Human immunodeficiency virus and oral microbiota: mutual influence on the establishment of a viral gingival reservoir in individuals under antiretroviral therapy.

The role of the oral microbiota in the overall health and in systemic diseases has gained more importance in the recent years, mainly due to the systemic effects that are mediated by the chronic inflammation caused by oral diseases, such as periodontitis, through the microbial communities of the mouth. The chronic infection by the human immunodeficiency virus (HIV) interacts at the tissue level (e.g. gut, genital tract, brain) to create reservoirs; the modulation of the gut microbiota by HIV infection is a good example of these interactions. The purpose of the present review is to assess the state of knowledge on the oral microbiota (microbiome, mycobiome and virome) of HIV-infected patients in comparison to that of HIV-negative individuals and to discuss the reciprocal influence of HIV infection and oral microbiota in patients with periodontitis on the potential establishment of a viral gingival reservoir. The influence of different clinical and biological parameters are reviewed including age, immune and viral status, potent antiretroviral therapies, smoking, infection of the airway and viral coinfections, all factors that can modulate the oral microbiota during HIV infection. The analysis of the literature proposed in this review indicates that the comparisons of the available studies are difficult due to their great heterogeneity. However, some important findings emerge: (i) the oral microbiota is less influenced than that of the gut during HIV infection, although some recurrent changes in the microbiome are identified in many studies; (ii) severe immunosuppression is correlated with altered microbiota and potent antiretroviral therapies correct partially these modifications; (iii) periodontitis constitutes a major factor of dysbiosis, which is exacerbated in HIV-infected patients; its pathogenesis can be described as a reciprocal reinforcement of the two conditions, where the local dysbiosis present in the periodontal pocket leads to inflammation, bacterial translocation and destruction of the supporting tissues, which in turn enhances an inflammatory environment that perpetuates the periodontitis cycle. With the objective of curing viral reservoirs of HIV-infected patients in the future years, it appears important to develop further researches aimed at defining whether the inflamed gingiva can serve of viral reservoir in HIV-infected patients with periodontitis.

Use of genotypic HIV DNA testing: a DELPHI-type consensus.

OBJECTIVES: As many disparities in the clinical use of HIV DNA sequencing are observed, a DELPHI-type consensus was initiated in France to homogenize use, techniques and interpretation of results. METHODS: Based on a literature review and clinical experience, a steering committee (SC) of eight virologists and one infectious disease specialist formulated statements. Statements were submitted to an independent and anonymous electronic vote of virologists and HIV clinicians in France, between October 2022 and December 2022. RESULTS: The SC developed 20 statements grouped into six categories: clinical situations for the use of HIV DNA genotyping; techniques for performing HIV DNA genotyping; consideration of apolipoprotein B mRNA editing enzyme (APOBEC) mutations; genotyping results reporting; recycling of antiretrovirals; and availability of HIV DNA genotyping tests and delays. Twenty-one virologists and 47 clinicians participated in two voting rounds and 18/20 (90%) assertions reached a 'strong' consensus. For example, that prior genotyping on HIV DNA is useful for clinical decision-making when considering switching to some long-acting regimens or to reduce the number of antiretroviral agents in virologically suppressed patients for whom RNA data are unavailable/not exploitable/not sufficiently informative. Two statements achieved no consensus: reporting any detected viral minority population for discussion in multidisciplinary meetings (virologists), and possible risk of virological failure when using a second-generation InSTI plus lamivudine or emtricitabine regimen in patients with undetectable viral load within ≥1 year and in the presence of a documented M184V mutation within the last 5 years (clinicians). CONCLUSIONS: This DELPHI-type consensus will facilitate the strengthening and harmonization of good practice when performing HIV DNA sequencing.

Ultrafast inactivation of SARS-CoV-2 by 254-nm UV-C irradiation on porous and non-porous media of medical interest using an omnidirectional chamber.

