Early Stages Of HIV Infection Research Articles

Footprints of innate immune activity during HIV-1 reservoir cell evolution in early-treated infection.

Antiretroviral treatment (ART) initiation during the early stages of HIV-1 infection is associated with a higher probability of maintaining drug-free viral control during subsequent treatment interruptions, for reasons that remain unclear. Using samples from a randomized-controlled human clinical trial evaluating therapeutic HIV-1 vaccines, we here show that early ART commencement is frequently associated with accelerated and efficient selection of genome-intact HIV-1 proviruses in repressive chromatin locations during the first year after treatment initiation. This selection process was unaffected by vaccine-induced HIV-1-specific T cell responses. Single-cell proteogenomic profiling demonstrated that cells harboring intact HIV-1 displayed a discrete phenotypic signature of immune selection by innate immune responses, characterized by a slight but significant upregulation of HLA-C, HLA-G, the IL-10 receptor, and other markers involved in innate immune regulation. Together, these results suggest an accelerated immune selection of viral reservoir cells during early-treated HIV-1 infection that seems at least partially driven by innate immune responses.

The Role of Tumor Suppressor p53 Protein in HIV-Host Cell Interactions.

The virus-host relationship is indispensable for executing successful viral infection. The pathogenesis of HIV is determined by an intricate interaction between the host and the virus for the regulation of HIV infection, thereby influencing various aspects, including the regulation of signaling pathways. High mutation rates and population heterogeneity characterize HIV with consequences for viral pathogenesis and the potential to escape the immune system and anti-viral inhibitors used in therapy. The origin of the high mutation rates exhibited by HIV may be attributed to a limited template-copied fidelity that likely operates in the cytoplasm. HIV-1 infection induces upregulation and activation of tumor suppressor p53 protein in the early stages of HIV-1 infection. p53 plays a multifaceted role in the context of HIV infection, thereby affecting viral replication. p53 is involved in maintaining genetic integrity, actively participating in various DNA repair processes through its various biochemical activities and via its ability to interact with components of the repair machinery. This report focuses on the impact of the p53 protein on the HIV-1 reverse transcription process while incorporating various incorrect and non-canonical nucleotides. The presence of functional host-coded p53 protein with proofreading-repair activities in the cytoplasm may lead to various biological outcomes.

The nuclear localization signal of CPSF6 governs post-nuclear import steps of HIV-1 infection.

The early stages of HIV-1 infection include the trafficking of the viral core into the nucleus of infected cells. However, much remains to be understood about how HIV-1 accomplishes nuclear import and the consequences of the import pathways utilized on nuclear events. The host factor cleavage and polyadenylation specificity factor 6 (CPSF6) assists HIV-1 nuclear localization and post-entry integration targeting. Here, we used a CPSF6 truncation mutant lacking a functional nuclear localization signal (NLS), CPSF6-358, and appended heterologous NLSs to rescue nuclear localization. We show that some, but not all, NLSs drive CPSF6-358 into the nucleus. Interestingly, we found that some nuclear localized CPSF6-NLS chimeras supported inefficient HIV-1 infection. We found that HIV-1 still enters the nucleus in these cell lines but fails to traffic to speckle-associated domains (SPADs). Additionally, we show that HIV-1 fails to efficiently integrate in these cell lines. Collectively, our results demonstrate that the NLS of CPSF6 facilitates steps of HIV-1 infection subsequent to nuclear import and additionally identify the ability of canonical NLS sequences to influence cargo localization in the nucleus following nuclear import.

Dynamic analysis of HIV infection model with CTL immune response and cell-to-cell transmission

HIV infection is still a serious worldwide public health problem. During the early stage of HIV infection, the number of infected cells and viruses are extremely low and the process of infection is stochastic. In this paper, we use a stochastic model consisting of continuous-time Markov chain to investigate CTL immune response and two modes of infection (viral transmission and cellular transmission). A multitype branching process is used to approximate the probability of clearance and outbreak of HIV infection near the infection-free equilibrium. In addition, we compare the dynamics of the deterministic model with the results of the stochastic model, and the differences are as follows: (1) when R0>1, the deterministic model shows HIV infection outbreak, while the stochastic model indicates a positive probability of HIV infection elimination; (2) the initial number of infected cells and viruses have no effect on the dynamics of the deterministic model, whereas the dynamics of the stochastic model are highly dependent on the initial sizes and cannot be ignored.

