Motivation and accessing care among drug treatment court involved women: A sequential, mixed-methods approach.

Drug treatment courts (DTC) address substance use disorders (SUD) but not cooccurrencing HIV or hepatitis C virus (HCV). This pilot explored feasibility and preliminary outcomes of the Women's Initiative Supporting Health (WISH) intervention and health-related motivation, both based in self-determination theory (SDT) regarding HIV/HCV and SUD treatment. WISH feasibility study: 79 DTC women completed a one-time survey regarding motivation and willingness to engage in future interventions. WISH intervention: 22 women from DTC with SUD and HIV or HCV received a 6-session, peer motivational enhancement health behavior-oriented interventions. Recruitment strategies were feasible. SDT-based measures demonstrated internal consistency in this under-studied population, with perceived competence/autonomy associationed with motivation to reduce HIV/HCV/SUD risk. Women DTC participants indicated acceptance and showed internally consistent results in SDT-based motivation measures These WISH feasibility and intervention pilot studies lay a foundation for future studies addressing motivation to access healthcare among women DTC participants.

Low Spontaneous Clearance Rates of Recently Acquired Hepatitis C Virus in Human Immunodeficiency Virus-Positive Men Who Have Sex With Men (PROBE-C Study).

BACKGROUND: Using direct-acting antivirals (DAAs) for recently acquired hepatitis C virus (RAHCV) infections, particularly in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM), dramatically reduced the incidence of hepatitis C. However, implementation into clinical practice is challenging. The aim of this study was to analyze spontaneous clearance (SC) rates of RAHCV and to identify predictors of SC. METHODS: The PROBE-C study is an observational European cohort on RAHCV infections in HIV-positive MSM. Between 2007 and 2017, RAHCV infections were documented with ≥12 months of follow-up. Fisher exact, χ2, and Mann-Whitney U tests were used for statistical analysis. RESULTS: A total of 464 RAHCV infections were documented; 457 of 464 patients (98%) were male, and the median age (interquartile range [IQR]) was 41 (38-46) years. The main risk group for hepatitis C virus (HCV) transmission was MSM (98.9%). Most participants were infected with HCV genotype 1 (78.3%). The median baseline HCV RNA level (IQR) was 230 000 (135 000-474 432) IU/mL, and the median CD4+ T-cell count was 574/µL (547-604/µL. Of all cases, 92% received combination antiretroviral therapy, with 91% showing suppressed HIV RNA levels (<200 copies/mL). The median maximum alanine aminotransferase level (IQR) was 445 (402-522) U/L. SC of RAHCV infection occurred in 55 of 464 cases (11.9%). A >2-log decline in HCV RNA levels 4 weeks after diagnosis of RAHCV infection was the strongest predictor of SC (P < .001; sensitivity, 96.4%; specificity, 97.5%; positive predictive value, 84.1%; negative predictive value, 99.5%). CONCLUSIONS: SC of RAHCV in HIV-positive MSM is found in only 11.9% of cases and a <2-log drop in HCV RNA level at week 4 after diagnosis should prompt early DAA-based treatment. However, immediate DAA treatment for RAHCV infection may also be favored in patients with ongoing transmission risk behavior.

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

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.

Evidence for Implementation: HIV/HCV Coinfection and Pregnancy.

PURPOSE OF REVIEW: In the context of the opioid epidemic, hepatitis C virus (HCV) infection prevalence is increasing among women of reproductive age. Pregnant people with HIV/HCV coinfection may be at increased risk of adverse pregnancy and neonatal outcomes, although research in this key population is lacking. RECENT FINDINGS: Treatment with directly acting antivirals (DAAs) has transformed the clinical care for most patients with HCV. However, pregnant people were excluded from trials of these medications. A recent phase I study has shown promise with excellent safety profile for ledipasvir-sofosbuvir; demonstrating no episodes of perinatal transmission, 100% sustained virologic response, and no safety concerns. Pregnancy represents a time of maximal interaction with the healthcare system and therefore an ideal window of opportunity to cure HCV. Current observational data regarding pregnant people who are co-infected with HCV and HIV suggest poor outcomes such as increased risk of preterm birth; however, there are no prospective and well-controlled studies to fully understand the impact of HIV/HCV coinfection on pregnancy. Phase 1 studies suggest that DAAs are well-tolerated and effective during pregnancy. Only through large, prospective clinical trials will we be able to understand the interaction of HCV and HIV during pregnancy and to evaluate safety and efficacy of DAAs in this key population.

