Current HIV Research最新文献

Objectives: This study aimed to analyze the antiretroviral drug resistance in antiretroviral treatment-naïve HIV-positive patients in the Aegean Region of Turkey from 2012 to 2019.

Methods: The study included 814 plasma samples from treatment-naïve HIV-positive patients. Drug resistance analysis was performed by Sanger sequencing (SS) between 2012-2017 and by next-generation sequencing sequencing (NGS) between 2018-2019. SS was used to analyze resistance mutations in the protease (PR) and reverse transcriptase (RT) gene regions using a ViroSeq HIV-1 Genotyping System. PCR products were analyzed with an ABI3500 GeneticAnalyzer (Applied Biosystems). The sequencing of the HIV genome in the PR, RT, and integrase gene regions was carried out using MiSeq NGS technology. Drug resistance mutations and subtypes were interpreted using the Stanford University HIV-1 drug resistance database.

Results: Transmitted drug resistance (TDR) mutation was detected in 34/814 (4.1 %) samples. Nonnucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), and protease inhibitor (PI) mutations were identified in 1.4 % (n =12), 2.4 % (n =20), and 0.3 % (n = 3) of samples, respectively. The most common subtypes were B (53.1 %), A (10.9%), CRF29_BF (10.6%), and B + CRF02_AG (8,2%). The most common TDR mutations were E138A (3.4%), T215 revertants (1.7%), M41L (1.5%), and K103N (1.1%).

Conclusion: Transmitted drug resistance rate in the Aegean Region is compatible with national and regional data. Routine surveillance of resistance mutations may guide the safe and correct selection of initial drug combinations for antiretroviral therapy. The identification of HIV-1 subtypes and recombinant forms in Turkey may contribute to international molecular epidemiological data.

HIV is one of the world's most devastating viral infections and has claimed tens of millions of lives worldwide since it was first identified in the 1980s. There is no cure for HIV infection. However, with tremendous progress in HIV diagnosis, prevention, and treatment, HIV has become a manageable chronic health disease. CCR5 is an important coreceptor used by HIV to infect target cells, and genetic deficiency of the chemokine receptor CCR5 confers a significant degree of protection against HIV infection. In addition, since CCR5 deficiency does not appear to cause any adverse health effects, targeting this coreceptor is a promising strategy for the treatment and prevention of HIV. Monoclonal antibodies are frequently used as therapeutics for many diseases and therefore are being used as a potential therapy for HIV-1 infection. This review reports on CCR5 antibody research in detail and describes the role and advantages of CCR5 antibodies in HIV prevention or treatment, introduces several main CCR5 antibodies, and discusses the future strategy of antibody-conjugated nanoparticles including the potential challenges. CCR5 antibodies may be a novel therapy for treating HIV infection effectively and could overcome the limitations of the currently available options.

Background: Pre-exposure prophylaxis (PrEP) has recently been introduced in Mexico. Still, there are no data exploring the frequency and related factors of willingness to recommend it among non-physician health providers (Non-PHP).

Objective: Compare awareness, knowledge, attitudes, and willingness to recommend PrEP and combined HIV prevention among Mexican non-PHP.

Methods: We conducted an online survey assessing data on sociodemographics, awareness, knowledge, and willingness to recommend PrEP. We performed a descriptive and comparative analysis between those willing and unwilling to recommend PrEP.

Results: The final sample was 142 participants, and most were willing to recommend PrEP (79.6%). This group reported higher confidence in evaluating PrEP eligibility (90.1%, p<.01), identified that populations at increased risk of HIV would benefit the most from PrEP (p≤.05), and considered the lack of professionals to prescribe PrEP as a barrier (60.7%, p<.01), and were more likely to recommend post-exposure prophylaxis (95.6%, p<.01) compared to those not willing to recommend PrEP. On the other hand, more non-PHP unwilling to recommend PrEP considered that behavioral interventions should be prioritized over PrEP (89.3%, p<.05), PrEP should not be provided in public services (43.3%, p<.001), and the demand of PrEP users would be low to maintain PrEP as a public policy (34.5%, p<.05).

Conclusion: A high proportion of Mexican non-PHP is willing to recommend PrEP. Still, it is necessary to increase their PrEP knowledge, including improving their prejudices and beliefs, so they can identify and refer potential PrEP users based on their risk of getting HIV.

Background: This study compared and evaluated the performance of a commercially available HIV POC rapid test with assays commonly used in clinical laboratories, including enzymelinked immunosorbent assay (ELISA), western blot (WB), and reverse transcription-polymerase chain reaction (RT-PCR).

Methods: 500 patients' samples were detected by the POC rapid test and clinically common tests (WB, ELISA, and RT-PCR) to compare detection performance, test time, and test cost.

Results: Taking the WB results as the gold standard, the results of RT-PCR were completely consistent with WB. The concordance of ELISA and POC with WB was 82.00% and 93.80%, respectively, with statistically significant differences (p<0.05).