Covid-19 has spurred a renewed interest in decontamination techniques for air, objects and surfaces. Beginning in 2020, urgent effort was done to permit the reuse of UV-C for inactivating SARS-CoV-2. However, those studies diverged widely on the dose necessary to reach this goal; until today, the real value of the sensitivity of the virus to a 254-nm illumination is not known precisely. In this study, decontamination was performed in an original UV-C large decontamination chamber (UVCab, ON-LIGHT, France) delivering an omnidirectional irradiation with an average dose of 50 mJ/cm2 in 60 s. Viral inactivation was checked by both cell culture and PCR test. SARS-CoV-2 was inactivated by UV-C light within 3 s on both porous (disposable gown) and non-porous (stainless steel and apron) surfaces. For the porous surface, an irradiation of 5 min was needed to achieve a completely negative PCR signal. The Z value estimating the sensitivity of SARS-CoV-2 to UV-C in the experimental conditions of our cabinet was shown to be > 0.5820 m2/J. These results illustrate the ability of this apparatus to inactivate rapidly and definitively high loads of SARS-CoV-2 deposited on porous or non-porous supports and opens new perspectives on material decontamination using UV-C.

Detection of HPV in urine for cervical cancer screening: Feasibilty of an assay system.

The detection of urine HPV is considered as a promosing alternative to increase the screening coverage of cervical cancer. However, the validated assay of urine HPV is still scarse. We described a nouvel assay syetem for the urine-based detection of HPV in the framework of HPV screening. This sytsem consisted of Automate Nimbus extraction of DNA and Anyplex™ II HPV HR Detection PCR of HPV DNA. We validated this system by spiking HPV-infected cervical cancer cell line HeLa cells into normal urine and compared the prelimary results of cervical samples and urine samples. We found that this system could detect as few as 5 HeLa cells in normal urine model. Some discordances of HPV results between cervical samples and urine samples were observed. We concluded that this assay system could be applied for the detection of HPV in urine. A large scale study is necessary to evaluate the clinical significance of this assay system.

Urine-based detection of HPV for cervical cancer screening: Time for standardized tests.

Cervical cancer is preventable because it has an established etiology, mainly attributed to a detectable pathogen, human papillomavirus (HPV). In 2018, the world health organization issued an unprecedented call for global action to eliminate cervical cancer by 2030. The adaptation of regular screening programs is fundamental to achieve the goal of cervical cancer elimination. However, it is still difficult to achieve satisfactory coverage rates of screening in developing countries as well as in developed countries because many women are reluctant to participate in gynecologic examination. HPV detection in urine is a convenient, widely acceptable by women and relatively affordable without the necessity for clinical visits to improve the coverage rates of cervical cancer screening. Unfortunately, the clinical implementation of urine-based tests for HPV detection has been hindered by the lack of standardized tests. Further optimization of protocols and standardization of urinary HPV detection are expected to be realized. With the advantages of urine sampling to overcome cost, personal, and cultural barriers, time has come for the standardized tests to facilitate a wide clinical implementation of urinary HPV detection that will significantly contribute to the WHO's goal, that is, to eliminate the cervical cancer globally.

Prior COVID-19 Immunization Does Not Cause IgA- or IgG-Dependent Enhancement of SARS-CoV-2 Infection.

Antibody-dependent enhancement (ADE) can increase the rates and severity of infection with various viruses, including coronaviruses, such as MERS. Some in vitro studies on COVID-19 have suggested that prior immunization enhances SARS-CoV-2 infection, but preclinical and clinical studies have demonstrated the contrary. We studied a cohort of COVID-19 patients and a cohort of vaccinated individuals with a heterologous (Moderna/Pfizer) or homologous (Pfizer/Pfizer) vaccination scheme. The dependence on IgG or IgA of ADE of infection was evaluated on the serum samples from these subjects (twenty-six vaccinated individuals and twenty-one PCR-positive SARS-CoV-2-infected patients) using an in vitro model with CD16- or CD89-expressing cells and the Delta (B.1.617.2 lineage) and Omicron (B.1.1.529 lineage) variants of SARS-CoV-2. Sera from COVID-19 patients did not show ADE of infection with any of the tested viral variants. Some serum samples from vaccinated individuals displayed a mild IgA-ADE effect with Omicron after the second dose of the vaccine, but this effect was abolished after the completion of the full vaccination scheme. In this study, FcγRIIIa- and FcαRI-dependent ADE of SARS-CoV-2 infection after prior immunization, which might increase the risk of severe disease in a second natural infection, was not observed.

