How much will it cost? Estimation of resource needs and availability for HIV prevention,treatment and care for people who inject drugs in Asia

As countries in Asia strive to meet their universal access targets, harm-reduction programmes are yet to be scaled up to reach effective levels of coverage. Resource tracking and estimation of resource needs and gaps is critical to inform the financing decisions of major donors of harm-reduction programmes in the region. This study aimed at estimating the financial resource needs and gaps for scaling-up harm reduction in the region, building on previous research conducted by the Independent Commission on AIDS in Asia. The overall resource need for achieving universal access in the target population in 2009 was US $0.5 billion, with NSP and OST accounting for nearly 70% of the overall regional resource need. A significant resource gap, approximately 90%, of the resource need in 2009, was identified for harm reduction in the region, representing less than 2% of the overall global resource need to address AIDS. Additional resources will be required to support the introduction and scaling-up of integrated, comprehensive harm-reduction programmes that provide a full range of services to reduce HIV transmission among people who inject drugs.     

HIV and hepatitis C treatment uptake among people who use drugs participating in the Amsterdam Cohort Studies, 1985–2015

BackgroundHIV-positive people who use drugs (PWUD) start antiretroviral therapy (ART) later than other risk groups, and among HCV-positive PWUD, HCV treatment uptake is low. Nowadays, HCV direct-acting antivirals (DAAs) are available and reimbursed in the Netherlands (since 2014). The Amsterdam Cohort Studies (ACS), initiated in 1985, provides us the opportunity to describe temporal trends in ART and HCV-treatment uptake among PWUD through 2015.MethodsWe analyzed data from PWUD participating in the ACS between 1985 and 2015. ART and HCV-treatment data were obtained from ACS questionnaires and medical records. Treatment uptake was defined by: treatment initiation (the proportion initiating any kind of ART/HCV treatment when treatment-naïve) and coverage (the proportion ever treated for HIV/HCV) among all HIV-/HCV-RNA-positive PWUD. Each was calculated per calendar year. We estimated the cumulative probability of ART uptake in the pre-cART (<1996) and cART era (January 1, 1996) among HIV seroconverters, with all-cause mortality as a competing risk.ResultsOf 1305 PWUD, 263 (20.2%) were HIV-antibody positive and 810 (62.1%) were HCV-antibody positive, at study entry. ART coverage increased over time, from 5.7% in 1990 and 42.2% in 1996 to 91.7% in 2015. The proportion initiating ART ranged from 4.8% in 1990 to 33.3% in 2011. At 8 years after HIV seroconversion, cumulative probability of ART uptake was 42.5% in the pre-cART era and 61.5% in the cART era. HCV treatment initiation peaked in 2006 (9.7%). HCV-treatment coverage was 43.9% in 2015 but lower among HIV-coinfected (23.5%) than HCV-monoinfected PWUD (52.5%). In 2015, 3.0% initiated HCV treatment with DAAs.ConclusionWe observed an increase in ART and HCV-treatment coverage among PWUD over time. As expected, ART uptake was higher in the cART era than the pre-cART era. Although in 2015 HCV treatment coverage was relatively high, DAA uptake was still low.     

Hepatitis C testing for people who inject drugs in the United Kingdom: Why is uptake so low?

Background: Hepatitis C virus (HCV) related morbidity and mortality will continue to rise unless HCV testing and treatment uptake increases. People who inject drugs constitute those at highest risk for HCV in the UK, yet over a third who access drug and alcohol services have never received an HCV test.

Method: We conducted qualitative life history research with people who have injected drugs for over six years to explore the social conditions of long-term HCV avoidance. In order to ascertain previous HCV exposure, participants were required to have an HCV antibody test at a recruiting service. We concentrate here on analyses of participant accounts in relation to HCV testing, and specifically, barriers to uptake. Thirty-seven participants were interviewed two to three times over three months. Data were analyzed according to grounded theory principles.

Results: Participants had injected an average of nine years before their first HCV test. Key themes in participant accounts included: concerns regarding the process of HCV testing, including phlebotomy practices; concerns regarding the impacts of HCV diagnosis, exacerbated by confusion regarding test results and HCV effects, and fears of concomitant HIV diagnosis; optimism that testing was unnecessary given HCV risk potentials; and institutional mistrust, often internalized as felt stigma, especially in hospital settings.

Conclusions: To maximize HCV testing uptake among people who inject drugs, we emphasize the need for: testing at community-based drug services; on-site skilled and non-judgemental phlebotomists; the decoupling of HCV and HIV testing; and peer-supported testing interventions.     

