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Multicenter Study
. 2023 Feb 8;76(3):e702-e709.
doi: 10.1093/cid/ciac540.

Impact of Hepatitis C Virus Cure on Depressive Symptoms in the Human Immunodeficiency Virus-Hepatitis C Virus Coinfected Population in Canada

Gayatri Marathe  1   2 , Erica E M Moodie  1 , Marie-Josée Brouillette  2   3 , Charlotte Lanièce Delaunay  1   2 , Joseph Cox  1   2 , Valérie Martel-Laferrière  4 , John Gill  5 , Curtis Cooper  6 , Neora Pick  7 , Marie-Louise Vachon  8 , Sharon Walmsley  9 , Marina B Klein  1   2   10 ; Canadian Co-Infection Cohort
Collaborators, Affiliations
Multicenter Study

Impact of Hepatitis C Virus Cure on Depressive Symptoms in the Human Immunodeficiency Virus-Hepatitis C Virus Coinfected Population in Canada

Gayatri Marathe et al. Clin Infect Dis. .

Abstract

Background: Depression is common in people with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), with biological and psychosocial mechanisms at play. Direct acting antivirals (DAA) result in high rates of sustained virologic response (SVR), with minimal side-effects. We assessed the impact of SVR on presence of depressive symptoms in the HIV-HCV coinfected population in Canada during the second-generation DAA era (2013-2020).

Methods: We used data from the Canadian CoInfection Cohort (CCC), a multicenter prospective cohort of people with a HIV and HCV coinfection, and its associated sub-study on food security. Because depression screening was performed only in the sub-study, we predicted Center for Epidemiologic Studies Depression Scale-10 classes in the CCC using a random forest classifier and corrected for misclassification. We included participants who achieved SVR and fit a segmented modified Poisson model using an interrupted time series design, adjusting for time-varying confounders.

Results: We included 470 participants; 58% had predicted depressive symptoms at baseline. The median follow-up was 2.4 years (interquartile range [IQR]: 1.0-4.5.) pre-SVR and 1.4 years (IQR: 0.6-2.5) post-SVR. The pre-SVR trend suggested depressive symptoms changed little over time, with no immediate level change at SVR. However, post-SVR trends showed a reduction of 5% per year (risk ratio: 0.95 (95% confidence interval [CI]: .94-.96)) in the prevalence of depressive symptoms.

Conclusions: In the DAA era, predicted depressive symptoms declined over time following SVR. These improvements reflect possible changes in biological pathways and/or better general health. If such improvements in depression symptoms are durable, this provides an additional reason for treatment and early cure of HCV.

Keywords: HCV cure; HIV-HCV coinfection; depressive symptoms; direct acting antivirals; sustained virologic response.

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Conflict of interest statement

Potential conflicts of interest. J. C. received grants and consulting fees from ViiV Healthcare, Merck, and Gilead and personal fees from Bristol-Myers Squibb and reports payment or honoraria from Gilead Sciences for a presentation and support from Gilead Sciences for conference travel. J. G. has served as ad hoc member on National HIV advisory boards to ViiV healthcare, Gilead, and Merck. C. C. has received personal fees for being a member of the national advisory boards, consulting fees, payment or honoraria, and/or support for attending meetings and/or travel of Gilead, Merck, Janssen, Abbvie, MK, and Bristol-Myers Squibb. S. W. received grants, consulting fees, lecture fees, nonfinancial support, and fees for the development of educational presentations from Merck, ViiV Healthcare, GlaxoSmithKline, Pfizer, Gilead, AbbVie, Bristol-Myers Squibb, and Janssen. N. P. reports honoraria from Gilead and ViiV Healthcare. M. B. K. reports grants for investigator-initiated studies from ViiV Healthcare, AbbVie, Merck, and Gilead; and consulting fees from ViiV Healthcare, Merck, AbbVie, and Gilead. G. M. reports support for attending meetings and/or travel from CROI new investigator scholarship 2022. M. L. V. reports grant or contracts for Clinical Trials from AbbVie and Merck outside of the submitted work and consulting fees from AbbVie, Gilead, and Merck. V. M. L. reports grants or contracts outside of the submitted work from Gilead Science and Merck and consulting fees and payment or honoraria from Abbvie. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Flowchart of participants included in the analytical sample. The Canadian Co-Infection Cohort (CCC) had recruited 2018 HIV-HCV coinfected participants (HCV RNA positive/HCV seropositive) until July 2020. In our analysis, we included 503 participants who were treated with IFN-free second-generation direct acting antiviral (DAA) regimens after 25 November 2013, when the first second-generation DAA, Simeprevir, was approved for use by Health Canada. Of the participants who were treated, we excluded those who did not achieve sustained virologic response (SVR) (n = 32) and did not have a treatment response date (n = 1). Thus, in the final analytical sample we included a total of 470 participants who had achieved SVR. Abbreviations: HCV, hepatitis C virus; HIV, human immunodeficiency virus; IFN, interferon.
Figure 2.
Figure 2.
Impact of sustained virologic response (SVR) on depressive symptoms in the HIV-HCV coinfected population (A). Results of the primary analysis model with outcome misclassification correction. The graph shows that pre-treatment the probability trend for presence of depressive symptoms was stable over time. There was no evidence of immediate change at SVR; however, the probability trends post-SVR indicate a gradual decline in depressive symptoms over time (B). Results of the sensitivity analysis model to assess lead time bias with outcome misclassification correction. In this model, we lagged SVR by 1 year to assess possibility of lead time bias. The graph shows a stable pre-treatment trend like the primary analysis. The increase in the immediate level of depressive symptoms prevalence 1-year pre-SVR, provides evidence for no lead time bias in this analysis, meaning depressive symptoms did not seem to improve in anticipation of the cure. Abbreviations: HCV, hepatitis C virus; HIV, human immunodeficiency virus.
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