Safety and immunogenicity of heterologous COVID-19 vaccine regimens to deal with product shortage: A randomised clinical trial in an elderly population.

Objectives: In a context of COVID-19 vaccine shortages, this study sought to evaluate the safety and efficacy of receiving one dose of Gam-COVID-Vac rAd26 followed by a second COVID-19 vaccine dose of either Gam-COVID-Vac rAd5, ChAdOx1 nCoV-19 or BBIBP-CorV in a cohort of older adults. Study design: Single-centre, randomised, open label, non-inferiority trial. Methods: Adults aged ≥65 years who had received one dose of Gam-COVID-Vac rAd26 were randomised in a 1:1:1 ratio to receive a second-dose COVID-19 vaccination of either Gam-COVID-Vac rAd5, ChAdOx1 nCoV-19 or BBIBP-CorV. The primary outcome was the assessment of the humoral immune response to vaccination (i.e. antibody titres of SARS-CoV-2 spike protein at 28 days after second-dose vaccination). In addition, neutralising antibody titres at day 28 for the three schedules were measured. Results: Of 85 participants who were enrolled in the study between 26 and July 30, 2021, 31 individuals were randomised to receive Gam-COVID-Vac rAd5, 27 to ChAdOx1 nCoV-19 and 27 to BBIBP-CorV. The mean age of participants was 68.2 years (SD 2.9) and 49 (57.6%) were female. Participants who received Gam-COVID-Vac rAd5 and ChAdOx1 nCoV1-19 showed significantly increased anti-S titres at 28 days after second-dose vaccination, but this magnitude of difference was not observed for those who received BBIBP-CorV. The ratio between the geometric mean at day 28 and baseline within each group was 11.8 (6.98-19.89) among patients assigned to Gam-COVID-Vac rAd26/rAd5, 4.81 (2.14-10.81) for the rAd26/ChAdOx1 nCoV-19 group and 1.53 (0.74-3.20) for the rAd26/BBIBP-CorV group. All of the schedules were shown to be safe. Conclusions: The findings in this study contribute to the scarce information published on the safety and immunogenicity of Gam-COVID-Vac heterologous regimens and will help the development of guidelines and vaccine programme management.

Analysis of serious non-AIDS events among HIV-infected adults at Latin American sites.

OBJECTIVE: Acquired immune deficiency appears to be associated with serious non-AIDS (SNA)-defining conditions such as cardiovascular disease, liver and renal insufficiency and non-AIDS-related malignancies. We analysed the incidence of, and factors associated with, several SNA events in the LATINA retrospective cohort. MATERIALS AND METHODS: Cases of SNA events were recorded among cohort patients. Three controls were selected for each case from cohort members at risk. Conditional logistic models were fitted to estimate the effect of traditional risk factors as well as HIV-associated factors on non-AIDS-defining conditions. RESULTS: Among 6007 patients in follow-up, 130 had an SNA event (0.86 events/100 person-years of follow-up) and were defined as cases (40 with cardiovascular events, 54 with serious liver failure, 35 with non-AIDS-defining malignancies and two with renal insufficiency). Risk factors such as diabetes, hepatitis B and C virus coinfections and alcohol abuse showed an association with events, as expected. The last recorded CD4 T-cell count prior to index date (P = 0.0056, with an average difference of more than 100 cells/µL) and area under the CD4 cell curve in the year previous to index date (P = 0.0081) were significantly lower in cases than in controls. CD4 cell count at index date was significantly associated with the outcome after adjusting for risk factors. CONCLUSIONS: The incidence and type of SNA events found in this Latin American cohort are similar to those reported in other regions. We found a significant association between immune deficiency and the risk of SNA events, even in patients under antiretroviral treatment.

Motivos de internación vinculados a la infección por HIV en la era pre y post-tratamiento antirretroviral de alta eficacia / HIV patient hospitalization during the pre and post-HAART era

