Point-of-care technology for early infant HIV diagnosis speeds up return of HIV test results

Point-of-care testing for early infant HIV diagnosis is highly effective in reducing turnaround time for HIV test results, enabling earlier antiretroviral treatment initiation in infants, in sub-Saharan Africa. An observational study by Flavia Bianchi and colleagues from the Elizabeth Glaser Pediatric Foundation compared conventional testing programmes and new point-of-care testing devices, and is published in The Lancet HIV.

Carefully selected sites in eight countries reflected real-world settings of early infant diagnosis.

Background

In 2017, 180,000 children were living with HIV. Without prompt diagnosis and treatment, the greatest risk for death is between eight and ten weeks of age with half of the infants dying before the age of two. The Children with HIV (CHER) study showed a 76% reduction in disease and a 75% reduction in death, with notable short-term cost reductions, when HIV-positive infants started antiretroviral therapy (ART) under three months of age.

Infants are usually diagnosed with HIV testing performed at central laboratories. The challenges of this conventional form of early infant diagnosis (EID) are well documented, notably the significant delays in getting results to clinicians and caregivers. Devices for EID used at the point of care (POC) are simple to operate, can be used in a wide variety of settings and deliver results within 90 minutes. They have the potential to speed up initiation of treatment.

Glossary

modelling study

See ‘mathematical models’.

powered

A study has adequate statistical power if it can reliably detect a clinically important difference (i.e. between two treatments) if a difference actually exists. If a study is under-powered, there are not enough people taking part and the study may not tell us whether one treatment is better than the other.

observational study

A study design in which patients receive routine clinical care and researchers record the outcome. Observational studies can provide useful information but are considered less reliable than experimental studies such as randomised controlled trials. Some examples of observational studies are cohort studies and case-control studies.

However, given their relatively recent introduction, studies assessing the effect on service delivery and clinical outcomes are scant.

The study

With the support of the Elizabeth Glaser Pediatric Foundation (EGPAF), phased introduction of point-of-care early infant diagnosis (POC EID) testing as part of routine care for infants exposed to HIV began in December 2016 in Cameroon, Côte d’Ivoire, Kenya, Lesotho, Mozambique, Rwanda, Swaziland and Zimbabwe.

The researchers implemented a hub and spoke model in seven of the eight countries, in which the POC EID devices were kept at ‘hub’ clinics. Other healthcare facilities, within one hour’s drive of the hub, were ‘spokes’ which sent samples to the hub.

A wide range of sites were selected, including regional hospitals, primary healthcare facilities, prevention of mother-to-child transmission services, and maternity services. They were in both rural and urban environments, some with high demand for EID and some with low demand.

Two battery powered, quality-assured POC testing devices, m-PIMA and GeneXpertGX-IV, were used in the intervention sites. Healthcare workers were trained on sample collection. The ministry of health in each country gave EGPAF approval to update the testing algorithm to include POC EID.

The authors compared outcomes before and after the introduction of POC EID. The baseline pre-intervention sample comprised 30 HIV-exposed infants per study site tested with conventional EID at a central laboratory. The post-intervention sample included all infants tested with POC EID at a study site.

Retrospective data on conventional EID was collected on 2875 infants exposed to HIV and tested at 96 healthcare facilities prior to March 2017.

Data on POC testing was collected on 18,220 infants tested at 339 healthcare facilities in the 12 months from December 2016.

There was loss to follow-up for both conventional and POC testing at each step, from sample collection to return of results or antiretroviral initiation.

Outcomes

Compared to conventional testing, POC was highly effective and showed significant improvements in service delivery.

The median time from sample collection to return of results to caregivers was reduced from 55 days to 0 days (p < 0.00001) and from sample collection to start of ART initiation in HIV-positive infants from 49 days to 0 days (p < 0.0001).

The proportion of infants started on ART within 60 days of sample collection was 43.3% (42/97 infants) for conventional testing and 92.3% (639/692 infants) for POC, p < 0.0001.

The median age for antiretroviral initiation among infants with HIV who were tested at six to eight weeks was 3.3 (IQR: 2.5-4.4) months for conventional testing and 1.6 (IQR: 1.5-2.0) for POC testing, p < 0.0001.

Eighty-five per cent of infants were tested at prevention of mother-to-child transmission clinics and 6% at maternity clinics, with an HIV prevalence of 3.2% and 1.1% respectively.

However, there was a higher prevalence of HIV at inpatient and outpatient services, 15.2% and 17.7%, respectively. POC EID would be highly beneficial in such settings where children often have advanced disease and are in urgent need of treatment. In addition, the success of prevention of mother-to-child transmission programmes means POC EID will become increasingly important to identify infants with HIV in other healthcare settings.

The cost for each test result returned within 30 days was US$27.24 for POC compared to US$131.02 for conventional testing. Cost efficacy was confirmed and supported by an earlier modelling study.

Conclusions

This approach, the authors conclude, has the potential to reduce death and disease in infants with HIV. They call for national programmes, funders and implementing partners to consider implementing POC EID as a preferred testing strategy.

In an accompanying comment Drs Cotton and Rabie state that while the benefits and necessity of point-of-care early diagnosis are indisputable, they question its implementation and maintenance in the same settings without the support of a research infrastructure. Barriers include maintenance of the devices, adequate power, cartridge availability and a lack of trained personnel.

They note a discrepancy in antiretroviral initiation at prevention of mother-to-child clinic settings (95.1%), which was extremely successful compared to other settings (ranging from 66.7 to 87.2%). The discrepancy should be rectified, and communication between hubs and spokes supported. They say data on performance should be collected prospectively and coupled with implementable plans.

The benefits of POC for EID cannot be ignored, nor can this programme afford to fail, they stress.

References

Bianchi F et al. Evaluation of a routine point-of-care intervention for early infant diagnosis of HIV: an observational study in eight African countries. Lancet HIV http://dx.doi.org/10.1016/S2352-3018(19)30033-5, 2019.

Cotton MF and Rabie H. Is point-of-care early infant HIV diagnosis sustainable? Lancet HIV https://doi.org/10.1016/S2352-3018(19)30078-5, 2019.