Infektion mit resistentem Virus: Resistenzprüfung verbessert Behandlungsresultat (TH LB B108)

Nicht überall ist akzeptiert, dass man vor der ersten Therapie eine Resistenzprüfung machen soll. Diese Late-Braker Untersuchung hat gezeigt, dass das Wissen um eine Resistenzmutation vor Therapiebeginn das Behandlungsresultat positiv beeinflusst. 

Impact of transmitted drug resistance (TDR) on virological and immunological response to initial combination antiretroviral therapy (cART) – EuroCoord-CHAIN joint project

L. Wittkop, on behalf of the EuroCoord-CHAIN Joint Project Team

INSERM U897, ISPED, Université Victor Segalen, Centre of Epidemiology and Biostatistics, Bordeaux, France
 

Background: The impact of TDR on first line treatment is discussed controversially in the recent literature. We studied the impact of TDR on treatment outcome in the first year of cART in patients from 4 constitutive networks of EuroCoord (CASCADE, COHERE, EuroSIDA and PENTA-EPPICC).
Methods: We used the WHO-list 2009 and the Stanford algorithm v6.0.5 to classify patients in three categories: no mutation, ≥1 mutation but receiving a fully active treatment and ≥1 mutation and at least low-level resistance to ≥1 prescribed drug. Time to the first of two consecutive viral load (VL) measurements >500 cp/mL after 6 months (M6) of therapy was assessed by adjusted Cox proportional Hazards models.
Results: Of 10,458 patients from 25 cohorts, 9505 (90.9%) patients had no mutation, 476 (4.5%) patients had ≥1 mutation but receiving a fully active cART and 477 (4.6%) patients had ≥1 mutation and were classified resistant for ≥1 drug. Patients with resistance to ≥1 drug had a 2.6 fold higher risk of VF (95% confidence interval [CI]: 2.0; 3.4, P< 10^-4) compared to patients without mutation. Overall, there was no significant difference between patients with TDR but receiving a fully active cART and patients without mutation (HR: 1.2, 95%CI: 0.8; 1.8, P=0.34). In stratified analysis, patients 2NRTIs+1NNRTI harbouring ≥1 mutation predicted to receive a fully active cART tended to have a higher risk for VF. The CD4 cell increase was consistent with the virological response.
Conclusions: TDR caused a poor virological and immunological response when patients received cART containing ≥1 drug classified with at least low-level resistance. A higher trend for VF was found in presence of ≥1 mutation in patients receiving 2NRTIs+1NNRTI classified to be fully active. First line cART should thus be carefully selected using genotypic test results and already drugs classified with low level resistance should be avoided.

Links:

• Wittkop et.al. – THLBB108
• Slides mit Audio
• Präsentation (.ppt)