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Integrating HIV-related care with treatment for substance use disorder provides an opportunity to better meet the needs of people living with these conditions. People with substance use disorder are rendered especially vulnerable by prevailing policies, structural inequalities, and stigmatisation. In this Series paper we analyse existing literature and empirical evidence from scoping reviews on integration designs for the treatment of HIV and substance use disorder, to understand barriers to and facilitators of care integration and to map ways forward. We discuss how approaches to integration address two core gaps in current models: a failure to consider human rights when incorporating the perspectives of people living with HIV and people who use drugs, and a failure to reflect critically on structural factors that determine risk, vulnerability, health-care seeking, and health equity. We argue that successful integration requires a person-centred approach, which is grounded in human rights, treats both concerns holistically, and reconnects with underlying social, economic, and political inequalities.

Rohit Ramchandani and colleagues propose a framework to ensure essential public health tools are fairly distributed in future pandemics

In contrast to global patterns, the HIV epidemic in the Russian Federation continues to expand. The epidemic remains largely concentrated among key populations and their sexual partners but has the potential of affecting the general population. We have focused our analysis on legislative, policy-related, structural, and cultural obstacles that the country faces in confronting its epidemic.The Russian Federation has the largest HIV epidemic in Europe. Recent epidemiological analyses have shown a decrease in the annual growth of new reported infections. However, stigma and discrimination, marginalization, legislative provisions, harsh policing, and the lack of relevant prevention programs remain compounding factors that limit access of at-risk populations to information, prevention, and care, including to treatment for a number of people who would know their serological status.The ability of the Russian Federation to address the challenges it faces in dealing with a concentrated epidemic, will determine the future of the epidemic in the country.

SCOPUS: re.j, info:eu-repo/semantics/published

International audience; Natural antibodies (nAbs) are most commonly defined as immunoglobulins present in the absence of pathological conditions or deliberate immunizations. Occurrence of nAbs in germ- and antigen-free mice suggest that their production is driven, at least in part, by self-antigens. Accordingly, nAbs are constituted of natural autoantibodies (nAAbs), and can belong to the IgM, IgG, or IgA subclasses. These nAbs provide immediate protection against infection while the adaptive arm of the immune system mounts a specific and long-term response. Beyond immediate protection from infection, nAbs have been shown to play various functional roles in the immune system, which include clearance of apoptotic debris, suppression of autoimmune and inflammatory responses, regulation of B cell responses, selection of the B cell repertoires, and regulation of B cell development. These various functions of nAbs are afforded by their reactivity, which is broad, cross-reactive, and shown to recognize evolutionarily fixed epitopes shared between foreign and self-antigens. Furthermore, nAbs have unique characteristics that also contribute to their functional roles and set them apart from antigen-specific antibodies. In further support for the role of nAbs in the protection against infections and in the maintenance of immune homeostasis, the therapeutic preparation of polyclonal immunoglobulins, intravenous immunoglobulin (IVIG), rich in nAbs is commonly used in the replacement therapy of primary and secondary immunodeficiencies and in the immunotherapy of a large number of autoimmune and inflammatory diseases. Here, we review several topics on nAbs features and functions, and therapeutic applications in human diseases.

Gay, bisexual, and other men who have sex with men (MSM) continue to have disproportionately high burdens of HIV infection in countries of low, middle, and high income in 2016. 4 years after publication of a Lancet Series on MSM and HIV, progress on reducing HIV incidence, expanding sustained access to treatment, and realising human rights gains for MSM remains markedly uneven and fraught with challenges. Incidence densities in MSM are unacceptably high in countries as diverse as China, Kenya, Thailand, the UK, and the USA, with substantial disparities observed in specific communities of MSM including young and minority populations. Although some settings have achieved sufficient coverage of treatment, pre-exposure prophylaxis (PrEP), and human rights protections for sexual and gender minorities to change the trajectory of the HIV epidemic in MSM, these are exceptions. The roll-out of PrEP has been notably slow and coverage nowhere near what will be required for full use of this new preventive approach. Despite progress on issues such as marriage equality and decriminalisation of same-sex behaviour in some countries, there has been a marked increase in anti-gay legislation in many countries, including Nigeria, Russia, and The Gambia. The global epidemic of HIV in MSM is ongoing, and global efforts to address it remain insufficient. This must change if we are ever to truly achieve an AIDS-free generation.

