The integrase strand-transfer inhibitors (INSTIs) are an important class in the arsenal of antiretroviral drugs designed to block the integration of HIV-1 cDNA into the host DNA through the inhibition of DNA strand transfer. In this study for the first time in Morocco, the complete HIV-1 integrase gene was analysed from newly diagnosed patients to evaluate the prevalence of natural polymorphisms and INSTIs resistance-associated mutations in the integrase gene. The 864pb IN coding region was successfully sequenced from plasma sample for 77 among 80 antiretroviral naïve patients. The sequences were interpreted for drug resistance according to the Stanford algorithm. Sixty samples were HIV-1 subtype B (78%), fourteen CRF02_AG (18%), two subtype C and one subtype A. Overall 81 of 288 (28%) amino acid IN positions presented at least one polymorphism each. We found 18 (36.73%), 42 (25.76%) and 21 (27.27%) of polymorphic residues assigned to the N-Terminal Domain, Catalytic Core Domaine and the C-Terminal Domain positions respectively. Primary INSTIs resistance mutation were absent, however secondary mutations L74IM, T97A were detected in four samples (5.2%). These results demonstrate that untreated HIV-1 infected Moroccans will be susceptible to INSTIs.

The goal of our study was to explore the association of the polymorphisms in the JAK/STAT pathway among Moroccan COVID-19 patients, using a case-control approach. Next-generation sequencing was employed to investigate the IFNAR1, IFNAR2, JAK1, TYK2, STAT2, and IRF9 genes within the JAK/STAT pathway. We also performed an in silico study to examine the rare variants in this pathway. Statistical analyses were conducted using MedCalc software. Protein 3D structures were determined via the I-TASSER server, with variant structures generated using PyMOL. YASARA View allowed local 3D analysis comparing native and variant structures for pathogenic rare variants. The study encompassed 206 COVID-19 patients, averaging 45.70 ± 12.73 years and a control group (N=118). Among the examined genes, 15 common polymorphisms and 7 rare variants were identified. Adjustment for age and gender revealed a significant association between TYK2 p.Gly363Ser (p=0.036) and COVID-19 infection, where the GA variant exhibited protective effects (0.6361 [0.3405-1.1884], p=0.035). Additionally, STAT2 p.Met594Ile showed an association to COVID-19 risk (p=0.042), with heterozygous GC being linked to infection (p=0.037, OR=2.7135 [0.5684 -12.9532]). Notably, IFNAR1 p.Val168Leu mutated C allele was significantly associated with reduced susceptibility to COVID-19 severity (p=0.028, OR=0.5936 [0.3725 - 0.9461]), under the additive model (p=0.045, OR=0.626 [0.3958 - 0.9899]). Rare variants IFNAR1 p.Trp318Cys, p.Ser476Phe, and IFNAR2 p.Cys271Tyr were predicted deleterious, impacting protein structure via hydrogen bond and hydrophobic interaction alterations. Burden analysis of rare variants revealed a protective cumulative effect against COVID-19 severity for TYK2 (p=0.0013, OR=0.1438 [0.04237 - 0.4803]) under the dominant model. This study underscores the role of genetic factors in COVID-19 susceptibility and advocates further explorations regarding functional impacts of JAK/STAT pathway rare variants.

The growing use of antiretroviral therapy (ART) has transformed HIV infection into a chronic, manageable disease, yet the emergence of drug resistance continues to threaten global progress. Morocco, located at the crossroads of Sub-Saharan Africa and Europe, offers a unique context for understanding the molecular evolution of HIV in the Middle East and North Africa. This systematic review synthesizes all available data on HIV-1 genotyping and resistance mutations in Morocco from 2009 to 2024, providing the first national overview of molecular resistance patterns. Six studies comprising 673 individuals met the inclusion criteria, spanning 2004-2015. Subtype B predominated (73.8%), followed by CRF02_AG (17.6%), reflecting increasing viral diversification linked to cross-regional transmission. Among ART-experienced patients, acquired drug resistance reached 19.5% at the population level and 53.3% among successfully sequenced samples, with NRTI (48.9%) and PI (22.2%) mutations predominating. The most frequent mutations were M184V (44%), K103N (8.9%), and V82A/L (13.3%). In ART-naïve individuals, transmitted resistance remained limited (1.55%), with no major integrase strand-transfer inhibitor mutations detected, though accessory polymorphisms such as L74M/I and E157Q were present in 3-5% of cases. CD4 counts and viral load suppression improved in later cohorts. These findings underline the critical need to re-establish molecular surveillance in Morocco to capture post-2019 resistance dynamics under dolutegravir-based therapy. Strengthening genotypic monitoring and integrating resistance testing into clinical care will be pivotal to preserving long-term ART efficacy and achieving the UNAIDS 95-95-95 and HIV elimination targets by 2030.

