Treatment for Viral Hepatitis as Secondary Prevention for Hepatocellular Carcinoma

Chronic infections with either hepatitis B or C virus (HBV or HCV) are among the most common risk factors for developing hepatocellular carcinoma (HCC). The hepatocarcinogenic potential of these viruses is mediated through a wide range of mechanisms, including the induction of chronic inflammation and oxidative stress and the deregulation of cellular pathways by viral proteins. Over the last decade, effective anti-viral agents have made sustained viral suppression or cure a feasible treatment objective for most chronic HBV/HCV patients. Given the tumorigenic potential of HBV/HCV, it is no surprise that obtaining sustained viral suppression or eradication proves to be effective in preventing HCC. This review summarizes the mechanisms by which HCV and HBV exert their hepatocarcinogenic activity and describes in detail the efficacy of anti-HBV and anti-HCV therapies in terms of HCC prevention. Although these treatments significantly reduce the risk for HCC in patients with chronic viral hepatitis, this risk is not eliminated. Therefore, we evaluate potential strategies to improve these outcomes further and address some of the remaining controversies.

Earlier antiretroviral initiation is independently associated with better arterial stiffness in children living with perinatally acquired HIV with sustained viral suppression in Mozambique

Background: Cardiovascular disease is a major driver of morbidity and mortality in adults living with HIV. The drivers of cardiovascular disease in children living with perinatally acquired HIV (PHIV) with sustained HIV viral suppression are unclear.Objectives: We explored the contribution of HIV-specific risk factors to arterial stiffness independently of traditional risk factors (metabolic syndrome [MetS]) in prepubertal children with PHIV with sustained viral suppression in a low-income country in Africa.Method: For this cross-sectional analysis, arterial stiffness was assessed by pulse wave velocity z-score (PWVz), measured using a Vicorder device. Metabolic syndrome components were measured. We retrospectively collected the antiretroviral therapy (ART) exposures, HIV stage, CD4 count and HIV viral load. A multivariate linear regression model was constructed for MetS components, retaining age and gender as obligatory variables. We then added HIV-related metrics to assess whether these had an independent or additive effect.Results: We studied 77 virally suppressed children with PHIV without evidence of cardiovascular disease (from medical history and physical examination). In the initial model, the PWVz was independently associated with each MetS component. The PWVz was higher in participants with proportionally greater visceral fat (waist/height ratio), elevated lipids (triglyceride/high-density lipoprotein ratio) and insulin resistance (log homeostatic model assessment [HOMA]). The addition of age at ART initiation increased the model R2 value from 0.36 to 0.43. In the resulting model, younger age at ART initiation was independently associated with a better PWVz (P 0.001).Conclusion: Earlier ART initiation was independently associated with lower large artery stiffness. This effect was independent of the effect of elevated lipids, visceral fat and insulin resistance.

CRISPR/Cas9-Induced Mutagenesis Corroborates the Role of Transportin-SR2 in HIV-1 Nuclear Import

Combination antiretroviral therapy (cART) effectively controls HIV-1 by reducing viral loads, but it does not cure the infection. Lifelong treatment with cART is a prerequisite for sustained viral suppression.

HIV and antiretroviral treatment knowledge gaps and psychosocial burden among persons living with HIV in Lima, Peru

This study aims to describe knowledge on HIV and antiretroviral (ARV) treatment and psychosocial factors among people living with HIV (PLWH) in Lima, Perú, to explore characteristics associated to this knowledge, and determine its impact on sustained viral suppression. A cross-sectional survey was conducted among 171 PLWH at the largest referral health care center in Lima. The psychosocial factors measured were depression, risk of alcoholism, use of illegal drugs and disclosure. A participant had “poor knowledge” when less than 80% of replies were correct. Sustained viral suppression was defined as two consecutive viral loads under 50 copies/mL. A total of 49% and 43% had poor HIV and ARV knowledge respectively; 48% of the study population screened positive for depression and 27% reported feeling unsupported by the person they disclosed to. The largest gaps in HIV and ARV knowledge were among 98 (57%) that did not recognize that HIV increased the risk of cancer and among 57 (33%) participants that did not disagree with the statement that taking a double dose of ARV if they missed one. Moderate depression was significantly associated to poor HIV and ARV knowledge. Non-disclosure and being on ARVs for less than 6 months were associated with not achieving sustained viral suppression. Our findings highlight important HIV and ARV knowledge gaps of PLWH and a high burden of psychosocial problems, especially of depression, among PLWH in Lima, Peru. Increasing knowledge and addressing depression and disclosure could improve care of PLWH.

Suboptimal Immune Recovery Despite Sustained HIV Suppression Among a Yi Ethnic Population in Southwest China

