Inflammatory profile of vertically HIV-1 infected adolescents receiving ART in Cameroon: a contribution toward optimal pediatric HIV control strategies

Antiretroviral therapy (ART) has improved the lifespan of people living with HIV. However, their immune system remains in a state of sustained activation/inflammation, which favors viral replication and depletion of helper T-cells with varying profiles according to ART-response. We herein sought to ascertain the inflammatory profile of adolescents living with perinatal HIV-1 infection (ALPHI) receiving ART in an African context. In this cross-sectional and comparative study among ART-experienced ALPHI in Yaoundé-Cameroon, HIV-1 RNA was measured by Abbott Real-time PCR; CD4 cells were enumerated using flow cytometry; serum cytokines were measured by ELISA; HIV-1 proviral DNA was genotyped by Sanger-sequencing; and archived drug resistance mutations (ADRMs) were interpreted using Stanford HIVdb.v9.0.1. Overall, 73 adolescents were enrolled (60 ALPHI and 13 HIV-1 negative peers) aged 15 (13-18) years; 60.00% were female. ART median duration was 92 (46-123) months; median viral load was 3.99 (3.17-4.66) RNA Log10 (copies)/mL and median CD4 count was 326 (201-654) cells/mm3. As compared to HIV-negative adolescents, TNFα was highly expressed among ALPHI (p<0.01). Following a virological response, inflammatory cytokines (IFNγ and IL-12), anti-inflammatory cytokines (IL-4 and IL-10) and inflammation-related cytokines (IL-6 and IL-1β) were highly expressed with viral suppression (VS) vs. virological failure (VF), while the chemokine CCL3 was highly expressed with VF (p<0.01). Regarding the immune response, the inflammatory cytokine TNFα was highly expressed in those that are immunocompetent (CD4≥500 cell/mm3) vs. immunocompromised (CD4<500 cell/mm3), p ≤ 0.01; while chemokine CCL2 was highly expressed in the immunocompromised (p<0.05). In the presence of ADRMs, IL-4 and CCL3 were highly expressed (p=0.027 and p=0.043 respectively). Among ART-experienced ALPHI in Cameroon, the TNFα cytokine was found to be an inflammatory marker of HIV infection; IFNγ, IL-1β, IL-6, and IL-12 are potential immunological markers of VS and targeting these cytokines in addition to antiretroviral drugs may improve management. Moreover, CCL3 and CCL2 are possible predictors of VF and/or being immunocompromised and could serve as surrogates of poor ART response

Genotypic resistance testing improves antiretroviral treatment outcomes in a cohort of adolescents in Cameroon: Implications in the dolutegravir‑era

Background: Acquired drug resistance (ADR) is common among adolescents living with perinatal HIV (APHI) in sub-Saharan Africa (SSA). Personalized management has the potential to improve pediatric antiretroviral therapy (ART), even in the presence of long-term treatment and HIV-1 subtype diversity. Objective: We sought to evaluate the effect of HIV-1 mutational profiling on immuno-virological response and ADR among APHI. Methods: A cohort-study was conducted from 2018-2020 among 311 APHI receiving ART in Cameroon. Clinical, immunological and virological responses were measured at enrolment (T1), 6-months (T2) and 12-months (T3). Immunological failure (IF: CD4<250 cells/mm3), VF (viremia≥1000 copies/ml), and ADR were analyzed, with p<0.05 considered significant. Results: Mean age was 15(±3) years; male-female ratio was 1:1; median [IQR] ART-duration was 36[21-81] months. At T1, T2, and T3 respectively, adherence-level was 66.4%, 58.3% and 66.5%; 14 viral clades were found, driven by CRF02_AG (58.6%); ADR-mutations favored increased switch to second-line ART (16.1%, 31.2%, and 41.9%, p<0.0001). From T1-T3 respectively, there were declining rates of IF (25.5%, 18.9%, and 9.83, p<0.0001), VF (39.7%, 39.9%, and 28.2%, p=0.007), and HIVDR (96.4%, 91.7%, and 85.0%, p=0.099). Predictors of ADR were being on first-line ART (p=0.045), high viremia at enrolment (AOR=12.56, p=0.059), and IF (AOR=5.86, p=0.010). Of note, optimized ART guided by mutational profile (AOR=0.05, p=0.002) was protective. Moreover, full Tenofovir+Lamivudine+Dolutegravir efficacy was predicted in 77% and 62% of APHI respectively after first- and second-line failure. Conclusions: Among APHI in this SSA setting, viral mutational profiling prompts the use of optimized Dolutegravir-based ART regimens, leading to improved immuno-virological response and declining ADR burdens. Thus, implementing personalized HIV medicine in this vulnerable population would substantially improve ART response and the achievement of the 95-95-95 goals in these underserved populations

Inflammatory profile of vertically HIV-1 infected adolescents receiving ART in Cameroon: a contribution toward optimal pediatric HIV control strategies

