART took part in the DART trial. All had severe or advanced HIV infection and had been assessed for ART eligibility using clinical staging and laboratory tests including CD4 cell count (a measure of how well the body’s immune system, which is damaged by HIV, is working). The trial began six years ago when treatment for people with HIV was just starting to become more widely available in Uganda and Zimbabwe.

DART participants were randomly allocated to one of two groups. People in the first group received ART and their doctor was given the results of blood tests done every three months to check for drug side-effects and measure their CD4 cell count. People in the second group had the same ART and the same blood tests done, but their doctors did not see CD4 count results and only saw the results of safety tests if they were seriously abnormal. People in both groups received free medical care and free diagnostic tests for episodes of illness throughout the trial.

The results show that 90% of people in the first group were still alive after five years compared to 87% of people in the second group, a difference of only 3 percentage points. Over the five years data was collected, 78% of people in the first group survived and had developed no new AIDS-related illnesses, compared with 72% in the second group. These differences only became apparent from the third year of ART. The research team believes this may be a result of the participants in the lab-monitoring group switching to a different combination of ART earlier than those in the second group. No difference in the occurrence of side effects caused by ART was found between the two groups.

Irrespective of group, the survival rate in the DART trial is amongst the best reported from any trial, ART programme or study in Africa. Historical comparisons, based on data from follow-up of similar patients in Uganda who did not have access to ART make it clear that few of the DART trial participants would have been alive after five years without ART.

DART co- principal investigator Professor Peter Mugyenyi of the Joint Clinical Research Centre in Uganda said:

‘‘It is estimated that two-thirds of people who need treatment for HIV in Africa currently don’t have access to antiretroviral therapy. Thanks to DART, Governments now have evidence that expensive blood tests aren’t needed routinely for HIV treatment to be successful and safe. It also means that treatment could be delivered locally as long as health care workers have the right training, support and supervision. This could make a huge difference to people who live in remote areas that are many days’ walk from the nearest hospital or laboratory.’’

DART was sponsored and funded by the UK Medical Research Council. Further funding was provided by the UK Department for International Development and the Rockefeller Foundation. Antiretroviral drugs given to trial participants were donated by GlaxoSmithKline, Gilead Sciences, Abbott Laboratories and Boehringer Ingelheim. These pharmaceutical companies also provided funding for some of the sub-studies that were part of the DART trial.

Scientists and health care workers from Africa and the UK collaborated closely to run the trial. Healthcare and research centres in Uganda were the Joint Clinical Research Centre, Kampala, the Infectious Diseases Institute at Mulago Hospital, Kampala and the MRC/Uganda Virus Research Institute Uganda Research Unit on AIDS, Entebbe. In Zimbabwe, researchers were based at the University of Zimbabwe Medical School Clinical Research Centre, Harare. The MRC Clinical Trials Unit in London provided overall coordination and the secretariat was provided by the International HIV Clinical Trials Research Management Office at Imperial College London.

DART co-principal investigator Professor James Hakim of the University of Zimbabwe Medical School Clinical Research Centre in Harare explains the impact the DART results could have for people with HIV who don’t have access to a clinic with lab facilities:

‘‘The health economists in the DART team who have analysed the trial data have concluded that a third more people could be successfully treated for HIV in Africa if expensive lab tests weren’t used routinely. DART has shown that giving ART without these routine tests is safe and effective and suggests how the limited funding available could be used most effectively as by treating more people the number of deaths and disease related to HIV infection can be reduced. The challenge now is for policy-makers to widen availability of ART.’’

Co-principal investigator Professor Charles Gilks of Imperial College London and now UNAIDS, noted that:

“DART has been a landmark trial in Africa in many ways, not only in the numbers involved and its length, but for the way the patient communities were involved and engaged. For example, the strong partnerships developed with the pharmaceutical industry in a trial that was looking at treatment strategies, rather than comparing one product with another, and the exceptional participation, survival and low loss to follow-up that we achieved. The results provide compelling evidence for planners and policy-makers that, until universal access is achieved, the priority should be getting untreated patients on to ART, provided by well-trained and well-supported health workers who can deliver high quality clinical care.”

Co-principal investigator Professor Diana Gibb of the MRC Clinical Trials Unit in London said:

‘‘The survival of people who took part in the trial was remarkable; without treatment only about 10% of HIV-infected African people like those in DART would be expected to survive for five years. In DART, 87% of those receiving treatment without routine blood test monitoring were still alive and well after five years, only 3 percentage points less than in the group that had routine blood test monitoring. For health policy-makers in Africa, DART provides evidence that more people could be treated for the same amount of money by not using routine laboratory tests. This would substantially reduce the number of people dying with serious disease due to HIV infection.’’

Commenting on the DART trial MRC Chief Executive Sir Leszek Borysiewicz said:

‘‘The DART trial is an example of how working in partnership can deliver excellent results by sharing expertise and resources. Along the way, this collaboration between publically-funded researchers and industry has also helped to develop research capacity in Africa.’’

International Development Minister, Mike Foster of DfID said:

"It’s absolutely clear that anti-retroviral treatment saves lives – but the cost of accompanying laboratory tests significantly reduces the number of people that this treatment can reach. The DART trial, for which DFID provided £2.5m in funding, shows that this life saving treatment can still be safely provided without this additional cost.’’
"Crucially, the money saved from paying for these tests could enable more people to safely receive treatment, including those who for whatever reason are unable to travel to the laboratories. Such a step would be an important move towards our ultimate aim of achieving universal access to treatment for HIV/AIDS by 2010."

The results of the DART trial were presented at the International AIDS Society (IAS) Conference 2009 in Cape Town on the 21 July.

Notes

Abstract titles: Impact of routine laboratory monitoring over 5 years after antiretroviral therapy (ART) initiation on clinical disease progression of HIV-infected African adults: the Dart Trial final results and Cost Effectiveness Analysis of Routine Laboratory or Clinically Driven Strategy Monitoring Anti-Retroviral Therapy in Uganda and Zimbabwe.

As the DART trial centres are key centres for ART treatment, most patients are staying at the same clinical centre for their ongoing clinical care, unless for practical reasons they wish to be transferred (e.g. to a health centre nearer to where they live).

All participants will continue to receive ART free of charge and most will stay on the same regimen they were taking at the end of the study. All the information from the trial, including all their CD4 results have been summarised for each participant at the end of the trial and shared with the participants and their health carers. Some participants will have the opportunity to enrol in other ART studies if they wish to.

The main DART trial closed on 31 December 2008. Two additional sub-studies are ongoing that will continue to August/September 2009.

The Ministries of Health in Uganda and in Zimbabwe have been informed of the results and a meeting for trial participants is scheduled to be held immediately after the IAS conference.

About the Medical Research Council

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