Author(s): Bekker, Linda-Gail; Alleyne, George; Baral, Stefan; Cepeda, Javier; Daskalakis, Demetre; Dowdy, David; Dybul, Mark; Eholie, Serge; Esom, Kene; Garnett, Geoff; Grimsrud, Anna; Hakim, James; Havlir, Diane; Isbell, Michael T; Johnson, Leigh; Kamarulzaman, Adeeba; Kasaie, Parastu; Kazatchkine, Michel; Kilonzo, Nduku; Klag, Michael; Klein, Marina; Lewin, Sharon R; Luo, Chewe; Makofane, Keletso; Martin, Natasha K; Mayer, Kenneth; Millett, Gregorio; Ntusi, Ntobeko; Pace, Loyce; Pike, Carey; Piot, Peter; Pozniak, Anton; Quinn, Thomas C; Rockstroh, Jurgen; Ratevosian, Jirair; Ryan, Owen; Sippel, Serra; Spire, Bruno; Soucat, Agnes; Starrs, Ann; Strathdee, Steffanie A; Thomson, Nicholas; Vella, Stefano; Schechter, Mauro; Vickerman, Peter; Weir, Brian; Beyrer, Chris

The immunoregulatory and anti-infective properties of normal circulating polyclonal Abs have been exploited for the therapeutic purposes in the form of IVIG as well as several hyperimmune globulins. Current knowledge on the therapeutic use of normal Igs is based on the discoveries made by several pioneers of the field. In this paper, we review the evolution of IVIG over the years. More importantly, the process started as an s.c. replacement in γ globulin–deficient patients, underwent metamorphosis into i.m. Ig, was followed by IVIG, and is now back to s.c. forms. Following successful use of IVIG in immune thrombocytopenic purpura, there has been an explosion in the therapeutic applications of IVIG in diverse autoimmune and inflammatory conditions. In addition to clinically approved pathological conditions, IVIG has been used as an off-label drug in more than 100 different indications. The current worldwide consumption of IVIG is over 100 tons per year.

This article examines the AIDS epidemic and what the international community has gotten right what we have done wrong and why we need to urgently dispel several emerging myths about the epidemic and the global response to it. It suggests that we have to identify how to finance a sustained response to AIDS for another several decades develop long-lasting links with broader efforts to strengthen health systems continue to invest in research and development and put a more serious effort into tackling stigma and discrimination.

On Tuesday 14 October 2014, 850 family members, friends, colleagues, prominent scientists and dignitaries from all over the world gathered in Amsterdam to pay tribute to the lives and legacies of Joep Lange and Jacqueline van Tongeren. The remembrance was held at the Amsterdam Medical Centre (AMC) where Joep and Jacqueline met and worked together for many years. The day was organized by the AMC, the Amsterdam Institute for Global Health and Development (AIGHD) and PharmAccess Foundation. The latter two were both founded by Joep. A morning symposium titled ‘Research in action: from AIDS to global health to impact’ highlighted Joep's scientific legacy (Figure 1). During the remembrance in the afternoon, a range of speakers shared memories of Joep and Jacqueline. As was the case during their lives, the personal and the professional were closely intertwined throughout the day. As Prof Peter Piot said, Joep and Jacqueline shared a common perspective on life: ‘La folie suprême est de voir la vie comme elle est et non comme elle devrait être.’ If there was one thing that defined them both, it was indeed that they saw life – and lived it – not as it was, but as it should be. ‘Joep's place in history is really as the visionary architect of combination therapy,’ Prof Piot stated, adding that ‘it cannot be stressed enough that he was ahead of his time, a true innovator.’ Joep's contribution didn't stop at science. Dr Khama Rogo of the World Bank explained that ‘it's not enough to be a doctor or a researcher if you're not also an activist.’ Joep fully understood the importance of translating research into action and generating impact for people. Prof Marcel Levi, chairman of the AMC, summarized the enormity of the impact Joep had on the world with the words ‘it's rare to know someone who has saved millions of lives.’ The scientific symposium traced Joep's career, starting in the early eighties with the treatment of the first AIDS patients and the design of antiretroviral therapy, moving towards the emerging field of global health and ending with his most recent focus: using knowledge derived from scientific research to improve access to quality health care in real-world settings. From Prof Françoise Barré-Sinoussi, who won the Nobel Prize for the discovery of HIV, to Prof Michael Merson, who founded Duke University's Global Health Institute, the list of presenters reads like a who's who of people involved at key moments in the history of HIV and global health (Figure 2). ‘And Joep,’ as Barré-Sinoussi said, ‘contributed to all eras of HIV.’ More memories of Joep and Jacqueline shared throughout the day are available at http://www.joepandjacqueline.org/remembrance/ .

