Case report of antibody reversion and negative viral load four-years after treatment discontinuation

In contrast to the extensive publicity given to the New York case study above, amongst the basic science posters at the meeting was a report of a patient with documented HIV infection, who has apparently cleared HIV.

Diagnosis was confirmed by antibody test (Elisa and Western Blot) and viral load at two labs both at diagnosis in 1995 and subsequently on frozen samples. Viral load was 4,000 copies/mL at diagnosis and rose to 29,000 and 24,000 copies/mL two years later prior to starting HAART. CD4+ T-cell count was 856 cells/mm³.

This person used HAART for three years, achieving undetectable viral load within four months although CD4 count didn’t increase. He tested negative for antibody when being screened for a study. On stopping treatment, viral load was found to be negative and both viral load and antibody have remained negative for four years since discontinuing treatment.

Further results and tests on stored samples will hopefully be presented at future meetings, although natural scepticism about these results will mean that they need to be thoroughly verified.

Comment

The most likely explanation for these results would appear to be failure of the assays used to test for HIV antibodies. However the possibility must be considered that sero-reversion has taken place. It would be highly recommendable that these results should be validated by other labs.

The main problem here is that there is no clinical indication to re-test HIV positive patients for p24 antibodies following diagnosis, so we have no idea if there is an actual phenomena here that has until now been missed. Whatever the case, sero-reversion should not be taken to be equivocal with viral eradication.

One possible explanation for a reduction in HIV p24 IgG to undetectable levels, might be persistent suppression of virus by HAART, resulting in loss of viral antigen which may support long-term memory B cell production of antibodies. However there is still much debate about the means by which memory B cells maintain their levels and whether or not any level of persistent antigen is required for this.

That considered, there is an abundance of evidence that B cells do not behave normally in HIV-infection and so premature loss of HIV-specific memory B cells may be a real phenomena in some long-term HAART treated patients that requires further investigation, and that may have important implications (re blood donation, other screening etc). Speculatively, such a phenomena might be more expected in patients receiving HAART who have very limited viral reservoirs due to early treatment, as in this reported patient.

Levy I, Rahav G, Bakhanashwili M et al. Negative HIV antibody test and negative viral RNA in a patient with documented HIV infection. 12th CROI, Boston, 2005.
Abstract 310.