[Viruses present in the environment: virological considerations and examples of their impact on human health]. / Les virus dans l'environnement, considérations virologiques et exemples de leur impact en santé humaine.

Animal viruses are present in most human environments. Their viability in these media is very variable and the most important element that conditions this viability is the existence or not of a phospholipid envelope surrounding the nucleocapsid. After some general considerations on the structure of viruses, their multiplication cycle and their resistance to different physico-chemical agents, some examples of the impact of animal viruses present in the environment on human health will be presented. The situations that are related concern recent epidemiological events: circulation of type 2 polioviruses derived from the Sabin vaccine strain in the wastewater of New York, London and Jerusalem; risk of transmission of Sars-CoV-2 during the spreading of sludge from wastewater treatment plants on agricultural land in the era of the Covid-19 pandemic; « new ¼ forms of food-borne poisoning of viral origin (hepatitis E, tick-borne encephalitis, Nipah virus infection); contamination by epidemic viruses of mobile phones used by pediatricians; role of fomites in the spread of orthopoxvirus infections (smallpox, cowpox, monkeypox). The risk attached to animal viruses present in the environment must be assessed in a measured way without overestimating or underestimating their potential consequences for human health.

Monitoring of Both Humoral and Cellular Immunities Could Early Predict COVID-19 Vaccine Efficacy Against the Different SARS-CoV2 Variants.

Reliable immunoassays are essential to early predict and monitor vaccine efficacy against SARS-CoV-2. The performance of an Interferon Gamma Release Assay (IGRA, QuantiFERON® SARS-CoV-2), and a current anti-spike serological test, compared to a plaque reduction neutralization test (PRNT) taken as gold standard were compared. Eighty vaccinated individuals, whose 16% had a previous history of COVID-19, were included in a longitudinal prospective study and sampled before and two to four weeks after each dose of vaccine. In non-infected patients, 2 doses were required for obtaining both positive IGRA and PRNT assays, while serology was positive after one dose. Each dose of vaccine significantly increased the humoral and cellular response. By contrast, convalescent subjects needed a single dose of vaccine to be positive on all 3 tests. Both IGRA and current serology assay were found predictive of a positive titer of neutralizing antibodies that is correlated with vaccine protection. Patients over 65 or 80 years old had a significantly reduced response. The response tended to be better with the heterologous scheme (vs. homologous) and with the mRNA-1273 vaccine (vs. BNT162b2) in the homologous group, in patients under 55 and under 65 years old, respectively. Finally, decrease intensity or absence of IGRA response and to a less extent of anti-spike serology were also correlated to reinfection which has occurred during the follow up. In conclusion, both IGRA and current anti-spike serology assays could be used at defined thresholds to monitor the vaccine response against SARS-CoV-2 and to simply identify non-responding individuals after a complete vaccination scheme. Two available specific tests (IGRA and anti-spike antibodies) could early assess the vaccine-induced immunity against SARS-CoV-2 at the individual scale, to potentially adapt the vaccination scheme in non-responder patients.

Impact of Dextran-Sodium-Sulfate-Induced Enteritis on Murine Cytomegalovirus Reactivation.

(1) Background: Ulcerative colitis (UC) is an inflammatory bowel disease that causes inflammation of the intestines, which participates in human cytomegalovirus (HCMV) reactivation from its latent reservoir. CMV-associated colitis plays a pejorative role in the clinical course of UC. We took advantage of a model of chemically induced enteritis to study the viral reactivation of murine CMV (MCMV) in the context of gut inflammation. (2) Methods: Seven-week-old BALB/c mice were infected by 3 × 103 plaque-forming units (PFU) of MCMV; 2.5% (w/v) DSS was administered in the drinking water from day (D) 30 to D37 post-infection to induce enteritis. (3) Results: MCMV DNA levels in the circulation decreased from D21 after infection until resolution of the acute infection. DSS administration resulted in weight loss, high disease activity index, elevated Nancy index shortening of the colon length and increase in fecal lipocalin. However, chemically induced enteritis had no impact on MCMV reactivation as determined by qPCR and immunohistochemistry of intestinal tissues. (4) Conclusions: Despite the persistence of MCMV in the digestive tissues after the acute phase of infection, the gut inflammation induced by DSS did not induce MCMV reactivation in intestinal tissues, thus failing to recapitulate inflammation-driven HCMV reactivation in human UC.

