Evaluation of the ELITechGroup solution for plasma HIV-1 RNA quantification.

In the last few years, many manufacturers have developed new kits for plasma HIV-1 RNA quantification. Recently, a solution consisting of the ELITe InGenius® instrument and the HIV1 ELITe MGB®kit has been commercialized worldwide. Our aim was to compare its clinical performance with the Aptima® HIV-1 Quant Dx kit by Hologic, on a panel of HIV-1 group M circulating variants, representative of viral load levels found during the pre- and post-treatment follow-up of patients. The linearity was evaluated on the AcroMetrix® HIV-1 Panel. Clinical specificity was evaluated on 100 plasma samples negative for HIV; and clinical sensitivity and sequential follow-up were evaluated on 166 HIV-1 positive plasma samples from 126 patients. The linearity data showed a difference obtained for each point of less than 0.2 Log cp/mL. No amplification was found for the 100 HIV negative clinical specimens. The overall agreement between the two kits was 83.7 %; the differences corresponded to a slightly higher detection for the Aptima kit (with more samples detected below the lower limit of quantification). A Bland & Altman analysis of the quantifiable samples showed a mean difference of -0.05 Log and Spearman's coefficient was 0.975. Only six samples presented discrepancies (above 0.5 Log), but these differences were overall similar between the two kits. Our study has shown that the HIV1 ELITe MGB® Kit can be successfully used for the monitoring of patients infected with various epidemic HIV-1 strains, and for the precise quantification of the viral load.

Knowledge, attitudes and practices of French university students towards COVID-19 prevention-are health students better?

During the COVID-19 outbreak in 2020, public health measures (PHM) were implemented to prevent the spread of SARS-CoV-2. At university, we wondered whether health students would be more likely to comply with these safety measures against infectious disease transmission compared to other students. Thus, we collected 1 426 university students' responses to an online anonymous survey to describe their knowledge, attitudes and practices (KAP) of COVID-19 prevention measures and to compare the opinions and practices of health students and science students at the same university of Rouen Normandy (France). A higher proportion of science students (84.6%) compared to health students (73.9%) reported knowledge of the university's COVID-19 protocol, p<0.001. However, the health students compared to science students reported a higher compliance with PHM at home (91.4% vs 88.0%) and at university (94.1% vs 91.1%). In a multiple regression analysis, after adjustment for age, sex and university department, factors associated with higher compliance with PHM were knowledge of the university's COVID-19 protocol and a high perceived efficacy of PHM. A SARS-CoV-2 PCR result was not predictive of compliance with PHM. The results of this online survey in French students show a high level of knowledge and practices of COVID-19 prevention Although their performances could still be improved by training, the good results of health students regarding knowledge, attitudes and practices are encouraging as these students could be an added backup force to fight against viral pandemics.

Performance Analysis of Three Commercial Kits Designed for RNA Quantification of HIV-1 Group O Variants.

BACKGROUND: The genetic divergence of HIV-1 group O is high relative to pandemic group M, which could impact detection and quantification of plasma RNA. Recent commercial kits for RNA quantification seem to show good performances in HIV-1/O, but discrepancies are still observed. Here, we compare the performances of 3 commercial assays for the RNA quantification of HIV-1/O. METHODS: We studied the RNA quantification of 117 clinical samples using Abbott RealTime HIV-1, Cepheid Xpert HIV-1 Viral Load, or Roche Cobas TaqMan HIV-1 v2. First, we conducted a qualitative description, and second, we focused on a quantitative analysis of the results above 40 cp/mL. The degree of agreement between methods and the strength of the correlation of viral load determination were estimated using Bland-Altman plot and Passing-Bablok regression with the Spearman coefficient, respectively. RESULTS: Our 2-by-2 analysis showed that the Abbott and Cepheid assays were very close in terms of correlation and dispersion of points, whereas Roche presented higher values in the highest range of quantification (>5 log10). The Cepheid assay combined better correlation with the consensus value and a lower dispersion of values, leading to an overall better performance of quantification. The quantification was still impacted by intragroup genetic diversity with, here, 1 strain (YBF26). CONCLUSIONS: Using a new approach to compare the performances of RNA quantification between more than 2 techniques, we demonstrated that Cepheid could be the most suitable assay for HIV-1/O quantification, although the results from all assays remained strain dependent.