Background: Limited molecular surveillance continues to constrain Morocco’s HIV response, leaving subtype dynamics largely underreported. Once characterized by a predominance of subtype B, the Moroccan epidemic now appears to reflect shifting patterns shaped by regional and international connectivity. This study aimed to investigate HIV-1 molecular diversity, monitor circulating HIV-1 genetic variants, and inter-gene recombination in a cohort of people living with HIV in Morocco. Methods: We conducted an analysis of individuals diagnosed with HIV-1 infection or receiving follow-up care. Demographic and clinical data were extracted. Genotypic testing was performed on the protease/reverse transcriptase (PR/RT) and integrase (IN) regions of the pol gene using the HIV-1 Genotyping Kit with Integrase. Subtypes were assigned via Stanford HIVdb and HIV Blast, and phylogenetic relationships were analyzed using MEGA 12. Results: Of the 73 individuals enrolled, 64 were successfully sequenced. The median age was 43 years (IQR 35–51.3), with over half aged 25–44, and 85.9% were male. Heterosexual transmission was the main route (87.5%), and 59.4% were ART-naïve. Non-B subtypes predominated (87.5%), led by CRF02_AG (73.4%), followed by B (12.5%), C (7.8%), and A3 (3.1%). The cohort showed significant genetic diversity, including multiple CRFs such as CRF45_cpx (1.6%), CRF01_AE (1.6%), B/CRF02_AG (7.8%), G/CRF02_AG (3.1%), C/CRF02_AG (1.6%), CRF02_AG/CRF45_cpx (1.6%) and CRF02_AG/CRF22_01A1 (1.6%). Conclusions: This study provides updated insight into HIV-1 diversity in Morocco, showing a predominance of non-B subtypes, particularly CRF02_AG, and signals of increasing heterogeneity compared with reports from more than a decade ago that described subtype B predominance. These findings suggest a viral transition shaped in part by regional connectivity and highlight a gap in Morocco’s HIV strategy, underscoring the need to implement nationwide molecular surveillance to inform future HIV control efforts.

Introduction: Morocco has made substantial progress in expanding human immunodeficiency virus (HIV) testing and treatment, yet longitudinal data on immuno-virologic outcomes remain limited. Objective: We sought to define the clinical profile at presentation and analyze long-term immuno-virologic outcomes under expanding integrase inhibitor-based treatment. Methods: We performed a retrospective analysis of patients with confirmed HIV-1 infection who initiated antiretroviral therapy at the Center of Virology, Infectious, and Tropical Diseases at the Military Training Hospital between 2017 and 2025. Demographic, clinical, immunological, and virological data were collected at baseline and throughout follow-up. Statistical analyses were conducted using the Statistical Package for Social Sciences software. Results: Late presentation was common: 35.7% presented with Centers for Disease Control and Prevention stage C, and 41.5% had CD4 < 200 cells/μL. Women had higher baseline cluster of differentiation 4 (CD4) counts than men (416 vs. 250 cells/μL; p = 0.001), whereas men displayed higher viral loads (1.19 × 105 vs. 5.51 × 104 copies/mL; p = 0.005). Opportunistic infections remained substantial, including cytomegalovirus (16.5%), tuberculosis (12.5%), and toxoplasmosis (5.8%). First-line therapy was initially non-nucleoside reverse transcriptase inhibitor-based in half of the patients, but rapid national adoption of updated guidelines led to 93.8% receiving dolutegravir plus two nucleoside reverse transcriptase inhibitors at the last follow-up. Viral loads declined sharply within the first month, with most patients achieving and maintaining suppression from months 6–12 onward. CD4 counts rose from a median of 279 cells/μL at baseline to 560 at year 3, peaking at 610 at year 5 before stabilizing. Conclusion: Morocco’s transition to dolutegravir-based antiretroviral therapy has produced durable virologic control and robust immune recovery. Persistent late diagnosis, sex-based disparities, and limited access to genotyping remain major obstacles. Strengthening early testing, expanding molecular monitoring, and enhancing differentiated care services will be essential to sustain national progress.

Introduction: Colorectal cancer (CRC) is a heterogeneous and multifactorial malignancy driven by a series of genetic and epigenetic alterations. In this field, telomere/telomerase dysfunction contributes to CRC carcinogenesis by impairing genomic stability and cellular replication. Objective: This study aimed to evaluate genetic and epigenetic alterations in CRC by examining mutation rates in the human telomerase reverse transcriptase (hTERT) promoter region, relative telomere length (RTL), hTERT gene expression, and DNA methylation in the TERT hypermethylated oncological region (THOR). Methods: A total of 45 CRC and 34 adjacent normal tissue samples from Moroccan patients were analyzed using molecular approaches, such as Sanger sequencing, quantitative PCR (qPCR), reverse transcription qPCR (RT-qPCR), and methylation-specific PCR (MSP). Results: No mutations in the hTERT promoter region were identified. However, hypermethylation in the THOR region was reported in 82.2% of CRC samples and 79.4% of adjacent normal tissues. High hTERT expression was detected in 50% of CRC patients. In addition, telomere length was significantly shorter (p=0.002) in cancerous tissues (1.41 [1.36 – 1.43]) compared to normal mucosa (1.559 [1.46 – 1.63]), with an RTL ratio less than 1 (0.90 [0.86 – 0.95]). No significant differences were found between clinicopathological features and hTERT expression, THOR methylation, or RTL, except for a significant correlation between THOR hypermethylation and smaller tumor size (p=0.017) and between THOR methylation and RTL in CRC tissues (p=0.034). Conclusion: These results suggest that telomere lengthening is crucial for CRC initiation and progression, and cancer cells tend to shorten telomeres to maintain the chromosomal instability (CIN) required for tumor progression. Further research is needed to elucidate the mechanisms underlying telomere shortening in CRC and understand the role of telomerase/telomere complex in CRC initiation and progression, which could provide new diagnostic, prognostic, and therapeutic targets.