Human immunodeficiency virus, hepatitis C virus and hepatitis B virus incidence in blood donors from 2000 to 2020 in France: Trends and lessons from haemovigilance surveillance.

BACKGROUND AND OBJECTIVES: Data from 21 years (2000-2020) of haemovigilance were used to assess human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) incidence rates in repeat blood donors and the occurrence of transfusion-transmitted (TT) viral infections. MATERIALS AND METHODS: Blood donors who converted for HIV, HCV or HBV markers within serial three-year analysis periods were included. Epidemiological and virological data were retrieved from the national epidemiological donor database and were supplemented with information on blood components and the infection status of recipients of the previous negative donation (D.N-1) of donors who seroconverted. RESULTS: Incidence rates declined from 1.27 to 0.35/100,000 person-years for HIV, from 0.59 to 0.19 for HCV and from 1.66 to 0.18 for HBV. Risk factors and lookback for 232 HIV, 90 HCV and 74 HBV seroconversions were investigated. The main risk factor identified at post-donation interview was having sex with men (47.8% of males) for HIV and a sexual risk for HCV (30.6%) and HBV (37.1%). The viral loads and sequences were retrospectively tested in 191 HIV, 74 HCV and 62 HBV D.N-1 archived samples. Six (five HBV and one HIV-1) were positive all low viral loads. Two recipients were infected by red blood cells from two HBV seroconverting donors before the introduction of HBV-nucleic acid testing. CONCLUSION: HIV, HCV and HBV incidence rates in blood donors declined over the two past decades in France. There is a very small risk of a blood component that tests negative entering the blood supply resulting in TT infections, especially after introduction of molecular assays in donor screening.

Perceptions Towards HCV Treatment with Direct Acting Antivirals (DAAs): A Qualitative Analysis with Persons with HIV/HCV Co-infection Who Delay or Refuse Treatment.

In the United States, approximately 25% of people with HIV (PWH) are co-infected with hepatitis C (HCV). Since 2014, highly effective and well-tolerated direct-acting antivirals (DAAs) have revolutionized HCV treatment. Uptake of DAAs by people with HIV/HCV co-infection has improved but remains suboptimal due to system, provider, and patient-level barriers. To explore patient-level issues by better understanding their attitudes towards DAA treatment, we conducted qualitative interviews with 21 persons with HIV/HCV co-infection who did not consent to DAA treatment or delayed treatment for at least 1 year after diagnosis. We found PWH perceived DAA treatment barriers and facilitators on multiple levels of the social-ecological environment: the individual (HCV disease and treatment literacy), interpersonal (peer influence), institutional (media and healthcare provider relationship), and structural levels (treatment cost and adherence support). Recommendations to improve DAA treatment uptake include HCV-treatment adherence support, HCV disease and treatment literacy training (particularly for substance use and DAA treatment interactions), and encouraging PWH who have successfully completed DAA treatment to speak with their peers.

Estimating the number of people who inject drugs using repeated respondent-driven sampling (RDS) in a community-based program: implications for the burden of hepatitis C and HIV infections and harm reduction coverage.

Estimates of the population size of people who inject drugs (PWID) are essential for efficient program planning and for monitoring key targets. Existing estimates in Greece are based on the capture-recapture method applied to drug treatment sources. We aimed to obtain estimates based on data collected from a community-based program addressing PWID in Athens, Greece. The program was implemented in 2012-2013 to increase diagnosis and treatment for HIV among PWID during an HIV outbreak. Five Responden-Driven Sampling (RDS) rounds were used to recruit participants. A unique code was used to identify participants among rounds. Capture-recapture was applied to estimate the population size in 2013 (PWID with injection in the past 12 months; active PWID with injection in the past 30 days). Log-linear models were applied. In 2013, the estimated number of active PWID in Athens was 4,117 [95% confidence interval (CI): 3,728-4,507] (vs. 1,956 [95% CI: 1,525-2,565] the existing population size estimate). Based on this estimate, the coverage of needle and syringe programs in 2013 was 103 syringes/PWID/year (vs. 216 based on the existing estimate). The population prevalence of injecting drug use in Athens (past 12 months) was 0.222% (95% CI: 0.200-0.245). The inclusion of data from community-based programs in the estimation of the PWID population size resulted in 2.1-fold higher estimates, compared to the official estimates obtained from drug treatment data, and indicates the need for re-evaluation of necessary resources for harm reduction and elimination of HIV and hepatitis C in PWID.