Eastern Europe and Central Asia have the largest drug epidemic globally and the fastest and still expanding HIV epidemic. The Russian Federation and Ukraine together account for over 90% of the reported AIDS cases in the region. If small in absolute numbers, the epidemics are however significant in prevalence rate in most countries of Central Asia. Most heroin and many of the new synthetic or home-made drugs are injected, which has led to high prevalence levels (up to 90%) of HCV infection in people who inject drugs (PWID). The two epidemics of HIV and HCV are in turn interlinked with TB and MDR-TB that are highly prevalent among marginalized populations in the region. Despite progress in the last two years, access to antiretroviral treatment remains far below global levels and increases more slowly than new reported cases of HIV. Access to prevention is limited with low coverage of needle exchange programs and very low or inexistent access to opioid substitutive therapy. There are few exceptions to this situation, including Ukraine where harm reduction programs are being scaled up together with significant peer outreach programs for PWIDs. This is likely to be the reason why the epidemic curves in the Russian Federation and Ukraine are now diverging. The region faces many structural, cultural, societal and political obstacles in responding to these quadruple epidemics. Without a significantly expanded and strengthened response, these epidemics will remain major causes of illness and premature deaths in the region. (Published: 2 November 2014) Citation : Abstracts of the HIV Drug Therapy Glasgow Congress 2014 Kazatchkine M. Journal of the International AIDS Society 2014, 17(Suppl 3) :19501 http://www.jiasociety.org/index.php/jias/article/view/19501 | http://dx.doi.org/10.7448/IAS.17.4.19501

A new collaborative model of research is needed to increase resources, to prioritize the RD (ii) to increase the pace, reduce the overlap, and more systematically explore the elements of and delivery systems for vaccines; (iii) to use common standards for the prompt comparative testing of vaccine candidates; (iv) to expand resources for manufacturing vaccine candidates to speed their use in human trials; and (v) to increase the capacity for international clinical trials and to focus this effort toward quickly measuring the effectiveness of vaccine protection as prototype vaccine candidates are identified.

The primordial combinatorial immune recognition repertoire arose in the evolution of jawed vertebrates approximately 450 million years ago as a rapid genetic process independent of antigenic selection. We propose that it encompassed the entire repertoire of innate immunity involving molecules that had evolved over billions of years. The 'antigen-driven' compartment involving invasive pathogens operates in 'real time' showing inducibility and increases in affinity. Individuals within a species differ in their repertoires because of distinct antigenic challenges, genetics, or local environmental effects. The 'homeostatic' compartment that recognizes invariant cell and serum components should be conserved in all individuals of a species. The potential to recapitulate the entire recognition spectrum must be regenerated during the formation of new species. Evidence for the capacity of the combinatorial response to encompass the entire preexisting repertoire was obtained in studies of natural human IgG antibodies present in intravenous immunoglobulin. Since essential cellular recognition and regulatory elements are conserved throughout evolution, we propose that the natural antibodies of sharks, the most anciently emerged vertebrates to possess the combinatorial immune response, will resemble those of mammals in showing specificity for the conserved recognition/regulatory molecules. If verified, this hypothesis will establish the fundamental importance of natural antibodies not only in defense, but in regulation and functional homeostasis of the individual.