Forgiveness of Dolutegravir-Based Triple Therapy Compared With Older Antiretroviral Regimens: A Prospective Multicenter Cohort of Adherence Patterns and HIV-RNA Replication.

BACKGROUND: For many people with HIV (PWH), taking antiretroviral therapy (ARV) every day is difficult. METHODS: Average adherence (Av-Adh) and log-transformed treatment interruption (TI) to ARV were prospectively measured over 6 months using electronic drug monitoring (EDM) in several cohorts of PWH. Multivariate linear regression models including baseline confounders explored the influence of EDM-defined adherence (R 2) on 6-month log10 HIV-RNA. Multivariate logistic regression models were used to compare the risk of HIV-RNA detection (VR) within subgroups stratified by lower (≤95%) and higher (>95%) Av-Adh. RESULTS: Three hundred ninety-nine PWH were analyzed with different ARVs: dolutegravir (n = 102), raltegravir (n = 90), boosted PI (bPI; n = 107), and NNRTI (n = 100). In the dolutegravir group, the influence of adherence pattern measures on R 2 for HIV-RNA levels was marginal (+2%). Av-Adh, TI, and Av-Adh × TI increased the R 2 for HIV-RNA levels by 54% and 40% in the raltegravir and bPI treatment groups, respectively. TI increased the R 2 for HIV-RNA levels by 36% in the NNRTI treatment group. Compared with the dolutegravir-based regimen, the risk of VR was significantly increased for raltegravir (adjusted odds ratio [aOR], 45.6; 95% CI, 4.5-462.1; P = .001), NNRTIs (aOR, 24.8; 95% CI, 2.7-228.4; P = .005), and bPIs (aOR, 28.3; 95% CI, 3.4-239.4; P = .002) in PWH with Av-Adh ≤95%. Among PWH with >95% Av-Adh, there were no significant differences in the risk of VR among the different ARVs. CONCLUSIONS: These findings support the concept that dolutegravir in combination with 2 other active ARVs achieves greater virological suppression than older ARVs, including raltegravir, NNRTI, and bPI, among PWH with lower adherence.

Comparative Immunovirological and Clinical Responses to Antiretroviral Therapy Between HIV-1 Group O and HIV-1 Group M Infected Patients.

BACKGROUND: Little is known about impact of genetic divergence of human immunodeficiency virus type 1 group O (HIV-1/O) relative to HIV-1 group M (HIV-1/M) on therapeutic outcomes. We aimed to determine if responses to standardized combination antiretroviral therapy (cART) were similar between groups despite strain divergence. METHODS: We performed an open nonrandomized study comparing the immunological, virological, and clinical responses to cART based on 2 nucleoside reverse transcriptase inhibitors plus 1 ritonavir-boosted protease inhibitor, in naive and paired HIV-1/O vs HIV-1/M infected (+) patients (ratio 1:2), matched on several criteria. The primary endpoint was the proportion of patients with undetectable plasma viral load (pVL, threshold 60 copies/mL) at week (W) 48. Secondary endpoints were the proportion of patients with undetectable pVL at W24 and W96 and CD4 evolution between baseline and W24, W48, and W96. RESULTS: Forty-seven HIV-1/O+ and 94 HIV-1/M+ patients were included. Mean pVL at baseline was significantly lower by 1 log for HIV-1/O+ vs HIV-1/M+ patients. At W48, no significant difference was observed between populations with undetectable pVL and differences at W24 and W96 were not significant. A difference in CD4 gain was observed in favor of HIV-1/M at W48 and W96, but this was not significant when adjusted on both matched criteria and pVL at baseline. CONCLUSIONS: Our data demonstrate similar immunovirological and clinical response between HIV-1/O+ and HIV-1/M+ patients. They also reveal significantly lower baseline replication for HIV-1/O variants, suggesting specific virological properties and physiopathology that now need to be addressed. CLINICAL TRIALS REGISTRATION: NCT00658346.