Is the severity of the Great Recession's aftershocks correlated with changes in access to the combined prevention environment among people who inject drugs?

BackgroundThe 2008 Recession was a global event that led to funding cuts for programs and services in the United States; though this recession officially ended in 2009, its aftershocks continued through 2012. We evaluated the relationship between the severity of the Great Recession's aftermath and spatial access to combined prevention services (i.e. HIV testing, syringe service programs, substance use disorder treatment program) for people who inject drugs (PWID) living in 19 metropolitan statistical areas (MSAs) in the United States.MethodsThe unit of analysis was the ZIP code; we sampled ZIP codes in these 19 MSAs where ≥1 PWID lived in 2009 and 2012, according to the CDC's National HIV Behavioral Surveillance. We used administrative data to describe the combined prevention environment (i.e., spatial access to HIV testing) for each ZIP code, and measured the severity of the recession's aftermath in each ZIP code, and in the counties and MSAs where these ZIP codes were located. Multilevel modeling estimated associations between changes in the aftermath of the Great Recession and ZIP code-level changes in spatial access to combined prevention services from 2009 to 2012.Results675 ZIP codes located in 36 counties and 19 MSAs were included in this analysis. From 2009 to 2012, 21% of ZIP code areas lost access to combined prevention services and 14% gained access. ZIP codes with higher poverty rates relative to their respective MSAs were less likely to lose access (aOR: 0.91; 95% CI: 0.88, 0.95) and more likely to gain access (aOR: 1.05; 95% CI: 1.01, 1.09); there is some evidence to suggest the former association was attenuated for ZIP codes with higher percentages of non-Hispanic white residents.ConclusionCombined prevention services for PWID living in these 675 ZIP codes demonstrated resilience in the aftermath of the Great Recession. Future research should explore whether community-based and federal HIV prevention initiatives contributed to this resilience, particularly in areas with higher concentrations of people of color.     

Initial outcomes of integrated community-based hepatitis C treatment for people who inject drugs: Findings from the Queensland Injectors’ Health Network

BackgroundIntegrated treatment and harm reduction services provide a unique opportunity to facilitate direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV)-infected people who inject drugs (PWID). We examine outcomes of community-based delivery of DAA therapy for PWID.MethodsThe Queensland Injectors’ Health Network (QuIHN) is a community-based agency providing harm reduction and treatment services. Data (including current injecting, involvement in opioid substitution therapy and other treatment, level of case management support) for participants initiating DAA therapy were collected. The primary endpoint was sustained virological response at 12 weeks (SVR) after the end of therapy.ResultsBy the end of February 2017, 127 treatment clients who consented for research had completed therapy and were due for post-treatment sustained virological response (SVR) testing. In an intent-to-treat analysis, 96% completed their course of prescribed treatment, 80% had confirmed SVR and 92% adhered to treatment. There were no confirmed cases of treatment non-response. The clients without confirmed SVR (20%) had not attended their post-treatment test. No client characteristics, including involvement in less-than-daily (odds ratio (OR) 0.27, 95% confidence interval (CI): 0.06–1.17) or daily injecting drug use (OR 0.65, 95% CI: 0.17–2.43) were associated with non-attendance at the SVR test.ConclusionPWID can be effectively treated for HCV and comply with DAA therapy in an integrated community-based service. However, strategies are required to support client retention until SVR is confirmed.     

Drugs,discipline and death: Causes and predictors of mortality among people who inject drugs in Tijuana, 2011–2018

BackgroundPeople who inject drugs (PWID) experience multiple risk factors for mortality; yet, we know little about causes of death among PWID in Tijuana, Mexico, an area with high levels of injecting and changes in policy/law enforcement responses to substance use. This study examines rates, causes, and predictors of mortality among Tijuana PWID.MethodsData come from a community-based cohort of PWID aged ≥18 who injected drugs in the past month. Mortality was confirmed by death certificate over 78 months during 2011–2018. Predictors of mortality were identified using time-updated Cox regression, controlling for age.ResultsAmong 734 participants, there were 130 deaths (54 confirmed, 76 unconfirmed), with an incidence rate of 17.74 deaths per 1000 person-years for confirmed deaths (95% Confidence Interval (CI)=13.01, 22.48) and 39.52 for unconfirmed deaths (CI=32.72, 46.31). Confirmed deaths resulted from homicide/trauma (26%), overdose (26%), septic shock (18%) and HIV-related causes (9%). In multivariable analysis of confirmed deaths, baseline HIV seropositivity (adjusted Hazard Ratio [aHR]=6.77, CI=1.98, 23.17), incident HIV infection (aHR=3.19, CI=1.02, 9.96), and number of times being beaten by police in the past 6 months at baseline (aHR=1.08 per time, CI=1.04, 1.12) were predictive of death; whereas, injection cessation for 6+ months during time at risk (aHR=0.25, CI=0.33, 0.79) was protective.ConclusionIn addition to overdose and HIV prevention efforts, attention to structural conditions that potentiate mortality is needed, including improved access to medication-assisted treatment to support injection cessation and a shift from police as a source of harm to harm reduction.     

