The Body Covers: The 6th Conference on Retroviruses and Opportunistic Infections
Late Breaker No. LB12: Viral Rebound in the Presence of Indinavir Without Protease Inhibitor Resistance
February 4, 1999
The observed phenomenon of viral rebound in the absence of resistance to all components of the antiviral regimen was discussed at ICAAC in September, and further described here in Havlir et al's report of 26 patients from ACTG 343. In this study, some patients were randomized to receive indinavir monotherapy folllowing a six month induction course of AZT/3TC/indinavir. Nine of these patients achieved undetectable level of virus in blood (<400 copies) at six months of therapy but then rebounded above 400 (range varied between 1000 and 100,000 copies). Upon phenotypic analysis of isolates from these patients, all were sensitive to indinavir and demonstrated no indinavir resistance mutations. An additional 17 patients were studied who were randomized to continue triple therapy (AZT/3TC/indinavir) but who also experienced viral rebound after achieving undetectable levels of virus in their blood. Again, all were found to be sensitive to indinavir on phenotypic testing, and only one out of the 17 demonstrated any genotypic resistance mutation. By contrast, 82% exhibited 3TC resistance.Abstract: Viral Rebound in the Presence of Indinavir Without Protease Inhibitor Resistance
Discussion continues around the reasons behind this observation. One thought -- that patients were simply not taking their drug on study -- was refuted when random indinavir levels were measured and compared between the rebounders and the non-rebounders, revealing no discernable difference. Clearly, the data cannot be explained on the basis of inadherence. One other thought is that wild-type virus (that is virus still sensitive to indinavir) emerges first after a period of immune reconstitution has occurred as a consequence of antiretroviral therapy: because there are more CD4 cells circulating during therapy, and because wild-type virus is more fit than mutant virus (though with the passage of time indinavir-resistant virus would be most certain to emerge). When performed in a similar clinical setting where viral rebound has developed after a achieving levels of undetectability, viral resistance testing may help with clinical decision-making.
Authored by: D. Havlir, N. Hellmann, C. Petropoulos, J. Whitcomb, A. Collier, M. Hirsch, P. Tebas, and D. Richman
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