'25 at 25': Making HIV treatment accessible to people living in sub-Saharan Africa – the DART and ARROW trials and Lablite study
31 Jul 2024
While HIV used to be seen as a death sentence, antiretroviral therapy (ART) means people living with HIV can live healthy lives. But in 2000, only around 7000 people in sub-Saharan Africa were receiving ART, out of around 25 million people living with HIV. One of the barriers to treatment was the perceived need for laboratory monitoring, such as CD4 tests (to measure the health of people’s immune systems) and tests to monitor for potential side-effects from the medication. There was not sufficient laboratory capacity to carry out these tests, which were also relatively expensive.
DART
To address this challenge, the DART trial was carried out between 2003-2008, to see if ART could be safely given without routine laboratory monitoring, focusing instead on clinical monitoring. 3,316 people from Uganda and Zimbabwe took part, making it the largest ever clinical trial of ART for people living with HIV in sub-Saharan Africa at the time. DART found that routine laboratory tests made no difference to patient outcomes over 5 years compared to clinically driven monitoring.
Irrespective of which group of the trial people were in, the survival rate in the DART trial was amongst the best reported from any trial, ART programme or study in Africa at the time. 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.
The DART trial included cost-effectiveness analysis, which showed that use of routine laboratory testing, as used in DART in Uganda and Zimbabwe, was not cost-effective. The economic analysis, which used the DART results to make predictions for 20 years, showed that for routine CD4 tests to be cost-effective, their costs needed to fall below US$3.78. These tests costed around $10-20 each in Africa at the time, and were not easily accessible for many people living in rural areas. Routine laboratory tests for side effects were not cost-effective, as they did have any benefits for patients.
The researchers concluded that priority should be given to widening access to first- and second-line drugs to treat HIV infection, rather than using resources for routine laboratory monitoring.
ARROW
While access to ART for adults living with HIV in SSA was low in the early 2000s, it was even lower for children. By the end of 2011 only 28 per cent of the 2 million children who needed treatment were on it, compared with 51 per cent of adults in need. Furthermore, more than half of HIV-infected infants and young children died before their second birthday if they did not receive ART.
The ARROW trial compared laboratory vs clinically driven monitoring for children living with HIV. 1206 children living with HIV in Uganda and Zimbabwe took part in the study, which ran from 2007-2012.
ARROW found that children on HIV treatment can be safely monitored without the need for expensive routine laboratory tests. These findings mean treatment can be given much more cheaply, which may help more children get access to life-saving treatment.
In 2014, the ARROW trial was awarded the BMJ UK Research Paper of the Year award. On receiving the award, Diana Gibb, Chief Investigator for the trial, said "We are very pleased to receive this award. When the ARROW trial started, children in Africa were not even tested for HIV, let alone getting treatment. Even now, only around a third of children in need of HIV treatment have access to it. ARROW showed that children’s access to treatment should not be limited by lack of laboratory facilities, providing a way to help increase coverage. This award is recognition of the importance of the results, and the efforts of the participants and teams in Uganda, Zimbabwe and the UK in carrying out the trial."
Both DART and ARROW also built research capacity in Africa; many of the investigators are now considered to be leading researchers in the HIV field, and their trial clinics are considered national centres of excellence.
Lablite
DART and ARROW provided evidence that ART can be safely and successfully delivered without expensive routine blood tests; this opened up the possibility for ART to be delivered locally by suitably trained and supervised healthcare workers. Following on from DART and ARROW, we carried out the Lablite project. Lablite worked closely alongside Ministries of Health in Malawi, Zimbabwe and Uganda, to evaluate strategies to roll-out ART to smaller rural health centers, nearer to where people live.
Lablite supported 9 lower-level clinics in Malawi, Uganda and Zimbabwe to gain national ART accreditation to initiate and follow-up patients on ART. These clinics initiated ~3,200 HIV patients on ART during Lablite, with substantial numbers of additional patients benefitting from transferring into local care. As well as this, Lablite supported 6 clinics who were already delivering ART before the start of Lablite, developing their capacity to deliver ART and provide mentoring and support to spoke sites. The hub sites initiated ~7,700 new patients on ART during Lablite and continued to care for patients on ART pre-Lablite, and act as referral facilities for complex cases from the spokes and other lower-level facilities.
A representative from the Uganda Ministry of Health reported that Lablite have helped to build confidence that capacity can be built at spoke sites to deliver ART. Some of the training resources developed by Lablite have been adopted into practice at district and national level.
Decentralisation of ART to spoke facilities has had a positive impact on patients. Patients accessing ART at spoke clinics benefit from a reduction in travel time and /or cost, compared to those accessing ART at hubs. Qualitative research has also revealed positive impacts for patients, with reduced queuing times in central health facilities.
Together, DART, ARROW and Lablite have shown that ART can safely be used without routine laboratory monitoring, facilitating the roll-out to health services closer to where people live. This has contributed to the global effort to increase access to ART for people living with HIV, with 82% of people living with HIV in the Africa region on ART in 2022.
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