Evaluation of Rapid Lateral-Flow Tests Directed against the SARS-CoV-2 Nucleoprotein Using Viral Suspensions Belonging to Different Lineages of SARS-CoV-2.

Within the successive waves that occurred during the SARS-CoV-2 pandemic, recommendations arose to test symptomatic and contact subjects by using rapid antigen devices directed against the viral nucleocapsid protein with the aim to isolate contagious patients without delay. The objective of this study was to evaluate the ability of four rapid lateral-flow tests (RLFT) that were commercially available on the French market in 2022 to recognize various strains of SARS-CoV-2. Series of five-fold dilutions of seven viral suspensions belonging to different lineages of SARS-CoV-2 (19A, 20A, Alpha, Beta, Gamma, Delta and Omicron) were used to evaluate the analytical sensitivity of four commercially available RLFTs (manufacturers: Abbott, AAZ, Becton-Dickinson and Biospeedia). Cell culture and quantitative RT-PCR were used as references. Excellent correlations were observed for each lineage strain between the viral titer obtained via cell culture and the number of RNA copies measured by quantitative RT-PCR. Although the four tests were able to recognize all the tested variants, significant differences in terms of sensitivity were observed between the four RLFTs. Despite the limitation represented by the small number of devices and clinical isolates that were tested, this study contributed by rapidly comparing the sensitivity of SARS-CoV-2 RLFTs in the Omicron era.

Role of the humoral immune response during COVID-19: guilty or not guilty?

Systemic and mucosal humoral immune responses are crucial to fight respiratory viral infections in the current pandemic of COVID-19 caused by the SARS-CoV-2 virus. During SARS-CoV-2 infection, the dynamics of systemic and mucosal antibody infections are affected by patient characteristics, such as age, sex, disease severity, or prior immunity to other human coronaviruses. Patients suffering from severe disease develop higher levels of anti-SARS-CoV-2 antibodies in serum and mucosal tissues than those with mild disease, and these antibodies are detectable for up to a year after symptom onset. In hospitalized patients, the aberrant glycosylation of anti-SARS-CoV-2 antibodies enhances inflammation-associated antibody Fc-dependent effector functions, thereby contributing to COVID-19 pathophysiology. Current vaccines elicit robust humoral immune responses, principally in the blood. However, they are less effective against new viral variants, such as Delta and Omicron. This review provides an overview of current knowledge about the humoral immune response to SARS-CoV-2, with a particular focus on the protective and pathological role of humoral immunity in COVID-19 severity. We also discuss the humoral immune response elicited by COVID-19 vaccination and protection against emerging viral variants.

Antiviral Activities of HIV-1-Specific Human Broadly Neutralizing Antibodies Are Isotype-Dependent.

Broadly neutralizing antibodies (bNAbs) offer promising opportunities for preventing HIV-1 infection. The protection mechanisms of bNAbs involve the Fc domain, as well as their Fab counterpart. Here, different bNAb isotypes including IgG1, IgA1, IgA2, and IgA122 (IgA2 with the hinge of IgA1) were generated and then produced in CHO cells. Their ability to neutralize pseudovirus and primary HIV-1 isolates were measured, as well as their potential ADCC-like activity using a newly developed assay. In our work, gp41-specific IgA seems to be more efficient than IgG1 in inducing ADCC-like activity, but not in its virus neutralization effect. We show that either gp120-specific IgA or IgG1 isotypes are both efficient in neutralizing different viral strains. In contrast, gp120-specific IgG1 was a better ADCC-like inducer than IgA isotypes. These results provide new insights into the neutralization and ADCC-like activity of different bNAbs that might be taken into consideration when searching for new treatments or antibody-based vaccines.

