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Human immunodeficiency virus type 1 (HIV-1) infection varies substantially among individuals. One of the factors influencing viral infection is genetic variability. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is a genetic factor that has been correlated with different types of pathologies, including HIV-1. The MTHFR gene encodes the MTHFR enzyme, an essential factor in the folate metabolic pathway and in maintaining circulating folate and methionine at constant levels, thus preventing the homocysteine accumulation. Several studies have shown the role of folate on CD4+ T lymphocyte count among HIV-1 subjects. In this case-control study we aimed to determine the association between the MTHFR C677T polymorphism and HIV-1 infection susceptibility, AIDS development, and therapeutic outcome among Moroccans. The C677T polymorphism was genotyped by polymerase chain reaction followed by fragment length polymorphism digestion in 214 participants living with HIV-1 and 318 healthy controls. The results of the study revealed no statistically significant association between MTHFR C677T polymorphism and HIV-1 infection (P > .05). After dividing HIV-1 subjects according to their AIDS status, no significant difference was observed between C677T polymorphism and AIDS development (P > .05). Furthermore, regarding the treatment response outcome, as measured by HIV-1 RNA viral load and CD4+ T cell counts, no statistically significant association was found with MTHFR C677T polymorphism. We conclude that, in the genetic context of the Moroccan population, MTHFR C677T polymorphism does not affect HIV-1 infection susceptibility, AIDS development, or response to treatment. However, more studies should be done to investigate both genetic and nutritional aspects for more conclusive results.

Monkeypox virus (MPV) is closely related to the smallpox virus, and previous data from Africa suggest that the smallpox vaccine (VARV) is at least 85% effective in preventing MPV. No multi-epitope vaccine has yet been developed to prevent MPV infection. In this work, we used in silico structural biology and advanced immunoinformatic strategies to design a multi-epitope subunit vaccine against MPV infection. The designed vaccine sequence is adjuvanted with CpG-ODN and includes HTL/CTL epitopes for similar proteins between vaccinia virus (VACV) that induced T-cell production in vaccinated volunteers and the first draft sequence of the MPV genome associated with the suspected outbreak in several countries, May 2022. In addition, the specific binding of the modified vaccine and the immune Toll-like receptor 9 (TLR9) was estimated by molecular interaction studies. Strong interaction in the binding groove as well as good docking scores confirmed the stringency of the modified vaccine. The stability of the interaction was confirmed by a classical molecular dynamics simulation and normal mode analysis. Then, the immune simulation also indicated the ability of this vaccine to induce an effective immune response against MPV. Codon optimization and in silico cloning of the vaccine into the pET-28a (+) vector also showed its expression potential in the E. coli K12 system. The promising data obtained from the various in silico studies indicate that this vaccine is effective against MPV. However, additional in vitro and in vivo studies are still needed to confirm its efficacy. Communicated by Ramaswamy H. Sarma

Hepatitis A virus (HAV) is the common cause of acute hepatitis worldwide. Indeed, hepatitis A is endemic in developing countries such in Morocco and most residents are exposed in childhood. The characterisation of circulating strains of HAV remains crucial to understand the virological evolution and geo-temporal characteristics, which are essential for controlling infections and outbreaks. The purpose of the current study was the detection and characterisation of HAV strains circulating in Morocco by performing serological test, RT-PCR, sequencing and phylogenetic analysis. In this cross-sectional study, 618 suspected acute hepatitis cases were examined by Architect HAV abIgM. Of the 162 positives, 64 underwent RNA extraction. None of the suspected cases was immune to HAV and none of them had received a blood transfusion. Samples found positive by RT-PCR using primers targeting the VP1/VP2A junction and the VP1/VP3 capsid region of HAV were subjected to sequencing and phylogenetic analyses. HAV Acute infection rate was 26.2% [95% CI, 22.8–29.9], while viraemia reached 45% (29/64) after amplification of the VP3/VP1 region. Phylogenetic analysis of the VP1/2A segment revealed the presence of sub-genotypes IA and IB. Eighty-seven percent of the strains belonged to the subgenotype IA, while twelve percent to IB subgenotype. This first molecular study of acute hepatitis A in Morocco provided information about genetic diversity of HAV, revealing the co-circulating of only two subgenotypes (IA and IB). Notably, subgenotype IA was found to be the predominant subgenotype in Morocco.

