Advances in cell-based delivery of oncolytic viruses as therapy for lung cancer.

Lung cancer's intractability is enhanced by its frequent resistance to (chemo)therapy and often high relapse rates that make it the leading cause of cancer death worldwide. Improvement of therapy efficacy is a crucial issue that might lead to a significant advance in the treatment of lung cancer. Oncolytic viruses are desirable combination partners in the developing field of cancer immunotherapy due to their direct cytotoxic effects and ability to elicit an immune response. Systemic oncolytic virus administration through intravenous injection should ideally lead to the highest efficacy in oncolytic activity. However, this is often hampered by the prevalence of host-specific, anti-viral immune responses. One way to achieve more efficient systemic oncolytic virus delivery is through better protection against neutralization by several components of the host immune system. Carrier cells, which can even have innate tumor tropism, have shown their appropriateness as effective vehicles for systemic oncolytic virus infection through circumventing restrictive features of the immune system and can warrant oncolytic virus delivery to tumors. In this overview, we summarize promising results from studies in which carrier cells have shown their usefulness for improved systemic oncolytic virus delivery and better oncolytic virus therapy against lung cancer.

HIV drug resistance among naïve HIV-infected patients in Iran.

BACKGROUND: Antiretroviral (ARV) therapy extends life for persons living with HIV. Antiretroviral treatment (ART) has been rapidly expanding coverage around the world, including in Iran. However, ART drug resistance also rapidly develops with expanding use and limits effectiveness and treatment options. The aim of this study was to monitor the appearance of new mutations conferring HIV pretreatment drug resistance in the treatment of naïve patients with HIV in Iran. MATERIALS AND METHODS: Blood samples were obtained from ARV treatment-naïve patients from 8 different provinces in Iran in 2016 for genotyping for drug resistance mutations. RESULTS: Sequences were successfully obtained from 90 specimens. Of these, 2 (2%) mutations conferring resistance to protease inhibitors, 2 (3%) conferring resistance to nucleoside reverse transcriptase inhibitors (NRTIs), and 9 (13%) conferring resistance to non-NRTI (NNRTI) were detected. Any ARV-resistant drug mutation was found in 11 patients (12%). CONCLUSION: Nearly one in 8 ARV-naïve patients had mutations associated with NNRTI resistance in diverse areas of Iran in 2016. Iranian ARV therapy guideline for HIV could consider non-NNRTI-based first-line therapies and expand routine drug resistance testing before treatment initiation as according to HIV drug resistance recommendations of the World Health Organization.

Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran.

BACKGROUND: This study aimed to determine drug resistance mutations in patients with virological failure and find correlation between HIV drug resistance test and viral load. METHODS: Blood sample was collected from 51 patients who suspicious treatment failure in the center of Imam Khomeini Hospital, Tehran, Iran in 2015. Viral voluntary counseling and testing load test was done and the patients with viral load above 1000 copies choose for detection of drug resistance mutations by genotyping method (29 patients). RESULTS: The majority of patients (82.75) harbored the HIV subtype CRF 35 A-D. The 86.2% patients compromised at least one resistance mutation. The analysis of reverse transcriptase showed M184V (68.9%), T215YISF (44.8%), K103N (27.6%) and the analysis results of protease revealed G73SC (13.8%) and I47VA (6.9%). Eventually, the significant correlation between viral load and drug resistance was found. CONCLUSION: The result of our research stress the significance of recognizing drug resistant on time that prohibits the accumulation of drug resistance mutation and circulates the resistance strain of HIV-1 virus and the importance of national study according to the reliable findings for treatment guidelines.

The First Characterization of HIV-1 Subtypes and Drug Resistance Mutations among Antiretrovirally Treated Patients in Kermanshah, Iran.