Objectives: Despite sustained viral suppression with effective antiretroviral therapy (ART), HIV-infected patients with suboptimal immune recovery are still at high risk of non-AIDS-related and AIDS-related events. The aim of this study was to investigate the potential determinants associated with suboptimal CD4+ T cell count recovery during free ART with sustained viral suppression among a HIV-infected Yi ethnic population in Liangshan Prefecture, an area with high HIV prevalence in China.Method: This retrospective study included all HIV-infected Yi adults (≥ 18 years and with baseline CD4+ T cell count less than 500 cells/μL) who initiated ART supported by NFATP between January 2015 and December 2018 in Zhaojue county, Liangshan Prefecture (Figure 1), and achieved virological suppression (viral load < 50 copies/mL) within 12 months after ART initiation and maintained sustained virological suppression. Univariate and multivariate log-binomial regression models were used to assess determinants of suboptimal immune recovery, producing adjusted odds ratios (aORs) and confidence intervals (CIs).Results: A total of 277 HIV-infected Yi patients (male/female, 140/137) with a mean age of 36.57 ± 7.63 years and a mean baseline CD4+ T cell count of 284.49 ± 117.11 cells/μL were included. Nearly half of the Yi patients were infected through injection drug use (48.7%, 135/277), and the prevalence of anti-HCV antibody was high (43.7%, 121/277). The free ART regimens were 91% efavirenz-based, 5.1% nevirapine-based, and 3.9% lopinavir/ritonavir-based. After a mean 3.77 ± 1.21 years of ART, optimal immune recovery (CD4+ T cell count ≥ 500 cells/μL), intermediate immune recovery (350≤CD4 < 500 cells/μL), and suboptimal immune recovery (CD4 < 350 cells/μL) occurred in 32.9%, 31%, and 36.2% of the included patients, respectively. After adjustments, multivariable analysis revealed that low pre-ART CD4+ cell count, WHO clinical stage III and IV, and coinfection with HCV were associated with suboptimal immune recovery. Conclusions: Our study support prompt ART initiation after HIV diagnosis, and curative HCV treatment in HCV/HIV co-infected patients for improving the immunological effectiveness of ART among HIV-infected Yi patients in Liangshan Prefecture.Trial registration: None

Sustained viremia suppression by SHIVSF162P3CN-recalled effector-memory CD8+ T cells after PD1-based vaccination

HIV-1 functional cure requires sustained viral suppression without antiretroviral therapy. While effector-memory CD8+ T lymphocytes are essential for viremia control, few vaccines elicit such cellular immunity that could be potently recalled upon viral infection. Here, we investigated a program death-1 (PD1)-based vaccine by fusion of simian immunodeficiency virus capsid antigen to soluble PD1. Homologous vaccinations suppressed setpoint viremia to undetectable levels in vaccinated macaques following a high-dose intravenous challenge by the pathogenic SHIVSF162P3CN. Poly-functional effector-memory CD8+ T cells were not only induced after vaccination, but were also recalled upon viral challenge for viremia control as determined by CD8 depletion. Vaccine-induced effector memory CD8+ subsets displayed high cytotoxicity-related genes by single-cell analysis. Vaccinees with sustained viremia suppression for over two years responded to boost vaccination without viral rebound. These results demonstrated that PD1-based vaccine-induced effector-memory CD8+ T cells were recalled by AIDS virus infection, providing a potential immunotherapy for functional cure.

Population Impact and Efficiency of Improvements to HIV PrEP Under Conditions of High ART Coverage among San Francisco Men Who Have Sex with Men

ABSTRACTBackgroundKey components of Ending the HIV Epidemic (EHE) plan include increasing HIV antiretroviral therapy (ART) and HIV preexposure prophylaxis (PrEP) coverage. One complication to addressing this service delivery challenge is the wide heterogeneity of HIV burden and healthcare access across the U.S. It is unclear how the effectiveness and efficiency of expanded PrEP will depend on different baseline ART coverage.MethodsWe used a network-based model of HIV transmission for men who have sex with men (MSM) in San Francisco. Model scenarios increased varying levels of PrEP coverage relative under current empirical levels of baseline ART coverage and two counterfactual levels. We assessed the effectiveness of PrEP with the cumulative percent of infections averted (PIA) over the next decade and efficiency with the number needed to treat (NNT) by PrEP required to avert one HIV infection.ResultsIn our projections, only the highest levels of combined PrEP and ART coverage achieved the EHE goals. Increasing PrEP coverage up to 75% showed that PrEP effectiveness was higher at higher baseline ART coverage with the PIA ranging from 61% in the lowest baseline ART coverage population to 75% in the highest ART coverage. The efficiency declined with increasing ART (NNT range from 41 to 113).ConclusionsImproving both PrEP and ART coverage would have a synergistic impact on HIV prevention even in a high baseline coverage city like San Francisco. Efforts should focus on narrowing the implementation gaps to achieve higher levels of PrEP retention and ART sustained viral suppression.

Viral Reservoir in Early-Treated HIV-Infected Children and Markers for Sustained Viral Suppression

Background The impact of very early infant treatment on HIV reservoir, and markers for treatment success, require study. Methods The Early Infant Treatment Study (EIT) enrolled 40 children living with HIV started on antiretroviral treatment (ART) at &lt;7 days of age and 23 who had started treatment between 30-365 days to serve as controls. Quantitative HIV DNA was evaluated every 1-3 months in PBMCs. 84-week repeat qualitative whole blood DNA PCR and dual enzyme EIA were performed. Results Median quantitative cell-associated DNA after at least 84 weeks was significantly lower among the first 27 EIT children tested than among 10 controls (40.8 vs. 981.4 copies/million cells; p&lt;0.001) and correlated with pre-ART DNA. Median DNA after 84 weeks did not differ significantly by negative or positive serostatus at 84 weeks (p=0.94), and appeared unaffected by periods of unsuppressed plasma RNA from 24-84 weeks (p=0.70). However, negative 84-week serostatus was 67% predictive for sustained RNA suppression and positive serostatus was 100% predictive for viremia. Loss of qualitative DNA positivity at 84 weeks was 73% predictive for sustained suppression and persistent positivity was 77% predictive for viremia. Conclusions Lower viral reservoir was associated with starting ART at &lt;1 week. Negative serostatus and qualitative DNA were useful markers of sustained viral suppression from 24-84 weeks.