Improving the evidence for indicator condition guided HIV testing in Europe: Results from the HIDES II Study - 2012 - 2015.

BACKGROUND: It is cost-effective to perform an HIV test in people with specific indicator conditions (IC) with an undiagnosed HIV prevalence of at least 0.1%. Our aim was to determine the HIV prevalence for 14 different conditions across 20 European countries. METHODS: Individuals aged 18-65 years presenting for care with one of 14 ICs between January 2012 and June 2014 were included and routinely offered an HIV test. Logistic regression assessed factors associated with testing HIV positive. Patients presenting with infectious mononucleosis-like syndrome (IMS) were recruited up until September 2015. RESULTS: Of 10,877 patients presenting with an IC and included in the analysis, 303 tested positive (2.8%; 95% CI 2.5-3.1%). People presenting with an IC in Southern and Eastern Europe were more likely to test HIV positive as were people presenting with IMS, lymphadenopathy and leukocytopenia/ thrombocytopenia. One third of people diagnosed with HIV after presenting with IMS reported a negative HIV test in the preceding 12 months. Of patients newly diagnosed with HIV where data was available, 92.6% were promptly linked to care; of these 10.4% were reported lost to follow up or dead 12 months after diagnosis. CONCLUSION: The study showed that 10 conditions had HIV prevalences > 0.1%. These 10 ICs should be adopted into HIV testing and IC specialty guidelines. As IMS presentation can mimic acute HIV sero-conversion and has the highest positivity rate, this IC in particular affords opportunities for earlier diagnosis and public health benefit.

Open-label Phase II clinical trial in 75 patients with advanced hepatocellular carcinoma receiving daily dose of tableted liver cancer vaccine, hepcortespenlisimut-L.

BACKGROUND: An increasing number of studies is now devoted to immunotherapy of cancer. We evaluated the clinical benefit of hepcortespenlisimut-L (Hepko-V5 [formerly known as V5])-an oral therapeutic vaccine designated by the United States Food and Drug Administration (FDA) as an orphan drug for treatment of hepatocellular carcinoma (HCC). V5 was initially developed by us in 2002 to treat hepatitis B or C viral infections and liver cirrhosis. METHODS: The outcome of open-label Phase II trial of daily dose of V5 pill was analyzed retrospectively. Over a period of 5 years, 75 patients with advanced HCC were enrolled, consisting of 29 (38.7%) females and 46 (61.3%) males with a median age of 60 years (mean 61.6±8.1 years). Out of these, 23 (30.7%) had hepatitis B and 34 (45.3%) had hepatitis C infections, including 9 (12%) with dual infection, 4 (5.3%) negative for both viruses, and 5 (6.7%) without established viral diagnosis. Most patients (94.7%) had underlying liver cirrhosis of varying severity. RESULTS: After a median of 2 months of treatment, 50 out of 75 patients had experienced a decline in serum levels of the tumor marker, alpha-fetoprotein (AFP) (66.7%; P=0.006 by Wilcoxon signed rank test). Baseline median AFP levels were 245.2 IU/mL (mean 4,233; range 7.2-92,407; 95% confidence interval [CI] 1,186-7,280) and post-treatment values were 102.3 IU/mL (mean 2,539; range 0.9-54,478; 95% CI 503-4,575). The decrease in AFP was correlated either with tumor clearance or regression on computed tomography scans. The median overall survival time could not be established since 68 out of 75 (90.7%) patients were still alive after median follow-up of 12 months (mean 15±9.7; range 7-59; 95% CI 12.8-17.2). The first patient in this study received immunotherapy 5 years ago and still remains in complete remission. None of the patients experienced any serious adverse effects or toxicity. CONCLUSION: The results indicate that hepcortespenlismut-L is a safe, effective, and fast-acting immunomodulatory intervention for HCC. The Phase III, randomized, double-blind, placebo-controlled trial is now initiated at the Mongolian National Cancer Center to confirm these promising findings.

The cardiovascular risk management for people living with HIV in Europe: how well are we doing?

