艾滋病病毒重叠肝炎病毒感染患者肝功能受损分析

目的 探讨艾滋病病毒（HIV）重叠乙型肝炎病毒（HBV）和/或丙型肝炎病毒（HCV）感染肝功能受损情况.方法 检测134例住院HIV阳性患者HBV、HCV感染血清标志物,分为HIV＋HCV、HIV＋HBV、HIV＋HCV＋HBV重叠感染三组,单纯性HIV感染作为对照组,对四组患者的肝功能指标进行回顾性分析.结果 HIV合并HCV感染最常见达74%.对照组ALT值中位数为26U/L（16.25～37）,重叠感染组HIV＋HBV、HIV＋HCV、HIV＋HBV＋HCV的ALT值中位数分别为77（23～96）、43（23～75.5）、54（33.5～108）U/L,对照组与重叠感染组差异均有统计学意义（均P〈0.05）.PT值HIV＋HBV＋HCV组中位数为14.6 s（12.9～15.2）,明显高于其他三组（P〈0.05）.结论HIV重叠感染以合并HCV最高,重叠感染会加重肝功能损害,以同时重叠HCV、HBV感染组为明显.     

Dual antiviral therapy for HIV and hepatitis C – drug interactions and side effects

Introduction: Roughly 20% of HIV-positive persons worldwide are coinfected with hepatitis C virus (HCV). The recent advent of direct-acting antivirals (DAA) that cure most hepatitis C patients has attracted much attention. Knowledge on drug interactions between DAA and antiretrovirals (ARV) may allow maximizing antiviral efficacy while minimizing drug-related toxicities.

Areas covered: We review the most frequent side effects and clinically significant drug interactions between DAA and ARV. We further discuss how they can be prevented and managed in HIV/HCV-coinfected patients.

Expert opinion: The safety profile of current DAA and the most recently approved ARV is quite favorable. Interactions between DAA and ARV could be frequent in clinical practice. The most common drug interactions affect drug metabolism by inducing or inhibiting the cytochrome P450 system, leading to abnormal drug exposures. Throughout this mechanism HCV and HIV protease inhibitors interact, especially when co-formulated with ritonavir as a pharmacoenhancer, and non-nucleoside HCV and HIV polymerase inhibitors. In contrast, HIV and HCV nucleos(t)ide polymerase inhibitors, and most HCV NS5A inhibitors (i.e., ledipasvir) and HIV integrase inhibitors (i.e., dolutegravir), do not or only marginally affect CYP450, and therefore are free of significant drug interactions. Exposure to HIV and HCV nucleos(t)ide analogues (i.e., tenofovir and sofosbuvir, respectively) is subject to induction/inhibition of drug transporters (i.e., P-glycoprotein).     

Not All Injection Drug Users Are Created Equal: Heterogeneity of HIV,Hepatitis C Virus,and Hepatitis B Virus Infection in Georgia

Injection drug users (IDU) are widely believed to have accelerated the looming HIV/AIDS epidemic now faced by the Russian Federation and countries of the former Soviet Union. However, IDUs may be heterogeneous with regard to risk behaviors, and a subpopulation may be responsible for the majority of blood-borne pathogen transmission. We studied 926 adult injection drug users (IDU) from the cities of Tbilisi, Batumi, and Poti in Georgia, a small country in the Caucuses region between the Black and Caspian Seas, between 1997 and 1998. Study participants were administered a confidential questionnaire and were tested for antibody to HIV, hepatitis C virus (HCV), hepatitis B virus surface antigen (HBsAg), and hepatitis B core antibody (anti-HBc). Five (0.5%) individuals were positive for HIV; 539 (58.2%), for HCV; 67 (7.2%), for HBsAg; and 475, for (51.3%) anti-HBc. Surveyed individuals, 88.7%, reported sharing needles with others, and needle sharing with more than 10 other individuals versus no sharing was a highly significant predictor (OR: 278.12, 95% CI: 77.57, 997.20) of HCV seropositivity. In adjusted analysis, individuals who usually injected stolen medical/synthetic drugs had significantly lower odds of HCV (OR: 0.38, 95% CI: 0.22, 0.68) and HBV (OR: 0.58, 95% CI: 0.37, 0.90) than individuals most commonly injecting opium. Despite some limitations, these results suggest the presence of substantial heterogeneity between different injection drug-using groups in Georgia. Identification of high-risk IDU subpopulations is vital to efficiently target risk reduction programs and to prevent confounding by risk status in large HIV/AIDS behavioral intervention and vaccine trials.     