NEUROTROPIC PROPERTIES OF RETROVIRUSES IN THE CONTEXT OF ANXIETY-DEPRESSIVE AND COGNITIVE DISORDERS IN HIV-POSITIVE PATIENTS

The aim: a comprehensive assessment and comparison of the prevalence of undiagnosed anxiety-depressive and cognitive symptoms in HIV-positive individuals at different stages of the disease who have been undergoing treatment for an extended period. Materials and methods According to the criteria of the scientific project, 71 HIV-positive individuals undergoing outpatient treatment with a compensated condition were involved. To explore dependencies on clinical stages (ClSt) of HIV infection and search for gender differences, the study was divided into 2 stages, respectively. The research included the collection of epidemiological and clinical-anamnestic data, as well as laboratory studies. Clinical-psychopathological and psychometric methods were used. Inclusion criteria for the study were HIV-positive status, receiving ART for more than 6 months, adulthood, and voluntary consent to participate. The obtained information was statistically processed by mathematical methods of statistics, using ANOVA criteria, Student's t-test, etc. Elements of neurocognitive and anxiety-depressive symptomatology were considered, utilizing GAD-7, HADS, and MMSE scales. Results: In patients of different groups in the first stage of the study, a gradually increasing level of anxiety and cognitive impairments was identified, depending on the stage of HIV infection. In the second stage of the study, gender and stage-related differences in anxiety and cognitive disorders were found in patients of all groups. Conclusions. Individuals in the first clinical stage (I ClSt) exhibited the least anxiety-depressive and cognitive disorders, indicating emotional and cognitive stability at this stage of HIV infection. HIV-infected individuals in the second and third clinical stages (II and III ClSt) demonstrated a progressive tendency toward anxious and depressive disorders, indicating a stage-dependent relationship to the progression of the disease. Patients in the fourth clinical stage (IV ClSt) showed the most pronounced anxious, depressive, and cognitive symptoms, which may be associated with the duration of the illness and antiretroviral therapy (ART). Research results in the female group (Group A1) suggest their lower susceptibility to disorders compared to males (Group A2) in the early stages of HIV infection. In the later stages (III-IV), it was found that women had pronounced anxious and depressive disorders (Group B1), while men exhibited signs of cognitive and depressive disorders (Group B2).

Antibody response to mycobacterial Rpf B protein and its immunodominant peptides in HIV-TB co-infected individuals

Diagnosis of TB at early stages of HIV infection may lead to timely intervention for improving patient outcome. Antibodies to Mycobacterium tuberculosis recombinant RpfB protein and two immunodominant peptides of Rpf B protein were evaluated in the sera of HIV +TB+, HIV+ and HIV− pulmonary TB patients by ELISA. Serum antibodies from 90 % and 65 % of HIV+TB+ patients reacted to recombinant RpfB protein and synthetic peptide RpfP1 respectively. Overall, this study shows that resuscitation promoting factor B elicits humoral antibody response in HIV+TB+ co-infected individuals and be proposed as a potential biomarker for diagnosis of HIV+TB+ patients, however further longitudinal follow up studies are warranted.

HIV rapidly targets a diverse pool of CD4+ T cells to establish productive and latent infections

Upon infection, HIV disseminates throughout the human body within 1-2weeks. However, its early cellular targets remain poorly characterized. We used a single-cell approach to retrieve the phenotype and TCR sequence of infected cells in blood and lymphoid tissue from individuals at the earliest stages of HIV infection. HIV initially targeted a few proliferating memory CD4+ Tcells displaying high surface expression of CCR5. The phenotype of productively infected cells differed by Fiebig stage and between blood and lymph nodes. The TCR repertoire of productively infected cells was heavily biased, with preferential infection of previously expanded and disseminated clones, but composed almost exclusively of unique clonotypes, indicating that they were the product of independent infection events. Latent genetically intact proviruses were already archived early in infection. Hence, productive infection is initially established in a pool of phenotypically and clonotypically distinct Tcells, and latently infected cells are generated simultaneously.

