Determinants of sustained viral suppression in HIV-infected patients with self-reported poor adherence to antiretroviral therapy

Glass, Tracy R; Rotger, Margalida; Telenti, Amalio; Decosterd, Laurent; Csajka, Chantal; Bucher, Heiner C; Günthard, Huldrych F; Rickenbach, Martin; Nicca, Dunja; Hirschel, Bernard; Bernasconi, Enos; Wandeler, Gilles; Battegay, Manuel; Marzolini, Catia; Swiss HIV Cohort Study, (2012). Determinants of sustained viral suppression in HIV-infected patients with self-reported poor adherence to antiretroviral therapy. PLoS ONE, 7(1), e29186. Lawrence, Kans.: Public Library of Science 10.1371/journal.pone.0029186

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Background Good adherence to antiretroviral therapy (ART) is critical for successful HIV treatment. However, some patients remain virologically suppressed despite suboptimal adherence. We hypothesized that this could result from host genetic factors influencing drug levels. Methods Eligible individuals were Caucasians treated with efavirenz (EFV) and/or boosted lopinavir (LPV/r) with self-reported poor adherence, defined as missing doses of ART at least weekly for more than 6 months. Participants were genotyped for single nucleotide polymorphisms (SNPs) in candidate genes previously reported to decrease EFV (rs3745274, rs35303484, rs35979566 in CYP2B6) and LPV/r clearance (rs4149056 in SLCO1B1, rs6945984 in CYP3A, rs717620 in ABCC2). Viral suppression was defined as having HIV-1 RNA <400 copies/ml throughout the study period. Results From January 2003 until May 2009, 37 individuals on EFV (28 suppressed and 9 not suppressed) and 69 on LPV/r (38 suppressed and 31 not suppressed) were eligible. The poor adherence period was a median of 32 weeks with 18.9% of EFV and 20.3% of LPV/r patients reporting missed doses on a daily basis. The tested SNPs were not determinant for viral suppression. Reporting missing >1 dose/week was associated with a lower probability of viral suppression compared to missing 1 dose/week (EFV: odds ratio (OR) 0.11, 95% confidence interval (CI): 0.01–0.99; LPV/r: OR 0.29, 95% CI: 0.09–0.94). In both groups, the probability of remaining suppressed increased with the duration of continuous suppression prior to the poor adherence period (EFV: OR 3.40, 95% CI: 0.62–18.75; LPV/r: OR 5.65, 95% CI: 1.82–17.56). Conclusions The investigated genetic variants did not play a significant role in the sustained viral suppression of individuals with suboptimal adherence. Risk of failure decreased with longer duration of viral suppression in this population.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine

UniBE Contributor:

Wandeler, Gilles

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:22

Last Modified:

17 Nov 2015 13:13

Publisher DOI:

10.1371/journal.pone.0029186

PubMed ID:

22235271

Web of Science ID:

000301123400032

BORIS DOI:

10.7892/boris.7556

URI:

https://boris.unibe.ch/id/eprint/7556 (FactScience: 212846)

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