The impact of transmitted drug-resistance on treatment selection and outcome of first-line highly active antiretroviral therapy (HAART)

Objective: The study aim was to determine how resistance testing influences outcome of first-line highly active antiretroviral therapy (HAART) in routine practice in the United Kingdom. Methods: The prevalence of transmitted drug resistance and the genotypic sensitivity score (GSS) of first-line HAART regimens were determined using data from the UK Collaborative HIV Cohort (CHIC) Study. Factors associated with starting a regimen with a reduced GSS and subsequent virological responses were analyzed by logistic and Cox regression. Results: Amongst patients tested in 1999-2006, 116 of 1175 (10%) had ≥1 resistance mutation; 64 patients (5.4%) had ≥1 mutation associated with resistance to drugs in the initial HAART regimen and 54 (4.6%) showed a GSS <3. Factors independently associated with a GSS <3 were starting HAART in 1999-2001 vs. 2004-2006 (odds ratio = 2.63; 95% confidence interval: 1.19 to 5.83) and use of ritonavir-boosted protease inhibitor (PI/r)-based vs. nonnucleoside reverse transcriptase inhibitor-based regimens (1.97; 1.06 to 3.64). A GSS >3 was independently associated with virological suppression (hazard ratio for GSS <3 = 0.60; 95% confidence interval 0.41 to 0.87). Conclusions: Most patients starting HAART after undergoing resistance testing received regimens with a GSS <3. PI/r-based therapy was often selected in patients with resistance to the nucleoside reverse transcriptase inhibitor backbone. Low GSS predicted poor virological suppression and the association persisted after adjusting for PI/r use