DNAJB8 facilitates autophagic-lysosomal degradation of viral Vif protein and restricts HIV-1 virion infectivity by rescuing APOBEC3G expression in host cells.

HSP40/DNAJ family of proteins is the most diverse chaperone family, comprising about 49 isoforms in humans. Several reports have demonstrated the functional role of a few of these isoforms in the pathogenesis of various viruses, including HIV-1. Our earlier study has shown that several isoforms of HSP40 get significantly modulated at the mRNA level during HIV-1 infection in T cells. To explore the biological role of these significantly modulated isoforms, we analyzed their effect on HIV-1 gene expression and virus production using knockdown and overexpression studies. Among these isoforms, DNAJA3, DNAJB1, DNAJB7, DNAJC4, DNAJC5B, DNAJC5G, DNAJC6, DNAJC22, and DNAJC30 seem to positively regulate virus replication, whereas DNAJB3, DNAJB6, DNAJB8, and DNAJC5 negatively regulate virus replication. Further investigation on the infectivity of the progeny virion demonstrated that only DNAJB8 negatively regulates the progeny virion infectivity. It was further identified that DNAJB8 protein is involved in the downregulation of Vif protein, required for the infectivity of HIV-1 virions. DNAJB8 seems to direct Vif protein for autophagic-lysosomal degradation, leading to rescue of the cellular restriction factor APOBEC3G from Vif-mediated proteasomal degradation, resulting in enhanced packaging of APOBEC3G in budding virions and release of less infective progeny virion particles. Finally, our results also indicate that during the early stage of HIV-1 infection, enhanced expression of DNAJB8 promotes the production of less infective progeny virions, but at the later stage or at the peak of infection, reduced expression of DNJAB8 protein allows the HIV-1 to replicate and produce more infective progeny virion particles.

A More Comprehensive Clinical and Laboratory Characterization of 61 Acute HIV Infection Patients in Southwest China

Acute HIV infection (AHI), i.e., the early stage of HIV infection, plays an important role in immune system failure and HIV transmission, but most AHI patients are missed due to their non-specific symptoms. To facilitate the identification of patients with high AHI risk and reduction of missed diagnosis, we characterized 61 AHI patients in a Southwest China hospital with 4300 beds; specifically, we characterized their general clinical characteristics, evolution in results of a novel HIV screening assay called Elecsys® HIV Duo, and by programming, we analyzed the ability of all routine laboratory tests (e.g., routine blood analysis) to identify AHI patients. Among 61 AHI patients, 85.2% were male and the median age was 42 (interquartile range, 25-62) years. A total of 61.9% of patients visit the emergency department first during AHI. Clinical presentation of AHI patients included fever, fatigue, chills, rash, and various respiratory, digestive, and nervous system symptoms. Two of three results from Elecsys® HIV Duo show clear evolution trends: HIV P24 antigen decreased while HIV antibody increased in consecutive samples of nearly all patients. High fluorescence lymphocytes have a very high positive likelihood ratio (LR+) of 10.33 and a relatively high "rate of out-of-range tests" of 56.8% (21 in 37 patients who received this test had a result outside the reference range). In addition, we identified more than ten tests with LR+ greater than two. In summary, the emergency department is important for AHI screening. The evolution of HIV P24 Ag and HIV Ab and those laboratory tests with a high "rate of out-of-range tests" or high LR+ may aid the AHI identification and missed diagnosis reduction.

The role of tunneling nanotubes during early stages of HIV infection and reactivation: implications in HIV cure.