Transmission of Human immunodeficiency virus type 1 (HIV-1) to permissive CD4+T cells requires the dissemination of virus from sites of infection to secondary lymphoid organs, where extensive viral replication occurs in CD4+T cells. Several studies demonstrated that DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) molecules located on the surface of Dendritic Cell subsets showed high-affinity binding to HIV-1 and Mycobacterium tuberculosis (Mtb). It is exploited by HIV-1 and Mtb as a part of their immune evasion strategy. In this study, we investigated the possible involvement of DC-SIGN encoding gene CD209 variants in the development of tuberculosis (TB) among HIV-1 infected patients as well as AIDS development and treatment response outcomes in a Moroccan population. Two single nucleotide polymorphisms in the CD209 promoter − 336A > G (rs4804803) and − 139G > A (rs2287886) were investigated. Two hundred eighteen Moroccan subjects living with HIV-1 were genotyped using direct DNA sequencing. Out of 218 patients, 90 were co-infected with Mtb. Stratification of patient was performed according to TB status: as HIV-1+/TB- and HIV-1+/TB+ patients and their AIDS status as: AIDS and Non-AIDS patients. Our results revealed that genotype and allele frequencies of the − 336A > G and − 139G > A polymorphisms were not significantly different between HIV-1+/TB- and HIV-1+/TB+ patients (p > 0.05). Likewise, the development of AIDS doesn’t appear to be affected by these two SNPs either (p > 0.05). Haplotype analysis showed that none of the 4 possible haplotypes is associated with HIV-1 and TB co-infection (p > 0.05). Interestingly, the analysis of the − 139 G > A genotype distribution according to the HIV-1 viral load showed an improvement in AG and GG patients, after ART, compared to AA patients (p = 0.0069 and p = 0.0476; respectively). Overall, -336A > G and − 139G > A polymorphisms don’t influence the susceptibility of HIV-1 infected individuals to develop TB and AIDS. However, -139G > A polymorphism may affect the response to treatment as measured by RNA viral load levels. Further investigations are needed for a better understanding of the role of DC-SIGN in HIV-1 infection to provide new therapeutic pathways.

Background: It has been reported that interferon-λ3 (IFNL3)might influence the pathogenesis and clearance of human papillomavirus (HPV) infection. The impact of IFNL3 single-nucleotide polymorphism (SNP) on HPV infection is currently unknown. The aim of this study was to investigate the association between variants in the IFNL3 region and HPV infection in women with human immunodeficiency virus (HIV) infection. Methods: A total of 236 HIV patients, including 65 HPV-negative and 171 HPV DNA-positive women, were enrolled into this study. The IFNL3 rs12979860 polymorphism was genotyped using a predesigned TaqMan SNP genotyping assay. Results: Data showed no significant differences in genotypes or allele frequencies between the HPV DNA-positive and the HPV-negative women (p > 0.05). After dividing the HPV-positive women according to cytology results into patients with abnormal and normal lesions, the genotype and allele distribution of the SNP did not significantly differ between the 2 groups (p > 0.05). Conclusions: Our results showed that the IFNL3 rs12979860 polymorphism is not a major determinant of the susceptibility to HPV infection and their progression to abnormal cervical lesions in women living with HIV.

Human Immunodeficiency Virus (HIV-1) infections are characterized by dysfunctional cellular and humoral antiviral immune responses. The progressive loss of effector functions in chronic viral infection has been associated with the up-regulation of programmed death-1 (PD-1), a negative regulator of activated T cells and Natural Killer cells. In HIV-1 infection, increased levels of PD-1 expression correlate with CD8 + T-cell exhaustion. In vitro, PD-1 blockade using PD-1 antibodies led to an increase in HIV-1 specific CD8 + T and memory B cell proliferation. We aimed to investigate the impact of PDCD1 rs10204525 polymorphism on HIV-1 susceptibility, AIDS development, and treatment response outcomes in HIV-1 infection in a Moroccan population. A total of 214 HIV-1 seropositive and 250 seronegative subjects were enrolled to investigate the association between the between the single-nucleotide polymorphism (SNP) rs10204525 of PDCD1 gene and HIV-1 pathogenesis using a predesigned TaqMan SNP genotyping assay. No significant association was found between rs10204525 and susceptibility to HIV-1 infection and AIDS development (p 0.05). Genotype frequencies were significantly associated with the viral load before ART (p = 0.0105). HIV-1 viral load was significantly higher among subjects with the CC compared to TT genotype (p = 0.0043). In treated subjects, the median of viral load levels was significantly higher in CC and CT groups than TT subjects (p 0.005). However, analysis of the correlation between CD4 + T-cell levels and PDCD1 polymorphism before and after ART showed no significant difference (p 0.05). Our results demonstrated that rs10204525 polymorphism does not affect HIV-1 infection. However, this polymorphism may affect the response to treatment as measured by RNA viral load levels.

