p24 test works for HIV+ newborns with subtype C virus, but not cost-effective?

Researchers from South Africa’s National Health Laboratory Service have found that modified p24 antigen tests, using heat treatment to separate the HIV viral protein from antibodies in a plasma sample, can be used to diagnose HIV in young babies with subtype C virus. In theory, this is a ‘lower tech’ alternative to using nucleic acid tests that probe for viral RNA or DNA. In practice, the most cost-effective strategy for diagnosing babies and for monitoring HIV viral load in adult treatment in southern Africa will probably be to use dried blood spots sent to a central lab.

In a presentation given to the South African AIDS Conference in Durban last week, Dr Gwynn Stevens reported on tests carried out on stored samples taken from infants born to mothers with HIV-1 subtype C in South Africa.

Blood samples were taken at birth, 6 weeks, 3 months and 7 months from 90 infants, whose final HIV status was later confirmed using antibody tests. 24 babies were HIV positive, 66 negative. The stored samples were tested using p24 antigen test kits from Perkin Elmer Life and Analytical Sciences and also using qualitative HIV PCR tests (Roche Amplicor). At 6 weeks and 3 months, the p24 tests were almost as sensitive as the PCR tests (only one positive result was missed), and were highly specific (no false positives).

These results should resolve any lingering doubts that the test, which was based on subtype B viral proteins, could be used in countries where subtype C is prevalent. However, the question remains as to whether it is worth taking this technology further.

In South Africa, it is now clear that in the emerging public sector treatment programme, diagnosis of babies and also viral load monitoring for patients on treatment will be carried out using nucleic acid tests on dried blood spots. The cost of these is already being driven below US $10 a time, with a 24-hour turn-around for results on receipt of the sample. In fact, the South African National Health Laboratory Service is even carrying out some tests for neighbouring countries, such as Malawi.

While p24 antigen test kits - which are shortly to be discontinued by Perkin Elmer, though the reagents will continue to be available - have a similar price tag, there are hidden extras. When sample collection, preparation, transport, and technician training are taken into account, the balance tips strongly in favour of the nucleic acid tests.

In particular:

• Blood spot samples are easy to collect, without a syringe, on a very cheap medium. (In fact, a cheap filter paper works better than the more specialised media that have been developed for this purpose.) p24 tests need plasma samples which means taking blood with a syringe and separating the plasma.
• Samples are stable for at least 28 days at room temperature (and possibly a lot longer, if stored carefully) – so there is no problem transporting samples from remote locations if necessary and they can safely be sent by ordinary post. Plasma samples are more difficult to store and transport.
• The central labs can take part in international quality assurance programmes as well as operating internal quality controls, without having to support quality assurance schemes for a network of local labs running p24 tests, whose technicians would need to be trained and supported to do them.

Early diagnosis of both HIV positive and HIV negative babies has enormous value for their parents and for health services.

Diagnosed early enough, positive babies could benefit greatly from breast feeding rather than formula feeding, and the family can be given the extra support they will need to access treatment as and when this is needed. (At present, with definitive tests only at 18 months of age, many babies are 'lost to follow-up' by family services.)

Early diagnosis for negative babies is a huge relief for their parents, reinforces the value of adhering to any strategies used to protect them from HIV, and may also be of critical importance for clinical services, allowing them to focus their resources as they gear up to treat positive babies.