Tunneling nanotubes (TNTs), also called cytonemes or tumor microtubes, correspond to cellular processes that enable long-range communication. TNTs are plasma membrane extensions that form tubular processes that connect the cytoplasm of two or more cells. TNTs are mostly expressed during the early stages of development and poorly expressed in adulthood. However, in disease conditions such as stroke, cancer, and viral infections such as HIV, TNTs proliferate, but their role is poorly understood. TNTs function has been associated with signaling coordination, organelle sharing, and the transfer of infectious agents such as HIV. Here, we describe the critical role and function of TNTs during HIV infection and reactivation, as well as the use of TNTs for cure strategies.

Effectiveness of Antiretroviral Treatment on the Transition Probability of Immunological State of HIV/AIDS Patients: A Markov Chain Model on the Iranian “National Registry of HIV/AIDS Care” Database

Antiretroviral therapy (ART) has improved survival and clinical course amongst HIV/AIDS patients. CD4 cell count is one of the most critical indicators of the disease progression. With respect to the dynamic nature of CD4 cell count during the clinical history of HIV/AIDS, modeling the CD4 cell count changes, which represents the likelihood of disease progression, is of interest to establish or revise treatment strategies and, specifically, to determine the stage at which giving ART is more clinically effective. In this historical cohort study on 917 HIV/AIDS patients in the Iranian “National Registry of HIV/AIDS Care” database, we used the Markov chain model to predict the effectiveness of the ART based on the transition probability of CD4 cell count, measured before and after initiating ART. We found that when the ART was initiated in the earlier stages of HIV infection, good prognosis might be more accessible; that is, after initiating ART at state CD4 ≥ 500, the probability of staying at this state was statistically increased than before the treatment (P < 0.001). Also, it was found that initiating ART significantly decreased the probability of CD4 cell count transition to the lower counts (PCD4≥500‐to‐350≤CD4<500 < 0.001, P350≤CD4<500‐to‐200≤CD4<350 < 0.001, and P200≤CD4<350‐to‐CD4<200 < 0.001). In addition, initiating ART showed a statistically significant increase in the probability of CD4 cell count transition from a lower state (350 ≤ CD4 < 500) to a higher state (CD4 ≥ 500) (P = 0.009). Furthermore, When CD4 count reaches under 200, even after the initiation of therapy, the probability of CD4 cell count transition to higher levels was not significant (P > 0.05). In summary, these results have a message for primary healthcare organizations to extensively identify HIV patients and initiating ART as early as possible.

Targeting the HIV-1 Tat and Human Tat Protein Complex through Natural Products: An In Silico Docking and Molecular Dynamics Simulation Approach

Background: Tat protein is considered essential for substantial HIV-1 replication, and is also required to break HIV-1 latency, resulting in productive HIV replication. The multifaceted regulatory role of HIV Tat and the fact that it is expressed in the early stages of HIV infection justify its potential as an anti-HIV drug target. Objective: The present study was undertaken with the aim to target HIV-1 Tat protein with natural compounds which could help in identifying potential inhibitors against HIV-1 Tat. Methods: In this study, we compared the binding of Tat protein and Human P-TEFb Tat protein complex (TPC) with phyto-steroids and terpenes to evaluate their potential for HIV-1 treatment. The docking ability of plant products with HIV-1 Tat and TPC was studied with respect to dissociation constant, geometric shape complementary score, approximate interface area, and binding energy using Patch dock and YASARA. Molecular dynamics simulation was set up to investigate the interactions of the natural compounds with Tat protein and human tat protein complex (TPC). Results: The binding energy and dissociation constant of Diosgenin, Catharanthine and Ginkgolide A with Tat and TPC were comparable to antiretroviral drugs, Maraviroc and Emtricitabine. The natural products, Diosgenin, Ginkgolide A and Catharanthine, showed the highest binding energy and were stable with Tat protein and TPC in the entire MD simulation run. Conclusion: The natural products, Diosgenin, Ginkgolide A and Catharanthine, showed highest binding energy and were stable with Tat protein and TPC in the entire MD simulation run. The binding energy and dissociation constant of Diosgenin, Catharanthine and Ginkgolide A with Tat and TPC were comparable to antiretroviral drugs, Maraviroc and Emtricitabine.