Future Directions for HIV/HCV Care: Lessons Learned From Local Evaluation Projects in Texas and Connecticut and Implications for Practice and Health Promotion.

The Health Resources Service Administration (HRSA) Special Projects of National Significance (SPNS) project titled "Curing Hepatitis C among People of Color Living with HIV," funded two sites, University of Texas (TX) San Antonio and Yale University School of Medicine in Connecticut (CT) to explore barriers and facilitators towards achieving HCV cure in the era of curative DAAs for HCV in different local contexts. Through individualized approaches that study patient, provider and system level barriers, the nine articles in this Focus Issue highlight key themes that are important in designing local implementation strategies that will enable achievement of HCV elimination goals in priority populations.

Improving HIV and HCV Testing in Substance Use Disorder Programs (SUDs) That Provide Medications for Opiate Use Disorder (MOUD): Role of Addressing Barriers and Implementing Universal and Site-Specific Approaches.

Introduction. National strategies to end the HIV epidemic and eliminate hepatitis c (HCV) through a syndemic approach require improvements in testing for HIV and HCV. Given the intersection of the opioid crisis with HIV and HCV acquisition, substance use disorder (SUD) treatment centers providing medications for opiate use disorder (MOUD) provide a critical opportunity to expand testing. Rates of testing in MOUD clinics have been suboptimal. Method. We employed the Nominal Group Technique (NGT), Ishikawa cause and effect diagrams, and individualized Quality Improvement (QI) efforts at two SUD clinics (SUD A and B) in Connecticut (CT) as part of an HRSA-funded grant focused on improving HCV cure in persons with HIV/HCV coinfection. Baseline and longitudinal data were collected on rates of HIV and HCV testing and positivity as well as linkage to treatment. Results. Between April 1, 2019, and May 31, 2021, for SUD A and B respectively, HIV testing increased from 13% to 90% and 33% to 83%; HCV testing increased from 4% to 90% and 30% to 82%, with few reported cases of HIV/HCV coinfection. HCV testing revealed new and prior diagnoses at both sites, with subsequent referrals for treatment. Qualitative assessments identified best practices which included the institution of formal policies and procedures, streamlining of testing logistics, designation of a site champion, and broadening relevant education to staff and clients. Conclusion. Strategic assessment of barriers and facilitators to HIV and HCV testing at MOUD clinics can lead to improved testing and referral rates that are key to improving the cascade of care for both diseases.

Characterizing Persons With HIV/HCV Coinfection Who Remain Untreated for Hepatitis C at Four HIV Clinics in Connecticut (CT): Role of Multiple Overlapping Barriers at the Individual and Clinic System Levels.

Introduction. Direct-acting antiviral medications have made hepatitis C virus (HCV) cure possible for >95% of persons with chronic HCV infection, including those coinfected with HIV. Achieving strategic HCV elimination targets requires an understanding of system, provider, and patient-level barriers to treatment. We explored such barriers among persons with HIV/HCV coinfection who remained untreated for HCV. Methods. Among four primary care HIV clinics in CT with high rates of HCV cure, 25 patients with HIV/HCV coinfection were eligible (no HCV treatment as of March 31, 2021). We conducted retrospective chart reviews of demographics, clinical practice patterns, patient-specific issues such as housing, transportation, food security, and presence of mental health and substance use problems. Results. Among untreated patients, 13 (51%) were female; 17 (68%) were Black; median age was 62 years old. The majority (84%) had injecting drug use (IDU) as HIV transmission risk factor; 14 (56%) were prescribed medication-assisted treatment. Median time since HIV and HCV diagnosis was 25 and 19 years, respectively. Clinic-level barriers were noted in 19 (76%) and included lack of evaluation, treatment not recommended or implemented. Concomitant structural barriers included unstable housing for 11 (44%) and lack of transportation for eight (32%). Most patients had history of illicit substance use (84%) and mental health issues (68%). Many (76%) had multiple potential barriers. Conclusions. Multiple overlapping barriers spanning clinic and patient level domains including social determinants of health were the norm in persons with long-standing HIV/HCV coinfection who have not received HCV treatment. Interventions will require innovative, multi-disciplinary and personalized approaches.