Prohibition can prevent access to harm reduction treatment, including methadone, for people who inject drugs, writes Michel Kazatchkine

Introduction : Scientific research has demonstrated the clinical benefits of earlier initiation of antiretroviral treatment (ART), and that ART can markedly reduce HIV transmission to sexual partners. Ensuring universal access to ART for those who need it has long been a core principle of the HIV response, and extending the benefits of ART to key populations is critical to increasing the impact of ART and the overall effectiveness of the HIV response. However, this can only be achieved through coordinated efforts to address political, social, legal and economic barriers that key populations face in accessing HIV services. Discussion : Recent analyses show that HIV prevalence levels among key populations are far higher than among the general population, and they experience a range of biological and behavioural factors, and social, legal and economic barriers that increase their vulnerability to HIV and have resulted in alarmingly low ART coverage. World Health Organization 2014 consolidated guidance on HIV among key populations offers the potential for increased access to ART by key populations, following the same principles as for the general adult population. However, it should not be assumed that key populations will achieve greater access to ART unless stigma, discrimination and punitive laws, policies and practices that limit access to ART and other HIV interventions in many countries are addressed. Conclusions : Rights-based approaches and investments in critical enablers, such as supportive legal and policy environments, are essential to enable wider access to ART and other HIV interventions for key populations. The primary objective of ART should always be to treat the person living with HIV; prevention is an important, additional benefit. ART should be provided only with informed consent. The preventive benefits of treatment must not be used as a pretext for failure to provide other necessary HIV programming for key populations, including comprehensive harm reduction and other prevention interventions tailored to meet the needs of key populations. An end to AIDS is only possible if we overcome the barriers of criminalization, stigma and discrimination that remain key drivers of the HIV epidemics among key populations. Keywords: treatment; HIV/AIDS; human rights. (Published: 18 July 2014) Citation: Grubb IR et al. Journal of the International AIDS Society 2014, 17:19320 http://www.jiasociety.org/index.php/jias/article/view/19320 | http://dx.doi.org/10.7448/IAS.17.1.19320

Andy Guise, Michel Kazatchkine, Tim Rhodes, and Steffanie A. Strathdee Public Health and Policy, London School of Hygiene and Tropical Medicine, and International HIV/AIDS Alliance, Brighton, United Kingdom; United Nations Secretary-General Special Envoy on HIV/AIDS in Eastern Europe and Central Asia, Geneva, Switzerland; and Division of Global Public Health, Department of Medicine, University of California San Diego

Injecting drug use drives the huge HIV/AIDS epidemic in the region, but Russian law does not permit the substitution treatment that is shown to help. The end of its provision on 1 May will have huge repercussions, says Michel Kazatchkine

Naturally occurring autoantibodies (NAbs) with germline or close to germline configurations are specific to self- and altered self-components, and they exist in the serum of healthy individuals, independent of deliberate immunization with a target antigen. Human intravenous immunoglobulin (IVIg) consists of pooled immunoglobulin (IgG) from several thousand healthy volunteers. In addition to immune deficiency, IVIg is used in the treatment of several autoimmune and inflammatory conditions. The polyreactive, low- to moderate-affinity but high-avidity NAbs are an important part of the composition of IVIg. It is well established that NAbs play a significant role in maintaining tissue and immune homeostasis in a healthy individual. It is thus conceivable that NAbs present within IVIg may participate in exerting the beneficial effects observed during the course of treatment of patients with autoimmune and inflammatory diseases. Understanding the mechanisms by which NAbs operate under different clinical settings is of critical significance. In this chapter, we summarize the roles of NAbs in IVIg.

The long-standing quest for the development of vaccines that confer protection against highly mutable viruses such as HIV, hepatitis C, and influenza has elicited numerous structural and functional studies on virus-neutralizing human antibodies. These studies have aimed at translating the knowledge acquired on broadly neutralizing antibodies to the design of better immunogens for the induction of specific and protective immune responses. The last few months were marked by several seminal articles that investigate HIV-neutralizing human antibodies. These studies have characterized essential mechanistic details of the neutralization of HIV and imply that both exquisite specificity and degeneracy of the specificity of antibodies may be equally important for HIV neutralization. In this Opinion, we highlight and further discuss the potential of polyreactive (promiscuous) antibodies in defense against promptly evolving viruses. Despite having been somewhat neglected by mainstream immunologists in the last 20 years, polyreactive antibodies may come to light as new weapons against HIV.

