Immune response and safety to inactivated COVID-19 vaccine: A comparison between People Living with HIV and HIV-naive individuals

Background: Multi-types COVID-19 vaccines have shown safety and efficacy against COVID-19 in adults. Although current guidelines encourage people living with HIV(PLWH) to take COVID-19 vaccines, whether their immune response to COVID-19 vaccines is distinct from HIV-free individuals is still unclear. Methods: Between March to June 2021, 48 PLWH and 40 HNC, aged 18 to 59 years, were enrolled in the study in Wuchang district of Wuhan city. All of them received inactivated COVID-19 vaccine at day 0 and the second dose at day 28. The primary safety outcome was the combined adverse reactions within 7days after each injection. The primary immunogenicity outcomes were neutralizing antibodies (nAbs) responses by chemiluminescence and total specific IgM and IgG antibodies responses by ELISA and colloidal gold at baseline (day 0), day 14, day 28, day 42, and day 70.Results: In total, the study included 46 PLWH and 38 HNC who finished 70 days’ follow-up. The frequency of adverse reactions to the first and second dose was not different between PLWH (30% and 11%) vs HNC (32% and 24%). There were no serious adverse events. NAbs responses among PLWH peaked at day 70, while among HNC peaked at day 42. At day 42, the geometric mean concentration (GMC) and seroconversion rate of nAbs among PLWH were 4.46 binding antibody units (BAU)/mL (95% CI, 3.18-5.87) and 26% (95% CI, 14-41), which were lower than that among HNC [GMC (18.28 BAU/mL, 95% CI, 10.33-32.33), seroconversion rate (63%, 95% CI, 44-79)]. IgG responses among both PLWH and HNC peaked at day 70. At day 70, the geometric mean ELISA units (GMEU) and seroconversion rate of IgG among PLWH were 0.193 ELISA units (EU)/mL (95% CI, 0.119-0.313) and 51% (95% CI, 34-69), which was lower than that among HNC [GMEU (0.379 BAU/mL, 95% CI, 0.224-0.653), seroconversion rate (86%, 95% CI, 64-97)]. Conclusion: Early humoral immune response to the inactivated COVID-19 vaccine was weaker and delayed among the PLWH population than that among HNC. This observation remained consistent regardless of a high CD4 count and a low HIV viral load suppressed by antiretroviral therapy (ART).

Quantitative Isothermal Amplification on Paper Membranes using Amplification Nucleation Site Analysis

Quantitative nucleic acid amplification tests (qNAATs) are critical in treating infectious diseases, such as in HIV viral load monitoring or SARS-CoV-2 testing, in which viral load indicates viral suppression or infectivity. Quantitative PCR is the gold standard tool for qNAATs; however, there is a need to develop point-of-care (POC) qNAATs to manage infectious diseases in outpatient clinics, low- and middle-income countries, and the home. Isothermal amplification methods are an emerging tool for POC NAATs as an alternative to traditional PCR-based workflows. Previous works have focused on relating isothermal amplification bulk fluorescence signals to input copies of target nucleic acids for sample quantification with limited success. In this work, we show that recombinase polymerase amplification (RPA) reactions on paper membranes exhibit discrete fluorescent amplification nucleation sites. We demonstrate that the number of nucleation sites can be used to quantify HIV-1 DNA and RNA in less than 20 minutes. An image-analysis algorithm quantifies nucleation sites and determines the input nucleic acid copies in the range of 67-3,000 copies per reaction. We demonstrate a mobile phone-based system for image capture and onboard processing, illustrating that this method may be used at the point-of-care for qNAATs with minimal instrumentation.

HIV and Malaria co-infection and the impact of viral load and HAART usage on the development of Plasmodium falciparum Artemisinin and Lumefantrine resistant genes in Nnewi, Anambra State, Nigeria

Background: Human Immunodeficiency virus (HIV) and malaria co-infection poses a serious health threat in sub-Saharan Africa and other endemic countries. Highly active anti-retroviral therapy (HAART) is currently used to suppress viral loads. Methods: Blood samples collected from 400 participants comprising 200 HIV sero-positive and 200 sero-negative individuals was added to EDTA sample containers. Malaria parasitemia was evaluated using standard parasitological techniques followed by PCR techniques using the Quick Load One Taq One Step Polymerase Chain Reaction (PCR) for characterization of species of Plasmodium and resistant studies using specific primers. HIV viral load estimation was done using COBAS® TaqMan® Analyzer. Results: Malaria has prevalent rate of 22.75% in the study population, while the prevalence of malaria infection among the HIV sero-positive and sero-negative is 77.0% and 23% respectively. Socio-demographic factors had no significant association with the development of resistant genes. HAART exposed individuals had prevalence of PfK13 (6.9%) and Pfmdr-1 (20.8%). Viral load was significantly related with the development of resistant genes (100%) and (86.1%) for PfK13 and Pfmdr-1 respectively. Conclusion: Unsuppressed viral load in HIV sero-positive individuals heightens the prevalence of malaria parasitaemia and increases the chances of possible emergence and spread of PfK13 and Pfmdr-1 genes.

