Current HIV Research

The aim of the present investigation is to identify effective anti-HIV drugs through the in-silico virtual screening of the coumarin pharmacophore with or without substituents. Virtual screening started with target identification through computation docking and interactions, binding affinity through molecular dynamics, and the ADMET profile through the use of various enzymes. The target study suggests that the target is involved in various stages of HIV replication and in determining the ways in which non-nucleoside reverse transcriptase inhibitors (RTIs) influence it. The interaction pattern and simulation study conclude the specific affinity of coumarin pharmacophore to the HIV's reverse transcriptase enzyme, especially 3HVT. Moreover, the amide linkage worked as a synergistic bridge to provide more interaction to the pharmacophore. The initial results led to the determination of 83 virtual amide-like molecules, which were screened through docking and MD studies (100 ns) on the best-suited enzyme HIV's reverse transcriptase enzyme, such as PDB ID "3HVT". The virtual screening study revealed the high affinity of compounds 7d and 7e with the lowest IC₅₀ values of 0.729 and 0.658 µM; moreover, their metabolism pattern study, toxicity, and QED values in a range of 0.31-0.40 support a good drug candidate. The two compounds were also synthesized and characterized for future in vitro and in vivo studies. The in silico-based descriptor of compounds 7d and 7e indicates the potential future and provides the best two molecules and their synthetic route for the development of a more effective drug to combat HIV/AIDS epidemics.

Background:In the Hebei province, Human Immunodeficiency Virus type one (HIV-1) recombinant strains of subtypes B, C, and CRF01_AE are emerging very rapidly and diversely.

Objective:In order to confirm the characteristics of novel recombination forms, we aimed to analyze HIV-1 Near-full-length Genome sequences (NFLGs) obtained from three Men who have Sex with Men (MSM) in this study.

Methods:Phylogenetic trees were constructed and breakpoints analysis was performed based on the NFLGs and each gene fragment to examine the gene recombination patterns of three new HIV-1 NFLGs.

Results:HIV-1 subtypes CRF01_AE and B were combined to generate the recombinant structures of the NFLGs 610 and 687. CRF01_AE, B, and C were combined to generate the recombinant structures of the NFLG 825. According to the NFLG phylogenetic tree, the NFLG 825 clustered with CRF65_cpx and the NFLGs 610 and 687 clustered with CRF68_01B. The recombination breakpoints analysis revealed that the recombination pattern of the NFLGs 610 and 687 was the insertion of subtype B fragment into the CRF01_AE backbone. Subregions I, II, and III were derived from CRF01_AE, subtype B, and CRF01_AE, respectively. The recombination pattern of the NFLG 825 contained ten fragments of subtypes CRF01_AE, C, and B. Finally, the above factors were formed using phylogenetic trees and breakpoints analysis, which were combined to get two CRF68_01B forms and one CRF65_cpx form.

Conclusion:Our findings have suggested that it is crucial to keep an eye on the genetic diversity of HIV-1 in Hebei province.

Introduction:People with the human immunodeficiency virus (PWH) who were diagnosed long ago are more prone to age-related conditions and comorbidities than the general population. We hypothesized that older PWH have endocrine abnormalities that may influence the patient’s health status.

Methods:Mean hormonal values across the thyrotropic, somatotropic, corticotropic, and gonadal axis, and percentage of subjects with abnormal values, were compared between PWH aged ≥50 years (n=30) and people without HIV (n=30) (Over50 cohort). Clinical factors were also analyzed as independent variables.

Results:PWH had a higher prevalence of comorbidities (36.67% PWH and 20.69% controls had ≥3 comorbidities). Male PWH exhibited lower estradiol levels than male controls (29.75±7.68 pg/mL vs. 35.45±10.04 pg/mL; p=0.0041). Abnormal concentrations of testosterone were found in 35% of male PWH compared to 55% of male controls (mostly above reference values). Cortisol levels were significantly lower among PWH (9.97±4.33 µg/dL vs. 13.56±3.39 µg/dL; p=0.002); 16.6% of PWH exhibited abnormally low levels (<5 µg/dL), compared to 0% of controls, and 3 PWH met criteria for a definitive diagnosis of adrenal insufficiency (<3.6 µg/dL). For the somatotropic axis, growth hormone (GH) levels were significantly lower in male PWH than in controls (p=0.0394). No significant differences were found in relation to the thyroid axis.

Conclusion:Hormones are generally similar between the chronic PWH who are receiving ART treatment and the general control population, except for cortisol in both sexes and testosterone and estradiol in men. Some special attention should be given to cortisol in PWH due to a presumably higher risk of adrenal complications.

Background:Virological failure (VF) among children remains concerning, with high risks of HIV drug resistance (HIVDR) emergence and increased disease progression. Therefore, monitoring of viral non-suppression and emerging HIVDR is crucial, especially in the frame of sociopolitical unrest.

Objective:The study sought to determine the prevalence of VF and evaluate the acquired HIVDR and viral genetic diversity among children in the northwest region of Cameroon during the ongoing sociopolitical crisis.

Methods:A cross-sectional facility-based study was conducted among HIV-infected children aged ≤18 years, receiving antiretroviral therapy (ART) in urban and rural settings of Northwest Cameroon, from November 2017 through May 2018. Viral load (VL) was done using the Abbott m2000RealTime. Unsuppressed VL was defined as viral load ≥1,000 copies/ml. HIVDR testing was performed by sequencing of HIV-1 protease-reverse transcriptase at the Chantal Biya International Reference Center (CIRCB) using an in-house protocol. Drug resistance mutations (DRM) were interpreted using Stanford HIVdbv8.5 and phylogeny using MEGAv.6. Data were compared between urban and rural areas with p(<0.05 considered statistically significant.

Results:A total of 363 children were recruited, average age of 12 years (urban) and 8 years (rural). VL coverage was 100% in the urban setting and 77% in the rural setting. Overall, VF was 40.5% (39% [130/332] in the urban setting and 41% (13/31) in the rural setting; p=0.45). Overall, viral undetectability (defined as VP<00 copies/ml) was 45.5% (46% (urban) and 45% (rural); p=0.47). Among those experiencing confirmed virological failure and who were successfully sequenced (n=35), the overall rate of HIVDR was 100% (35/35). By drug class, HIVDR rates were 97.1% (34/35) for non-nucleoside reverse transcriptase inhibitors (NNRTIs), 97.1% (34/35) for NRTIs and 17.1% (6/35) for protease inhibitors (22.7% (5/22) in the urban setting and 7.7% [1/13] in the rural setting). CRF02_AG was the most prevalent viral clade (75%), followed by other recombinants (09_cpx, 11_cpx, 13_cpx, 22_01A1, 37_cpx) and pure subtypes (A1, F2, G, H).

Conclusion:In this population of children and adolescents living with HIV in a context of socio-political instability in the North-West region of Cameroon, rates of viral non-suppression are high, and accompanied by HIVDR selection. Our suggests the need for a more differentiated care of these CAHIV, especially those in these regions faced with significant socio-economic and health impacts due to the ongoing crisis.