INVESTIGATIONS OF CHRONIC HEPATITIS B and C IN HIV-INFECTION

Relevance. Today, there are controversies regarding the influence of hepatitis B and C viruses on the course of HIV infection.
 Objective assess the course and outcomes of chronic hepatitis B and C in HIV-infected patients, as well as to analyze the causes of death of such patients.
 Materials and methods. A retrospective pseudorandomized study was conducted with a depth of 5 years. 114 medical records of inpatients (HIV infection in association with hepatitis B and C) were selected. The analysis of the causes of death in patients with HIV infection was carried out based on the study of autopsy materials of 21 patients.
 Results. It was established that the frequency of CHV exacerbation in III-IV clinical stages of HIV infection is significantly higher, and remission is lower than in I-II stages - (36.8±4.5) versus (7.0±2.4)% and (35.1±4.5) and (7.9±2.5)%, respectively (p<0.001). The frequency of liver cirrhosis was characterized by a clear tendency to increase with the deepening of immunodeficiency.
 The calculation of the frequency of findings in liver cirrhosis showed that in the I-II clinical stage of HIV infection, this value was equal to 0.17, and in the III-IV stage - 0.33. The relative risk of developing liver cirrhosis in HIV-infected patients was 0.52. Moreover, the probability of a fatal outcome in cirrhosis of the liver in HIV-infected patients in the I-II clinical stage was equal to 0.16, and in the III-IV stage - 0.29, with a relative risk of 0.63. The reduction in the relative risk of a fatal outcome taking into account the stage of HIV infection is 0.32.
 The average life expectancy of patients from the moment of detection of HIV antibodies was (3.4±0.6) years (from 4 months to 9 years). Such a short average life expectancy of HIV-infected patients was caused by a large number of patients diagnosed for the first time already in the IV clinical stage. In more than half (13 out of 21) the causes of death were AIDS-related diseases (61.9 %).
 Conclusions. A retrospective pseudorandomized study showed that cirrhosis of the liver in the early stages of HIV infection was registered 2.7 times less often than in patients with HIV infection in the stage of secondary diseases.
 Exacerbation of chronic hepatitis B and C is significantly more often established in the III-IV clinical stage of concomitant HIV infection. Under the same circumstances, signs of cirrhosis of the liver are more often registered, and fatal outcomes occupy one of the leading places in patients with HIV infection. This indicates the need to revise the tactics of clinical management of this category of patients.
 In 61.9 % of cases, the causes of death were AIDS-indicative diseases. Tuberculosis turned out to be the leading cause of death (46.1 %) of HIV-infected patients and was mainly in a generalized form. Toxoplasmosis (30.8 %) with damage to the brain and other organs takes the second place in terms of the frequency of fatal AIDS-indicative diseases. Meningoencephalitis of unspecified (probably herpetic) etiology was found in 23.1 % of the deceased. An important place in the structure of fatal outcomes in HIV-infected patients is occupied by the terminal stage of cirrhosis of the liver of mixed etiology - viral and alcoholic (38.1 %).

TLR3 polymorphisms in HIV infected individuals naïve to ART.

