Current HIV Research - Volume 17, Issue 2, 2019

Background: Among the various types of pharmaceuticals, vaccines have a special place. However, in the case of HIV, nearly after 40 years of its discovery, an effective vaccine still is not available. The reason lies in several facts mainly the variability and smartness of HIV as well as the complexity of the interaction between HIV and immune responses. A robust, effective, and longterm immunity is undoubtedly what a successful preventive vaccine should induce in order to prevent the infection of HIV. Failure of human trials to this end has led to the idea of developing therapeutic vaccines with the purpose of curing already infected patients by boosting their immune responses against the virus. Nevertheless, the exceptional ability of the virus to escape the immune system based on the genetically diverse envelope and variable protein products have made it difficult to achieve an efficient therapeutic vaccine. Objective: We aimed at studying and comparing different approaches to HIV therapeutic vaccines. Methods: In this review, we summarized the human trials undergoing on HIV therapeutic vaccination which are registered in the U.S. clinical trial database (clinicaltrials.gov). These attempts are divided into different tables, according to the type of formulation and application in order to classify and compare their results. Result/Conclusion: Among several methods applied in studied clinical trials which are mainly divided into DNA, Protein, Peptide, Viral vectors, and Dendritic cell-based vaccines, protein vaccine strategy is based on Tat protein-induced anti-Tat Abs in 79% HIV patients. However, the studies need to be continued to achieve a durable efficient immune response against HIV-1.

The aim of this review is to describe long-term HIV epidemiology and prevention trends in Guangxi, a provincial-level region located along a major drug trafficking corridor in southwestern China. Between 1996 and 2006, HIV transmission in Guangxi was primarily fueled by Injection Drug Use (IDU). Since 2006, heterosexual sex has become the dominant mode of HIV transmission, followed by drug injection. Moreover, older, heterosexual adults appear to be at increased risk for HIV. The vast majority of new HIV cases are attributed to local HIV subtypes already circulating within Guangxi (93%), though imported subtypes are associated with younger age groups. Since 2011, HIV incidence in Guangxi has stabilized, due in part to HIV prevention efforts that include expanded HIV testing, antiretroviral treatment, and other intervention measures. Between 1996 and 2017, Guangxi, China experienced dramatic changes in the primary HIV transmission mode and at-risk age group. Due in part to local and National AIDS control and prevention campaigns, HIV incidence trends in Guangxi no longer appear to be increasing.

The US is in the midst of a major epidemic of opioid addiction and related comorbidities. People with opioid use disorder (OUD) are at significant risk for transmission of several blood-borne pathogens including the human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). Commonly abused opioids and their receptors promote viral replication and virus-mediated pathology. However, most studies demonstrating an adverse effect of drugs of abuse have been conducted in vitro, the specific effects of synthetic opioids on viral replication have been poorly characterized, and the evaluation of opioid-virus interactions in clinically relevant populations is rare. Rigorous characterization of the interactions among synthetic opioids, host cells, and common injection-associated viral infections will require an interdisciplinary research approach and translational studies conducted on humans. Such research promises to improve clinical management paradigms for difficult-to-treat populations, facilitate rational public health policies given severely strained resources, and reveal additional pathways for novel target-specific therapeutic interventions. This mini-review examines the published literature on the effects of opioids on HIV, HBV, and HCV pathogenesis and proposes a series of scientific questions and considerations to establish a translational research agenda focused on opioid-virus interactions.

Background: Lack of effective early-stage HIV-1 inhibitor instigated the need for screening of novel gp120-CD4 binding inhibitor. Polyphenols, a secondary metabolite derived from natural sources are reported to have broad spectrum HIV-1 inhibitory activity. However, the gp120-CD4 binding inhibitory activity of polyphenols has not been analysed in silico yet. Objectives: To establish the usage of phytopolyphenols (Theaflavin, Epigallocatechin (EGCG), Ellagic acid and Gallic acid) as early stage HIV-1 inhibitor by investigating their binding mode in reported homology of gp120-CD4 receptor complex using in silico screening studies and in vitro cell line studies. Methods: The in silico molecular docking and molecular simulation studies were performed using Schrödinger 2013-2 suite installed on Fujitsu Celsius Workstation. The in vitro cell line studies were performed in the TZM-bl cell line using MTT assay and β-galactosidase assay. Results: The results of molecular docking indicated that Theaflavin and EGCG exhibited high XP dock score with binding pose exhibiting Van der Waals interaction and hydrophobic interaction at the deeper site in the Phe43 cavity with Asp368 and Trp427. Both Theaflavin and EGCG form a stable complex with the prepared HIV-1 receptor and their binding mode interaction is within the vicinity 4 Å. Further, in vitro cell line studies also confirmed that Theaflavin (SI = 252) and EGCG (SI = 138) exert better HIV-1 inhibitory activity as compared to Ellagic acid (SI = 30) and Gallic acid (SI = 34). Conclusion: The results elucidate a possible binding mode of phytopolyphenols, which pinpoints their plausible mechanism and directs their usage as early stage HIV-1 inhibitor.