Synthetic drugs for the treatment of vitiligo: a patent review (2010–2015)

Introduction: Vitiligo is one of the most important acquired depigmentation disorders, with an average worldwide prevalence of 0.5–2.0%. The exact etiology of vitiligo is not fully understood, but the principle theories focus on the mechanism responsible for the destruction of melanocytes, which is proposed to be autoimmune, neurogenic, or self-destructive. There is no cure for vitiligo and the results of current treatments vary between individuals, being unsatisfactory in most cases. Despite being a cosmetic disease, the disorder can be psychologically devastating and stigmatizing.

Areas covered: In this review, the authors summarize new synthetic drugs for the treatment of vitiligo developed between 2010 and 2015, which include MC1 R agonists and peptides, as well as considering new approaches and strategies using existing drugs.

Expert opinion: In conclusion, we found significant advancement in this field of research, demonstrating the growing interest of academic and industrial groups in developing successful products for the treatment of vitiligo. New therapeutic options could contribute to improving the quality of life of patients and advance the search for a truly effective treatment of vitiligo.     

Retention in methadone maintenance treatment in mainland China, 2004–2012: A literature review

Background

Methadone maintenance treatment (MMT) was implemented in mainland China since 2004. Numerous individual studies have investigated MMT retention but the overview still remains unclear. The aim of the study was to review MMT retention rates and predicting factors in mainland China during 2004–2012.

Methods

Chinese and English databases of literature were searched for studies reporting on retention rates and predicting factors in non-transfer MMT patients of fixed-site clinics in mainland China (2004–2012). Qualitative methods were used to synthesize the results.

Results

Nineteen studies were eligible for review, with sample size ranging from 29 to 3758. Retention rates varied between 30.0% at 6 months in Shanghai and 70.3% at 12 months in Xi'an. Predicting factors were non-treatment including sociodemographics (n = 14), support system and social function (n = 9), economic status (n = 2) and psychological status (n = 1), and treatment-related including drug use (n = 15), methadone use (n = 12), MMT clinics (n = 9), MMT participation (n = 7), awareness on MMT (n = 5) and HIV serostatus (n = 3). Methadone dose (n = 12) and age (n = 7) were the first two important specific factors.

Conclusions

In mainland China, MMT retention rates are heterogeneous and relatively lower, and predicting factors mainly focus on objective aspects. Future work should further explore subjective predicting factors regarding MMT retention.     

The role of prison-based interventions for hepatitis C virus (HCV) micro-elimination among people who inject drugs in Montréal,Canada

BackgroundIn Canada, hepatitis C virus (HCV) transmission primarily occurs among people who inject drugs (PWID) and people with experience in the prison system bare a disproportionate disease burden. These overlapping groups of individuals have been identified as priority populations for HCV micro-elimination in Canada, which is currently not on track to achieve its elimination targets. Considering the missed opportunities to intervene in provincial prisons, this study aims to estimate the population-level impact of prison-based interventions and post-release risk reduction strategies on HCV transmission among PWID in Montréal, a Canadian city with high HCV burden.MethodsA dynamic HCV transmission model among PWID was developed and calibrated to community and prison bio-behavioural surveys in Montréal. Then, the relative impact of prison-based testing and treatment or post-release linkage to care (both 90% testing and 75% treatment coverage), alone or in combination with strategies that reduce the heightened post-release transmission risk by 50%, was estimated from 2018 to 2030, and compared to counterfactual scenarios.ResultsPrison-based test-and-treat strategies could lead to the greatest declines in incidence (48%; 95%CrI: 38–57%) over 2018–2030 and prevent the most new first chronic infections (22%; 95%CrI: 16−28%) among people never exposed to HCV. Prison testing and post-release linkage to care lead to a slightly lower decrease in incidence and prevented fraction of new chronic infections. Combining test-and-treat with risk reduction measures could further its epidemiological impact, preventing 35% (95%CrI: 29−40%) of new first chronic infections. When implemented concomitantly with community-based treatment scale-up, prison-based interventions had synergistic effects, averting a higher fraction of new first chronic infections.ConclusionOffering HCV testing and treatment in provincial prisons, where incarcerations are frequent and sentences short, could change the course of the HCV epidemic in Montréal. Prison-based interventions with potential integration of post-release risk reduction measures should be considered as an integral part of HCV micro-elimination strategies in this setting.     