Virological response to integrase strand transfer inhibitor-based antiretroviral combinations in HIV-1 group O-infected patients.

: Although integrase strand transfer inhibitors (INSTIs) are widely used in HIV-1 group M (HIV-1/M) infections, little is known about their efficacy against genetically divergent HIV-1 group O (HIV-1/O) strains. Previous phenotypic works have demonstrated the variable susceptibility of HIV-1/O strains, depending on INSTI drugs. Clinical data are very limited and obtained from a few patients. OBJECTIVES: To investigate the virological success rate of an INSTI-based combination of antiretroviral therapy (cART) in a large population of HIV-1/O-infected patients, and to describe resistance-associated mutations (RAM) at virological failure. METHODS: The virological response of 39 patients receiving INSTI-based cART during their follow-up was analysed i) at the last point of the first INSTI initiation and ii) at their most recent visit. RAM analysis was performed at virological failures. Resistance interpretation was based on the French National Agency of Research on AIDS and viral hepatitis (ANRS) rules. RESULTS: Virological success at both time points of analysis was high, with more than 87% of the patients with undetectable plasma viral load. Among the six patients with virological failure, three selected RAM described for HIV-1/M resistance, and two had already RAM, before INSTI initiation. CONCLUSION: Our results show that HIV-1/O infected patients receiving INSTI-based cART presented a high rate of virological success whatever their previous lines; we have also shown that resistance rules for HIV-1/M could be considered when failure occurs. These data are of importance especially in the context of WHO recommendations for a wider use of this class.

Human Immunodeficiency Virus Type 1 Group O Infection in France: Clinical Features and Immunovirological Response to Antiretrovirals.

Background: To obtain reliable clinical data of human immunodeficiency virus type 1 group O (HIV-1/O) infection, and immunovirological responses to combination antiretroviral therapy (cART), in a large series of 101 patients. Methods: Piecewise linear models were used to estimate CD4 count before and after cART initiation. Kaplan-Meier survival curves were used to estimate time to reach clinical stage C before antiretroviral therapy (ART) and to analyze time to achieve a plasma viral load (pVL) <40 copies/mL following cART initiation. Immunovirological response was assessed at the most recent visit in patients on active follow-up. Results: Data showed a 16.6% cumulative probability of reaching stage C within 5 years following diagnosis, and a mean CD4 decrease of -30.5 cells/µL/year. cART initiation in ART-naive patients led to a mean CD4 gain of 147 cells/µL after 12 months, and to a median pVL of <40 copies/mL after 3.8 months for 89.3%. Initiation with a nonrecommended nonnucleoside reverse transcriptase inhibitor-based vs a ritonavir-boosted protease inhibitor-based regimen resulted in a much smaller gain of around 100 CD4 cells/µL after 1 year. Patients on follow-up since 2007 had a median CD4 count of 498 cells/µL, and 87% had a pVL <40 copies/mL at the most recent follow-up visit. Conclusions: This work provides unique data on HIV-1/O infection, in favor of a milder natural evolution than HIV-1 group M (HIV-1/M) and of a highly efficient current management, based on HIV-1/M guidelines, despite genetic divergence. Studies of comparable HIV-1/M and HIV-1/O populations are needed to confirm these results.

Antiretroviral Therapy as Prevention of Pneumococcal Infections?

