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By
PLoS Guest Blogger
Posted: January 3, 2012
Guest post by Leslie Shanks of MSF, the second of three guest posts from the 2011 ICASA conference in Addis Ababa.
The International Conference on HIV/AIDS and Sexually Transmitted Infections in Africa (ICASA) is the principal forum on HIV/AIDS
& STIs in Africa.
"Finally, someone is talking about this." I heard this refrain frequently at the recent ICASA conference in Addis-Ababa,
Ethiopia after telling people about the satellite session hosted by Doctors Without Borders/Médecins Sans Frontières (MSF). The
difficult topic: false positive HIV tests.
In resource-limited settings, HIV diagnosis is done with rapid diagnosis tests (RDT) using two or three different
RDTs in either a serial or parallel algorithm (according to national guidelines). Rapid tests allow scale up and decentralization
of treatment, both of which are essential to saving lives. Yet RDTS are screening tests -they were not designed
for definitive diagnosis [1]. They work well
for screening blood transfusions and identifying people who need further tests, but are known to yield false positive results due to
serological cross-reactivity (or to inadequate quality control and human error (e.g. mislabeling of specimens). I first came across
this unpleasant reality in Bukavu, DRC while working as a medical coordinator for MSF in 2005. We were running the first program
offering ART to the province and had tested nearly 6000 people. But late in 2004 we came to realize that some people in our
program did not have HIV, so we re-tested a number of them-and identified almost 50 who were suspect for 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 program. Then we piloted a confirmation test for
people who screen 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 [2] . All patients with a suspected false diagnosis were counseled and re-tested 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+ 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 program. But in fact we saw no decrease in uptake of testing or loss of confidence in
our program. In fact, we learned that many local people were encouraged to come to MSF for testing due to the additional
guarantees our program introduced.
At the MSF satellite session on HIV testing, we presented an interim analysis of our data from Ethiopia. The 2 study sites
initially showed a 7% false positive rate using the national algorithm, which relies on 2 out of 3 positive tests
("tie-breaker" algorithm). Using an improved algorithm (with the confirmation test) the number of false
positives dropped to zero. The UNHCR (UN Refugee Agency) presented its experience in Uganda: after
recognizing problems with testing in its PMTCT programs, they adopted new measures to improve
quality control and accuracy of the tests. Audience members shared similar experiences from
their programs in several countries. Many spoke of policy makers' reluctance to allow
re-testing 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 RDTs bring for scaling up access to care. However, it's not either-or: 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.
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.
The author has completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from
the corresponding author) and declares: no support from any organisation for the submitted work; no financial relationships with any
organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities
that could appear to have influenced the submitted work.
The first module for FDA review was submitted to the agency in the third quarter of 2011 and contained data from all
studies performed prior to the final phase of testing. The second module was submitted to the FDA several weeks ago and included
information about manufacturing and the customer care call center.
1] Greenwald JL, Burstein GR, Pincus J, Branson B. A Rapid Review of Rapid HIV
Antibody Tests. Curr Infect Dis Rep. 2006 Mar;8(2):125-31
[2] Klarkowski, D.B et al. The evaluation of a rapid in situ HIV confirmation test in a program with a high failure
rate of the WHO HIV two test diagnostic algorithm. PLoS ONE February 2009 4 (2): e4351
Source: PLoS Blogs
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