Programmed Death Ligand-1 Expression Is Associated With Poorer Survival in Anal Squamous Cell Carcinoma

Context.— Upregulation of programmed death ligand-1 (PD-L1), an immunoregulatory protein, is associated with an adverse outcome in several malignancies. Very few studies have evaluated PD-L1 expression in invasive anal squamous cell carcinoma (ASCC). Objective.— To assess PD-L1 expression in patients with ASCC and correlate it with clinicopathologic factors and clinical outcomes. Design.— Fifty-one cases of ASCC were immunostained for PD-L1. PD-L1 expression by combined positive score and tumor proportion score was correlated with age, gender, HIV status, HIV viral load, CD4 count, stage, and outcomes. Kaplan-Meier curves for overall survival were plotted and compared using the log-rank test. Cox regression analysis was performed to identify significant prognostic factors (2-tailed P < .05 was considered statistically significant). Results.— PD-L1 was positive in 24 of 51 cases (47%) by combined positive score and in 18 of 51 (35%) by tumor proportion score. The median cancer-specific survival and 5-year overall survival were significantly lower in PD-L1+ patients. Age, gender, HIV status, HIV viral load, stage, and cancer progression were not significantly different between the two groups. CD4 count of more than 200/μL was significantly higher in PD-L1+ patients. PD-L1+ status remained statistically significant for worse overall survival on multivariate analysis. Conclusions.— PD-L1+ status is an independent adverse prognostic factor for overall survival in ASCC. This study highlights the potential of PD-L1 targeted therapy in better management of ASCC.

Evaluation of multi-assay algorithms for identifying individuals with recent HIV infection: HPTN 071 (PopART)

Background Assays and multi-assay algorithms (MAAs) have been developed for population-level cross-sectional HIV incidence estimation. These algorithms use a combination of serologic and/or non-serologic biomarkers to assess the duration of infection. We evaluated the performance of four MAAs for individual-level recency assessments. Methods Samples were obtained from 220 seroconverters (infected <1 year) and 4,396 non-seroconverters (infected >1 year) enrolled in an HIV prevention trial (HPTN 071 [PopART]); 28.6% of the seroconverters and 73.4% of the non-seroconverters had HIV viral loads ≤400 copies/mL. Samples were tested with two laboratory-based assays (LAg-Avidity, JHU BioRad-Avidity) and a point-of-care assay (rapid LAg). The four MAAs included different combinations of these assays and HIV viral load. Seroconverters on antiretroviral treatment (ART) were identified using a qualitative multi-drug assay. Results The MAAs identified between 54 and 100 (25% to 46%) of the seroconverters as recently-infected. The false recent rate of the MAAs for infections >2 years duration ranged from 0.2%-1.3%. The MAAs classified different overlapping groups of individuals as recent vs. non-recent. Only 32 (15%) of the 220 seroconverters were classified as recent by all four MAAs. Viral suppression impacted the performance of the two LAg-based assays. LAg-Avidity assay values were also lower for seroconverters who were virally suppressed on ART compared to those with natural viral suppression. Conclusions The four MAAs evaluated varied in sensitivity and specificity for identifying persons infected <1 year as recently infected and classified different groups of seroconverters as recently infected. Sensitivity was low for all four MAAs. These performance issues should be considered if these methods are used for individual-level recency assessments.

HIV-1 co-infection increases relapse rate and shortens survival in patients with visceral leishmaniasis

Patients co-infected with visceral leishmaniasis (VL) and HIV-1 (VL/HIV patients) suffer from recurrent VL relapses and increased mortality. The aim of our study was to test the hypothesis that HIV patients who present with their first episode of VL (primary VL/HIV patients) experience less relapses and lower mortality as compared to VL/HIV patients who have a previous history of VL relapses (recurrent VL/HIV patients). Our results show that primary VL/HIV patients have a lower parasite load and that their relapse-free survival is significantly longer. Relapses in both groups of patients occur independently of HIV viral load. Our clinical and immunological analyses of these patients at the time of diagnosis and during follow-up show that the poorer prognosis of recurrent VL/HIV patients is accompanied by lower weight gain and lower recovery of all blood cell lineages, as well as lower production of antigen-specific IFN-gamma, lower CD4+ T cell counts and higher expression levels of the inhibitory receptor PD1 on CD4+ and CD8+ T cells. We propose that in addition to the current treatments, novel interventions should be considered at the time of VL diagnosis in VL/HIV patients and suggest that improved anti-leishmanial and antiretroviral treatments, as well as immune therapy, through PD1/PDL-1 blockade and/or through IFN-gamma administration, could result in more efficient parasite killing and thereby reduce the relapse rate and improve survival.