TLR3 polymorphisms affect the risk of HIV infection and modify the disease course. Consequently, we analyzed the association of TLR3 polymorphism (rs5743312, rs3775296, and rs3775291) with susceptilbity to HIV-1 acquisition and disease progression. This is a cross-sectional study. Genotyping of TLR3 polymorphisms were completed by the utilization of the PCR-RFLP technique in 153 HIV naive subjects and 158 healthy controls. A haplotype is a physical grouping of genomic variants that tend to be inherited together. The TCC haplotype was increased in HIV infected individuals compared with healthy controls (0.05% versus 0.03%). TLR3 rs3775291CT genotype was associated to the early stage of HIV infection (OR=2.19, P=0.04), with a higher occurrence in advance stage of HIV infection when contrasted with healthy controls (41.2% versus 32.3%). TLR3 rs3775296 CA genotype was likely to be associated with intermediate stage of HIV infection (19.5% versus 31.6%, OR=0.42, P=0.06). TLR3 rs5743312TT genotype was used to be greater prevalence in advanced stage of HIV infection compared with healthy controls (2.9% versus 1.9%). TLR3 rs3775296CA genotype was less prevalent in HIV subjects devouring tobacco when contrasted with non-users (9.1% versus 34.9%, OR=0.25, P=0.09). TLR3 rs3775296AA and rs3775291CT and TT genotypes have been overrepresented in HIV subjects using alcohol when contrasted with non-users (5.6% versus 1.1%, OR=1.83, P=0.67; 50.0% versus 42.2%, OR=1.84, P=0.31; 5.6% versus 3.3%, OR=2.70, P=0.50). In multivariate examination, rs5743312TT genotype showed a greater risk for HIV infection (OR=1.86, P=0.50). TLR3 rs3775291 C/T polymorphism may assist the risk of disease progression in alcohol consumers. TLR3 rs3775291 CT genotype may enhance the disease progression whereas the TLR3 rs3775296 CA genotype may protect for disease progression.

Increased HBV Coinfection and Decreased IFN-γ-Producing HBV-Specific CD8+ T Cell Numbers During HIV Disease Progression.

ObjectiveTo investigate the characteristics and mechanism of the dynamics of HBV infection with the progression of HIV disease and to explore the different responses of T lymphocytes to HBV in HIV patients in different stages of disease.MethodsWe compared the rates and characteristics of HBV coinfection between 372 early HIV-infected and 306 chronically HIV-infected men who have sex with men (MSM) in the Beijing Youan Hospital from October 2006 to November 2014. We further analysed IFN-γ-producing HBV-specific CD8+ T cells in 15 early HIV-infected individuals and 20 chronic HIV-infected individuals with HBV coinfection.ResultsTwenty-three HBsAg-positive cases were detected among the 372 early HIV-infected patients of this cohort, and the coinfection rate was 6.18%, while 35 HBsAg-positive cases were detected among the 306 chronically HIV-infected patients, with a coinfection rate of 11.44%. The coinfection rate of the chronically HIV-infected patients was significantly higher than that of the early-infected patients (p=0.0005). The median CD4+ T cell count in the early HIV infection patients was 445 cells/μL (196-1,030 cells/μL), which was higher than that in the chronic HIV infection patients [358 cells/μL (17-783 cells/μL)] (p<0.001). The proportion of IFN-γ-producing CD8+ T cells in early HIV-infected patients was significantly higher than that in chronically HIV-infected patients.ConclusionThe coinfection rate of HBV in HIV patients increases with HIV disease progression, which might be related to the decreased IFN-γ-producing HBV-specific CD8+ T cell numbers. The closely monitored HBV serum markers from the early stage of HIV infection are warranted.

Mucosal-associated invariant T cells: A cryptic coordinator in HIV-infected immune reconstitution.

Human immunodeficiency virus type 1 (HIV-1) infection causes considerable morbidity and mortality worldwide. Although antiretroviral therapy (ART) has largely transformed HIV infection from a fatal disease to a chronic condition, approximately 10%-40% of HIV-infected individuals who receive effective ART and sustain long-term viral suppression still cannot achieve optimal immune reconstitution. These patients are called immunological nonresponders, a state associated with poor clinical prognosis. Mucosal-associated invariant T (MAIT) cells are an evolutionarily conserved unconventional T-cell subset defined by expression of semi-invariant αβ T-cell receptor (TCR), which recognizes metabolites derived from the riboflavin biosynthetic pathway presented on major histocompatibility complex-related protein-1. MAIT cells, which are considered to act as a bridge between innate and adaptive immunity, produce a wide range of cytokines and cytotoxic molecules upon activation through TCR-dependent and TCR-independent mechanisms, which is of major importance in defense against a variety of pathogens. In addition, MAIT cells are involved in autoimmune and immune-mediated diseases. The number of MAIT cells is dramatically and irreversibly decreased in the early stage of HIV infection and is not fully restored even after long-term suppressive ART. In light of the important role of MAIT cells in mucosal immunity and because microbial translocation is inversely associated with CD4+ T-cell counts, we propose that MAIT cells participate in the maintenance of intestinal barrier integrity and microbial homeostasis, thus further affecting immune reconstitution in HIV-infected individuals.