“I held on to the police’s leg for mercy”: Experiences of adversity,risk and harm among people who inject drugs during an anti-drug drive in Dhaka,Bangladesh

BackgroundA number of countries across Asia have instituted “drug wars”, aimed at eradicating drug supply and consumption. These wars often employ strategies like arbitrary arrest and detention, increased surveillance, harassment and sometimes extrajudicial killings. However, these measures have not been shown to effectively eliminate drug supply and consumption; rather they often predispose people who use drugs to increased risk and harm. Such a drug war was declared in the form of an anti-drug drive (ADD) in Bangladesh in 2018. This article examined the impact of the ADD on drug injecting activities and harm reduction service uptake among people who inject drugs (PWID).MethodsAn ethnographic study was conducted in Dhaka, Bangladesh. Study participants included PWID, harm reduction service providers and other drug and alcohol experts. Data collection consisted of 2500 hours of observations, 25 in-depth interviews, five focus group discussions and 15 key informant interviews. Data were analysed using thematic analysis.ResultsADD operations and activities subjected PWID to multifaceted forms of violence and harassment including extrajudicial killings, which significantly affected drug procurement and drug using practices and led to increased needle and syringe sharing and a likely increase in HIV transmission. The gradual disappearance of established drug markets, alongside the emergence of new ones at alternate locations, resulted in the dislocation of PWID from outreach services and further increased risky injecting practices such as needle and syringe sharing between new and unfamiliar injecting partners. These harms were compounded by unpredictable drug supply and price increases stemming from the ADD, which in turn also increased needle and syringe sharing. Harm reduction outreach services were not able to adequately adapt to the volatile, dynamic and risky nature of the ADD.ConclusionThe ADD not only precipitated risky injecting practices but also hindered the effective implementation of harm reduction outreach services and thus undermined public health. This warrants concerted efforts to nurture local evidence-based harm reduction approaches as opposed to punitive measures.     

A rapid review of the impacts of “Big Events ” on risks,harms, and service delivery among people who use drugs: Implications for responding to COVID-19

Background“Big Events” are major disruptions to physical, political, and economic environments that can influence vulnerability to drug-related harms. We reviewed the impacts of Big Events with relevance to the COVID-19 pandemic on drug-related risk and harms and access to drug treatment and harm reduction services.MethodsWe conducted a rapid review of quantitative, qualitative, and mixed methods literature relating to the following Big Events: respiratory infection pandemics, natural disasters, financial crises, and heroin shortages. Included studies reported data on changes to risks, harms, and/or service provisioning for people who use illicit drugs (other than cannabis) in the context of these Big Events. Searches were conducted in PubMed in May 2020, and two reviewers screened studies for inclusion. Peer-reviewed studies published in English or French were included. We used a narrative synthesis approach and mapped risk pathways identified in the literature.ResultsNo studies reporting on respiratory infection pandemics were identified. Twelve studies reporting on natural disaster outcomes noted marked disruption to drug markets, increased violence and risk of drug-related harm, and significant barriers to service provision caused by infrastructure damage. Five studies of the 2008 global financial crisis indicated increases in the frequency of drug use and associated harms as incomes and service funding declined. Finally, 17 studies of heroin shortages noted increases in heroin price and adulteration, potentiating drug substitutions and risk behaviors, as well as growing demand for drug treatment.ConclusionCurrent evidence reveals numerous risk pathways and service impacts emanating from Big Events. Risk pathway maps derived from this literature provide groundwork for future research and policy analyses, including in the context of the COVID-19 pandemic. In light of the findings, we recommend responding to the pandemic with legislative and financial support for the flexible delivery of harm reduction services, opioid agonist treatment, and mental health care.     