Toll-like receptors (TLRs) play an important role in activating the innate immune response, inducing inflammation and initiating the adaptive immune response. In this study, we assess the influence of TLR7 and TLR8 gene polymorphisms on HIV-1 susceptibility, AIDS development, and treatment outcomes. The TLR7 and TLR8 single nucleotide polymorphisms (SNPs) were genotyped through real-time PCR in 222 patients living with HIV-1 and 141 healthy controls. Frequencies of the TLR7-IVS2-151 G/A and TLR7-IVS1 + 1817 G/T genotypes and alleles were not significantly increased in patients with HIV-1 infection compared to healthy controls both in males and females. Whereas, males carrying TLR8 Met allele were twice susceptible to HIV-1 infection compared to subjects with A allele (OR = 2.04, 95 % CI 1.10-3.76; p = 0.021). Interestingly, for TLR8-129 G/C, both males and females carrying G allele and GG genotype, respectively were significantly associated with HIV-1 infection (p0.0001). Moreover, the TLR7 IVS1 + 1817 G/T and the TLR8 rs3764880 were associated with protection to progress the AIDS stage in male and female, respectively (p0.05). Males carrying TLR7 IVS2-151-A allele showed a significant increased level of HIV-1 viral load pre-treatment, in comparison with individuals carrying the G allele (p-value = 0.036). Additionally, males carrying TLR8 Met allele showed statistically higher HIV viral load at baseline (p-value = 0.04) and after treatment (p-value = 0.013). Regarding CD4 + T cell counts, no significant association was found with TLR7 and TLR8 SNPs before and after antiretroviral treatment. This data demonstrates that TLR8 polymorphisms could affect HIV-1 infection. Moreover, an association between TLR7 IVS2-151-A and TLR8 Met alleles and plasma HIV viral load level was found.

Introduction: Women infected with human immunodeficiency virus (HIV) have a higher risk of contracting human papillomavirus (HPV) infections and are more prone to develop cervical cancer. The objective of this study was to determine the prevalence of HPV and its association with risk factors among Moroccan women living with HIV/AIDS. Methodology: We enrolled 251 HIV-infected non-pregnant women in Morocco from February 2013 to September 2016. Sociodemographic, lifestyles, behavioral and clinical data were collected. Polymerase chain reaction followed by sequencing were performed for molecular detection and HPV genotyping in cervical samples, respectively. Results: Abnormal cervical smears were found in 34/246 patients (13.82%). The overall prevalence of HPV was 74.50%. HPV 58 was the most prevalent (39.29%) followed by HPV 18 (10.71%), HPV 70 (8.93%), HPV 33 (7.14%), HPV 6 (6.25%) and other genotypes (< 3%). Overall, high-risk HPV (HR-HPV) types were present in 75% (84/112) of patients and the prevalence of HR-HPV types in samples with abnormal Pap was higher than in normal Pap (55/83, 66.27% vs. 28/83, 33.33%, p < 0.0001). Univariate analyses showed that none of the socio-demographic and behaviors factors was associated with HPV infection. Moreover, Pap results were not affected by HPV status (p = 0.532). Whereas, CD4 T-cell counts above 200/mm3 at enrolment were apparently not protective to HPV infection. We found a high prevalence of HPV infection and HR-HPV types among HIV-positive women that significantly associated with abnormal Pap. Conclusion: Our findings suggest a high prevalence of HPV infection with high-risk types was observed among HIV-positive women warrant to implement a regular screening by Pap smear.