Sustained Effect on Hepatitis C Elimination Among Men Who Have Sex With Men in the Swiss HIV Cohort Study: A Systematic Re-Screening for Hepatitis C RNA Two Years Following a Nation-Wide Elimination Program.

BACKGROUND: The Swiss HCVree Trial (NCT02785666) was conducted in 2015-2017 with the goal of implementing a population-based systematic hepatitis C virus (HCV) micro-elimination program among men who have sex with men (MSM) with human immunodeficiency virus (HIV) enrolled in the Swiss HIV Cohort Study (SHCS). The trial led to a 91% and 77% decline of HCV prevalence and incidence, respectively. The long-term effect of this HCV micro-elimination program is yet to be explored. METHODS: All MSM enrolled in the SHCS were screened for HCV RNA using stored plasma samples obtained in 2019, termed "Swiss HCVree Post" screen. The incidence of HCV infection over time was assessed using additional information on HCV testing routinely collected in the SHCS. Characteristics of participants with replicating HCV infection were analyzed. RESULTS: The point-prevalence of "Swiss HCVree Post" (N = 4641) was 0.6%, reflecting a decline of 48% compared to the end of the Swiss HCVree Trial where the prevalence was 1.2%. Further, the incidence of HCV among MSM in the SHCS declined from 0.31/100 person-years (py) (95% confidence interval [CI] [.17, .55]) in 2017 to 0.19/100 py (95% CI [.09, .39]) in 2019. CONCLUSIONS: A systematic HCV RNA-based screening among MSM with HIV conducted 2 years after the Swiss HCVree Trial revealed a sustained effect and further decline of the prevalence and incidence of replicating HCV infection. This indicates that the Swiss HCVree Trial was successful in curbing the HCV epidemic among MSM with HIV in Switzerland. CLINICAL TRIALS REGISTRATION: NCT02785666.

Hepatitis C virus micro-elimination within a clinic for people with HIV: challenges in the home stretch.

OBJECTIVES: To describe a pharmacist-led campaign aimed at reducing the proportion of people with HIV with ongoing chronic hepatitis C virus (HCV) infection and delineating barriers to HCV care in this patient population. METHODS: An electronic report and retrospective chart review were used to identify patients who remained with HCV infections after a previous treatment initiative. A clinical pharmacist and pharmacy resident approached the remaining HCV patients during their routine visits for HIV care to offer and coordinate direct-acting antiviral (DAA) treatment. The primary end-point was to compare the prevalence of chronic HCV before and after the intervention period. Barriers to care were also evaluated, with logistic regression performed to identify predictors of sustained virologic response (SVR) attainment. RESULTS: Forty-six patients were included in the analysis (4.2% of clinic population), with HCV prevalence falling to 0.6% (six patients) by the end of the study (p < 0.0001). The HCV care cascade in the cohort was as follows: 70% agreed to and received DAA therapy, 63% initiated therapy, and 50% achieved SVR. The top barriers to care at baseline included recreational drug use (67%), poor engagement in care (61%), and mental health disorders (28%). Poor engagement in care and active recreational drug use were associated with decreased odds of achieving SVR in bivariate analysis. CONCLUSIONS: A coordinated effort can make strides towards reducing the overall burden of HCV in this challenging population. The HCV care cascade remains tied to the HIV continuum of care, with poor engagement in care remaining an important rate-limiting step impeding micro-elimination.

Predicting the presence of depressive symptoms in the HIV-HCV co-infected population in Canada using supervised machine learning.

BACKGROUND: Depression is common in the human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infected population. Demographic, behavioural, and clinical data collected in research settings may be of help in identifying those at risk for clinical depression. We aimed to predict the presence of depressive symptoms indicative of a risk of depression and identify important classification predictors using supervised machine learning. METHODS: We used data from the Canadian Co-infection Cohort, a multicentre prospective cohort, and its associated sub-study on Food Security (FS). The Center for Epidemiologic Studies Depression Scale-10 (CES-D-10) was administered in the FS sub-study; participants were classified as being at risk for clinical depression if scores ≥ 10. We developed two random forest algorithms using the training data (80%) and tenfold cross validation to predict the CES-D-10 classes-1. Full algorithm with all candidate predictors (137 predictors) and 2. Reduced algorithm using a subset of predictors based on expert opinion (46 predictors). We evaluated the algorithm performances in the testing data using area under the receiver operating characteristic curves (AUC) and generated predictor importance plots. RESULTS: We included 1,934 FS sub-study visits from 717 participants who were predominantly male (73%), white (76%), unemployed (73%), and high school educated (52%). At the first visit, median age was 49 years (IQR:43-54) and 53% reported presence of depressive symptoms with CES-D-10 scores ≥ 10. The full algorithm had an AUC of 0.82 (95% CI:0.78-0.86) and the reduced algorithm of 0.76 (95% CI:0.71-0.81). Employment, HIV clinical stage, revenue source, body mass index, and education were the five most important predictors. CONCLUSION: We developed a prediction algorithm that could be instrumental in identifying individuals at risk for depression in the HIV-HCV co-infected population in research settings. Development of such machine learning algorithms using research data with rich predictor information can be useful for retrospective analyses of unanswered questions regarding impact of depressive symptoms on clinical and patient-centred outcomes among vulnerable populations.

