Current HIV Research最新文献

Objective: The study aimed to compare the prevalence of surveillance HIV drug resistance mutations (SDRMs) across the main federal districts of Russia.

Methods: A pooled analysis was conducted to examine data on HIV primary drug resistance (HIV PrimDR). The analysis was based on published results primarily from Russian regional clinical and scientific laboratories, covering a span of 20 years.

Results: The findings indicate that three surveyed regions, namely Central, Far Eastern, and Volga, exhibit a low level of HIV PrimDR prevalence (not exceeding 5%), and this prevalence does not show a tendency to increase. In contrast, three major regions, namely Northwestern, Southern, and Siberian, demonstrate a significant and progressive increase in HIV PrimDR prevalence, with recent values surpassing 10%.

Conclusion: Consequently, it was concluded that a change in the HIV treatment strategy in these regions is imperative, emphasizing the need to expedite the transition to the utilization of secondgeneration integrase inhibitors.

Background: Alkaloids are nitrogen-containing compounds that are naturally occurring and have a variety of biological activities, including antimicrobial properties. In this study, the authors used a molecular docking approach to evaluate the anti-HIV potential of 64 alkaloids.

Methods: The authors used the Molegro Virtual Docker software to dock the alkaloids into the active sites of three HIV enzymes: protease, integrase, and non-nucleoside reverse transcriptase (NNRT). The docking scores were used to assess the potential of the alkaloids to inhibit the enzymes.

Results: The results showed the alkaloids to have good potential to inhibit the enzymes. Tubocurarine and reserpine were found to be the most potent alkaloids, with docking scores of -123.776 and - 114.956, respectively.

Conclusion: The authors concluded that tubocurarine and reserpine could be further promoted as potential lead molecules for the development of new anti-HIV drugs.

Introduction: A "Shock and Kill" strategy has been proposed to eradicate the HIV latent viral reservoir. Effective Latency Reversal Agents (LRA) are a key requirement for this strategy. The search for LRAs with a novel mechanism of action is ongoing. This is the first study to propose aptamers for the reactivation of HIV.

Objective: The purpose of this study was to identify an aptamer that potentially reactivates HIV via the NF-κβ pathway, specifically by binding to IkB and releasing NF-κβ.

Methods: Aptamer selection was performed at Aptus Biotech (www.aptusbiotech.es), using ikB human recombinant protein with His tag bound to Ni-NTA agarose resin using the SELEX procedure. Activation of NF-κβ was measured by SEAP Assay. HIV reactivation was measured in JLat cells using a BD FACS-Canto™ II flow cytometer. All flow cytometry data were analyzed using Kaluza analyzing software.

Results: Clones that had equivalent or greater activation than the positive control in the SEAP assay were regarded as potential reactivators of the NF-κβ pathway and were sequenced. The three ikb clones namely R6-1F, R6-2F, and R6-3F were found to potentially activate the NF-κβ pathway. Toxicity was determined by exposing lymphocytes to serial dilutions of the aptamers; the highest concentration of the aptamers that did not decrease viability by > 20% was used for the reactivation experiments. The three novel aptamers R6-1F, R6-2F, and R6-3F resulted in 4,07%, 6,72% and 3,42% HIV reactivation, respectively, while the untreated control showed minimal (<0.18%) fluorescence detection.

Conclusion: This study demonstrated the reactivation of latent HIV by aptamers that act via the NF-κβ pathway. Although the effect was modest and unlikely to be of clinical benefit, future studies are warranted to explore ways of enhancing reactivation.

Introduction: Comorbidities are increasing in people living with HIV (PLHIV), and different treatment options have advantages and disadvantages. It is important to compare information from real-life treated cases. The aim of this study was to retrospectively evaluate the data on efficacy and clinical and laboratory findings during different antiretroviral therapies.

Methods: Retrospective file data of 47 PLHIV using Dolutegravir and Lamivudine (3TC/DTG), Tenofovir Alafenamide Emtricitabine and Elvitegravir Cobicistat (EVG/c/TAF/FTC) and Tenofovir Disoproxil Fumarate and Emtricitabine and Efavirenz (EFV/FTC/TDF) were analyzed. Data of the patients at baseline and 12 months after antiretroviral therapy (ART) were compared.