Not all injection drug users are created equal: heterogeneity of HIV, hepatitis C virus, and hepatitis B virus infection in Georgia

Injection drug users (IDU) are widely believed to have accelerated the looming HIV/AIDS epidemic now faced by the Russian Federation and countries of the former Soviet Union. However, IDUs may be heterogeneous with regard to risk behaviors, and a subpopulation may be responsible for the majority of blood-borne pathogen transmission. We studied 926 adult injection drug users (IDU) from the cities of Tbilisi, Batumi, and Poti in Georgia, a small country in the Caucuses region between the Black and Caspian Seas, between 1997 and 1998. Study participants were administered a confidential questionnaire and were tested for antibody to HIV, hepatitis C virus (HCV), hepatitis B virus surface antigen (HBsAg), and hepatitis B core antibody (anti-HBc). Five (0.5%) individuals were positive for HIV; 539 (58.2%), for HCV; 67 (7.2%), for HBsAg; and 475, for (51.3%) anti-HBc. Surveyed individuals, 88.7%, reported sharing needles with others, and needle sharing with more than 10 other individuals versus no sharing was a highly significant predictor (OR: 278.12, 95% CI: 77.57, 997.20) of HCV seropositivity. In adjusted analysis, individuals who usually injected stolen medical/synthetic drugs had significantly lower odds of HCV (OR: 0.38, 95% CI: 0.22, 0.68) and HBV (OR: 0.58, 95% CI: 0.37, 0.90) than individuals most commonly injecting opium. Despite some limitations, these results suggest the presence of substantial heterogeneity between different injection drug-using groups in Georgia. Identification of high-risk IDU subpopulations is vital to efficiently target risk reduction programs and to prevent confounding by risk status in large HIV/AIDS behavioral intervention and vaccine trials.     

Safely treating hepatitis C in patients with HIV or hepatitis B virus coinfection

Introduction: There are several clinical trials and prospective studies which support the use of direct-acting antiviral agents (DAAs) in hepatitis C virus (HCV)-coinfected patients. In this review, the safety of DAAs in HCV patients coinfected with hepatitis B virus (HBV) or HIV has been evaluated.

Areas covered: All available prospective studies, clinical trials and congress abstracts in the English language that assessed the safety and efficacy of DAAs in HCV coinfections have been considered.

Expert opinion: The newer DAAs in the treatment of HCV/HIV-coinfected patients resolved major limitations of the first-generation protease inhibitors including complex dosing, poor tolerability and interactions with antiretroviral drugs. There are not yet enough data regarding the safety and efficacy of DAAs in some coinfected patients with comorbidities, nor for pregnant, lactating or pediatric patients. Evaluating the safety and efficacy of these agents in these subgroups with HCV coinfection is recommended for future studies. The role of new direct-acting antiviral-based therapy for the treatment of patients with HCV/HBV coinfection remains to be evaluated.     

Incidence and cost of adverse drug reactions in a French cancer institute

Objectives: The incidence and the cost of adverse drug reactions (ADR) in patients treated by cancer chemotherapy were assessed using hospital database records from 1993 in a French regional cancer institute. Methods: Patients with ADRs were identified using a list of ICD-9 codes describing potential adverse events. Direct medical costs for treating these ADRs were assessed according to the hospital system of claims data. Results: Among the 3429 in-patients hospitalized in 1993, we found 171 patients (5% of the population) who presented at least one ADR (3.5% of the total number of hospital stays). A total of 313 ADRs occurred in 256 hospital stays (3.5% of the hospital stays in 1993). Of the patients with ADRs 60.2% were female and their mean age was 51.5 years; 106 patients presented with at least one “serious” ADR according to the WHO definition. These ADRs occurred during 130 hospitalizations. In 7 cases, ADRs led to death. There was no relationship between age or sex and the seriousness of the ADR. Of the ADRs 91% was type “A” (predictable). We estimated that the cost of “serious” ADRs was 1.8% of the global budget of the hospital. The average cost of ADRs leading to hospitalization was 33 037 French Francs at the current rate in 1993. This cost represented an additional cost of 32% of the overall cumulative yearly cost per patient in the institution. Conclusion: This study emphasizes the medical and economic impact of the management of ADR in anticancer treatments. Received: 10 February 1997 / Accepted in revised form: 29 April 1997     

