Research Article: Effect of therapy switch on time to second-line antiretroviral treatment failure in HIV-infected patients

Date Published: July 20, 2017

Publisher: Public Library of Science

Author(s): Amanda Häggblom, Michele Santacatterina, Ujjwal Neogi, Magnus Gisslen, Bo Hejdeman, Leo Flamholc, Anders Sönnerborg, Dimitrios Paraskevis.


Switch from first line antiretroviral therapy (ART) to second-line ART is common in clinical practice. However, there is limited knowledge of to which extent different reason for therapy switch are associated with differences in long-term consequences and sustainability of the second line ART.

Data from 869 patients with 14601 clinical visits between 1999–2014 were derived from the national cohort database. Reason for therapy switch and viral load (VL) levels at first-line ART failure were compared with regard to outcome of second line ART. Using the Laplace regression model we analyzed the median, 10th, 20th, 30th and 40th percentile of time to viral failure (VF).

Most patients (n = 495; 57.0%) switched from first-line to second-line ART without VF. Patients switching due to detectable VL with (n = 124; 14.2%) or without drug resistance mutations (DRM) (n = 250; 28.8%) experienced VF to their second line regimen sooner (median time, years: 3.43 (95% CI 2.90–3.96) and 3.20 (95% 2.65–3.75), respectively) compared with those who switched without VF (4.53 years). Furthermore level of VL at first-line ART failure had a significant impact on failure of second-line ART starting after 2.5 years of second-line ART.

In the context of life-long therapy, a median time on second line ART of 4.53 years for these patients is short. To prolong time on second-line ART, further studies are needed on the reasons for therapy changes. Additionally patients with a high VL at first-line VF should be more frequently monitored the period after the therapy switch.

Partial Text

Antiretroviral therapy (ART) has substantially reduced mortality and morbidity in individuals with human immunodeficiency virus type 1 (HIV-1) infection [1]. However, patients frequently switch to alternate drug combinations due to toxicity, convenience or costs [2–4], but also due to virological treatment failure. Reappearance of HIV RNA in plasma may or may not be associated with drug resistance mutations (DRM). Lack of DRM is frequently due to poor adherence, but is also due to a high genetic barrier to resistance for some drugs [5, 6]. In addition, standard genotypic resistance testing (GRT) may underestimate drug resistance[7] and DRM in minor quasispecies can contribute to treatment failure[8].

In this study we analyzed the effect of different causes to first line ART switch, and the level of VL at switch, on the long-term outcome of second-line treatment using the InfCare cohort, which represents >99% of all diagnosed HIV infected patients in Sweden. The majority of the patients switched therapy due to other reasons than VF with no difference over the calendar years (data not shown). This consistent pattern of reason for therapy switch could be due to that although the virological treatment failure was more common in the past, switches due to side effects of the older drugs also occurred to a higher extent. Our data thus confirm that toxicity and/or convenience are by far the most common reason for therapy switch of first-line ART in a real-life situation in a high-income country.




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