Antiretroviral therapy (ART) has improved the lifespan of people living with HIV. However, their immune system remains in a state of sustained activation/inflammation, which favors viral replication and depletion of helper T-cells with varying profiles according to ART-response. We herein sought to ascertain the inflammatory profile of adolescents living with perinatal HIV-1 infection (ALPHI) receiving ART in an African context. In this cross-sectional and comparative study among ART-experienced ALPHI in Yaoundé-Cameroon, HIV-1 RNA was measured by Abbott Real-time PCR; CD4 cells were enumerated using flow cytometry; serum cytokines were measured by ELISA; HIV-1 proviral DNA was genotyped by Sanger-sequencing; and archived drug resistance mutations (ADRMs) were interpreted using Stanford HIVdb.v9.0.1. Overall, 73 adolescents were enrolled (60 ALPHI and 13 HIV-1 negative peers) aged 15 (13-18) years; 60.00% were female. ART median duration was 92 (46-123) months; median viral load was 3.99 (3.17-4.66) RNA Log10 (copies)/mL and median CD4 count was 326 (201-654) cells/mm3. As compared to HIV-negative adolescents, TNFα was highly expressed among ALPHI (p&lt;0.01). Following a virological response, inflammatory cytokines (IFNγ and IL-12), anti-inflammatory cytokines (IL-4 and IL-10) and inflammation-related cytokines (IL-6 and IL-1β) were highly expressed with viral suppression (VS) vs. virological failure (VF), while the chemokine CCL3 was highly expressed with VF (p&lt;0.01). Regarding the immune response, the inflammatory cytokine TNFα was highly expressed in those that are immunocompetent (CD4≥500 cell/mm3) vs. immunocompromised (CD4&lt;500 cell/mm3), p ≤ 0.01; while chemokine CCL2 was highly expressed in the immunocompromised (p&lt;0.05). In the presence of ADRMs, IL-4 and CCL3 were highly expressed (p=0.027 and p=0.043 respectively). Among ART-experienced ALPHI in Cameroon, the TNFα cytokine was found to be an inflammatory marker of HIV infection; IFNγ, IL-1β, IL-6, and IL-12 are potential immunological markers of VS and targeting these cytokines in addition to antiretroviral drugs may improve management. Moreover, CCL3 and CCL2 are possible predictors of VF and/or being immunocompromised and could serve as surrogates of poor ART response

Acute Amazon toxoplasmosis in immunocompetent patients: a descriptive study of 42 cas in French Guiana

International audienc

A randomized study of defibrillator lead implantations in the right ventricular mid-septum versus the apex: the SEPTAL study.

International audienceINTRODUCTION: The study was designed to evaluate the feasibility and performance of right ventricular (RV) mid-septal versus apical implantable defibrillator (ICD) lead placement. METHODS AND RESULTS: SEPTAL is a randomized, noninferiority trial, which randomly assigned patients to implantation of ICD leads in the RV mid-septum versus apex, with a primary objective of comparing the implant success rate of implant at each site, based on strict electrical predefined criteria. We also compared the (1) pacing lead characteristics, (2) rates of appropriate and inappropriate ICD therapies, and (3) all-cause mortality between the 2 sites at 1 year. The trial enrolled 215 patients (mean age = 59.7 ± 12.4 years, mean LVEF = 34.0 ± 14.2%, 84.2% men), of whom 148 (68.8%) presented with ischemic heart disease. The ICD indication was primary prevention in 117 patients (54.4%). The lead was successfully implanted in 96/107 patients (89.7%) assigned to the RV mid-septum, and in 99/108 (91.7%) assigned to the apex (ns). The 1-year rate of lead-related adverse events was similar in both groups. A total of 8 first inappropriate ICD therapies (7.9%) were delivered in the RV mid-septal group, versus 8 (7.8%) in the apical group (ns), while first appropriate therapies were delivered to 22 (21.4%) and 24 patients (23.8%), respectively (ns). All-cause mortality was 7.9% in the RV mid-septal versus 2.9% in the RV apical group (ns). CONCLUSION: This study confirmed the technical feasibility and noninferior performance of ICD leads implanted in the RV mid-septum versus the apex

Staphylococcus capitis isolated from bloodstream infections: a nationwide 3-month survey in 38 neonatal intensive care units

International audienceTo increase the knowledge about S. capitis in the neonatal setting, we conducted a nationwide 3-month survey in 38 neonatal intensive care units (NICUs) covering 56.6% of French NICU beds. We demonstrated 14.2% of S. capitis BSI (S.capBSI) among nosocomial BSIs. S.capBSI incidence rate was 0.59 per 1000 patient-days. A total of 55.0% of the S.capBSIs were late onset catheter-related BSIs. The S. capitis strains infected preterm babies (median gestational age 26 weeks, median birth weight 855 g). They were resistant to methicillin and aminoglycosides and belonged to the NRCS-A clone. Evolution was favorable in all but one case, following vancomycin treatment