Exploration of the ocular surface infection by SARS-CoV-2 and implications for corneal donation: An ex vivo study.

BACKGROUND: The risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission through corneal graft is an ongoing debate and leads to strict restrictions in corneas procurement, leading to a major decrease in eye banking activity. The aims of this study are to specifically assess the capacity of human cornea to be infected by SARS-CoV-2 and promote its replication ex vivo, and to evaluate the real-life risk of corneal contamination by detecting SARS-CoV-2 RNA in corneas retrieved in donors diagnosed with Coronavirus Disease 2019 (COVID-19) and nonaffected donors. METHODS AND FINDINGS: To assess the capacity of human cornea to be infected by SARS-CoV-2, the expression pattern of SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE-2) and activators TMPRSS2 and Cathepsins B and L in ocular surface tissues from nonaffected donors was explored by immunohistochemistry (n = 10 corneas, 78 ± 11 years, 40% female) and qPCR (n = 5 corneas, 80 ± 12 years, 40% female). Additionally, 5 freshly excised corneas (80 ± 12 years, 40% female) were infected ex vivo with highly concentrated SARS-CoV-2 solution (106 median tissue culture infectious dose (TCID50)/mL). Viral RNA was extracted from tissues and culture media and quantified by reverse transcription quantitative PCR (RT-qPCR) (viral RNA copies) 30 minutes (H0) and 24 hours (H24) after infection. To assess the risk of corneal contamination by SARS-CoV-2, viral RNA was tested by RT-qPCR (Ct value) in both corneas and organ culture media from 14 donors diagnosed with COVID-19 (74 ± 10 years, 29% female) and 26 healthy donors (79 ± 13 years, 57% female), and in organ culture media only from 133 consecutive nonaffected donors from 2 eye banks (73 ± 13 years, 29% female). The expression of receptor and activators was variable among samples at both protein and mRNA level. Based on immunohistochemistry findings, ACE-2 was localized mainly in the most superficial epithelial cells of peripheral cornea, limbus, and conjunctiva, whereas TMPRSS2 was mostly expressed in all layers of bulbar conjunctiva. A significant increase in total and positive strands of IP4 RNA sequence (RdRp viral gene) was observed from 30 minutes to 24 hours postinfection in central cornea (1.1 × 108 [95% CI: 6.4 × 107 to 2.4 × 108] to 3.0 × 109 [1.4 × 109 to 5.3 × 109], p = 0.0039 and 2.2 × 107 [1.4 × 107 to 3.6 × 107] to 5.1 × 107 [2.9 × 107 to 7.5 × 107], p = 0.0117, respectively) and in corneoscleral rim (4.5 × 109 [2.7 × 109 to 9.6 × 109] to 3.9 × 1010 [2.6 × 1010 to 4.4 × 1010], p = 0.0039 and 3.1 × 108 [1.2 × 108 to 5.3 × 108] to 7.8 × 108 [3.9 × 108 to 9.9 × 108], p = 0.0391, respectively). Viral RNA copies in ex vivo corneas were highly variable from one donor to another. Finally, viral RNA was detected in 3 out of 28 corneas (11%) from donors diagnosed with COVID-19. All samples from the 159 nonaffected donors were negative for SARS-CoV-2 RNA. The main limitation of this study relates to the limited sample size, due to limited access to donors diagnosed with COVID-19 and concomitant decrease in the procurement corneas from nonaffected donors. CONCLUSIONS: In this study, we observed the expression of SARS-CoV-2 receptors and activators at the human ocular surface and a variable increase in viral RNA copies 24 hours after experimental infection of freshly excised human corneas. We also found viral RNA only in a very limited percentage of donors with positive nasopharyngeal PCR. The low rate of positivity in donors diagnosed with COVID-19 calls into question the utility of donor selection algorithms. TRIAL REGISTRATION: Agence de la Biomédecine, PFS-20-011 https://www.agence-biomedecine.fr/.