Longitudinal Assessment of Multiple Immunological and Inflammatory Parameters during Successful DAA Therapy in HCV Monoinfected and HIV/HCV Coinfected Subjects.

In the direct-acting antiviral (DAA) era, it is important to understand the immunological changes after HCV eradication in HCV monoinfected (mHCV) and in HIV/HCV coinfected (HIV/HCV) patients. In this study, we analyzed sub-populations of monocytes, dendritic cells (DCs), T-lymphocytes and inflammatory biomarkers following initiation of DAA in 15 mHCV and 16 HIV/HCV patients on effective antiretroviral therapy at baseline and after sustained virological response at 12 weeks (SVR12). Fifteen age- and sex-matched healthy donors (HD) were enrolled as a control group. Activated CD4+ and CD8+ T-lymphocytes, mDCs, pDCs, MDC8 and classical, non-classical and intermediate monocytes were detected using flow cytometry. IP-10, sCD163 and sCD14 were assessed by ELISA while matrix metalloproteinase-2 (MMP-2) was measured by zymography. At baseline, increased levels of IP-10, sCD163 and MMP-2 were found in both HIV/HCV and mHCV patients compared to HD, whereas sCD14 increased only in HIV/HCV patients. After therapy, IP-10, sCD163 and sCD14 decreased, whereas MMP-2 persistently elevated. At baseline, activated CD8+ T-cells were high in HIV/HCV and mHCV patients compared to HD, with a decrease at SVR12 only in HIV/HCV patients. Activated CD4+ T-cells were higher in HIV/HCV patients without modification after DAAs therapy. These results suggest complex interactions between both viruses and the immune system, which are only partially reversed by DAA treatment.

The Enhanced Liver Fibrosis Index Predicts Hepatic Fibrosis Superior to FIB4 and APRI in HIV/HCV Infected Patients.

BACKGROUND: Accurate noninvasive biomarkers of fibrotic progression are important for hepatitis C virus (HCV) management, but commonly used modalities may have decreased efficacy in human immunodeficiency virus (HIV)/HCV-coinfected persons. The enhanced liver fibrosis (ELF) index is a highly sensitive noninvasive marker of hepatic fibrosis that has had limited assessment in the HIV/HCV population. We compared ELF index performance to FIB4 and aspartate to platelet ratio index (APRI) at different stages of liver fibrosis as determined by liver histology, and validated the efficacy of the three noninvasive biomarkers in HIV/HCV-coinfected versus HCV-monoinfected. METHODS: The ELF index was determined in 147 HIV/HCV-coinfected and 98 HCV-monoinfected persons using commercial ELISA assays for the component elements of the index. Area under the receiver-operator curve was used to validate ELF and to compare its performance to liver histology as well as to other noninvasive biomarkers of liver fibrosis, FIB4, and APRI. RESULTS: The ELF index increased with histological stage of liver fibrosis and exhibited a linear relationship with Metavir score in all subjects. ELF performance was comparable between HIV/HCV and HCV with advanced liver fibrosis/cirrhosis. In the HIV/HCV cohort ELF cutoffs of 8.45 and 9.23 predicted mild and moderate fibrosis with 85% sensitivity, whereas the ELF cutoff of 9.8 had the highest specificity for advanced fibrosis and the cutoff of 10.4 was 99% specific for cirrhosis. ELF performance was superior to FIB4 and APRI in all subjects regardless of HIV status. CONCLUSIONS: ELF index demonstrated excellent characteristics toward accurate prediction of liver fibrosis and cirrhosis with superior performance to APRI and FIB4 in HIV/HCV coinfection. Applying this noninvasive biomarker index for diagnosis of liver fibrosis and progression in HIV/HCV is warranted.

