Compartmentalization of Resistance-Associated Substitutions in HIV/HCV-Infected Patients: Possible Correlation with Infecting HCV Genotype

Resistance-associated substitutions (RASs) may exist prior to treatment and contribute to the failure of treatment with direct-acting antivirals (DAAs). As the major site of HCV replication, naturally occurring variants with RASs may segregate into the liver. In the present study, we performed viral population sequencing to retrospectively investigate the NS3 and NS5A RAS profiles in 34 HIV/HCV coinfected patients naïve to anti-HCV treatment who underwent diagnostic liver biopsy between 2000 and 2006 and had liver and plasma samples available. Sixteen were infected by HCV genotype (GT) 1a, 11 by GT3a, and 7 by GT4d. The analysis of the NS3 domain in GT1a showed a difference in strain between the liver and plasma in three cases, with a preponderance of specific RASs in the liver compartment. In GT4d samples, 6/7 coupled liver and plasma samples were concordant with no RASs. Sequence analysis of the NS5A domain showed the presence of RASs in the livers of 2/16 patients harboring GT1a but not in the corresponding plasma. In GT4d, NS5A RASs were detected in 7/7 liver tissues and 5/7 plasma samples. NS3 domain and NS5A domain were found to be conserved in plasma and livers of patients infected with GT3a. Thus, RASs within GT1a and GT4d more likely segregate into the liver and may explain the emergence of resistant strains during DAA treatment.

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Declines in Depressive Symptoms Among People who Inject Drugs Treated With Direct-Acting Antivirals While on Opioid Agonist Therapy

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa380 ◽

2020 ◽

Vol 7 (10) ◽

Author(s):

Irene Pericot-Valverde ◽

Moonseong Heo ◽

Jiajing Niu ◽

Brianna L Norton ◽

Matthew J Akiyama ◽

...

Keyword(s):

Depressive Symptoms ◽

Illicit Drugs ◽

People Who Inject Drugs ◽

Sustained Viral Response ◽

Addiction Severity Index ◽

Psychiatric Diagnoses ◽

Direct Acting Antivirals ◽

Hcv Treatment ◽

Opioid Agonist ◽

Direct Acting

Abstract Background Hepatitis C virus (HCV) frequently co-occurs with symptoms of depression, which are aggravated on interferon-based regimens. However, it is unknown whether HCV treatment with direct-acting antivirals (DAAs) has effects on depressive symptoms among people who inject drugs (PWID). In this study, we examined changes in depressive symptoms during and after HCV treatment among PWID on opioid agonist therapies (OATs). Methods Participants were 141 PWID who achieved sustained viral response after on-site HCV treatment at 3 OAT programs. Depressive symptoms were assessed using the Beck Depression Inventory–II (BDI-II) at baseline, every 4 weeks during treatment, and 12 and 24 weeks after treatment completion. Current diagnosis of depression or other psychiatric diagnoses were obtained through chart review. Use of illicit drugs was measured by urine toxicology screening. Alcohol use was measured using the Addiction Severity Index–Lite. Results Of the 141 PWID infected with HCV, 24.1% had severe, 9.9% had moderate, 15.6% had mild, and 50.4% had minimal levels of depression as per BDI-II scores at baseline. HCV treatment was significantly associated with reductions in depressive symptoms that persisted long term, regardless of symptom severity (P < .001) or presence of depression (P ≤ .01) or other psychiatric diagnoses (P ≤ .01) at baseline. Concurrent drug use (P ≤ .001) or hazardous alcohol drinking (P ≤ .001) did not interfere with reductions in depressive symptoms. Conclusions Depressive symptoms are highly prevalent among HCV-infected PWID. HCV treatment was associated with sustained reductions in depressive symptoms. HCV therapy with DAAs may have important implications for PWID that go beyond HCV cure.

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Hepatitis C Virus Treatment Access Among Human Immunodeficiency Virus and Hepatitis C Virus (HCV)-Coinfected People Who Inject Drugs in Guangzhou, China: Implications for HCV Treatment Expansion

Open Forum Infectious Diseases ◽

10.1093/ofid/ofw065 ◽

2016 ◽

Vol 3 (2) ◽

Cited By ~ 6

Author(s):

Carissa E. Chu ◽

Feng Wu ◽

Xi He ◽

Kali Zhou ◽

Yu Cheng ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Social Workers ◽

People Who Inject Drugs ◽

Hiv Treatment ◽

Direct Acting Antivirals ◽

Hcv Treatment ◽

Treatment Access ◽

Immunodeficiency Virus ◽

Direct Acting

Abstract Background. Hepatitis C virus (HCV) treatment access among human immunodeficiency virus (HIV)/HCV-coinfected people who inject drugs is poor, despite a high burden of disease in this population. Understanding barriers and facilitators to HCV treatment uptake is critical to the implementation of new direct-acting antivirals. Methods. We conducted in-depth interviews with patients, physicians, and social workers at an HIV treatment facility and methadone maintenance treatment centers in Guangzhou, China to identify barriers and facilitators to HCV treatment. We included patients who were in various stages of HCV treatment and those who were not treated. We used standard qualitative methods and organized data into themes. Results. Interview data from 29 patients, 8 physicians, and 3 social workers were analyzed. Facilitators and barriers were organized according to a modified Consolidated Framework for Implementation Research schematic. Facilitators included patient trust in physicians, hope for a cure, peer networks, and social support. Barriers included ongoing drug use, low HCV disease knowledge, fragmented reimbursement systems, HIV exceptionalism, and stigma. Conclusions. Expanding existing harm reduction programs, HIV treatment programs, and social services may facilitate scale-up of direct-acting antivirals globally. Improving integration of ancillary social and mental health services within existing HIV care systems may facilitate HCV treatment access.

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