Prospective evaluation of the point-of-care use of a rapid antigenic SARS-CoV-2 immunochromatographic test in a paediatric emergency department.

OBJECTIVES: This study aimed to evaluate the immunochromatographic coronavirus disease 2019 (COVID-19) speed antigen test (BioSpeedia, France) as an antigen point-of-care test (AgPOCT) to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at the paediatric emergency department of the University Hospital of Saint-Etienne in France. METHODS: Between 15 January and 28 May, 2021, children presenting with respiratory symptoms compatible with COVID-19 infection (symptomatic group) or those requiring hospitalization for any reason (asymptomatic group) were included prospectively and received a nasopharyngeal aspiration to carry out both AgPOCT and quantitative reverse transcription (RT) PCR (RT-qPCR) tests, with the latter being used as the reference standard, for the diagnosis of SARS-CoV-2 infection. RESULTS: Among the 1009 enrolled children, we obtained a result from both techniques for 990: 33 (3.3%) tested positive with AgPOCT and 46 (4.6%) with RT-qPCR. The overall sensitivity and specificity of the AgPOCT were 69.6% (95% confidence interval (CI), 54.3-82.3) and 99.9% (95% CI, 99.4-100), respectively, compared with the RT-qPCR. Sensitivity increased to 82.9% (95% CI, 66.4-93.4) in symptomatic children. The mean cycle threshold value was significantly lower in positive samples for AgPOCT than in negative samples in the overall population and in both the symptomatic and asymptomatic groups. DISCUSSION: The use of the COVID-19 speed antigen test at the bedside in the emergency department has satisfactory performance for diagnosing SARS-CoV-2 infection in symptomatic children.

Gingival tissue as a reservoir for human immunodeficiency virus type 1: Preliminary results of a cross-sectional observational study.

BACKGROUND: Despite combined antiretroviral therapy (cART), total cure of immunodeficiency virus type 1 (HIV-1) infection remains elusive. Chronic periodontitis (CP) is strongly associated with HIV-1 infection. This condition is characterized by an intense inflammatory infiltrate mainly constituted of immune cells which in turn may be a valuable source of HIV-1 reactivation. This study aimed to determine if gingival tissue could act as a reservoir for HIV-1. METHODS: Twelve patients with HIV-1 and CP and 12 controls (no HIV-1-infection and no CP) were evaluated in a cross-sectional study. RNA viral load and interleukin (IL) levels were determined in blood plasma and saliva. Histological sections of gingival tissue were stained with fluorescent antibodies against p24 antigen and different cellular biomarkers. RESULTS: In six of the 12 patients, HIV RNA load was detected, despite cART; in three of them, expression of viral RNA was also detected in saliva. The levels of IL-2, IL-6, and IL-12 were higher in blood and saliva of patients with HIVand CP than controls. HIV-1 p24 antigen was detected by immunostaining in gingival biopsies of 10 of the 12 patients but in no controls. Immune markers for T cells and antigen-presenting cells were also identified in most patients and some controls. CONCLUSION: These preliminary data showing the detection of HIV-1 p24 antigen in the gingival biopsies of a significant part of patients with HIV-1 and CP under cART together with the presence of immune cells, plead for the existence of a HIV-1 reservoir in the gingival tissue of this population.

Diagnostic Accuracy of Dried Plasma Spot Specimens for HIV-1 Viral Load Testing: A Systematic Review and Meta-analysis.