Liver Fibrosis in Human Immunodeficiency Virus (HIV)-Hepatitis C Virus (HCV) Coinfection Before and After Sustained Virologic Response: What Is the Best Noninvasive Marker for Monitoring Regression?

BACKGROUND: Noninvasive markers of liver fibrosis such as aspartate aminotransferase-to-platelet ratio (APRI) and transient elastography (TE) have largely replaced liver biopsy for staging hepatitis C virus (HCV). As there is little longitudinal data, we compared changes in these markers before and after sustained virologic response (SVR) in human immunodeficiency virus (HIV)-HCV coinfected patients. METHODS: Participants from the Canadian Coinfection Cohort study who achieved SVR after a first treatment with either interferon/ribavirin or direct acting antivirals (DAAs), with at least 1 pre- and posttreatment fibrosis measure were selected. Changes in APRI or TE (DAA era only) were modeled using a generalized additive mixed model, assuming a gamma distribution and adjusting for sex, age at HCV acquisition, duration of HCV infection, and time-dependent body mass index, binge drinking, and detectable HIV RNA. RESULTS: Of 1981 patients, 151 achieved SVR with interferon and 553 with DAAs; 94 and 382 met inclusion criteria, respectively. In the DAA era, APRI increased (0.03 units/year; 95% credible interval (CrI): -.05, .12) before, declined dramatically during, and then changed minimally (-0.03 units/year; 95% CrI: -.06, .01) after treatment. TE values, however, increased (0.74 kPa/year; 95% CrI: .36, 1.14) before treatment, changed little by the end of treatment, and then declined (-0.55 kPa/year; 95% CrI: -.80, -.31) after SVR. CONCLUSIONS: TE should be the preferred noninvasive tool for monitoring fibrosis regression following cure. Future studies should assess the risk of liver-related outcomes such as hepatocellular carcinoma according to trajectories of fibrosis regression measured using TE to determine if and when it will become safe to discontinue screening.

Human Immunodeficiency Virus (HIV) Infection Is Associated With Lower Risk of Hepatocellular Carcinoma After Sustained Virological Response to Direct-acting Antivirals in Hepatitis C Infected Patients With Advanced Fibrosis.

BACKGROUND: The aim of this study was to assess the impact of human immunodeficiency virus (HIV) infection on the risk of developing hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV) who achieve sustained virological response (SVR) with direct-acting antiviral (DAA). METHODS: Multisite prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they met: (1) SVR with DAA-based combination; (2) liver stiffness (LS) ≥9.5 kPa previous to treatment; (3) LS measurement at the SVR time-point. The main endpoint was the occurrence of HCC. Propensity score (PS) was calculated to address potential confounders due to unbalanced distribution of baseline characteristics of HIV/HCV-coinfected and HCV-monoinfected patients. RESULTS: In total, 1035 HCV-infected patients were included, 667 (64%) coinfected with HIV. After a median (Q1-Q3) follow-up time of 43 (31-49) months, 19 (1.8%) patients developed HCC (11 [3.0%]; HCV-monoinfected, 8[1.2%]; HIV/HCV-coinfected individuals; P = .013). In the multivariable analysis, HIV coinfection was associated with a lower adjusted risk of developing HCC (subhazard ratio [sHR] = 0.27, 95% confidence interval [CI]: .08-.90; P = .034). Predictors of HCC emergence were: HCV genotype 3 (sHR = 7.9, 95% CI: 2.5-24.9; P < .001), MELD score at SVR >10 (sHR = 1.37, 95% CI: 1.01-1.86; P = .043) and LS value at SVR (sHR = 1.03, 95% CI: 1.01-1.06, for 1 kPa increase; P = .011). Using inverse probability weighting method on the PS, HIV-infected patients had a lower risk of HCC (powered HR = 0.33, 95% CI: .11-.85). CONCLUSIONS: Among HCV-infected patients with advanced fibrosis, who achieve SVR with DAA, HIV coinfection seems to be associated with a lower risk of HCC occurrence. The underlying causes for this finding need to be investigated.

Nonviral liver disease is the leading indication for liver transplant in the United States in persons living with human immunodeficiency virus.

