The appearance of resistance against new treatments and the fact that HIV-1 can infect various cell types and develop reservoirs and sanctuaries makes it necessary to develop new therapeutic approaches to overcome those failures. Studies of cytotoxicity, genotoxicity, complexes formation, stability, resistance, release and particle size distribution confirmed that G2-SN15-PEG, G3-SN31-PEG, G2-SN15-PEG-FITC and G3-SN31-PEG-FITC dendrimers can form complexes with miRNAs being biocompatible, stable and conferring protection to these nucleic acids. Confocal microscopy and flow cytometry showed effective delivery of these four dendrimers into the target cells, confirming their applicability as delivery systems. Dendriplexes formed with the dendrimers and miRNAs significantly inhibited HIV-1 infection in PBMCs. These dendrimers are efficient delivery systems for miRNAs and they specifically and significantly improved the anti-R5-HIV-1 activity of these RNA molecules.

/pdf/promising-pegylated-cationic-dendrimers-for-delivery-of-3veyysv7jq.pdf

Promising PEGylated cationic dendrimers for delivery of miRNAs as a possible therapy against HIV-1 infection.

BACKGROUND The advent of resistance-associated mutations in HIV-1 is a barrier to the success of the ARTs. OBJECTIVE In this study, the abundance of HIV-1 infection in Iranian children, and also detection of the TDR in naive HIV-1 infected pediatric (under 12 years old) were evaluated. MATERIALS From June 2014 to January 2019, a total of 544 consecutive treatment-naive HIV-1- infected individuals enrolled in this study. After RNA extraction, amplification, and sequencing of the HIV-1 pol gene, the DRM and phylogenetic analysis were successfully performed on the plasma specimens of the ART-naive HIV-1-infected-children under 12 years old. The DRMs were recognized using the Stanford HIV Drug Resistance Database. RESULTS Out of the 544 evaluated treatment-naive HIV-1-infected individuals, 15 (2.8%) cases were children under 12 years old. The phylogenetic analyses of the amplified region of pol gene indicated that all of the 15 HIV-1-infected pediatric patients were infected by CRF35_AD, and a total of 13.3% (2/15) of these children were infected with HIV-1 variants with SDRMs (one child harbored two related SDRMs [D67N, V179F], and another child had three related SDRMs [M184V, T215F, and K103N]), according to the last algorithm of the WHO. No PIs-related SDRMs were observed in HIV-1-infected children. CONCLUSION The current study demonstrated that a total of 13.3% of treatment-naive HIV-1-infected Iranian pediatrics (under 12 years old) were infected with HIV-1 variants with SDRMs. Therefore, it seems that screening to recognize resistance-associated mutations before the initiation of ARTs among Iranian children is essential for favorable medication efficacy and dependable prognosis.

The Frequency of HIV-1 Infection in Iranian Children and Determination of the Transmitted Drug Resistance in Treatment-Naïve Children.

BACKGROUND In the perspective of ART-free HIV remission, vertically infected children treated with suppressive ART from early infancy represent an optimal population model to better understand the genetic complexity of the reservoir. OBJECTIVES To evaluate the proportion of defective viral population and the genotypic resistance patterns in cell-associated HIV DNA. METHODS In a cohort including 93 ART-treated vertically HIV-infected (VHIV) children in Mali with plasma HIV-1 RNA ≤50 copies/mL for at least 6 months, we studied total HIV DNA, percentage of defective genomes and resistance by reverse transcriptase and protease bulk sequencing from whole blood in dried blood spots. RESULTS Children had a median age of 9.9 years at the time of inclusion (IQR = 7.6-13.4) and 3.3 years (IQR = 2-7) at ART initiation; median ART duration was 5.5 years (IQR = 3.7-7.3). The median level of total HIV DNA was 470 copies/106 cells with one patient presenting undetectable HIV DNA (<66 copies/106 cells). We observed the presence of at least one stop codon in viruses from 34 patients (37%). The presence of stop codons was not correlated with the level of HIV DNA or duration of ART. We showed a high prevalence of HIV-1 resistance in DNA with 26% of children harbouring virus resistant to at least one NRTI and 40% to at least one NNRTI. CONCLUSIONS While these VHIV children were successfully treated for a long time, they showed high prevalence of resistance in HIV DNA and a moderate defective HIV reservoir.

Characterization of drug resistance and the defective HIV reservoir in virally suppressed vertically infected children in Mali.

Treatment scale-up is leading to a progressive increase in HIV resistance to antiretrovirals, especially in children. To assess resistance to reverse transcriptase inhibitors (RTIs) in HIV-1 infected children in Cote d'Ivoire, genotypic resistance tests were performed and interpreted using the ANRS algorithm (www.hivfrenchresistance.org). Phylogenetic trees were created using BioEdit v7 and Mega7 software. The frequency of resistance to at least one RTI was 79%. It was 88% for nucleoside reverse transcriptase inhibitors (NRTIs), 71% for non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 63% for both classes (NRTI + NNRTI). The frequency of resistance was 50% for the AZT + 3TC + EFV combination, 42% for the ABC + 3TC + EFV combination, and 8% for the TDF + 3TC + EFV combination. Frequently encountered resistance mutations were for NRTIs: M184V (88%), TAMs (67%), T215F/I/V/Y (33%) and L74I/V (24%); for NNRTIs: K103N/S (74%), P225H (26%) and G190A/E/Q (24%). The synthesis of phylogenetic analyses showed the predominance of CRF02_AG (85%). These results show a high prevalence of resistance to RTI in children infected with HIV-1. Hence the interest of a more accessible monitoring of viral load and genotypic resistance tests in HIV-1 infected children undergoing treatment in Cote d'Ivoire.

