Current HIV Research - Volume 21, Issue 2, 2023

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: The genetic diversity in HIV-1 genes affects viral pathogenesis in HIV-1 positive patients. Accessory genes of HIV-1, including vpu, are reported to play a critical role in HIV pathogenesis and disease progression. Vpu has a crucial role in CD4 degradation and virus release. The sequence heterogeneity in the vpu gene may affect disease progression in patients, therefore, the current study was undertaken to identify the role of vpu in patients defined as rapid progressors. Objective: The objective of the study was to identify the viral determinants present on vpu that may be important in disease progression in rapid progressors. Methods: Blood samples were collected from 13 rapid progressors. DNA was isolated from PBMCs and vpu was amplified using nested PCR. Both strands of the gene were sequenced using an automated DNA Sequencer. The characterization and analysis of vpu was done using various bioinformatics tools. Results: The analysis revealed that all sequences had intact ORF and sequence heterogeneity was present across all sequences and distributed all over the gene. The synonymous substitutions, however, were higher than nonsynonymous substitutions. The phylogenetic tree analysis showed an evolutionary relationship with previously published Indian subtype C sequences. Comparatively, the cytoplasmic tail(77 – 86) showed the highest degree of variability in these sequences as determined by Entropy- one tool. Conclusion: The study showed that due to the robust nature of the protein, the biological activity of the protein was intact and sequence heterogeneity may promote disease progression in the study population.

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.

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.

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.

Introduction: Increasing evidence suggests that microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have emerged as attractive targets in viral infections, including Human immunodeficiency virus (HIV). Objective: To deepen the understanding of the molecular mechanisms that lead to HIV and provide potential targets for the future development of molecular therapies for its treatment. Methods: Four miRNAs were selected as candidates based on a previous systematic review. A combination of bioinformatic analyses was performed to identify their target genes, lncRNAs and biological processes that regulate them. Results: In the constructed miRNA–mRNA network, 193 gene targets are identified. These miRNAs potentially control genes from several important processes, including signal transduction and cancer. LncRNA-XIST, lncRNA-NEAT1 and lncRNA-HCG18 interact with all four miRNAs. Conclusion: This preliminary result forms the basis for improving reliability in future studies to fully understand the role these molecules and their interactions play in HIV.

Background: Previous studies have implicated human adenovirus 36 (Adv36) as a potential contributor to overweight and obesity. People living with HIV have an altered body composition compared to healthy individuals. There is still no evidence to confirm the relationship of Adv36 as one of the causes of lipohypertrophy. The main objective of this study was to verify the viral Adv36 infection as a factor associated with the presence of lipohypertrophy in HIV-infected individuals. Methods: A case-control study on people with HIV treated at a specialized public health service in southern Brazil. Subjects underwent interviews, diagnostic tests, and anthropometry to determine lipodystrophy and its classification. Demographic and clinical data were examined to investigate the presence of Adv36. The cases were participants with lipohypertrophy, and the controls were eutrophic participants. Results: 101 participants were included (38 cases and 63 controls), and the frequency of Adv36 infection was 10.9%. There was a statistically significant association between lipohypertrophy and the female sex (p < 0.001), and a trend for the presence of Adv36 (p = 0.059) and lipohypertrophy. After adjustment for confounders, Adv36 has not considered an independent risk factor for lipohypertrophy. Lower levels of glucose were associated with Adv36 infection. Conclusion: There was a significant association between lipohypertrophy and the female sex, and no association with lipohypertrophy and Adv36, perhaps due to the small sample size.