El objetivo del estudio fue describir y comparar las características de internación de pacientes infectadospor el HIV en dos períodos, uno previo y otro posterior a la disponibilidad del tratamientoantirretroviral de alta eficacia en nuestro medio. Diseñamos un estudio retrospectivo observacional. Se relevóla información demográfica y las características de las internaciones: motivo, días de hospitalización, evolucióny tratamiento antirretroviral al ingreso. Se revisaron 522 internaciones correspondientes a 330 pacientes en 2períodos: 1995-96 (n=289) y 2001-02 (n=233). Los motivos más frecuentes de internación fueron las enfermedadesmarcadoras de sida: 57.1% y 59.7% en los períodos 1 y 2 respectivamente. La tuberculosis fue la causaprincipal de internación en ambos períodos (23.9% y 15.5%), seguida de criptococosis (3.5% y 7.3%), neumoníapor Pneumocystis jiroveci (5.9% y 9.4%) y toxoplasmosis (6.9% y 8.6%). La mortalidad no se modificó de manerasignificativa (13.5% y 16.1%). La infección por HIV se diagnosticó en el 30% de los pacientes internados. Durante el 2º período, observamos una disminución en el número de pacientes que se internaron más de una vez (41.7% y 26.8%). El porcentaje de pacientes con tratamiento antirretroviral al ingreso aumentó del 8% al 25%. No observamos diferencias en las causas de internación y en la evolución de los pacientes en los períodos estudiados. Latuberculosis fue la enfermedad que más frecuentemente motivó la hospitalización. El número de internaciones se mantuvo estable, mientras que se observó un aumento en el número de consultas ambulatorias en ambos períodos (1678, 2512, 5670 y 7074 consultas para los años 1995, 1996, 2001 y 2002 respectivamente).(AU)

The purpose of this study was todescribe and to compare the characteristics of patient admissions during two periods, one pre HAARTand the other when HAART was fully available. A retrospective analysis of demographic data, ambulatory care information and hospitalization characteristics was performed. Causes of admission, outcome, mortality, length of hospitalization and type of antiretroviral therapy were analyzed. A total of 330 medical records were reviewed, corresponding to 522 admissions during both study periods: 1995-96 (n=289) and 2001-02 (n=233). The most frequent causes of hospitalization were AIDS defining events (period 1: 57.1%; period 2: 59.7%). Tuberculosis was the main cause of admission in both periods (23.9% and 15.5%). Criptococosis (3.5%-7.3%), Pneumocystis jiroveci pneumonia (5.9%-9.4%), and CNS toxoplasmosis (6.9 -8.6%) followed tuberculosis. Mortality did not vary significantly (13.5%-16.1%). HIV-1 infection was diagnosed at admission in 30% of cases. During 2nd period, a significant decrease in re-admission (41.6-26.8%) was observed, whereas there was an increase in the percentage of patients with previous antiretroviral treatment on admission (8%-25%). An increase in the ambulatory care clinic consultations (1995: n=1678; 1996: n=2512; 2001: n=5670; 2002: n=7074) was observed. No significant differences in the causes of admission and outcome in both periods were found. Tuberculosis is the most frequent disease that motivates hospitalization. The relation between ambulatory consultations and the amount of admissions significantly increased. (AU)

Motivos de internación vinculados a la infección por HIV en la era pre y post-tratamiento antirretroviral de alta eficacia / HIV patient hospitalization during the pre and post-HAART era

El objetivo del estudio fue describir y comparar las características de internación de pacientes infectadospor el HIV en dos períodos, uno previo y otro posterior a la disponibilidad del tratamientoantirretroviral de alta eficacia en nuestro medio. Diseñamos un estudio retrospectivo observacional. Se relevóla información demográfica y las características de las internaciones: motivo, días de hospitalización, evolucióny tratamiento antirretroviral al ingreso. Se revisaron 522 internaciones correspondientes a 330 pacientes en 2períodos: 1995-96 (n=289) y 2001-02 (n=233). Los motivos más frecuentes de internación fueron las enfermedadesmarcadoras de sida: 57.1% y 59.7% en los períodos 1 y 2 respectivamente. La tuberculosis fue la causaprincipal de internación en ambos períodos (23.9% y 15.5%), seguida de criptococosis (3.5% y 7.3%), neumoníapor Pneumocystis jiroveci (5.9% y 9.4%) y toxoplasmosis (6.9% y 8.6%). La mortalidad no se modificó de manerasignificativa (13.5% y 16.1%). La infección por HIV se diagnosticó en el 30% de los pacientes internados. Durante el 2° período, observamos una disminución en el número de pacientes que se internaron más de una vez (41.7% y 26.8%). El porcentaje de pacientes con tratamiento antirretroviral al ingreso aumentó del 8% al 25%. No observamos diferencias en las causas de internación y en la evolución de los pacientes en los períodos estudiados. Latuberculosis fue la enfermedad que más frecuentemente motivó la hospitalización. El número de internaciones se mantuvo estable, mientras que se observó un aumento en el número de consultas ambulatorias en ambos períodos (1678, 2512, 5670 y 7074 consultas para los años 1995, 1996, 2001 y 2002 respectivamente).