Conclusion: This study provides evidence that rapid HIV POC assays are superior to ELISA and that WB and RT-PCR have equal detection performance in detecting HIV. As a result, a rapid and costeffective HIV definition process based on the POC assays can be proposed.

Retrovirus integration is an obligatory step for the viral life cycle, but large amounts of unintegrated DNA (uDNA) accumulate during retroviral infection. For simple retroviruses, in the absence of integration, viral genomes are epigenetically silenced in host cells. For complex retroviruses such as HIV, preintegration transcription has been found to occur at low levels from a large population of uDNA even in the presence of host epigenetic silencing mechanisms. HIV preintegration transcription has been suggested to be a normal early process of HIV infection that leads to the syntheses of all three classes of viral transcripts: multiply-spliced, singly-spliced, and unspliced genomic RNA; only viral early proteins such as Nef are selectively translated at low levels in blood CD4 T cells and macrophages, the primary targets of HIV. The initiation and persistence of HIV preintegration transcription have been suggested to rely on viral accessory proteins, particularly virion Vpr and de novo Tat generated from uDNA; both proteins have been shown to antagonize host epigenetic silencing of uDNA. In addition, stimulation of latently infected resting T cells and macrophages with cytokines, PKC activator, or histone deacetylase inhibitors has been found to greatly upregulate preintegration transcription, leading to low-level viral production or even replication from uDNA. Functionally, Nef synthesized from preintegration transcription is biologically active in modulating host immune functions, lowering the threshold of T cell activation, and downregulating surface CD4, CXCR4/CCR5, and HMC receptors. The early Tat activity from preintegration transcription antagonizes repressive minichromatin assembled onto uDNA. The study of HIV preintegration transcription is important to understanding virus-host interaction and antagonism, viral persistence, and the mechanism of integrase drug resistance. The application of unintegrated lentiviral vectors for gene therapy also offers a safety advantage for minimizing retroviral vector-mediated insertional mutagenesis.

Viruses belong to the class of micro-organisms that are well known for causing infections in the human body. Antiviral medications are given out to prevent the spread of disease-causing viruses. When the viruses are actively reproducing, these agents have their greatest impact. It is particularly challenging to develop virus-specific medications since viruses share the majority of the metabolic functions of the host cell. In the continuous search for better antiviral agents, the United States Food and Drug Administration (USFDA) approved a new drug named Evotaz on January 29, 2015 for the treatment of human immunodeficiency virus (HIV). Evotaz is a combined once-daily fixed drug, containing Atazanavir, an HIV protease inhibitor, and cobicistat, an inhibitor of the human liver cytochrome P450 (CYP) enzyme. The medication is created such that it can kill viruses by concurrently inhibiting protease and CYP enzymes. The medicine is still being studied for a number of criteria, but its usefulness in children under the age of 12 is currently unknown. The preclinical and clinical characteristics of Evotaz, as well as its safety and efficacy profiles and a comparison of the novel drug with antiviral medications presently available in the market, are the main topics of this review paper.

Background: The intrinsic apoptotic pathway of neutrophils in Human Immunodeficiency Virus (HIV) infection results in spontaneous neutrophil death. There is a scarcity of data regarding the gene expression of an intrinsic apoptotic pathway of neutrophils in HIV patients.

Objective: The objective of this study was to observe the differential expression of some important genes involved in the intrinsic apoptotic pathway of HIV patients, including those who were receiving antiretroviral therapy (ART).

Methods: Blood samples were collected from asymptomatic, symptomatic, ART receiver HIV patients, and healthy individuals. Total RNA was extracted from neutrophils and subjected to quantitative real-time PCR assay. CD4⁺T cells and an automated complete blood count were performed.

Results: Among the asymptomatic, symptomatic, and ART receiver HIV patients (n=20 in each group), median CD4⁺T counts were 633, 98, and 565 cells/ml, and the length of HIV infection in months (± SD) was 24.06 ± 21.36, 62.05 ± 25.51, and 69.2 ± 39.67, respectively. Compared with healthy controls, intrinsic apoptotic pathway genes, i.e., BAX, BIM, Caspase-3, Caspase-9, MCL-1, and Calpain-1, were upregulated to 1.21 ± 0.33, 1.8 ± 0.25, 1.24 ± 0.46, 1.54 ± 0.21, 1.88 ± 0.30, and 5.85 ± 1.34 fold in the asymptomatic group, and even more significantly, i.e., 1.51 ± 0.43, 2.09 ± 1.13, 1.85 ± 1.22, 1.72 ± 0.85, 2.26 ± 1.34, and 7.88 ± 3.31 fold in symptomatic patients, respectively. Despite CD4⁺ T-cell levels increased in the ART receiver group, these genes did not approach the level of healthy or asymptomatic and remained significantly upregulated.

Conclusion: The genes involved in the intrinsic apoptotic pathway in circulating neutrophils during HIV infection were stimulated in vivo, and ART reduced the expression of those upregulated genes but did not return to the level of asymptomatic or healthy individuals.