Study of indicators of the immune status in HIV-infected patients with concurrent allergic pathology

Aim. To study the indicators of the immune status and manifestations of allergic diseases in HIV-infected patients in the Novgorod region. Methods. We studied the data of HIV-infected patients living in the Novgorod region for the years 20002021. A total of 1020 cases of HIV infection were studied, in which 121 (12%) patients were diagnosed with allergic reactions. In patients with allergic manifestations, the human immunodeficiency virus type 1 ribonucleic acid content was measured by the polymerase chain reaction method, and the indicators of the immune status (the content of lymphocytes, eosinophils, basophils, the levels of CD3+, CD3+CD4+, CD3+CD8+ cells, immunoregulatory index) were assessed. For statistical analysis, the Student's test (t) was used to assess the statistical significance of differences in immune status indicators, and the Pearson 2 test to assess the statistical significance of differences in allergic manifestations in patients with HIV. Results. The subjects of the study were divided into 2 groups based on the levels of HIV viral load. Analysis of these groups using the Pearson 2 test showed a statistically significant (p 0.012) correlation between high viral load and the development of drug hypersensitivity reaction in HIV-infected patients. The following etiology of allergic reactions was determined among the subjects: drug (59%), food (19%), pollen (5.7%), household (5.7%), chemical (1.9%), unspecified (6.7%). The study of the immune status in two groups did not reveal statistically significant differences (p 0.05). The study of the immune status indicators in HIV-infected patients with drug hypersensitivity reactions and different levels of viral load revealed a significantly higher level of CD3+ cells (p 0.003) in patients with drug hypersensitivity reactions and detectable viral load. Conclusion. The study revealed statistically significant differences in the immune status of HIV-infected patients with drug hypersensitivity reactions living in the Novgorod region compared with HIV-infected patients without drug allergies.

Safety and Immunogenicity of SARS-CoV-2 S-2P Protein Vaccine MVC-COV1901 in People Living with HIV

Objectives To provide data on the immune response to COVID-19 vaccines in people living with HIV (PWH), MVC-COV1901, a recombinant protein vaccine containing S-2P protein adjuvanted with CpG 1018 and aluminium hydroxide, was assessed. Methods A total of 57 PWH of ≥ 20 years of age who are on stable antiretroviral therapy and with CD4+ T cell ≥ 350 cells/mm3 and HIV viral load < 103 copies/ml were compared with 882 HIV-negative participants. Participants received 2 doses of MVC-COV1901 28 days apart. Safety and the immunogenicity were evaluated. Results No vaccine-related serious adverse events (SAEs) were recorded. Seroconversion rates (SCRs) of 100% and 99.8% were achieved in people living with HIV (PWH) and comparators, respectively, 28 days after second dose. The geometric mean titers (GMTs) (95% confidence interval [CI]) against wild type SARS-CoV-2 virus were 136.62 IU/mL (WHO Standardized International Unit) (95% CI 114.3-163.3) and 440.41 IU/mL (95% CI 421.3-460.4), for PWH and control groups, respectively, after adjusting for sex, age, BMI category, and comorbidity, and the adjusted GMT ratio of comparator/PWH was 3.22 (95% CI 2.6-4.1). A higher CD4/CD8 ratio was associated with a higher GMT (R=0.27, p=0.039). Conclusions MVC-COV1901 has shown robust safety but weaker immunogenicity responses in PWH. As a result, a third dose or booster doses of MVC-COV1901 may be appropriate for PWH.

Prevalence and Distribution of HPV Genotypes in Immunosuppressed Patients in Lorraine Region

Background: The primary objective of this work was to assess the prevalence and distribution of HPV genotypes in immunosuppressed patients, and to compare them with the French Monsonego cohort. Secondary objectives were to evaluate whether the risk of HPV infection was correlated with HIV viral load, CD4 cell count in HIV-infected patients and the type, number of immunosuppressive therapies or type of pathology (transplant vs. autoimmune diseases) in patients undergoing long-term immunosuppressive therapy. Methods: An observational, monocentric and historical study was conducted including all immunosuppressed patients having received an HPV testing, in the Laboratory of Virology, Nancy Regional Teaching Hospital Center, between 2014 and 2020. Immunosuppressed patients were either HIV-infected or received long-term immunosuppressive therapy. Results: In our cohort, the prevalence of HPV infection (75.6% vs. 16.1% p < 0.05), the proportion of patients with high-risk HPV infection (48.9% vs. 15.1% p < 0.05) and with multiple HPV infection (41.1% vs. 5.7% p < 0.05) were significantly higher than in the Monsonego cohort. HPV 52 (13%), 53 (13%) and 16 (10%) were the most common in the immunosuppressed population, while it was HPV 16, 42 and 51 in the Monsonego cohort. Conclusions: This study supports that a particular attention must be given to all the immunosuppressed patients for the screening and care of HPV-related diseases because of major modifications of HPV epidemiology compared with the overall population.