Background In Morocco, diagnosis of HIV infection remains late, which seriously compromises the timely management of HIV infection in the era of HAART therapies. Rapid test represents a good opportunity to improve the access to early screening of HIV. The objective of this study is to report the experience of the infectious diseases unit of the Ibn Rochd University hospital center of Casablanca, in the use of the rapid test in clinical screening of HIV. Patients and methods This retrospective study reports data relevant to the use of the rapid test Determine VIH-1/2, Abbott Diagnostics, since its introduction in the infectious diseases unit in April 2006 up to December 2009. The test was performed for patients from the infectious diseases unit and patients hospitalized in different units of the Ibn Rochd University hospital center, after their consent. Test was ordered systematically by clinicians in case of any suspected symptom related to HIV and immunodepression. Positive samples were confirmed by Western Blot test, at the National Reference Laboratory for HIV, within the Institut National d’Hygiene in Rabat. Results Between 2006 and 2009, 1105 rapid tests were performed, among which 16.3% were positive. All results were provided to patients and none were lost to follow-up. The main reasons for the prescription of an HIV test were tuberculosis (26.3%) and chronic diarrhea (9.9%) for inpatients. For outpatients, the main symptoms were sexually transmissible infections (16.7%) and weight loss (15.7%). Results of the tests allowed us to adapt the treatment in case of suspicion of pneumocystosis (12 cases) and toxoplasmosis (seven cases). Conclusion The introduction of the rapid test for HIV clinical screening in the hospital facilities improved considerably the access to diagnosis and consequently allowed a timely management of HIV infection.

The occurrence of invasive pulmonary aspergillosis is unusual during the course of AIDS. Patients at risk have a CD4 T-lymphocyte count under 50 cells/mm(3) combined with other risk factors in 50% of the cases. Positive diagnosis is based on chest CT scan imaging and isolation of Aspergillus in broncho-alveolar fluid. Detection of galactomannan antigen in serum and broncho-alveolar lavage fluid (BALF) is a reliable complementary tool in assessing the diagnosis. The first line therapy is Voriconazole. The prognosis, often severe, depends on prompt initiation of the appropriate antifungal treatment. We report two cases of invasive pulmonary aspergillosis in AIDS patients.

Background: Acute pancreatitis in HIV positive patients remains a management challenge even with a Highly Active Antiretroviral Therapy (HAART) era. Objective: Report the prevalence, clinical and radiological features of acute pancreatitis associated with HIV. Patients and methods: Retrospective study conducted from January 1999 to June 2015 in HIV positive patients admitted with acute pancreatitis in the Infectious Disease Unit, Ibn Rochd, Casablanca. The Balthazar Grade score was used to assess radiological severity of the disease. Results: During this period, 39 patients had an acute pancreatitis or an incidence of 0.6/1000 inhabitant/year. The mean age was 33.72 years (range: 18 to 48 years), mostly represented by females (68% to 32% male).The known risk factors included an alcohol abuse in 15 patients (52%), a history of pancreatitis in two patients (5%), cholecystitis in four patients (14%), and intravenous drug abuse in two patients (5%). Nineteen patients (65%) were on HAART regimen and only nine patients (31%) were receiving cotrimoxazole as prophylaxis. Twenty-two patients (76%) were in stage C of CDC. Twenty-one (72%) patients had a mean CD4 count below 200/mm³ and a HIV viral load above 1000 copies/ml in seventy nineteen (65%) patients. Pancreatitis was symptomatic in all cases. The median amylasemia level was 120 IU/L, serum lipase 672.7 IU/L and 1,23 mg/dl triglycerides. All patients had an abnormal pancreas CT scan of which twelve (41%) patients were in stage A of AP. The main causes found were drug toxicity of which 6 cases were due to stavudine, meglumine antimony in 3 cases, didanosine in 1 case, anti-tuberculous treatment in 1 case and opportunistic infections of which 4 cases were tuberculosis, 4 cases of cytomegalovirus disease and cryptosporidiosis in 2 cases respectively. The main complications were: shock in 9 cases, 2 cases of diabetes and pancreatic pseudocysts in 2 cases. The evolution was fatal in 45% of cases. The median duration for hospital course was 10 days (range 6-50 days). Conclusion: Acute pancreatitis is a serious condition in HIV-positive patients. Drug toxicity and opportunistic infections represented the most frequent causes.

Cryptococcosis is a cosmopolitan fungal serious condition due to an encapsulated yeast Cryptococcus neoformans. This is the systemic fungal infection the most common in HIV infection. This yeast is present in the environment and its main entrance in the body is the respiratory tract. Its gravity is linked to its tropism for the central nervous system. It generally affects subjects with severe deficit of cellular immunity and in particular, patients living with HIV. The diagnosis of neuromeningeal cryptococcosis is based on the detection of encapsulated yeasts at microscopic examination of cerebrospinal fluid, the detection of capsular polysaccharide antigen in serum or cerebrospinal fluid, but especially on the culture. A staging is always essential. The prognosis is severe. The control of intracranial hypertension is a major element of prognosis.