17 June 2008

HIV tests and ARVs

I recently discovered two interesting cases among individuals enrolled in studies at PSF. I was working on a query for a publication and noticed that there were two individuals who were HIV-negative but reported a date on which they began anti-retroviral (ARV) therapy, the treatment used for individuals who are HIV-positive. I assumed an error had been made during data entry, but, as I investigated these cases further, I became really concerned.

The first individual tested positive at PSF's couples' voluntary counseling and testing center on two out of three rapid tests, which, according to the national algorithm for HIV-testing, identifies this individual as HIV-positive. (It is not at all uncommon for individuals to have different results on different tests.) For several months, this individual continued to test positive. When a CD4 count (the test used as a diagnostic for HIV treatment) was ordered, it was found to be very low, so the individual began ARV treatment. At this point there was no indication that something was strange, no red flag that something was wrong, no indication that a protocol that had been followed incorrectly. But then, the individual began to test HIV-negative, and with more sophisticated laboratory tests, it was resolved that the individual was indeed HIV-negative.

The second individual had a similar testing history.

Were these individuals were cured by ARV therapy? No. Had an error been made in their lab tests or results? No.

Both of these cases were what we call "seroreverters", individuals who test HIV-positive for some period of time before reverting to HIV-negative test results. It is a curious situation that is not yet well-understood, but false-positive HIV test results are not uncommon. In fact, it is fairly common for HIV-negative individuals to test positive on a single rapid test, somewhat less common to test positive on multiple tests. Yet there are individuals who have separate infections or cross-reacting viruses that cause positive results on HIV tests even though the individuals are not actually infected with HIV. When the individuals' immune systems later clear this cross-reacting virus, they revert to negative HIV test results. This is what happened in both of these cases.

As for these individuals' low CD4 counts that indicated a need to begin ARV therapy, it is purely coincidence. Some individuals just have naturally low CD4 counts.

Even though there have only been two individuals for which this has happened at PSF, I feel like the implications of these facts are significant.

While we follow a strict testing algorithm at PSF and ZEHRP that involves diagnosis based on three rapid tests followed by more sensitive ELISA tests in cases of discrepant results, we have seen in Rwanda that most health centers use only a single rapid test for HIV diagnosis. Nurses and counselors report that there are just too many clients and too little time to do even one confirmatory test. Yet the single rapid test that they use is one that has shown a particularly high number of false positive results at PSF. While we at PSF can identify these false positive results by use of confirmatory tests, if the health centers are not using any confirmatory tests, then how many HIV-negative individuals are receiving positive diagnoses? The numbers must be high. And how many of these then have naturally low CD4 counts?

A whole series of questions and concerns then fills my mind - How many individuals are on ARVs who are actually HIV-negative? What effects do intense ARVs have on the bodies of individuals who are not infected with HIV? What are the economic implications when expensive ARVs are wasted on individuals who are actually HIV-negative? How does providing ARV therapy to HIV-negative individuals contribute to drug resistance if these individuals are later exposed to the HIV virus? What effect does this have on the community's understanding of HIV and ARV therapy when these individuals later receive HIV-negative results? Does the community believe they have been cured or do they believe HIV is a myth made up by the Western world?

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