BACKGROUND: Dried plasma spot specimens may be a viable alternative to traditional liquid plasma in field settings, but the diagnostic accuracy is not well understood. METHODS: Standard databases (PubMed and Medline), conferences, and gray literature were searched until January 2019. The quality of evidence was evaluated using the Standards for Reporting Studies of Diagnostic Accuracy and Quality Assessment of Diagnostic Accuracy Studies-2 criteria. We used univariate and bivariate random effects models to determine misclassification, sensitivity, and specificity across multiple thresholds, overall and for each viral load technology, and to account for between-study variation. RESULTS: We identified 23 studies for inclusion in the systematic review that compared the diagnostic accuracy of dried plasma spots with that of plasma. Primary data from 16 of the 23 studies were shared and included in the meta-analysis, representing 18 countries, totaling 1847 paired dried plasma spot:plasma data points. The mean bias of dried plasma spot specimens compared with that of plasma was 0.28 log10 copies/mL, whereas the difference in median viral load was 2.25 log10 copies/mL. More dried plasma spot values were undetectable compared with plasma values (43.6% vs. 29.8%). Analyzing all technologies together, the sensitivity and specificity of dried plasma spot specimens were >92% across all treatment failure thresholds compared and total misclassification <5.4% across all treatment failure thresholds compared. Some technologies had lower sensitivity or specificity; however, the results were typically consistent across treatment failure thresholds. DISCUSSION: Overall, dried plasma spot specimens performed relatively well compared with plasma with sensitivity and specificity values greater than 90% and misclassification rates less than 10% across all treatment failure thresholds reviewed.

Evidence of HIV-1 Genital Shedding after One Year of Antiretroviral Therapy in Females Recently Diagnosed in Bamako, Mali.

Little is known about the dynamic of HIV-1 shedding and resistance profiles in the female genital reservoir after antiretroviral therapy (ART) initiation in resource-limited countries (RLCs), which is critical for evaluating the residual sexual HIV-1 transmission risk. The present study aimed to evaluate the efficacy of 1 year duration ART at blood and genital levels in females newly diagnosed for HIV-1 from three centers in Bamako, Mali. Seventy-eight consenting females were enrolled at the time of their HIV-1 infection diagnosis. HIV-1 RNA loads (Abbott Real-Time HIV-1 assay) were tested in blood and cervicovaginal fluids (CVF) before and 12 months after ART initiation. Primary and acquired resistances to ART were evaluated by ViroseqTM HIV-1 genotyping assay. The vaginal microbiota was analyzed using IonTorrentTM NGS technology (Thermo Fisher Scientific). Proportions of primary drug resistance mutations in blood and CVF were 13.4% and 25%, respectively. Discrepant profiles were observed in 25% of paired blood/CVF samples. The acquired resistance rate was 3.1% in blood. At month 12, undetectable HIV-1 RNA load was reached in 84.6% and 75% of blood and CVF samples, respectively. A vaginal dysbiosis was associated with HIV RNA shedding. Our findings emphasize the need of reinforcing education to improve retention in care system, as well as the necessity of regular virological monitoring before and during ART and of implementing vaginal dysbiosis diagnosis and treatment in RLCs.

Immunogenicity and efficacy of          heterologous ChAdOx1-BNT162b2 vaccination.

Following severe adverse reactions to the AstraZeneca ChAdOx1-S-nCoV-19 vaccine1,2, European health authorities recommended that patients under the age of 55 years who received one dose of ChAdOx1-S-nCoV-19 receive a second dose of the Pfizer BNT162b2 vaccine as a booster. However, the effectiveness and the immunogenicity of this vaccination regimen have not been formally tested. Here we show that the heterologous ChAdOx1-S-nCoV-19 and BNT162b2 combination confers better protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than the homologous BNT162b2 and BNT162b2 combination in a real-world observational study of healthcare workers (n = 13,121). To understand the underlying mechanism, we conducted a longitudinal survey of the anti-spike immunity conferred by each vaccine combination. Both combinations induced strong anti-spike antibody responses, but sera from heterologous vaccinated individuals displayed a stronger neutralizing activity regardless of the SARS-CoV-2 variant. This enhanced neutralizing potential correlated with increased frequencies of switched and activated memory B cells that recognize the SARS-CoV-2 receptor binding domain. The ChAdOx1-S-nCoV-19 vaccine induced a weaker IgG response but a stronger T cell response than the BNT162b2 vaccine after the priming dose, which could explain the complementarity of both vaccines when used in combination. The heterologous vaccination regimen could therefore be particularly suitable for immunocompromised individuals.