Background: Periodontitis (PDT) has gained attention in the literature with the increase in life expectancy of people living with HIV on combined antiretroviral therapy (cART). Thus, the search for inflammatory biomarkers could be useful to understand the pathophysiology of chronic oral diseases in the cART era.

Objective: The aim of this study was to evaluate the impact of non-surgical periodontal therapy (NSPT) on clinical parameters of PDT, Candida spp. count and expression of lactoferrin (LF) and histatin (HST) in saliva and gingival crevicular fluid (GCF) of HIV-infected patients.

Methods: Bleeding index (BI), probing depth (PD), clinical attachment level (CAL), colonyforming units (CFUs) of Candida spp, and LF and HST levels were measured in saliva and GCF of both groups at three different times: baseline (before treatment), and 30 and 90 days after the NSPT. Clinical, mycological and immunoenzymatic analyses were also performed.

Results: Twenty-two HIV-infected patients and 25 non-HIV-infected patients with PDT participated in the study. NSPT was effective in improving periodontal clinical parameters, including ≤ 4 sites with PD ≤ 5mm and BI ≤ 10%. Significant change in oral Candida spp. count occurred neither between the two groups nor after NSPT. And the salivary and GCF levels of LF and HST were not influenced by the NSPT; by contrast, except for salivary LF, HST and LF were shown to exhibit significantly higher levels in HIV-infected than in non-HIV-infected patients.

Conclusion: NSPT was effective in improving periodontal disease parameters in HIV-infected patients, but did not affect LF and HST expression in saliva and GCF of HIV-infected patients.

Introduction: Toxoplasma gondii is an obligate intracellular protozoan that can infect almost all warm-blooded animals, including humans. Patients with co-infection with toxoplasmosis and HIV have a 30-40% risk of developing toxoplasmosis encephalitis. This study aimed to describe the epidemiology and burden of Toxoplasma gondii in HIV-infected individuals in Iran.

Methods: We searched the five English databases (Science Direct, PubMed, Scopus, Ovid, Embase, and Cochrane) and four Persian databases (Scientific Information Database (SID), Iran Medex, Iran Doc, and Magiran) with the terms of (Toxoplasma gondii OR "toxoplasmosis") AND (HIV OR "AIDS" OR immunodeficiency OR acquired immune deficiency syndrome) AND (Seroprevalence) AND (Seroepidemiologic Studies) AND (Elisa OR IgG) AND (PCR) AND (Iran) by two authors up to Feb 2021. Studies were included if they investigated people with HIV infection and presented data that allowed us to establish the prevalence of Toxoplasma gondii infection in Iran.

Results: According to the inclusion/exclusion criteria, 15 studies were selected. A total number of 2275 HIV-infected individuals were tested and evaluated for toxoplasmosis from 2005 up to 2018 in different regions of Iran. The weighted overall prevalence of toxoplasmosis in HIV-infected individuals with Elisa was obtained using a random-effects model, which was estimated at 47% (95% CI = 31% - 62%). Also, the Weighted overall prevalence of toxoplasmosis in HIV-infected individuals with PCR was obtained using a random-effects model, which was estimated at 7% (95% CI = 3% - 12%).

Conclusion: According to the results of this study, it can be clearly understood that a large population of HIV patients living in Iran have toxoplasmosis. Therefore, due to the high susceptibility of these groups to toxoplasmosis, healthcare professionals must consider measures such as training in the ways of transmission and prevention of the infection to this high-risk group in order to reduce the risk of infection.

Objective: It has been reported that carnitine deficiency is observed in various viral infections and in the follow-up of the prognosis of some diseases. In this cross-sectional study, we aimed to determine how carnitine ester derivatives change in HIV-positive patients.

Materials and methods: In this study, 25 HIV-infected patients who applied to Harran University Faculty of Medicine Education Research and Practice Hospital Infectious Diseases and Clinical Microbiology Outpatient Clinic and who did not receive any antiretroviral treatment, as well as 25 healthy volunteers were included in the study. Carnitine ester levels in serum samples were measured by Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) method (Shimadzu North America, Columbia, MD, USA).

Results: While suberoylcarnitine (C8DC), myristoleylcarnitine (C14:1), tetradecadienoylcarnitine (C14:2), palmitoleylcarnitine (C16:1), and linoleylcarnitine (C18:2) levels in HIV(+) patients were quite low compared to the control group, tiglylcarnitine (C5:1) levels were high (p ≤ 0.05). In addition, C5:1 and C14:2 index parameters according to VIP score, and C5:1 and C14:1/C16 index parameters according to ROC analysis were determined as markers with high potential to distinguish HIV(+) patients from healthy volunteers.

Conclusion: This study showed that levels of acylcarnitine derivatives might be altered in HIV(+) patients, and the results obtained may contribute to a better understanding of carnitine metabolism.