[798] RELATIONSHIP BETWEEN ADHERENCE AND THE DEVELOPMENT OF VIRAL RESISTANCE IN ANTIRETROVIRAL-NAïVE PATIENTS TREATED WITH LOPINAVIR/RITONAVIR (LPV/R) OR NELFINAVIR (NFV)

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] RELATIONSHIP BETWEEN ADHERENCE AND THE DEVELOPMENT OF VIRAL RESISTANCE IN ANTIRETROVIRAL-NAïVE PATIENTS TREATED WITH LOPINAVIR/RITONAVIR (LPV/R) OR NELFINAVIR (NFV)

[AUTHOR(S):] M King, S Brun, J Tschampa, J Moseley and D Kempf
Abbott Laboratories, Abbott Park, IL, USA

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 798
Antiviral Therapy 2003; 8(Suppl. 1):S407

[ABSTRACT:] Background: The relationship between adherence and virologic response has been extensively studied. However, the relationship between adherence and resistance development is not well understood and may differ substantially for different drugs.

Methods: In a Phase III study of antiretroviral-naïve patients (pts) receiving LPV/r (n=326) vs NFV (n=327), each with d4T/3TC, adherence was measured by pill count. The relationship of adherence to the probability of 3TC resistance, primary PI resistance or secondary PI mutations was assessed by local linear regression in all enrolled pts (analysis A) and in just those pts with detectable viral load and available genotype (analysis B).

Results: (Analysis A) Among all pts, the highest probability of 3TC resistance occurred at intermediate adherence, with lower probability at higher and lower adherence: At 80% adherence, P(3TC resistance)=49% [NFV] and 13% [LPV/r]. At 95% adherence, P(3TC resistance)=23% [NFV] and 5% [LPV/r]. A similar relationship was observed for the probability of secondary PI mutations/polymorphisms in each treatment group and for primary PI resistance in the NFV group (no primary PI resistance observed in the LPV/r group). The probability of 3TC resistance and of secondary mutations/polymorphisms was at least threefold higher for NFV vs LPV/r at every adherence level. (Analysis B) In contrast to the above, among NFVtreated pts with detectable viral load and genotype data, the probability of primary PI resistance or secondary PI mutations increased with higher adherence: at 100% adherence, P(primary PI resistance)=63%, P(primary or secondary PI mutations)=80%.

Conclusions: Among all pts, a bell-shaped relationship between resistance and pill count-based adherence was observed, with highest probability of resistance at 80–85% adherence. The decline in resistance at higher adherence was accounted for by higher viral suppression, since, for pts with detectable viral load, resistance was maximal at the highest adherence.

030714
798