RESUMEN

Introduction: This study sought to explore the immunogenicity of a booster dose of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in people living with human immunodeficiency virus (HIV) and identify the factors affecting the magnitude of anti-SARS-CoV-2 antibody levels. Materials and methods: A total of 34 people living with HIV (PLWH) and 34 healthy donors (HD) were administered a booster dose of the same SARS-CoV-2 vaccine. Anti-SARS-CoV-2 antibody and immunoglobulin G (IgG) levels were measured using the SARS-CoV-2 S protein neutralizing antibody Enzyme-Linked Immunosorbent Assay (ELISA) and 2019-nCov IgG Chemiluminescent Immunoassay Microparticles, respectively. Spearman correlation analysis was used to measure the correlation between laboratory markers and neutralizing antibody and IgG levels. Peripheral blood mononuclear cells (PBMCs) were extracted from each subject using density gradient centrifugation and the numbers of memory T and T follicular helper (Tfh) cells were determined using flow cytometry. Results: PLWH had a marked reduction in CD4 and B cell levels that was accompanied by a lower CD4/CD8 T cell ratio. However, those who received a supplementary dose of inactivated SARS-CoV-2 vaccines exhibited antibody positivity rates that were analogous to levels previously observed. The booster vaccine led to a reduction in IgG and neutralizing antibody levels and the amplitude of this decline was substantially higher in the PLWH than HD group. Correlation analyses revealed a strong correlation between neutralizing antibody levels and the count and proportion of CD4 cells. Anti-SARS-CoV-2 IgG antibody levels followed a similar trend. The expression of memory T and Tfh cells was considerably lower in the PLWH than in the HD group. Discussion: PLWH had an attenuated immune response to a third (booster) administration of an inactivated SARS-CoV-2 vaccine, as shown by lower neutralizing antibody and IgG levels. This could be attributed to the reduced responsiveness of CD4 cells, particularly memory T and cTfh subsets. CD4 and cTfh cells may serve as pivotal markers of enduring and protective antibody levels. Vaccination dose recalibration may be critical for HIV-positive individuals, particularly those with a lower proportion of CD4 and Tfh cells.

Asunto(s)

COVID-19 , Seropositividad para VIH , Humanos , Vacunas contra la COVID-19 , VIH , Células T Auxiliares Foliculares , Leucocitos Mononucleares , COVID-19/prevención & control , SARS-CoV-2 , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Inmunoglobulina G

RESUMEN

To assess the heterogeneity of HBV reverse transcriptase (RT) quasispecies during 10 years of antiviral therapy and their association with antiviral efficacy. Nineteen patients with chronic hepatitis B (CHB) infection receiving nucleos(t)ide analogues (NAs) were enrolled. Based on the antiviral efficacy after 1 year of treatment, 5 patients were grouped into an early virologic response (EVR) group, while 8 patients were grouped into a late virologic response (LVR) group. Furthermore, 6 CHB patients that had undergone antiviral treatment for 10 years were grouped into a virologic breakthrough (VBT) group. The HBV RT from each patient were amplified, cloned, and sequenced. The complexity of the RT gene in the EVR group was significantly higher than that in the LVR (P = 0.0393) and VBT groups (P = 0.0141). Phylogenetic tree analysis showed that the average branch length of the EVR and LVR groups were significantly greater than that of VBT group (P < 0.001). The complexity (at the nucleotide level) of the RT quasispecies was negatively correlated with the corresponding HBV DNA load (P = 0.0163) at one year post-antiviral treatment. Moreover, both the LVR and VBT groups accumulated more deleterious mutations than the EVR group. After 1 year of NAs treatment, the increased HBV quasispecies complexity and evolutionary topologies, coupled with less deleterious mutations, are likely associated with a favorable efficacy during long-term antiviral treatment.