The purpose of this study was todescribe and to compare the characteristics of patient admissions during two periods, one pre HAARTand the other when HAART was fully available. A retrospective analysis of demographic data, ambulatory care information and hospitalization characteristics was performed. Causes of admission, outcome, mortality, length of hospitalization and type of antiretroviral therapy were analyzed. A total of 330 medical records were reviewed, corresponding to 522 admissions during both study periods: 1995-96 (n=289) and 2001-02 (n=233). The most frequent causes of hospitalization were AIDS defining events (period 1: 57.1%; period 2: 59.7%). Tuberculosis was the main cause of admission in both periods (23.9% and 15.5%). Criptococosis (3.5%-7.3%), Pneumocystis jiroveci pneumonia (5.9%-9.4%), and CNS toxoplasmosis (6.9 -8.6%) followed tuberculosis. Mortality did not vary significantly (13.5%-16.1%). HIV-1 infection was diagnosed at admission in 30% of cases. During 2nd period, a significant decrease in re-admission (41.6-26.8%) was observed, whereas there was an increase in the percentage of patients with previous antiretroviral treatment on admission (8%-25%). An increase in the ambulatory care clinic consultations (1995: n=1678; 1996: n=2512; 2001: n=5670; 2002: n=7074) was observed. No significant differences in the causes of admission and outcome in both periods were found. Tuberculosis is the most frequent disease that motivates hospitalization. The relation between ambulatory consultations and the amount of admissions significantly increased.

Prospective evaluation of in-house polymerase chain reaction for diagnosis of mycobacterial diseases in patients with HIV infection and lung infiltrates.

SETTING: Rapid diagnosis of tuberculosis (TB) in AIDS is critical for optimal treatment to reduce mycobacterial dissemination, HIV-1 replication and mortality. The inadequate sensitivity of Ziehl-Neelsen staining and its inability to distinguish atypical mycobacteria delays accurate diagnosis. OBJECTIVE: To evaluate the polymerase chain reaction (PCR) for diagnosis of TB in bronchoalveolar lavage (BAL), blood and extra-pulmonary samples from patients with AIDS and pulmonary infiltrates. DESIGN: Specimens from 103 HIV-1-infected patients were prospectively analysed using bacteriological methods and IS6110-PCR. Smear-positive samples were also tested using 16S ribosomal-DNA-PCR to identify Mycobacterium avium complex (MAC) infections. Gold standard diagnosis relied on positive cultures or treatment outcome. RESULTS: Thirty-four patients exhibited TB, one TB and MAC and four MAC. The sensitivity of IS6110-PCR was 100% in smear-positive samples, 81.8% in smear-negative BAL, 66.7% in extra-pulmonary samples and 42.9% in blood. Its specificity was 97.1% in BAL and 100% in extra-pulmonary and blood specimens. The 16S rDNA-PCR identified M. avium from all smear-positive samples that grew MAC. CONCLUSIONS: IS6110-PCR proved useful in evaluating episodes with probable clinical diagnosis of pulmonary or mixed TB and negative smears, whereas 16S rDNA-PCR would be helpful for prompt differential diagnosis of MAC in smear-positive specimens.

A randomized, controlled, phase II trial comparing escalating doses of subcutaneous interleukin-2 plus antiretrovirals versus antiretrovirals alone in human immunodeficiency virus-infected patients with CD4+ cell counts >/=350/mm3.

A total of 73 patients with baseline CD4+ cell counts >/=350 cells/mm3 who were receiving combination antiretroviral therapy (ART) were randomized to receive subcutaneous interleukin-2 (IL-2; n=36) in addition to ART or to continue ART alone (n=37). Subcutaneous IL-2 was delivered at 1 of 3 doses (1.5 million international units ¿MIU, 4.5 MIU, and 7.5 MIU per dose) by twice-daily injection for 5 consecutive days every 8 weeks. After 24 weeks, the time-weighted mean change from baseline CD4+ cell count was 210 cells/mm3 for recipients of subcutaneous IL-2, compared with 29 cells/mm3 for recipients of ART alone (P<.001). There were no significant differences between treatment groups for measures of plasma human immunodeficiency virus RNA (P=.851). Subcutaneous IL-2 delivered at doses of 4.5 MIU and 7.5 MIU resulted in significant increases in CD4+ cell count (P=.006 and P<.001, respectively), compared with that seen in control patients. These changes were not significant in the 1.5 MIU dose group compared with that in the control patients (P=.105). Side effects that occurred from subcutaneous IL-2 administration were generally low grade, of short duration, and readily managed in an outpatient environment.

[Advances in antiretroviral treatment]. / Avances en el tratamiento antirretroviral.

Recent findings have led to important changes in the understanding of HIV kinetics that allowed a novel therapeutic approach. This article reviews the most common methods used to gauge viral load and their use in medical decision making, the characteristics of the protease inhibitors just released in Argentina, and preliminary reports from several trials of combined treatment that have changed the standard of care. The viral load is a surrogate marker with predictive value independent of the CD4 cell count. Combined treatment is the election in case it is decided to initiate treatment.