The role that human rights can play in the global response to HIVIAIDS is crucial. People around the world continue to be placed at risk of HIV due to ongoing human rights violations. In this article--based on a public lecture he gave at "From Evidence and Principle to Policy and Action", the 2nd Annual Symposium on HIV, Law and Human Rights, held on 10-12 June 2010 in Toronto, Canada--Michel Kazatchkine, Executive Director of the Global Fund to Fight AIDS, Tuberculosis and Malaria, discusses how the lack of support for programs that protect and promote human rights is one of the failures in the response to AIDS. He stresses that advocates must reinvigorate efforts for human rights and treatment and prevention for all, including for the most marginalized populations.

The published work on HIV in people who use drugs shows that the global burden of HIV infection in this group can be reduced. Concerted action by governments, multilateral organisations, health systems, and individuals could lead to enormous benefits for families, communities, and societies. We review the evidence and identify synergies between biomedical science, public health, and human rights. Cost-effective interventions, including needle and syringe exchange programmes, opioid substitution therapy, and expanded access to HIV treatment and care, are supported on public health and human rights grounds; however, only around 10% of people who use drugs worldwide are being reached, and far too many are imprisoned for minor offences or detained without trial. To change this situation will take commitment, advocacy, and political courage to advance the action agenda. Failure to do so will exacerbate the spread of HIV infection, undermine treatment programmes, and continue to expand prison populations with patients in need of care.

A randomized trial was launched in Côte d'Ivoire in 2002 to compare continuous antiretroviral treatment (hereafter, "C-ART") to an ART regimen of 2 months off and 4 months on therapy (hereafter, "2/4-ART"). We report the final analysis.A total of 435 adults who were receiving successful ART ((median CD4 cell count prior to ART, 272 cells/mm(3); 88% were receiving a zidovudine-lamivudine-efavirenz regimen) were randomized to receive C-ART or 2/4-ART. The main primary end point was the percentage of patients with350 CD4 cells/mm(3) at 24 months. The sample size ensured 80% power to demonstrate noninferiority (noninferiority bound, -15%), assuming that 30% of the patients in the C-ART arm would have350 CD4 cells/mm(3). Other end points were mortality, morbidity, cost of care, genotypic resistance, adherence, and toxicity.The percentage of patients with350 CD4 cells/mm(3) at 24 months was 5.6% (6 of 107) in the C-ART arm and 14.6% (46 of 315) in the 2/4-ART arm (lower bound of the 95% CI for the difference, -14%). Cost was 18% higher in the C-ART arm, and resistance to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) was 20% higher in the 2/4-ART arm. Other end points were nonconclusive.Although 2/4-ART met the predetermined criteria for noninferiority, the percentage of patients with350 CD4 cells/mm(3) in the C-ART arm was lower than anticipated, which makes the clinical significance of this noninferiority uncertain. In addition, 2/4-ART led to an unacceptable additional risk of selecting for drug-resistant virus. This new argument against episodic ART strategies is also a caveat against any unplanned ART interruptions in Africa, where most patients receive NNRTIs.

Since the Global Fund was established in 2002, it has expanded from 15 to 300 staff and plans to triple its current size by 2010, reaching a spending target of US$ 6 billion per year to meet projected demand. Single disease campaigns have recently come under fire for destroying health systems, but Kazatchkine argues that vertical funds can, in fact, strengthen health systems. He tells the Bulletin about his organization’s plans to finance health systems in developing countries while continuing to fund country programmes for AIDS, tuberculosis and malaria.

This commentary discusses how the pledges to the Global Fund to Fight AIDS Tuberculosis and Malaria from countries the private sector and innovative funding sources have fallen short of the demand estimates despite the pledged sum being the largest amount ever mobilized for global health. The US $11.7 billion pledge for the 2011-2013 time range is an increase of more than 20% over 2007-2010 and will go toward maintaining programs at their current scale and support further significant expansion of health services in many countries. It explains that the shortfall to meet the $13 billion will result in challenging decisions about which new programs to support and a slower rate of scale-up for new programs.

This article describes several urgent actions that are needed to promote rapid scale-up of effective and integrated services for tuberculosis and HIV and to tackle the factors that increase vulnerability and put people at risk of HIV-related tuberculosis. These include: bold national leadership health system restructuring to foster greater integration of tuberculosis and HIV services that provide routine tuberculosis screening treatment and prevention to people living with HIV; and to offer HIV counseling and testing to all patients with signs and symptoms of tuberculosis decentralized care to ensure improved access investment in new tools and better use of existing tools and global leadership from donors countries of the global south and key health agencies.