Reappearance of HIV multidrug-resistance in plasma and circulating lymphocytes after reintroduction of antiretroviral therapy.

After the discontinuation of antiretroviral therapy in HIV-infected patients with highly resistant virus, the detectability of viral resistance mutations quickly decreases. To which extent this represents a true loss of resistance or rather a detectability phenomenon remains unclear. To monitor virologic response and resistance pattern during a non-strategic treatment interruption in the presence of highly drug-resistant viral strains. We performed serial genotypic resistance analyses on viral DNA isolated from a patient with a multidrug-resistant human immunodeficiency virus infection who discontinued and later on reintroduced antiretroviral therapy. Sequencing was performed on viral DNA from plasma as well as DNA from circulating leukocytes. While under combination antiretroviral therapy with two nucleosidic reverse transcriptase inhibitors, a non-nucleosidic reverse transcriptase inhibitor and a protease inhibitor, the viral load of the patient was around five logs. Genotypic resistance to all available agents was detected during this time. Antiretroviral therapy was then interrupted, and 14 weeks later an almost complete reversion of the virus to wild type was observed. After introduction of a new antiretroviral therapy regimen, the reappearance of nearly all of the formerly present resistance mutations had to be noted within 6 weeks, including mutations without known relation to any of the drugs in the new regimen. We obviously observed not the de novo appearance of a complex resistance pattern under just 6 weeks of potent antiretroviral therapy, but a reappearing archival strain of the virus. This finding provides evidence for subdetectable persistence of resistant variants during treatment interruptions. Therefore, resistance analyses from peripheral blood performed in times of treatment interruptions should be interpreted with caution as they may provide incomplete information about the resistance profile soon after reintroduction of therapy.