OBJECTIVES: HIV has become a chronic condition associated with comorbidities. We investigated cardiovascular risk and risk modification in a European HIV cohort. METHODS: EuroSIDA patients (from 1 January 2000) for whom cardiovascular risk could be calculated (DAD risk equation) were included in the analysis. Moderate-to-high risk was defined as 5-year cardiovascular risk more than 5% and risk modification as two measurements meeting the European AIDS Clinical Society guidelines. Factors associated with risk development and modifications were investigated using Poisson regression. RESULTS: Of 8762 individuals, 32.1% were hypertensive, 45.0% had high cholesterol, 47.4% were current smokers, and 27.1% were overweight. A total of 1504 (17.2%) had a 5-year cardiovascular risk of more than 5%. Of 7258 individuals with a 5-year risk less than 5%, 1905 (26.2%) developed cardiovascular risk more than 5% (6.53/100 person-years). These patients were more likely to be older, men, living in East Europe, with traditional cardiovascular risk factors. MSM with longer exposure to antiretroviral therapy, low CD4 nadir, higher current CD4 and prior AIDs events were more likely to develop cardiovascular risk. Those on antihypertensive treatment and living in central Europe were less likely to develop cardiovascular risk. Of those clinically indicated for risk modification, 1205 of 2077 (58.0%) successfully modified BP; 1283 of 3919 (32.8%) stopped smoking; 277 of 1394 (19.9%) modified cholesterol and 543 of 2163 (25.1%) reduced their BMI. There was variation in modification of individual risk factors, by sex, age, HIV-related factors and region of follow-up. Risk modification for BP and smoking improved over time (P < 0.001). CONCLUSION: Cardiovascular risk was common. More than half modified their cardiovascular risk, and this improved over time.

Randomized, placebo-controlled Phase II trial of heat-killed Mycobacterium vaccae (Immodulon batch) formulated as an oral pill (V7).

AIM: A 1-month Phase II trial was conducted in 41 patients with pulmonary TB who were randomized into treatment (n = 20) and placebo (n = 21) arms to investigate the safety and efficacy of an orally-administered therapeutic TB vaccine (V7) containing 10 µg heat-killed Mycobacterium vaccae provided by Immodulon Therapeutics Ltd (London, UK). MATERIALS & METHODS: Both arms received conventional anti-TB therapy administered along with a daily pill of V7 or placebo. The subject population had four categories of TB: drug-sensitive TB; retreated TB; drug-resistant TB; and TB with HIV distributed in V7 and placebo arms at 9:4:7:6 and 14:1:6:8 ratios, respectively. RESULTS: The mycobacterial clearance in sputum smears was observed in 72.2% (p < 0.0001) and 19% (p = 0.03) of patients on V7 and placebo, respectively. The average weight accrual among V7 recipients was 2.6 kg (p = 0.002) versus -0.2 kg (p = 0.69) in the control group. Except reduction in fever and increased lymphocyte counts, the changes in other secondary end points, such as hemoglobin, erythrocyte sedimentation rate and leukocyte counts, were not statistically different, although the proportion of patients responding favorably to V7 was invariably higher compared with placebo (p = 0.002). In control patients, no difference from baseline levels was noted except decreased hemoglobin content (p = 0.02). CONCLUSION: Oral M. vaccae was safe and has potential as an adjunct immunotherapy, targeting mucosal immunity, to improve efficacy and shorten treatment duration of TB chemotherapy.

Targeting the vaginal mucosa with human papillomavirus pseudovirion vaccines delivering simian immunodeficiency virus DNA.

The majority of HIV infections occur via mucosal transmission. Vaccines that induce memory T and B cells in the female genital tract may prevent the establishment and systemic dissemination of HIV. We tested the immunogenicity of a vaccine that uses human papillomavirus (HPV)-based gene transfer vectors, also called pseudovirions (PsVs), to deliver SIV genes to the vaginal epithelium. Our findings demonstrate that this vaccine platform induces gene expression in the genital tract in both cynomolgus and rhesus macaques. Intravaginal vaccination with HPV16, HPV45, and HPV58 PsVs delivering SIV Gag DNA induced Gag-specific Abs in serum and the vaginal tract, and T cell responses in blood, vaginal mucosa, and draining lymph nodes that rapidly expanded following intravaginal exposure to SIV(mac251.) HPV PsV-based vehicles are immunogenic, which warrant further testing as vaccine candidates for HIV and may provide a useful model to evaluate the benefits and risks of inducing high levels of SIV-specific immune responses at mucosal sites prior to SIV infection.

Synthetic and natural immunomodulators acting as interferon inducers.

Interferons are first immunomodulatory molecules that have been shown to display a wide range of applications due to their antiviral, antibacterial, antitumor, and inflammatory activities. Natural and recombinant interferons are among most common biologic therapeutics worldwide. Interferon inducers, however, are less known and have been mostly developed and used in former socialist countries. Despite the fact that they are virtually unknown to the Western world, they represent a substantial market share of modern pharmacopoeia in former socialist republics. This review provides a brief description of most popular interferon inducers including Amyxin, Amizon, Anandin, Arbidol, Blasten, Cycloferon, Galavit, Groprinosine, Hepon, Immunoxel, Dzherelo, Kagocel, Larifan, Ligfol, Likopid, Mebavin, MIGI-KLP, V-5 Immunitor, SCV-07, Milife, Neovir, Poludan, Ragocin, Ridostin, Thymogen and Savratz, some of which were in use for several decades for the same clinical indications as for interferons. The variety and choice offered by the pharmaceutical industry behind the former "iron curtain" certainly deserves the appreciation, familiarity and application prospects for medical and research investigators worldwide.