BACKGROUND: Despite antiretroviral therapy, it is generally believed that the risk for pneumococcal infections (PnIs) is high among patients infected with human immunodeficiency virus (HIV). However, most studies in this field have been conducted before 2010, and the proportion of virologically suppressed patients has drastically increased in these latter years thanks to larger indications and more effective antiretroviral regimens. This study aimed to re-evaluate the current risk of PnI among adult patients infected with HIV. METHODS: The incidence of PnI was evaluated between 1996 and 2014 in 2 French regional hospitals. The 80 most recent cases of PnI (2000-2014) were retrospectively compared with 160 controls (HIV patients without PnI) to analyze the residual risk factors of PnI. RESULTS: Among a mean annual follow-up cohort of 1616 patients, 116 PnIs were observed over 18 years. The risk factors of PnI among patients infected with HIV were an uncontrolled HIV infection or "classic" risk factors of PnI shared by the general population such as addiction, renal or respiratory insufficiency, or hepatitis B or C coinfection. Pneumococcal vaccination coverage was low and poorly targeted, because only 5% of the cases had been previously vaccinated. The incidence of invasive PnIs among HIV patients with a nonvirologically suppressed infection or comorbidities was 12 times higher than that reported in the general population at the country level (107 vs 9/100000 patients), whereas the incidence among virologically suppressed HIV patients without comorbidities was lower (7.6/100000 patients). CONCLUSIONS: Human immunodeficiency virus infection no longer per se seems to be a significant risk factor for PnI, suggesting a step-down from a systematic to an "at-risk patient" targeted pneumococcal vaccination strategy.

Low immune response to hepatitis B vaccine among children in Dakar, Senegal.

HBV vaccine was introduced into the Expanded Programme on Immunization (EPI) in Senegal and Cameroon in 2005. We conducted a cross-sectional study in both countries to assess the HBV immune protection among children. All consecutive children under 4 years old, hospitalized for any reason between May 2009 and May 2010, with an immunisation card and a complete HBV vaccination, were tested for anti-HBs and anti-HBc. A total of 242 anti-HBc-negative children (128 in Cameroon and 114 in Senegal) were considered in the analysis. The prevalence of children with anti-HBs ≥ 10 IU/L was higher in Cameroon with 92% (95% CI: 87%-97%) compared to Senegal with 58% (95% CI: 49%-67%), (p<0.001). The response to vaccination in Senegal was lower in 2006-2007 (43%) than in 2008-2009 (65%), (p = 0.028). Our results, although not based on a representative sample of Senegalese or Cameroonian child populations, reveal a significant problem in vaccine response in Senegal. This response problem extends well beyond hepatitis B: the same children who have not developed an immune response to the HBV vaccine are also at risk for diphtheria, tetanus, pertussis (DTwP) and Haemophilus influenzae type b (Hib). Field biological monitoring should be carried out regularly in resource-poor countries to check quality of the vaccine administered.

Impact of HIV-1 group O genetic diversity on genotypic resistance interpretation by algorithms designed for HIV-1 group M.

BACKGROUND: HIV-1 group O (HIV-O) is characterized by a high genetic divergence from HIV-1 group M viruses. Little is known about the therapeutic impact of this diversity. The aim of this study was to assess in a large series of samples (1) the genotypic impact of natural polymorphism of the HIV-O reverse transcriptase and protease genes; and (2) the predictive value of resistance interpretation algorithms developed for HIV-1 group M when used for highly mutated HIV-O viruses. METHODS: Sixty-eight antiretroviral-naive and 9 highly antiretroviral-experienced HIV-O-infected patients were included. The viruses were sequenced and resistance-associated mutations were identified using 3 different algorithms (Agence Nationale de Recherches sur le SIDA et les hépatites virales, Rega, Stanford). RESULTS: All HIV-O samples naturally exhibited the A98G and V179E resistance mutations in the reverse transcriptase region; 54% of samples presented the Y181C mutation, conferring resistance to nonnucleoside reverse transcriptase inhibitors. Twelve minor resistance mutations, present in more than 75% of the protease sequences, led to the different algorithms giving discrepant results for nelfinavir and saquinavir susceptibility. A marked virological response was observed in 8 of the 9 antiretroviral-experienced patients, despite the prediction of limited activity of the combination for 5 to 8 patients according to the algorithm used. CONCLUSIONS: The high level of natural polymorphism in HIV-O genes, and the important discrepancies between genotypic resistance interpretation and the virological response, emphasize the need for resistance algorithm rules better adapted to HIV-O.