How has treatment changed for blast phase chronic myeloid leukemia patients in the tyrosine kinase inhibitor era? A review of efficacy and safety

Introduction: Management of chronic myeloid leukemia (CML) patients in advanced phases of disease has drastically changed since the introduction of tyrosine kinase inhibitors (TKIs) which provide tailored treatment strategies.

Areas covered: In this review, efficacy data of different TKIs are reported and reviewed when used as single agent or in combination for the management of blast phase (BP) CML.

Expert opinion: Although brilliant results were achieved, the outcome of BP patients did not change when TKIs were used as single agents. Newer strategies of association of TKI with intensified chemotherapy or new agents for different pathways are strongly needed as a bridge to possible allogeneic transplant.     

Mind–body practices: An alternative,drug-free treatment for smoking cessation? A systematic review of the literature

Objective

The limited success of current smoking cessation therapies encourages research into new treatment strategies. Mind–body practices such as yoga and meditation have the potential to aid smoking cessation and become an alternative drug-free treatment option. The aim of this article is to assess the efficacy of yoga and other meditation-based interventions for smoking cessation, to identify the challenges of clinical trials applying mind–body treatments, and to outline directions for future research on these types of therapies to assist in smoking cessation.

Methods

A systematic review of the scientific literature.

Results

Fourteen clinical trials met the inclusion criteria defined for this review. Each article was reviewed thoroughly, and evaluated for quality, design, and methodology. Although primary outcomes differed between studies, the fourteen articles, most with limitations, reported promising effects supporting further investigation of the use of these practices to improve smoking cessation.

Conclusions

The literature supports yoga and meditation-based therapies as candidates to assist smoking cessation. However, the small number of studies available and associated methodological problems require more clinical trials with larger sample sizes and carefully monitored interventions to determine rigorously if yoga and meditation are effective treatments.     

“With a PICC line,you never miss”: The role of peripherally inserted central catheters in hospital care for people living with HIV/HCV who use drugs

BackgroundPeople who use drugs (PWUD), and especially those who inject drugs, are at increased risk of acquiring bloodborne infections (e.g., HIV and HCV), experiencing drug-related harms (e.g., abscesses and overdose), and being hospitalized and requiring inpatient parenteral antibiotic therapy delivered through a peripherally inserted central catheter (PICC). The use of PICC lines with PWUD is understood to be a source of tension in hospital settings but has not been well researched. Drawing on theoretical and analytic insights from “new materialism,” we consider the assemblage of sociomaterial elements that inform the use of PICCs.MethodsThis paper draws on n = 50 interviews conducted across two related qualitative research projects within a program of research about the impact of substance use on hospital admissions from the perspective of healthcare providers (HCPs) and people living with HIV/HCV who use drugs. This paper focuses on data about PICC lines collected in both studies.ResultsThe decision to provide, maintain, or remove a PICC is based on a complex assemblage of factors (e.g., infections, bodies, drugs, memories, relations, spaces, temporalities, and contingencies) beyond whether parenteral intravenous antibiotic therapy is clinically indicated. HCPs expressed concerns about the risk posed by past, current, and future drug use, and contact with non-clinical spaces (e.g., patient's homes and the surrounding community), with some opting for second-line treatments and removing PICCs. The majority of PWUD described being subjected to threats of discharge and increased monitoring despite being too ill to use their PICC lines during past hospital admissions. A subset of PWUD reported using their PICC lines to inject drugs as a harm reduction strategy, and a subset of HCPs reported providing harm reduction-centred care.ConclusionOur analysis has implications for theorizing the role of PICC lines in the care of PWUD and identifies practical guidance for engaging them in productive and non-judgemental discussions about the risks of injecting into a PICC line, how to do it safely, and about medically supported alternatives.     

Is inhibition of cyclooxygenase required for the anti-tumorigenic effects of nonsteroidal, anti-inflammatory drugs (NSAIDs)? In vitro versus in vivo results and the relevance for the prevention and treatment of cancer