Background: The information about the dynamics of the viral population and migration events that affect the epidemic in different parts of the Russia is insufficient. Possibly, the huge size of the country and limited transport accessibility to certain territories may determine unique traits of the HIV-1 evolutionary history in different regions. Objective: The aim of this study was to explore the genetic diversity of HIV-1 in the Krasnoyarsk region and reconstruct spatial-temporal dynamics of the infection in the region. Methods: The demographic and virologic data from 281 HIV-infected individuals in Krasnoyarsk region collected during 2011-2016 were analyzed. The time to the most recent common ancestor, evolutionary rates, population growth, and ancestral geographic movements was estimated using Bayesian coalescent-based methods. Results: The study revealed moderate diversity of the HIV-1 subtypes found in the region, which included A6 (92.3%), CRF063_02A (4.3%), B (1.1%), and unique recombinants (2.5%). Phylogenetic reconstruction revealed that the A6 subtype was introduced into Krasnoyarsk region by one viral lineage, which arose around 1996.9 (1994.5-1999.5). The phylogeography analysis pointed to Krasnoyarsk city as the geographical center of the epidemic, which further spread to central neighboring districts of the region. At least two epidemic growth phases of subtype A6 were identified which included exponential growth in early-2000s followed by the decline in the mid/late 2010s. Conclusion: This study demonstrates a change in the genetic diversity of HIV-1 in the Krasnoyarsk region. At the beginning of the epidemic, subtype A6 prevailed, subtypes B and CRF063_02A appeared in the region later.

Background: Methamphetamine abuse and human immunodeficiency virus (HIV) are common comorbidities. HIV-associated proteins, such as the regulatory protein TAT, may contribute to brain reward dysfunction, inducing an altered sensitivity to methamphetamine reward and/or withdrawal in this population. Objective: These studies examined the combined effects of TAT protein expression and, chronic and binge methamphetamine regimens on brain reward function. Methods: Transgenic mice with inducible brain expression of the TAT protein were exposed to either saline, a chronic, or a binge methamphetamine regimen. TAT expression was induced via doxycycline treatment during the last week of methamphetamine exposure. Brain reward function was assessed daily throughout the regimens, using the intracranial self-stimulation procedure, and after a subsequent acute methamphetamine challenge. Results: Both methamphetamine regimens induced withdrawal-related decreases in reward function. TAT expression substantially, but not significantly increased the withdrawal associated with exposure to the binge regimen compared to the chronic regimen, but did not alter the response to acute methamphetamine challenge. TAT expression also led to persistent changes in adenosine 2B receptor expression in the caudate putamen, regardless of methamphetamine exposure. These results suggest that TAT expression may differentially affect brain reward function, dependent on the pattern of methamphetamine exposure. Conclusion: The subtle effects observed in these studies highlight that longer-term TAT expression, or its induction at earlier stages of methamphetamine exposure, may be more consequential at inducing behavioral and neurochemical effects.

Background: Viral kinetics impact humoral immune response to HIV; antibody avidity testing helps distinguish recent (<6 months) and long-term HIV infection. This study aims to determine the frequency of recent HIV-1 infection among clients attending ICTC (Integrated Counselling and Testing Centre) using a commercial EIA, to correlate it with a modified in-house avidity assay and to study the impact of ART on anti-HIV-1 antibody maturation. Methods: Commercial LAg Avidity EIA was used to detect antibody avidity among 117 treatment naïve HIV-1 infected individuals. A second-generation HIV ELISA was modified for in-house antibody avidity testing and cutoff was set based on Receiver Operating Characteristic (ROC) analysis. Archived paired samples from 25 HIV-1 infected individuals before ART and after successful ART; samples from 7 individuals responding to ART and during virological failure were also tested by LAg Avidity EIA. Results: Six individuals (5.1%) were identified as recently infected by a combination of LAg avidity assay and HIV-1 viral load testing. The modified in-house avidity assay demonstrated sensitivity and specificity of 100% and 98.2%, respectively, at AI=0.69 by ROC analysis. Median ODn values of individuals when responding to ART were significantly lower than pre-ART [4.136 (IQR 3.437– 4.827) vs 4.455 (IQR 3.748–5.120), p=0.006] whereas ODn values were higher during virological failure [4.260 (IQR 3.665 – 4.515) vs 2.868 (IQR 2.247 – 3.921), p=0.16]. Conclusion: This modified in-house antibody avidity assay is an inexpensive method to detect recent HIV-1 infection. ART demonstrated significant effect on HIV-1 antibody avidity owing to changes in viral kinetics.

Due to oversight of an author, in the manuscript entitled “Correlation of Apolipoprotein B mRNA-editing Enzyme, Catalytic Polypeptide- like 3G Genetic Variant rs8177832 with HIV-1 Predisposition in Pakistani Population” one author’s name in the authors’ list was erroneously published in the Journal “Current HIV Research” 2018; 16(4): 297-301.