Asunto(s)

Antivirales/farmacología , Heterogeneidad Genética , Virus de la Hepatitis B/enzimología , ADN Polimerasa Dirigida por ARN/genética , Adolescente , Adulto , Alanina Transaminasa/sangre , ADN Viral/genética , Femenino , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Humanos , Masculino , Adulto Joven

RESUMEN

China lacks data demonstrating associations of cervical neoplastic lesions with CD4 T-lymphocyte (CD4 cell) counts and antiretroviral therapy (ART) among HIV-infected women, suggesting relevant investigations are needed. A total of 545 HIV-infected women were enrolled in Yunnan, China, between 2011 and 2013. CD4 cell counts and ART were measured via medical records and cervical neoplastic lesions were measured by professional pathologists. Multivariable logistic models, which treated cervical intraepithelial neoplasia (CIN) 1+ and CIN2+ as outcomes, calculated adjusted odds ratio (aOR) of CD4 cell counts and ART. Subgroup analysis treating CIN1+ as the outcome was conducted by HIV infection duration (<4 vs ≥4 years), ethnicity (Han vs non-Han), and study site (Mangshi vs Kunming). The prevalence of CIN1+ and CIN2+ was 17.4% and 7.3%, respectively. Overall, 243 (44.6%) women had CD4 cell counts ≥500 cell/µL, 187 (34.3%) used ART for less than 2 years, and 236 (43.3%) used ART for at least 2 years. We found inverse associations of CIN1+ with CD4 cell counts (≥500 compared to <500 cells/µL: aOR = 0.46, 95% CI = 0.27-0.79) and ART use (<2 years: aOR = 0.43, 95% CI = 0.21-0.87; ≥2 years: aOR = 0.54, 95% CI = 0.27-1.10). Point estimates did not change substantially for CIN2+ but aORs of ART became nonsignificant. No significant interaction was observed for HIV infection duration. We found significant interaction between CD4 cell counts and ethnicity and study site in relation to CIN1+. Our study suggests potential protective effects of high CD4 cell counts against cervical neoplastic lesions among HIV-infected women, whereas associations of ART are less consistent.

Asunto(s)

Fármacos Anti-VIH/uso terapéutico , Linfocitos T CD4-Positivos/patología , Infecciones por VIH/patología , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Adulto , Anciano , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/virología , Cuello del Útero/inmunología , Cuello del Útero/patología , Cuello del Útero/virología , China/epidemiología , Etnicidad , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/etnología , Infecciones por VIH/virología , Humanos , Modelos Logísticos , Persona de Mediana Edad , Oportunidad Relativa , Prevalencia , Índice de Severidad de la Enfermedad , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/etnología , Neoplasias del Cuello Uterino/virología , Displasia del Cuello del Útero/tratamiento farmacológico , Displasia del Cuello del Útero/etnología , Displasia del Cuello del Útero/virología

RESUMEN

Background and Aims: The use of additional nucleos(t)ide analogues (NAs) without cross-resistance to previously used NAs as a rescue therapy is recommended by most international guidelines for chronic hepatitis B patients with NA-resistance. We aimed to investigate the efficacy and safety of combination therapy of peg-interferon (PegIFN) alfa-2a and NA in these patients, comparing to those who switch to an alternative NA therapy without cross-resistance. Methods: In this prospective, comparative and cohort study, data were collected from the patients' hospital records. Eligible patients were those with hepatitis B e antigen (HBeAg) positivity and resistance to one or more NAs. All patients were treated with alternative NA alone or in combination with PegIFN alfa-2a for 52 weeks or 72 weeks, respectively. HBeAg seroconversion was measured at the end of follow-up (EOF; more than 104 weeks after the end of treatment). Results: Sixty-three patients were recruited to the cohort study (NA-therapy group = 31 patients; combination therapy group of NA and PegIFN alfa-2a = 32 patients). At the EOF, significantly more patients in the combination therapy group (13/27, 48.2%) achieved primary outcome of HBeAg seroconversion than those in the NA therapy group (4/32, 12.5%) (p = 0.003). Four patients (14.8%) in the combination therapy group achieved hepatitis B surface antigen (HBsAg) loss and HBsAg seroconversion, but none in the NA therapy group did (p = 0.039). In the combination therapy group, 16 patients (51.6%) achieved HBeAg seroconversion at the end of treatment, of which, 11 patients (68.8%) maintained the response until EOF. Conclusions: Adding on PegIFN alfa-2a in combination with NA therapy might be an appropriate rescue treatment option for patients who have prior NA resistance. In addition, combination therapy induced sustained off-treatment biochemical responses in these patients.