Viral suppression in Uganda improved by more viral load tests, done faster

Slide from Dr Vivek Jain's presentation to IAS 2021.
Slide from Dr Vivek Jain's presentation to IAS 2021.

Simple measures to improve the ordering and turnaround of viral load tests in Uganda significantly improved viral suppression after one year, a cluster-randomised trial reported this week at the 11th International AIDS Society Conference on HIV Science (IAS 2021) found.

Although viral load testing is a well-established procedure in Uganda’s national HIV treatment programme, its uptake could be improved. Doctors do not always order viral load tests in situations where national guidelines recommend a test, and turnaround times from ordering the test to delivery of the result to the patient can be up to two months. Delays of this length are especially problematic in pregnant or breastfeeding women or people with detectable viral load who may need to be switched to another regimen to avoid drug resistance.

To test whether improvements in viral load testing procedures translated into better outcomes for patients, Dr Vivek Jain of University of California San Francisco and colleagues designed the RAPID-VL study. The trial tested a package of interventions in a cluster-randomised design, in which 20 clinics were randomised to adopt the intervention package or continue with standard-of-care viral load testing procedures.

The intervention package consisted of

  • A flow sheet in patients' files that required doctors to specify the antiretroviral therapy status and last viral load result of the patient, and to indicate whether a test was ordered, and if it was routine or urgent.
  • Availability of Cepheid Xpert near point-of-care device at a local testing hub, in addition to testing of dried blood spots. The Xpert machine has a high throughput and rapid turnaround, so results can be returned to the clinic within days.
  • A set of viral load counselling scripts to use with patients in various situations, including detectable or undetectable results. The script used the viral load test result to reinforce adherence messages.
  • Regular feedback to clinics on their performance.

The study recruited participants from four groups at higher risk of poor outcomes without timely viral load testing (pregnant and breastfeeding women, children and adolescents, people with detectable viral load and people overdue for viral load tests) as well as adults not at high risk.

The primary study outcomes were time for test results to be delivered to the patient and viral load test ordering that was compliant with guidelines. Outcomes were compared between the year prior to the study and the intervention period (2018-2020) in 1200 people, 60 per clinic. Viral suppression after one year was the secondary study outcome.

The adult study population was 66% female, with an average age of 37 years and had been on antiretroviral therapy for a median of 2.8 years. Children and adolescents were 50% female, with an average age of nine years and on antiretroviral therapy for a median of three years.

In the pre-intervention period, the average viral load turnaround time was 73 days, but ranged from 33 to 89 days between clinics. In the post-intervention period, average viral load turnaround time fell by 67 days in the intervention clinics but remained unchanged in the control group (P<0.0001). The median turnaround time was 1 day in the intervention clinics compared to 56 days in the control group clinics.

Guideline-compliant viral load ordering also improved significantly in the intervention clinics. Whereas test ordering was compliant with guidelines in 70% of intervention clinics and 72% of control group clinics during the pre-intervention period, it increased by 10% in intervention clinics but remained stable in control clinics during the intervention period (p<0.01). Sub-group analysis showed that test ordering improved significantly in all higher-risk sub-groups and in non-high-risk adults.

Glossary

virological suppression

Halting of the function or replication of a virus. In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy.

detectable viral load

When viral load is detectable, this indicates that HIV is replicating in the body. If the person is taking HIV treatment but their viral load is detectable, the treatment is not working properly. There may still be a risk of HIV transmission to sexual partners.

control group

A group of participants in a trial who receive standard treatment, or no treatment at all, rather than the experimental treatment which is being tested. Also known as a control arm.

transmission cluster

By comparing the genetic sequence of the virus in different individuals, scientists can identify viruses that are closely related. A transmission cluster is a group of people who have similar strains of the virus, which suggests (but does not prove) HIV transmission between those individuals.

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

Viral suppression also improved in the intervention clinics. After one year, viral suppression had improved by 7%, to 83% among those who underwent viral load testing as part of the study, whereas 76% of those in the control group clinics had suppressed viral load after one year. Sub-group analysis showed viral suppression improved in all sub-groups apart from pregnant and breastfeeding women in intervention clinics.

Asked which components of the intervention package may have the greatest effect, Dr Jain said that the study “cannot disaggregate the components because the intervention was designed to address multiple barriers simultaneously. The viral load availability at a local hub is an enabling technology but the prompt sheet helped encourage the use of the technology.”

He said that other countries should consider adopting the hub-and-spoke model employed in the RAPID-VL study, together with the flowsheet and counselling scripts. Feedback from patients and doctors had been very positive, he said. Moreover, the intervention was sustainable in government-run HIV clinics.

References

Jain V et al. RAPID-VL intervention improves viral load ordering, results turnaround time and viral suppression: a cluster randomized trial in HIV clinics in Uganda. 11th International AIDS Society Conference on HIV Science, abstract OALD01LB03, 2021.