Personalising drug safety—results from the multi-centre prospective observational study on Adverse Drug Reactions in Emergency Departments (ADRED)

Adverse drug reactions (ADR) account for 5 to 7% of emergency department (ED) consultations. We aimed to assess medication risk profiles for ADRs leading to ED visits. We analysed medication intake and patient demographics in a prospective multi-centre observational study collecting ADR cases in four large EDs in Germany. Odds ratios (OR) were calculated to relate drug classes taken to those suspicious for an ADR after a causality assessment. A total of 2215 cases of ED visits due to ADRs were collected. The median age of the cohort was 73 years; in median, six co-morbidities and an intake of seven drugs were documented. Antineoplastic/immunomodulating agents had the highest OR for being suspected for an ADR (OR 20.45, 95% CI 14.54–28.77), followed by antithrombotics (OR 2.94, 95% CI 2.49–3.47), antibiotics (OR 2.65, 95% CI 1.78–3.95), systemic glucocorticoids (OR 2.43, 95% CI 1.54–3.82) and drugs affecting the central nervous system (CNS), such as antipsychotics (OR 2.36, 95% CI 1.46–3.81), antidepressants (OR 2.10, 95% CI 1.57–2.83), antiparkinsonian medication (OR 2.11, 95% CI 1.15–3.84), opioids (OR 1.79, 95% CI 1.26–2.54) and non-opioid analgesics (OR 1.32, 95% CI 1.01–1.72). Patients experiencing ADRs leading to ED visits are commonly old, multi-morbid and multi-medicated. CNS drugs may be more relevant than prior expected. With calculating ORs, we could replicate involvement of antineoplastic agents, antithrombotics, antibiotics, systemic glucocorticoids and non-opioid analgesics as frequently suspected for ADRs in EDs. DRKS-ID: DRKS00008979.     

Treatment of adverse drug reactions in a dermatology department

The aim of the study was to evaluate the pattern of utilization of systemic drugs used in the management of adverse drug reactions (ADRs) leading to hospitalization. A prospective pharmacovigilance study was carried out among patients admitted to the Clinic of Dermatology and Venereology in Stara Zagora (July 1999–June 2009). ADRs were classified by type, severity and causality. Casecausality was scored according to Naranjo et al. (1981). Drug utilization was measured in defined daily doses (DDDs) per 100 hospital bed days. A total of 144 cutaneous ADRs, predominantly “type B” were the reason for hospitalization. Highest utilization for the management of ADRs was found for the drug groups “Blood and blood forming organs” (406.08 DDDs/100 bed days) and “Respiratory system” (111.15 DDDs/100 bed days). The use of DDD for measuring drug utilization reveals the importance of drug-induced exacerbations of chronic skin diseases like psoriasis which were associated with significant utilization of drugs belonging to the group “Blood and blood forming organs”. Considering the low preventability of “type B” ADRs, our findings suggest that potential reduction of drug-related hospitalizations may be achieved through the rational use of drugs in patients with comorbidities.     

Women encounter ADRs more often than do men

Background  Several publications indicate that the female gender experiences a higher incidence of adverse drug reactions (ADRs) than does the male gender. The reasons, however, remain unclear. Gender-specific differences in the pharmacokinetic and pharmacodynamic behaviour of drugs could not be identified as an explanation. The aim of this study was to analyse ADR risk with respect to gender, age and number of prescribed drugs. Methods  A prospective multicenter study based on intensive pharmacovigilance was conducted. Information on patient characteristics and evaluated ADRs was stored in a pharmacovigilance database—KLASSE. Results  In 2,371 patients (1,012 female subjects), 25,532 drugs were prescribed. In 782 patients, at least one ADR was found. A multivariate regression analysis adjusting for age, body mass index (BMI) and number of prescribed drugs showed a significant influence of female gender on the risk of encountering ADRs [odds ratio (OR) 1.596, confidence interval (CI) 1.31–1.94; p < 0.0001). Dose-related ADRs (51.8%) were the dominant type in female subjects. Comparing system organ classes of the World Health Organisation (SOC-WHO), cardiovascular (CV) ADRs were particularly frequent in female subjects (OR 1.92, CI 1.15–3.19; p = 0.012). Conclusion  Our data confirm the higher risk of ADRs among female subjects compared with a male cohort. Several explanations were investigated. No single risk factor could be identified.     