We evaluated whether indications for liver transplantation (LT) have changed among people with/without human immunodeficiency virus (HIV) infection and compared LT outcomes and trends by HIV serostatus. LT recipients (2008-2018) from the United Network for Organ Sharing and Organ Procurement and Transplantation Network (UNOS/OPTN) were identifed. Among 62 195 LT recipients, 352 (0.6%) were HIV-infected. The proportion of HIV-infected patients increased over time (P trend = .001), as did the number of transplant centers performing LT for HIV-infected recipients; average annual percentage change of 9.2% (p < .001). Nonviral causes became the leading indication in 2015 for HIV-uninfected and in 2018 for HIV-infected (P trend < .001). Three-year cumulative patient survival rates were 77.5%, for HIV-infected and 84.6%, for HIV-uninfected (p = .15). Over time, graft and patient survival rates improved for both HIV-infected and uninfected (p < .001). Among HCV-infected LT recipients, 3-year patient survival rates were 72.5% for HIV-infected and 81.8% for HIV-uninfected (p = .02). However, in a subanalysis restricted to 2014-2018, differences in graft and patient survival by HIV serostatus were no longer observed (3-year patient survival rates were 81.2% for HIV-infected and 86.4% for HIV-uninfected, p = .34). In conclusion, in the United States, nonviral liver disease is now the leading indication for LT in HIV-infected patients, and posttransplant outcomes have improved over time.

HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients.

OBJECTIVE: To evaluate the impact of hepatitis C virus (HCV) elimination via interferon (IFN)-based therapy on gene expression profiles related to the immune system in HIV/HCV-coinfected patients. METHODS: We conducted a prospective study in 28 HIV/HCV-coinfected patients receiving IFN-based therapy at baseline (HIV/HCV-b) and week 24 after sustained virological response (HIV/HCV-f). Twenty-seven HIV-monoinfected patients (HIV-mono) were included as a control. RNA-seq analysis was performed on peripheral blood mononuclear cells (PBMCs). Genes with a fold-change (FC) ≥ 1.5 (in either direction) and false discovery rate (FDR) ≤ 0.05 were identified as significantly differentially expressed (SDE). RESULTS: HIV/HCV-b showed six SDE genes compared to HIV-mono group, but no significantly enriched pathways were observed. For HIV/HCV-f vs. HIV/HCV-b, we found 58 SDE genes, 34 upregulated and 24 downregulated in the HIV/HCV-f group. Of these, the most overexpressed were CXCL2, PDCD6IP, ATP5B, IGSF9, RAB26, and CSRNP1, and the most downregulated were IFI44 and IFI44L. These 58 SDE genes revealed two significantly enriched pathways (FDR < 0.05), one linked to Epstein-Barr virus infection and another related to p53 signaling. For HIV/HCV-f vs. HIV-mono group, we found 44 SDE genes that revealed 31 enriched pathways (FDR < 0.05) related to inflammation, cancer/cell cycle alteration, viral and bacterial infection, and comorbidities associated with HIV/HCV-coinfection. Five genes were overrepresented in most pathways (JUN, NFKBIA, PIK3R2, CDC42, and STAT3). CONCLUSION: HIV/HCV-coinfected patients who eradicated hepatitis C with IFN-based therapy showed profound gene expression changes after achieving sustained virological response. The altered pathways were related to inflammation and liver-related complications, such as non-alcoholic fatty liver disease and hepatocellular carcinoma, underscoring the need for active surveillance for these patients.

A Randomized Trial Comparing Brief Advice and Motivational Interviewing for Persons with HIV-HCV Co-infection Who Drink Alcohol.

Alcohol use contributes to the progression of liver disease in HIV-HCV co-infected persons, but alcohol interventions have never addressed low levels of alcohol use in this population. We enrolled 110 persons consuming at least 4 alcoholic drinks weekly in a clinical trial comparing two active 18-month long interventions, delivered every 3 months by phone, brief advice about drinking versus a motivational intervention. Final assessment was at 24 months. MI had larger reductions in alcohol use days than the BA arm at all follow-up assessments. The treatment by time effect was not significant for days of drinking (p = 0.470), mean drinks per day (p = 0.155), or for the continuous FIB-4 index (p = 0.175). Drinking declined in both conditions from baseline, but given the small sample, we do not have sufficient data to make any conclusion that one treatment is superior to the other.Trial Registry Trial registered at clinicaltrials.gov; Clinical Trial NCT02316184.