Determination of reverse transcriptase inhibitor resistance mutations in HIV-1 infected children in Côte d'Ivoire.

Despite significant reductions in mother-to-child HIV-1 transmission risks due to the advancements and scale-up of antiretroviral therapy (ART), the global burden of HIV-1 drug resistance (HIVDR) in treatment-naive and treatment-experienced children and adolescents remains poorly understood. In this study, we conducted a systematic review and meta-analysis to estimate the prevalence of HIVDR in these populations globally, regionally, and at the country level. 

Global, regional, and national prevalence of HIV-1 drug resistance in treatment-naive and treatment-experienced children and adolescents: a systematic review and meta-analysis

Introduction In recent years, children born to HIV-infected mothers have been receiving antiretroviral treatment (ART) with limited or no virologic monitoring, which increases the likelihood of development and accumulation of drug resistance mutations, which itself may limit the effectiveness of future ART. The objective of this study was to evaluate the prevalence of resistance mutations in children infected with HIV-1 experiencing virological failure to second-line ART in the Pediatric Department of Gabriel Toure Hospital in Mali. Methods Children aged from 5 to 18 infected with HIV-1 on second-line antiretroviral therapy and whose viral load was greater than 1000 copies/mL after observance reinforcement were enrolled. The protease and reverse transcriptase genes were sequenced with ViroSeq®. The results were interpreted according to the last version of the Stanford algorithm in 2018. The study was approved by the Ethics Committee of the Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies of Bamako (Mali). Results Of 216 children, 33 (15.3%) who had a viral load (VL) > 1000 copies/mL in second line were recruited and included in the study. The median plasma viral load was 77,000 copies/mL [IQR (28,000–290,000)] and the median CD4 cell count was 310 cells/mm3 [IQR (152–412)]. The median age was 12 years; 48.5% of patients were treated with a combination of stavudine/lamivudine/nevirapine (Triomune®) for first-line treatment and 60.6% with abacavir/lamivudine/lopinavir/ritonavir for the second-line ART. The median treatment duration was 8.5 years [range, 3–13]. Of the 33 children whose treatment failed, the predominant HIV-1 subtype was CRF02_AG (66.7%). The prevalence of resistance to ART classes was 60.61% (20/33) to nucleoside reverse transcriptase inhibitors (NRTIs), 54.51% (18/33) to nonnucleoside reverse transcriptase inhibitors (NNRTIs), and 51.52% (17/33) to protease inhibitors (PIs). Of the patients studied, 90.9% were exposed to lopinavir/ritonavir (LPV/r) but only 15.2% (5/33) developed resistance to LPV/r. Conclusions This study demonstrated that LPV/r remains active in most patients after second-line ART failure. In children whose second-line ART fails, particular attention should be paid to their ART and adherence history when considering the next treatment option.

Second-line antiretroviral therapy failure and characterization of HIV-1 drug resistance patterns in children in Mali

PURPOSE OF WORK: The aim of our study was to evaluate the testing of Streptococcus pneumoniae Binax NOW® ICT from blood cultures in children with invasive bacterial infections in Bamako, Mali. MATERIAL AND METHODS: We recruited 382 children under 16 years hospitalized or treated as outpatients. The venous blood samples were collected from all the children in a sterile manner inoculated into blood culture bottles, transported to the laboratory and placed in automated growth machine called BACTECTM 9050. All broths of vials BACTEC (gold standard) that have grown on the usual agar, were subject to testing of Streptococcus pneumoniae Binax NOW® ICT, including also the negative vials BACTEC (for possibility of false positives). RESULTS: Of 382 children, 192 (50.2%) were aged 0 to 11 months, 225 (58.9%) were male. Of 382 blood cultures, 185 (48.4%) were positive, on these 185 positive, 75 (40.5%) were Streptococcus pneumoniae. All 382 blood cultures were detected by the Binax NOW® ICT, 75 (19.6%) were positive. In our study, the assessment analysis showed that the Binax NOW® ICT has sensitivity and a specificity of 100%. CONCLUSION: After assessment of the Binax NOW® ICT on CSF and urine in previous studies, we can say that this test is also effective in the detection of pneumococcal antigen in blood cultures as evidenced by the results of our study. However, we recommend the use of Binax NOW® ICT in the rapid diagnosis of pneumococcal infections and a future evaluation in large sample size.

Evaluation du test de dépistage de Streptococcus pneumoniae Binax NOW® ICT à partir des hémocultures réalisées chez les enfants atteints d’infections bactériennes invasives à Bamako au Mali

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Second-line antiretroviral therapy failure and characterization of HIV-1 drug resistance patterns in children in Mali

Evaluation du test de dépistage de Streptococcus pneumoniae Binax NOW® ICT à partir des hémocultures réalisées chez les enfants atteints d’infections bactériennes invasives à Bamako au Mali