Prevalence of HIV, hepatitis B and hepatitis C and associated risk behaviours amongst injecting drug users in three Afghan cities

Background

HIV amongst injecting drug users (IDUs) has been described in Kabul but little data exists for other Afghan cities. We assessed HIV, hepatitis B virus (HBV), and C virus (HCV) prevalence and associated risk behaviours amongst IDUs in Hirat, Jalalabad, and Mazar-i-Sharif, Afghanistan.

Methods

Consented participants reporting injecting drugs within the previous 6 months completed interviewer-administered questionnaires and testing for HIV, hepatitis C antibody (HCV Ab), and hepatitis B surface antigen (HBsAg). Logistic regression was used to determine characteristics associated with each infection.

Results

Of 623 participants, most (98.7%) were male. Prevalence of HIV, HCV, and HBV was 1.8% (95% CI: 0.88-3.2), 36.0% (95% CI: 33-41), and 5.8% (95% CI: 3.9-7.6), respectively. All HIV cases and highest HCV prevalence were detected in Hirat; HBV prevalence was highest in Jalalabad. Amongst male IDUs, 62.9% had been imprisoned, of whom 17.2% (n = 66) injected in prison. High risk behaviours were common; 30.2% reported needle sharing in the last 6 months, 23.1% reported sex with another male, and 50.4% reported paying females for sex. Behaviours varied significantly by site; generally, Hirat participants reported fewer sexual risk behaviours. Sex with other males was negatively associated with both HBV and HCV in multivariate logistic regression analysis; no injecting behaviours were associated with both HBV and HCV.

Conclusions

Whilst HIV prevalence is low, HCV prevalence and high risk behaviours were common in these populations. Regional variations should be considered in programming to prevent transmission of HIV and viral hepatitis amongst IDUs in Afghanistan.     

Drug Interactions Between Psychoactive Substances and Antiretroviral Therapy in Individuals Infected With Human Immunodeficiency and Hepatitis Viruses

The liver disease characteristic of alcohol dependence encompasses three main related entities: steatosis, alcoholic hepatitis, and cirrhosis. Alcoholic cirrhosis is a leading cause of global morbidity and mortality. Alcohol intake among injecting drug users is a major contributor to transmission of viral infections, such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C viruses (HCV). HIV and HCV coinfected patients develop liver diseases earlier and more severely than the monoinfected individuals, including hepatocellular carcinoma. Interactions exist between the therapeutic drugs used to minimize and control the drug and alcohol dependence. Furthermore, drug–drug interactions occur between the highly active antiretroviral therapy (HAART) and alcohol, different HAART components and methadone, or each one of the therapies with the other, thus contributing to a higher toxicity level. With the evolution of effective antiretroviral therapy, survival of persons with HIV, and the syndrome it causes, acquired immunodeficiency syndrome (AIDS) has increased dramatically. Drug–drug interactions may appear between alcohol and anti-HBV or anti-HCV, therapy in the presence or absence of anti-HIV therapy. Several other medical-, social-, and drug-related factors of this population have to be considered when providing HAART. Because many coinfected patients also have problems with substance use, dealing with their drug dependence is an important first step in an attempt to improve adherence to and tolerance of antiviral therapy. It is necessary to minimize the risk of liver disease acceleration and/or reinfection with hepatitis viruses. Knowledge of potential drug interactions between methadone, antiretroviral therapy, psychoactive drugs, and antipsychotics and the role of coinfection with HBV or HCV and the drugs used in eradicating viral hepatitis permits suitable antiretroviral combinations.     

