Ibalizumab Targeting CD4 Receptors, An Emerging Molecule in HIV Therapy.

The HIV infection is responsible for the most devastating global pandemic of the last century. More than 39 million people have died of HIV/AIDS since 1981. The development of the antiretroviral (ARV) treatment begins with the discovery of zidovudine a nucleoside reverse transcriptase inhibitor. This breakthrough was followed by other ARV drug classes and representatives. Presently, HIV treatment employs 27 ARV representatives belonging to five different classes. Despite the proven benefits of ARV treatment and its long-term control of the HIV infection, there is an increasing concern about the numerous adverse effects and resistance to current ARV drugs. Therefore, the new HIV treatment strategies focus on the development of new ARV agents with a high genetic barrier to resistance and low toxicity. Monoclonal antibodies (MAbs) belong to a new drug class with encouraging results in the treatment of cancer, autoimmune disorders and most recently against HIV infection. The advantages of using MAbs for HIV treatment are related to their antiviral effect, lack of toxicity, good resistance profile, additional synergy with other ARV drug classes and ability to restore CD4 T-cell responses. The current article is a short summary of ibalizumab, an anti-CD4 monoclonal antibody that interferes with HIV viral entry. Current studies on ibalizumab have underlined its antiviral potential, minimal adverse effects, and lack of crossed resistance with other ARV agents thus supporting its further therapeutic use in multidrug resistant HIV-infected patients.

Improving the Adherence to Antiretroviral Therapy, a Difficult but Essential Task for a Successful HIV Treatment-Clinical Points of View and Practical Considerations.

HIV infection is responsible for one the most devastating human pandemics. The advent of antiretroviral therapy has changed the course of the pandemic and saved millions of lives. Complex therapeutic regimens have been introduced since 1996 and have contributed to the transformation of HIV infection into a treatable chronic diseases. New types of potent antiretrovirals and their combinations, including "once daily" treatment, have simplified the regimens and diminished side effects. Nevertheless the adherence to antiretroviral therapy remains unsatisfactory and varies between 27 and 80% across different population in various studies, compared with the required level of 95%. The lack of adherence to antiretroviral therapy is a multi-factorial and dynamic process which raises considerable difficulties for long-term follow-up. Current solutions to this problem are complex. These should be applied by a multidisciplinary team and should take into account key features related to both the individual and social factors as well as to the population to whom it belongs (children, teenagers, elderly, marginalized population like drug users, incarcerated patients, sex workers, etc.). Importantly, adherence should continue to be monitored even in patients known to be compliant. In case of subsequent failure the team should identify the reasons for non-adherence and apply the appropriate methods. Where usual methods have no chance of success, a coordinated package of services also known as "harm reduction" can be offered in order to reduce the risks of transmission. The current article analyses the concept of adherence to antiretroviral therapy, the shortcomings of this medication and the methods that can be applied in practice to increase adherence. Emphasis is placed on the analysis of groups at high risk for HIV infection that currently represent the spearhead with which the HIV pandemic is spreading.

DRESS syndrome with hepatic involvement in a patient with depressive disorder.

We present a 31-year-old woman with a depressive disorder admitted in the Infectious Diseases Department with high fever, cervical lymphadenopathy, generalized rash and progressive jaundice. Sepsis with hepatic involvement was initially suspected, but the bacteriological and serological profiles for viral and bacterial pathogens remained negative. The exposure to antidepressant medication including lamotrigine, an aromatic anticonvulsant molecule, raised the suspicion of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome. The antidepressants were withdrawn and methylprednisolone therapy was started with a favorable outcome and lent recovery after two months. This case highlights a rare drug allergic complication to antidepressant medication evolving as a sepsis with hepatic dysfunction.

Antibacterial function of the human cathelicidin-18 peptide (LL-37) between theory and practice.

The human cathelicidin-18 is an antimicrobial, immunomodulatory and tissue repair peptide. The LL-37 fragment of this peptide which is in fact the active domain of the cathelicidin-18 is critical for the human antibacterial defense and epithelial integrity. It's activity against resistant pathogens, the potential of epithelial healing after microbial injury and the neutralization of bacterial endotoxin underlie the most important benefits of this peptide. However, there are still a number of questions that remain to be answered regarding the precise interactions of cathelicidin-18 within the immune system, the exact tissue concentrations or its possible pro-tumoral activity. In this respect, the therapeutic potential of cathelicidin-18 in various infections has been proved by in vitro experiments, but additional detailed clinical studies are still required to ascertain its antimicrobial role in vivo. We present a short review on the antibacterial activity of human cathelicidin-18 (LL-37) according to in vitro experiments while discussing its potential use in the clinical practice.

A case of irreversible leukoencephalopathy in a patient with C virus hepatitis treated with pegylated interferon-alpha-2b and ribavirin.

We describe the case of a patient with C chronic hepatitis and early virological response on pegylated-interferon-alpha based therapy who presented clinical manifestations and magnetic resonance imaging suggestive for toxic leukoencephalopathy after 5 months of treatment. The negative results for neurotropic infectious agents and autoimmune markers opened the discussion of toxic interferon-induced leukoencephalopathy as a rare, but threatening neurologic side effect of this therapy.