Results: About 47 PLHIV were included in the study. Of the patients, 22 (46.8%) were in the 3TC/DTG group, 19 (40.4%) in the EVG/c/TAF/FTC, and 6 (12.8%) in the EFV/FTC/TDF group. After 12 months of treatment, BMI, HIV-RNA, CD4, WBC, hemoglobin, MCV, PDW, RDW, platelet count, creatinine, eGFR, HDL, AST, glucose values of the 3TC/DTG group were significantly different (p<0.05). After 12 months of treatment, BMI, HIV-RNA, CD4 count, MCV, creatinine, eGFR, HDL, LDL, TG, TC, AST, and HOMA-IR values of the EVG/c/TAF/FTC treatment group were significantly different (p<0.05). After 12 months of treatment, HIV RNA, total bilirubin, and LDL values in the EFV/FTC/TDF treatment group were statistically different (p<0.05).

Conclusion: All treatment groups showed a decrease in HIV-RNA and an increase in CD4 at the end of one year. While CD4 elevation is lower in EFV recipients than in integrase inhibitor (INSTI) recipients, weight gain is higher in INSTI recipients. While the lipid profile was more positively affected in the 3TC/DTG group, lipid profiles were more negatively affected in the EVG/c/TAF/FTC group, although liver and kidney functions were preserved.

Background: The persistence of HIV mutations and the existence of multidrug resistance have produced an opportunity for an array of innovative anti-HIV medicines with a variety of structures that target HIV key enzymes.

Objective: The goal of this work was to find a new class of anti-HIV drugs founded on HIV integrase inhibitor pharmacophores.

Methods: A novel class of 2-hydroxy acetophenone analogs featuring substituted benzamide or N-phenylthiourea groups was designed and synthesized based on the general pharmacophore of HIV-1 integrase inhibitors (INs).

Results: Most of the synthesized analogs were found to be moderately active against the virus, with EC₅₀ values ranging from 40 to 140 μM. Additionally, it was found that most of the compounds presented no considerable cytotoxicity (CC₅₀ > 500 μΜ). The most potent compounds substituting with 4-fluorobenzamide (compound 7) and 4-methylbenzamide (compound 9) rings inhibited the HIV-1 replication by EC₅₀ values of 40 and 45 μΜ, respectively. Docking studies using the crystallographic data available for PFV IN indicated that the Mg²⁺ coordination might be the possible mechanism of the anti-viral activity.

Conclusion: Our findings proved that the synthesized analogs may suggest a very good basis for the development of new anti-HIV-1 agents.

Background: Retroviruses are described as a risk factor for chronic neuropathy. However, it is still unknown if they can work as amyotrophic lateral sclerosis triggers. Over the years, some cases of this association have been described with heterogenous disclosures.

Case representation: This study aimed to report a case of HIV and ALS-like neuropathy and briefly discuss peculiarities of clinical aspects, such as physiopathology and treatment options. The patient underwent neurological examination associated with blood tests, electromyography, analysis of cerebrospinal fluid, and imaging studies.

Discussion: A non-systematic review was performed in major databases regarding the topic. The case presented mixed upper and lower motor neuron signs and was framed as a probable case of ALS following the present criteria.

Conclusion: After a short follow-up and viral load cleansing, neurological stabilization was achieved.

Background: During HIV genotypic drug resistance testing of patient samples in Baoding, Hebei Province, China, in 2022, a recombinant fragment was detected in the pol region of an HIV-1 strain.

Objective: The objective of the study was to analyze the near full-length genome of a novel HIV-1 CRF01_AE/CRF07_BC recombinant with a complex genomic structure.

Methods: Viral RNA was extracted from the blood of the infected individual and reverse transcribed to cDNA. Two overlapping segments of the HIV-1 genome were amplified using a nearendpoint dilution method and sequenced. Recombinant breakpoints were determined using RIP, jpHMM, and SimPlot 3.5.1 software. MEGA 6.0 software was used to construct a neighbor-joining phylogenetic tree.

Results: We obtained the near full-length genome sequence (8680 bp) of a novel HIV-1 CRF01_AE/CRF07_BC recombinant. Recombination analysis showed that the genome comprised at least 12 overlapping segments, including six CRF07_BC and six CRF01_AE segments, with CRF07_BC as the backbone. The emergence of CRF01_AE/CRF07_BC recombinant strains indicated that HIV-1 co-infection is common. However, the increasing genetic complexity of the HIV-1 epidemic in China warrants continued investigation.