Drug interactions between psychoactive substances and antiretroviral therapy in individuals infected with human immunodeficiency and hepatitis viruses

The liver disease characteristic of alcohol dependence encompasses three main related entities: steatosis, alcoholic hepatitis, and cirrhosis. Alcoholic cirrhosis is a leading cause of global morbidity and mortality. Alcohol intake among injecting drug users is a major contributor to transmission of viral infections, such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C viruses (HCV). HIV and HCV coinfected patients develop liver diseases earlier and more severely than the monoinfected individuals, including hepatocellular carcinoma. Interactions exist between the therapeutic drugs used to minimize and control the drug and alcohol dependence. Furthermore, drug-drug interactions occur between the highly active antiretroviral therapy (HAART) and alcohol, different HAART components and methadone, or each one of the therapies with the other, thus contributing to a higher toxicity level. With the evolution of effective antiretroviral therapy, survival of persons with HIV, and the syndrome it causes, acquired immunodeficiency syndrome (AIDS) has increased dramatically. Drug-drug interactions may appear between alcohol and anti-HBV or anti-HCV, therapy in the presence or absence of anti-HIV therapy. Several other medical-, social-, and drug-related factors of this population have to be considered when providing HAART. Because many coinfected patients also have problems with substance use, dealing with their drug dependence is an important first step in an attempt to improve adherence to and tolerance of antiviral therapy. It is necessary to minimize the risk of liver disease acceleration and/or reinfection with hepatitis viruses. Knowledge of potential drug interactions between methadone, antiretroviral therapy, psychoactive drugs, and antipsychotics and the role of coinfection with HBV or HCV and the drugs used in eradicating viral hepatitis permits suitable antiretroviral combinations.     

HIV/hepatitis coinfection in eastern Europe and new pan-European approaches to hepatitis prevention and management

ISSUES: HIV/hepatitis coinfection in Europe; WHO European clinical protocols on the management of people coinfected with HIV/AIDS and hepatitis B or C (HBV or HCV); stakeholder recommendations for better HCV services. INTRODUCTION: The increasing availability of highly active antiretroviral therapy throughout Europe and central Asia has changed comorbidity and mortality patterns among people living with HIV/AIDS (PLWHA) as liver disease has increasingly replaced AIDS as the cause of death in PLWHA in western European countries. The average prevalence of HCV among PLWHA is 40 per cent, and much higher in countries where the HIV epidemic is driven by injecting drug use. Access to hepatitis treatment for PLWHA and IDUs is still very limited in Europe due to a lack of clear clinical management guidelines for HIV/hepatitis coinfections, high costs and a national failure to recognise hepatitis as a critical health issue. DESCRIPTION: In October 2006, the WHO Regional Office for Europe issued protocols for the clinical management of HIV/HCV and HIV/HBV coinfections. They include diagnostic algorithms adjusted for resource availability, and guidelines for the management of patients who do not yet need treatment, those who need only hepatitis or only HIV/AIDS treatment, and those who need both. Though the protocols should provide practical guidelines for physicians and assist in the development of national treatment standards, there is still a need for targeted prevention, treatment and care interventions. To expand access to hepatitis prevention and treatment, public awareness needs to be raised and national political leaders need to address hepatitis as a public health issue. Effective public health measures include price reductions for anti-hepatitis drugs; targeted testing, counselling and prevention activities; increased access to hepatitis B and C treatment and to HBV vaccination for the populations most at risk.     

Treatment of HBV/HCV coinfection

Importance of the field: Hepatitis B (HBV) and hepatitis C (HCV) virus infections are among the most common causes of advanced chronic liver disease worldwide. HBV/HCV coinfection is not uncommon with an estimated 7 – 20 million individuals affected worldwide. Patients with HBV/HCV coinfection have an increased risk for cirrhosis, hepatocellular carcinoma (HCC) and even death.

Areas covered in this review: The pathophysiology of HBV/HCV coinfection is complex, as different patterns of virological dominance may occur, which can even fluctuate over time. Recently, combination of pegylated interferon (PEG-IFN) plus ribavirin has been explored in HBV/HCV coinfected patients who are positive for HCV-RNA. HBV polymerase inhibitors may be indicated if HBV-DNA concentrations are above 2000 IU/ml. In this review, we summarize the epidemiology, viral interaction, its clinical features and the available treatment options.

What the reader will gain: Insights into viral interaction of HBV/HCV coinfection and treatment individualization strategies are provided in the review.

Take home message: Detailed serological and virological evaluations are required for HBV/HCV coinfected patients before initiation of antiviral therapy. At present, PEG-IFN-α plus ribavirin should be the treatment of choice in patients with dominant HCV replication. However, HBV rebound may occur after elimination of HCV, and thus close monitoring for both viruses is recommended even for patients with initially suppressed HBV-DNA.     