Active research is being conducted to unravel the cellular mechanisms mediating the anti-tumorigenic effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and their association with cyclooxygenase (COX) inhibition. The majority of NSAIDs inhibit either COX-1, COX-2, or both and exert their anti-COX, anti-inflammatory, and anti-tumorigenic effects in vivo in a parallel dose-dependent manner. The effects are seen at NSAID blood plasma concentrations of 0.1-5 microM. Significantly, the same compounds tested at the same concentrations in incubations with cultured tumor cells in vitro similarly inhibit COX activities but are devoid of anti-proliferative activity. Yet, at much higher concentrations (100-20,000 microM), these same NSAIDs do exert anti-proliferative effects in vitro due to apparent non-specific toxic effects, as evidenced by disruption of ion transport and mitochondrial oxidation in some cells. A small group of NSAIDs (e.g. sulindac) do not inhibit COX enzymes significantly but can reduce the synthesis of prostanoids by alternate mechanisms. One such mechanism is inhibition of agonist-stimulated phospholipase-mediated release of arachidonic acid from phospholipids leading to depressed synthesis of prostanoids, especially prostaglandin E(2) (PGE(2)). Another group of non-COX inhibitors are the R-isomers of NSAIDs, based on the structure of 2-arylpropionic acid. These compounds exert anti-proliferative effects in vivo, acting by an as yet undetermined mechanism. A possible caveat in these data is an R to S chiral transformation in vivo that would render the R-isomer effect as being due to the S-isomer generated in vivo from it. Demonstration of minimal or no R to S inversion under the experimental in vivo conditions employed is, therefore, a necessary control in these studies. The overall body of data supports the conclusion that, for COX-inhibiting NSAIDs, their anti-tumorigenic effect in vivo is due to, and depends upon, inhibition of tumor COX enzymes, primarily COX-2. The cellular effects seen when adding high concentrations of NSAIDs to tumor cells cultured in vitro and the mechanisms proposed to mediate these effects may not have substantial relevance to the mechanisms that mediate the effects of NSAIDs in vivo.     

“You need money to get high,and that&#x27;s the easiest and fastest way:” A typology of sex work and health behaviours among people who inject drugs

BackgroundIn the United States, the criminalization and stigmatization of drug use and sex work contribute to infectious disease transmission and healthcare disengagement. People who inject drugs (PWID) and engage in sex work experience exacerbated HIV risk. In the context of the ongoing HIV and overdose epidemics little research describes why PWID engage in sex work and its relative HIV risk. To inform intervention needs, we aimed to create a typology of sex work among PWID with a focus on HIV risk and healthcare utilization behaviours.MethodsWe drew from in-depth interviews conducted across Massachusetts and Rhode Island from 2016–2019. Participants were ≥18 years old and self-reported past-month injection drug use and HIV-negative status. Using data from individuals reporting sex work experience (n=33/78), we utilized the framework method to develop a typology of perspectives on sex work engagement and attributes pertaining to HIV risk and healthcare utilization behaviours.ResultsWe uncovered varying perspectives on sex work and associated HIV risks and prevention needs. A typology included three groups who viewed their sex work engagement as a (1) consistent job, (2) income supplement, or (3) survival method to abate withdrawal symptoms. The first group described more consistent sexual and injection behaviours to mitigate HIV risk than the second group. The third group appeared particularly vulnerable to HIV, describing inconsistent condom use and frequent sharing of injection equipment, low healthcare utilization, and limited disclosure of sex work and injection drug use to healthcare providers.ConclusionFindings highlight distinct perspectives on sex work among PWID involved in it and corresponding perceptions of HIV risk and healthcare utilization behaviours. Understanding the nuances in sex work engagement among PWID can inform interventions to prevent infectious disease transmission, including efforts to further connect this marginalized population to harm reduction, health, and low barrier opioid treatment services.     

Small-molecule inhibitors/modulators of amyloid-β peptide aggregation and toxicity for the treatment of Alzheimer's disease: a patent review (2010 – 2012)

Introduction: Genetic, physiological, and biochemical data indicate that agglomerates of the 42-amino acid form of the amyloid-β (Aβ₄₂) peptide are strongly linked to Alzheimer's disease (AD) etiology and thus represent a particularly attractive target for the development of an effective disease-modifying approach for AD treatment. A plethora of chemical entities able to modulate Aβ₄₂ self-assembly have been developed in recent years, among them, several are in clinical or preclinical development.

Areas covered: This review accounts for small-molecule inhibitors of Aβ peptide polymerization and toxicity, reported in the patent literature during the 2010 – 2012 period, and their potential use as disease-modifying therapeutics for AD cure.

Expert opinion: The earliest pathogenic event is the formation of soluble Aβ oligomers that disrupt synaptic communication. Drug design strategies targeting these primary toxic agents could hold considerable promises for obtaining effective anti-AD drugs candidate. The heterogeneous aggregation of Aβ and the resulting difficulty to structurally characterize the peptide represent important drawbacks.