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Resistance profiles and adherence at primary virological failure in three different highly active antiretroviral therapy regimens: analysis of failure rates in a randomized study
Author(s) -
Røge BT,
Barfod TS,
Kirk O,
Katzenstein TL,
Obel N,
Nielsen H,
Pedersen C,
Mathiesen LR,
Lundgren JD,
Gerstoft J
Publication year - 2004
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/j.1468-1293.2004.00233.x
Subject(s) - medicine , antiretroviral therapy , randomized controlled trial , resistance (ecology) , human immunodeficiency virus (hiv) , viral load , intensive care medicine , family medicine , biology , ecology
Objectives To investigate the interplay between resistance and adherence in the virological failure of three fundamentally different highly active antiretroviral therapy (HAART) regimens. Methods We retrospectively identified 56 verified primary virological failures (viral load >400 HIV‐1 RNA copies/mL) among 293 patients randomized to two nucleoside reverse transcriptase inhibitors (NRTIs)+ritonavir+saquinavir (RS‐arm) ( n =115), two NRTIs+nevirapine+nelfinavir (NN‐arm) ( n =118), or abacavir+stavudine+didanosine (ASD‐arm) ( n =60) followed up for a median of 90 weeks. Data on adherence were collected from patient files, and genotyping was performed on plasma samples collected at time of failure. Results Treatment interruption or poor adherence was mainly caused by side effects and accounted for 74% of failures, and was associated with absence of resistance mutations. In the 30 failing patients not switched from randomized treatment, we found resistance in two of 12 patients in the RS‐arm (M184 V only), four of six patients in the NN‐arm [all four had non‐nucleoside reverse transcriptase inhibitor (NNRTI) mutations], and seven of 12 patients in the ASD‐arm (NRTI mutations only). Two adherent patients on randomized treatment failed in the RS‐arm, none in the NN‐arm, and six in the ASD‐arm. Conclusions Primary virological failure was caused mainly by treatment interruption. No primary protease inhibitor (PI) mutations were found in patients failing on boosted saquinavir, whereas resistance to NNRTIs and NRTIs was prevalent in several patients failing on regimens based on these medications.