The Role of Cohort Studies in Drug Development: Clinical Evidence of Antiviral Activity of Serotonin Reuptake Inhibitors and HMG-CoA Reductase Inhibitors in the Central Nervous System

Background Effective antiretroviral therapy (ART) has reduced the incidence of HIV-associated neurocognitive impairment (HNCI) but its prevalence remains high. Clinical trials have yet to identify a consistently effective treatment for HNCI, other than ART, but in vitro data support that some drugs approved by the Food and Drug Administration (FDA) for other indications might benefit individuals with HNCI. Some of these drugs, such as serotonin reuptake inhibitors (SRIs) and HMG-CoA reductase inhibitors (statins), may do so by reducing HIV replication in the CNS and are already widely used by HIV-infected individuals. Methods Six-hundred fifty-eight HIV-infected participants of the CHARTER cohort had a baseline assessment, which included comprehensive neuropsychological (NP) testing and HIV RNA measurements in plasma and cerebrospinal fluid (CSF). Four-hundred sixty-seven (71%) subjects used ART, 195 (30%) used SRIs, and 63 (10%) used statins. Results SRI users were less likely to have HIV RNA levels in CSF above 50 copies (c)/mL (29 vs. 37% in non-SRI users, OR 0.69, p = 0.05). This association was most evident for three of the seven SRIs (citalopram, sertraline, and trazodone, or “antiviral” SRIs, combined 25 vs. 38% in non-SRI users, OR 0.56, p = 0.01) and was strongest in those not taking concomitant ART (61 vs. 83%, OR 0.31, p = 0.01). “Antiviral” SRI users also performed better on NP tests (median global deficit score 0.37 vs. 0.47, p = 0.04). Statin users were also less likely to have HIV RNA levels in CSF above 50 c/mL (16 vs. 37%, p < 0.001) but, in contrast to SRIs, the association was strongest in those taking ART (2 vs. 18%, p < 0.001). Statin use was not associated with better NP performance. Multivariate analyses indicated that the use of “antiviral” SRIs—but not statins—was associated with undetectable HIV RNA levels in CSF and better NP performance. Conclusions SRIs may reduce HIV replication in CSF and improve NP performance. This was particularly true for three SRIs—supporting differences in antiviral efficacy between drugs—in individuals who were not taking ART. In contrast, statins were not associated with lower HIV replication in CSF in multivariate analyses and were not associated with better NP performance. These analyses support the value of large observational cohort studies in identifying FDA-approved drugs that may be worth further investigation.     

Knowledge of HIV and its treatment among health care providers in South Africa

Background In South Africa, availability of antiretroviral (ARV) drugs has increased largely in the public sector since it became available in 2004. Follow-up of stabilized patients on ARV drugs are done in primary health care (PHC) facilities run by nurses, often without specialized training. This has deep impact on the patients’ drug adherence. Objective To investigate health care providers’ (HCPs) knowledge about human immunodeficiency virus (HIV) and antiretroviral therapy (ART) in the Eastern Cape Province, South Africa. The aim was also to investigate nurses’ knowledge and experience regarding adverse drug reaction (ADR) reporting. Setting Public PHC clinics in one district of the Eastern Cape Province. Method Personal interviews, using a structured questionnaire, were conducted with 102 HCPs (nurses and auxiliary staff) working at six PHC facilities, one community health centre and one health post. Main outcome measure Knowledge about HIV and ART among nurses and auxiliary staff. Results Both nurses and auxiliary staff had some basic knowledge about symptoms of HIV and modes of transmission, but great uncertainty was seen regarding specific topics including ARV drugs, ADRs and HIV complications. The PHC staff were uncertain about how to administer ARV drugs—with or without food—and some of them would advice their patients not to take ARV drugs at times when food was lacking. Both nurses and auxiliary staff knew that HIV was treated with ARV drugs. Only 60 % of the HCPs claimed that ART was the only effective treatment for HIV, whereas 39 % claimed that nutritious food also could treat HIV. Nurses showed lacking ability to manage ADRs. They also had very little knowledge about ADR reporting, and very few had ever submitted a report at all. Conclusion The study shows that both nurses and auxiliary staff are unable to provide the patients with adequate advice about administration of the ARV drugs and management of ADRs. Serious lack of knowledge among HCPs regarding the treatment of HIV presents structural barriers to the patients’ adherence.     

