Author: Leslie Shanks is a Canadian physician working for Médecins sans Frontières since 1994. She currently works in the position of Medical Director based in Amsterdam.
“Finally, someone is talking about this.” I heard this refrain frequently at the recent International Conference on HIV/AIDS and Sexually Transmitted Infections in Africa (ICASA) in Addis Ababa, Ethiopia, after telling people about the satellite session hosted by Médecins Sans Frontières (MSF). The difficult topic: false positive HIV tests.
In resource limited settings, HIV diagnosis is done with rapid diagnostic tests (RDTs). Two or three different RDTs are used in either a serial or parallel algorithm (according to national guidelines). RDTs allow scale-up and decentralisation of treatment, both of which are essential to saving lives. Yet RDTs are screening tests—they were not designed for definitive diagnosis. They work well for screening blood transfusions and identifying people who need further tests, but are known to yield false positive results owing to serological cross reactivity (or inadequate quality control and human error, e.g. mislabelling of specimens). I first came across this unpleasant reality in Bukavu, Democratic Republic of the Congo, while working as a medical coordinator for MSF in 2005. We were running the first programme offering antiretroviral therapy to the province and had tested nearly 6000 people. But late in 2004 we realised that some people in our programme did not have HIV, so we retested a number of them—and identified almost 50 who we suspected had a false positive HIV diagnosis. This news was devastating, considering the consequences a false diagnosis can have on people’s lives.
We immediately worked to put stricter quality control protocols in place to eliminate errors in the testing process, and we reviewed all aspects of the programme. Then we piloted a confirmation test for people who screened positive on two RDTs, using a test that is simple to use and interpret, requires no special equipment, and yields results in less than two hours. All patients with a suspected false diagnosis were counselled and retested using the confirmation test. The reaction of those identified as false-positive varied. One woman said that her husband had divorced her, and she had remarried someone from the HIV positive peer support group. A pastor was immensely relieved to hear that he was HIV negative, since he could never figure out how he got infected. Some felt it was a miracle from God, or evidence that the latest magic potion on the market cured HIV. Since people in the community were dying from lack of access to testing, we were very concerned about the potential consequences if people lost confidence in the testing programme. But we saw no decrease in uptake of testing or loss of confidence in our programme. In fact, we learned that many local people were encouraged to come to MSF for testing because of the additional guarantees our programme introduced.
At the MSF satellite session on HIV testing, we presented an interim analysis of our data from Ethiopia. The two study sites initially showed a 7% false positive rate when using the national algorithm, which relies on two out of three positive tests (“tie-breaker” algorithm). When an improved algorithm (with the confirmation test) was used the number of false positives dropped to zero. The UN Refugee Agency (UNHCR) presented its experience in Uganda. After recognising problems with testing in its preventing mother to child transmission programmes, the agency adopted new measures to improve quality control and accuracy of the tests. Audience members shared similar experiences from their programmes in several countries. Many spoke of policy makers’ reluctance to allow retesting of people already under care, even if a problem with false positives was identified, or to openly acknowledge the issue.
Given the vital importance of testing and getting people on life saving treatment, these testing problems are arguably outweighed by the greater good that RDTs bring for scaling up access to care. However, it’s not an either/or issue: there are feasible solutions that virtually eliminate the problem, such as improving the test algorithm, adding a simple confirmation test, and improving quality control.
In this era of initiating treatment earlier and scaling up community and door to door testing, confidence in the test algorithms is more important than ever. Fortunately for those still waiting to be tested, there are good solutions. It’s just a matter of putting them in place.