Click chemistry and molecular modeling methods in computer-aided design and identification of potential HIV-1 inhibitors

An integrated approach including the click chemistry methodology, molecular docking, quantum mechanics, and molecular dynamics was used to perform the computer-aided design of potential HIV-1 inhibitors able to block the membrane- proximal external region (MPER) of HIV-1 gp41 that plays an important role in the fusion of the viral and host cell membranes. Evaluation of the binding efficiency of the designed compounds to the HIV-1 MPER peptide was performed using the methods of molecular modeling, resulting in nine chemical compounds that exhibit the high-affinity binding to this functionally important site of the trimeric “spike” of the viral envelope. The data obtained indicate that the identified compounds are promising for the development of novel antiviral drugs, HIV fusion inhibitors blocking the early stages of HIV infection.

Design and Identification of Potential HIV-1 Entry Inhibitors Using In Silico Click Chemistry and Molecular Modeling Methods

An integrated approach including the click chemistry methodology, molecular docking, quantum mechanics, and molecular dynamics was used to computer-aided design of potential HIV-1 inhibitors able to block the membrane-proximal external region (MPER) of HIV-1 gp41, which plays an important role in the fusion of the viral and host cell membranes. Evaluation of the binding efficiency of the designed compounds to the HIV-1 MPER peptide was performed using the methods of molecular modeling, resulting in nine chemical compounds exhibiting high-affinity binding to this functionally important site of the trimeric “spike” of the viral envelope. The data obtained indicate that the identified compounds are promising for the development of novel antiviral drugs, HIV fusion inhibitors blocking the early stages of HIV infection.

Moving Toward a Functional Cure for HIV-1

Abstract Despite the recent success of suppressing human immunodeficiency virus 1 (HIV-1) replication in the peripheral blood with antiretroviral therapy, elimination of the provirus from infected cells remains challenging because the virus can integrate into the host genome and become a latent proviral reservoir. The removal of these latent viral reservoirs from tissue containing infected resting memory CD4+ T cells remains a major barrier to developing a cure for HIV-1. Several novel strategies have recently been developed for curing HIV infection. These include stem cell transplantation with CCR5-Δ32 mutated cells, initial antiretroviral treatment in the very early stage of HIV infection, gene editing to excise the HIV genome or generate CCR5-mutated HIV-1-resistant cells, “shock-and-kill” to reactivate latent HIV using latency reversal agents combined with enhanced immune clearance methods, and an emerging “block-and-lock” strategy to reactivate latent HIV using latency reversal agents combined with enhanced immune clearance methods. However, the high risks and limitations to scale-up in clinics, as well as poor performance in clinical trials, have hampered these efforts. This review aims to describe the present efforts that are being made to combat HIV latency, and critically discuss the limitations and future of the cure for HIV-1.

Diagnostic and genetic markers associated with pulmonary tuberculosis in HIV-infected individuals

An important aspect of monitoring, further timely and effective treatment of HIV-TB coinfection is timely and correct diagnosis based on comprehensive clinical, laboratory and instrumental studies. Many factors play a role in the development of tuberculosis in HIV-infected people, but the key and quite important elements are the study of genetic markers and biomarkers of inflammation. A number of studies have been carried out on inflammatory markers, but IL-6, INF-γ, MIG, CRP, IL-18 remain relevant and insufficiently studied in coinfection. A comprehensive study of them will be important in the screening of HIV-TB coinfection). Determining the presence of (SNP) rs4331426 located in chromosome 18q11.2 in HIV-infected and AIDS patients will solve the issue of predisposition to the development of tuberculosis in the early stages of HIV infection and contribute to the development of further tactics of patients treatment and management.