Hepatitis C virus infection in children coinfected with HIV: epidemiology and management

Mothers with hepatitis C virus (HCV) and HIV coinfection are the major source of HCV/HIV coinfection in infancy and childhood. There is no known intervention capable of interrupting HCV spread from mother to child, while the majority of infant HIV infections occurring in the developed world can be prevented by antiretroviral prophylaxis in the mother and child, elective caesarean section, and formula-feeding. In the era preceding treatment of HIV infection with highly active antiretroviral therapy, HCV coinfection was of little concern because the short-term survival of patients with HIV infection prevented the slowly developing consequences of chronic hepatitis C. As the life expectancy of patients with HIV infection increased with therapy, HCV has emerged as a significant pathogen. Several lines of evidence in adult patients suggest that liver disease may be more severe in patients coinfected with HIV and that progression of HIV disease may be accelerated by HCV coinfection. Whether coinfected children may share these clinical patterns remains a matter of speculation. Chronic hepatitis C in otherwise healthy children is usually a mild disease; liver damage may be sustained and fibrosis may increase over the years, suggesting slow progression of the disease. Interferon-alpha has been the only drug used in the past decade to treat hepatitis C in children and adolescents, with average response rates of 20%. Preliminary results of treatment with interferon-alpha and ribavirin suggest that the efficacy would be greater with combined therapy. These treatment protocols have not yet been applied to children coinfected with HIV, but the increasing number of long-term survivors will probably prompt further investigation in the near future. At present, treating HIV disease and monitoring HCV infection and hepatotoxicity induced by antiretroviral drugs seem to be the more reasonable approach to HCV/HIV coinfection in childhood.     

Direct anti-HCV agents

Unlike human immunodeficiency virus (HIV) and hepatitis B virus (HBV), hepatitis C virus (HCV) infection is a curable disease. Current direct antiviral agent (DAA) targets are focused on HCV NS3/4A protein (protease), NS5B protein (polymerase) and NS5A protein. The first generation of DAAs includes boceprevir and telaprevir, which are protease inhibitors and were approved for clinical use in 2011. The cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/ribavirin. More effective and less toxic second generation DAAs supplanted these drugs by 2013. The second generation of DAAs includes sofosbuvir (Sovaldi), simeprevir (Olysio), and fixed combination medicines Harvoni and Viekira Pak. These drugs increase cure rates to over 90% without the need for interferon and effectively treat all HCV genotypes. With these drugs the “cure HCV” goal has become a reality. Concerns remain about drug resistance mutations and the high cost of these drugs. The investigation of new HCV drugs is progressing rapidly; fixed dose combination medicines in phase III clinical trials include Viekirax, asunaprevir+daclatasvir+beclabuvir, grazoprevir+elbasvir and others.KEY WORDS: Hepatitis C virus, Cure HCV, Sustained virologic response, Direct antiviral agents, NS3/4A protease inhibitor     

Drug interactions in HIV-infected patients treated for hepatitis C

Introduction: The introduction of direct-acting antivirals (DAA) has revolutionized the hepatitis C field. Most hepatitis C patients can now be cured, including those coinfected with HIV. However, drug-drug interactions (DDI) between DAA and antiretrovirals (ARV) should be known to prevent either toxicity due to drug overexposure or treatment failures due to low drug concentrations.

Areas covered: Clinically significant DDI may be classified as major (when co-administration should be contraindicated) or minor (when they require close monitoring, changes in drug dosage or in timing). Strategies for preventing and managing DDI influence response rates in HIV/HCV-coinfected patients. Pharmacokinetic evidence of interactions from clinical trials and reports from real-world experience are discussed.

Expert opinion: The most frequent DDI between DAA and ARV affect drug metabolism by CYP450 induction/inhibition, leading to abnormal drug exposures. Throughout this mechanism interact HCV and HIV boosted protease inhibitors, and most non-nucleoside HCV and HIV polymerase inhibitors. In contrast, HIV and HCV nucleos(t)ide analogue polymerase inhibitors, most HCV NS5A inhibitors and HIV integrase inhibitors (e.g., dolutegravir), do not or only marginally affect CYP450, and therefore are relatively free of DDI. Exposure to some HIV and HCV nucleos(t)ide analogues (e.g., tenofovir and sofosbuvir, respectively) is subject to induction/inhibition of drug transporters (e.g., P-glycoprotein) and requires special attention in patients with renal insufficiency.