Conclusion: The increase in CRF01_AE/CRF07_BC recombinant viruses suggests that HIV-1 has a high genetic mutation rate in Hebei, China. This highlights the need for close monitoring of HIV-1 molecular epidemiologic changes to provide accurate, up-to-date information for effective disease control.

Objective: To evaluate the epidemiological profile and clinical findings of newly diagnosed HIV-infected patients in terms of changing trends over 16 years.

Methods: A total of 748 patients (mean ± SD age: 34 ± 11.6 years, 88.9% were males) newly diagnosed with HIV/AIDS at a tertiary care hospital located in Istanbul province between 2002 and 2017 were included in this retrospective study. Data on sociodemographic characteristics, potential routes of transmission, the reason for HIV testing, time from diagnosis to treatment onset, and the HIV RNA values and CD4⁺ T cell count (at diagnosis and treatment onset) were recorded in each patient and compared between the diagnoses made within the 2002-2009 (n = 141) vs. 2010-2017 (n = 607) periods.

Results: When compared to HIV diagnoses within the 2002-2009 period, the diagnoses made within the 2010-2017 period were associated with a significantly higher percentage of males (78.7 vs. 91.3%, p < 0.001), 18-29 years age group (23.6% vs. 35.5%, p = 0.029), singles (34.0 vs. 49.6%, p = 0.004), university graduates (9.9 vs. 23.4%, p < 0.001) and students (0.7 vs. 8.2%, p < 0.001) along with an increased likelihood of voluntary testing (6.4 vs. 15.2%, p = 0.048) and a lower percentage of heterosexual individuals (63.8 vs. 47.0%, p < 0.001). Sexual contact (88.0%) was the leading transmission route, and the presence of complaints (44.3%) was the leading reason for HIV testing. Overall, the time from diagnosis to treatment onset was a median 1 month (range, 1 to 97 months), and the median HIV RNA level at the time of diagnosis was 208065 copies/mL with no significant difference between study periods. The diagnoses within the 2010-2017 vs. 2002-2009 period were associated with significantly higher median (min-max) CD4⁺ T cell counts (378(0-2522) vs. 319(4-1270) cells/mm³, p < 0.001) and a lower percentage of patients with CD4⁺ T cell count < 200 cells/mm³ (22.1 vs. 39.0%, p = 0.002) at the time of diagnosis.

Conclusion: In conclusion, our findings on the epidemiological profile and clinical characteristics of newly diagnosed HIV patients over 16 years (2002-2017) in a tertiary care center in Turkey revealed a considerable increase in the number of new diagnoses, an improved earlier diagnosis and a change in epidemiologic profile over the years with increased likelihood of disease to be more commonly diagnosed among males, 18-29 years age group and MSM.

Aim: Weight gain with the use of dolutegravir, bictegravir, and tenofovir alafenamide for antiretroviral therapy has been reported. However, studies on changes in body composition and the leptin/adiponectin ratio after antiretroviral therapy initiation are limited. These factors are important because they can be used as indicators of metabolic syndrome and cardiovascular disease risk.

Introduction: This study aimed to investigate the changes in waist circumference, body composition, and adipokine levels after the initiation of antiretroviral therapy consisting of dolutegravir, bictegravir, and tenofovir alafenamide and evaluate the relationships between these parameters in Japanese patients living with human immunodeficiency virus.

Methods: This is a single-center, prospective, observational study. Waist circumference, body composition, and adipokine levels were measured at baseline and 12 months after antiretroviral therapy initiation in antiretroviral therapy-naive Japanese patients living with human immunodeficiency virus. Body composition was determined by bioelectrical impedance analysis.

Results: We included 11 patients (10 bictegravir/TAF/emtricitabine, 1 dolutegravir/lamivudine) in this study. The results showed no significant changes in waist circumference and body composition among the patients. The leptin/adiponectin ratio and serum leptin levels significantly increased after antiretroviral therapy initiation. Changes in waist circumference, fat mass, and visceral fat area showed a strong positive correlation.

Conclusion: The leptin/adiponectin ratio increased following antiretroviral therapy initiation. The waist circumference measurement can be a simple, inexpensive, and useful method to identify changes in fat mass and visceral fat area after initiation of antiretroviral therapy.