BACKGROUND: Insufficient therapy during HIV-1 replication can promote the emergence of drug-resistant strains, reduce the effectiveness of antiretroviral treatment (ART), and increase the likelihood of the onward transmission of drug-resistant viruses. We characterized, for the first time, the prevalence of HIV-1 subtypes and drug resistance mutations in a western region of Iran. METHODS: This study was conducted among 122 patients on ART at a major referral center in Kermanshah, Iran. Nested PCR was performed using RT gene-specific primers from the pol gene. Sequencing was followed by amplification and purification of the desired sequence. Subtypes and mutations were determined using the Stanford HIV Drug Resistance Database. RESULTS: Most patients (92.6%) had subtype CRF 35-AD; 7.4% had subtype B. In total, 36.1% of the patients had at least 1 mutation associated with resistance RT inhibitors. The greatest rates of high-level resistance were observed for nevirapine (21.3%) and efavirenz (19.7%). CONCLUSIONS: Our results showed a high prevalence of drug resistance mutations in strains isolated from patients on treatment. At our center, we therefore recommend that genotyping be performed. This would allow the physician to prescribe appropriate drugs, reduce treatment costs, and increase the longevity and quality of life of patients.

HIV Drug Resistance and Phylogeny Profile in Naïve and Antiretroviral-Experienced Patients in Tehran, Iran.

BACKGROUND: Increasing the accessibility of antiretroviral therapy (ART) has caused the emergence of drug resistance in patients receiving ART and in naïve patients. The aim of this study was to evaluate HIV subtype and drug resistance between naïve patients and ART-experienced patients. METHODS: Blood samples were collected from 78 antiretroviral and naïve HIV-1 patients; antiretroviral-resistant mutations and subtyping were then determined by sequencing pol regions. RESULTS: Phylogenetic analysis revealed that 96.1% of sequences belong to the CRF35-AD subtype. Transmitted drug resistance was determined in 14% of drug-naïve patients and 40% of ART-experienced patients. CONCLUSION: The findings of this study illustrated the importance of resistance testing before and during ART treatment. This study can be used to set up a best medicine strategy in Iranian guidelines.

Subtype classification of Iranian HIV-1 sequences registered in the HIV databases, 2006-2013.

BACKGROUND: The rate of human immunodeficiency virus type 1 (HIV-1) infection in Iran has increased dramatically in the past few years. While the earliest cases were among hemophiliacs, injection drug users (IDUs) fuel the current epidemic. Previous molecular epidemiological analysis found that subtype A was most common among IDUs but more recent studies suggest CRF_35AD may be more prevalent now. To gain a better understanding of the molecular epidemiology of HIV-1 infection in Iran, we analyzed all Iranian HIV sequence data from the Los Alamos National Laboratory. METHODS: All Iranian HIV sequences from subtyping studies with pol, gag, env and full-length HIV-1 genome sequences registered in the HIV databases (www.hiv.lanl.gov) between 2006 and 2013 were downloaded. Phylogenetic trees of each region were constructed using Neighbor-Joining (NJ) and Maximum Parsimony methods. RESULTS: A total of 475 HIV sequences were analyzed. Overall, 78% of sequences were CRF_35AD. By gene region, CRF_35AD comprised 83% of HIV-1 pol, 62% of env, 78% of gag, and 90% of full-length genome sequences analyzed. There were 240 sequences re-categorized as CRF_AD. The proportion of CRF_35AD sequences categorized by the present study is nearly double the proportion of what had been reported. CONCLUSIONS: Phylogenetic analysis indicates HIV-1 subtype CRF_35AD is the predominant circulating strain in Iran. This result differed from previous studies that reported subtype A as most prevalent in HIV- infected patients but confirmed other studies which reported CRF_35AD as predominant among IDUs. The observed epidemiological connection between HIV strains circulating in Iran and Afghanistan may be due to drug trafficking and/or immigration between the two countries. This finding suggests the possible origins and transmission dynamics of HIV/AIDS within Iran and provides useful information for designing control and intervention strategies.