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.

Reverse transcriptase and protease inhibitors mutational viral load in HIV infected pregnant women with transmitted drug resistance in Argentina.

OBJECTIVE: Argentina has reported high levels of transmitted drug resistance (TDR), in HIV-infected pregnant women by population sequencing. We aimed to describe, in patients with TDR, the percentage of quasispecies harboring resistance mutations (RAMs) and mutational load (ML). METHODS: Retrospective study in a cohort of 40 naïve HIV-infected pregnant women, whose pretreatment samples had been genotyped by TRUGENE (period 2008-2014). Samples were re-sequenced with Ultra-deep Sequencing and ML was calculated considering baseline HIV-1 RNA load multiplied by the frequency of quasispecies harboring RAMs. RESULTS: TDR for NNRTIs, NRTIs and PIs was 17.5% (n=7 patients), 10% (n=4), 12.5% (n=5) respectively. Predominant NNRTI RAMs were K103N (n=4; 10%) and G190A/E/S (n=3; 7.5%). For NNRTIs, 78% of RAMs were present in >93.5% of viral population and ML was >1000 copies/mL (c/mL) for 89%, with a median (IQR) of 8330 c/ml (7738-29796). The following NRTI RAMs were described (per patient: % of quasispecies, ML): T215I (99.7%, 11014 c/ml); D67G (1.28%, 502 c/mL); M41L (79.8%, 88578 c/mL) and M184I (1.02%, 173 c/mL). Most frequent PI-RAMs were I85V, M46I, I50V and L90M (n=2, 5% each). For PIs, quasispecies with RAMs were <2.3% of viral population and ML was <350 c/mL for 77.8% of them. CONCLUSIONS: NNRTI-RAMs are predominant within the viral population, usually exceeding the threshold of 1000 c/mL, indicating potential higher risk of perinatal transmission. Conversely, PI mutations appear mostly as minority variants, with potential lower risk of transmission. Among NRTI, quasispecies harboring RAMs and ML values were variable.

Pretreatment HIV-1 drug resistance in Argentina: results from a surveillance study performed according to WHO-proposed new methodology in 2014-15.

BACKGROUND: In Argentina, current national guidelines recommend starting with NNRTI-based regimens. Recently, there have been some local reports regarding concerning levels of NNRTI-transmitted resistance, but surveillance has never been carried out at a national level. OBJECTIVES: To determine the prevalence of HIV drug resistance in people starting ART in Argentina using a WHO-proposed methodology. METHODS: This was a cross-sectional, nationally representative study. Twenty-five antiretroviral-dispensing sites throughout the country were randomly chosen to enrol at least 330 persons starting ART, to generate a point prevalence estimate of resistance-associated mutations (RAMs) with a 5% CI (for the total population and for those without antiretroviral exposure). All consecutive patients older than 18 years starting or restarting ART in the chosen clinics were eligible. Samples were processed with Trugene and analysed using the Stanford algorithm. RESULTS: Between August 2014 and March 2015, we obtained 330 samples from people starting ART. The mean ±â€ŠSD age was 35 ±â€Š11 years, 63.4% were male, 16.6% had prior antiretroviral exposure and the median (IQR) CD4 count was 275 cells/mm3 (106-461). The prevalence of RAMs found was 14% (±4%) for the whole population (3% NRTI-RAMs; 11% NNRTI-RAMs and 2% PI-RAMs) and 13% (±4%) for those without prior antiretroviral exposure (3%, 10% and 2%, respectively). The most common mutation was K103N. CONCLUSIONS: This surveillance study showed concerning levels of HIV drug resistance in Argentina, especially to NNRTIs. Due to this finding, Argentina's Ministry of Health guidelines will change, recommending performing a resistance test for everyone before starting ART. If this is taken up properly, it also might function as a continuing surveillance tool.

HIV-1, HIV-2, HTLV-I/II and STD among female prostitutes in Buenos Aires, Argentina.

To determine the prevalence of HIV-1 and HTLV-I/II among female prostitutes from different areas of the city of Buenos Aires, we studied serum samples from 237 individuals (mean age: 25; range 17 to 39). Prostitutes were recruited from 16 different Buenos Aires locations with different economical status. Information on sexual behaviour, health and socioeconomic conditions was collected through a questionnaire. HIV-1 and HTLV-I/II antibodies (ab) were tested by ELISA (Abbott) and Particle agglutination (Fujirebio, Tokyo) respectively. Positive results were confirmed by immunofluorescence assay. Samples that were positive for HIV-1 antibodies were also tested for p24 antigen (Abbott). VDRL for syphilis was performed in all samples. Fifteen (6.3%) out of the 237 individuals were positive for HIV-1 antibodies. Moreover, 2 (0.8%) HIV-1 seropositive prostitutes were also positive for HTLV-I/II antibodies and for HIV p24-Ag. Even though PCR for HTLV-I/II was not performed, titration by IFA in these two samples suggests HTLV-I. Our serologic results indicate a relatively high HIV-1 infection among prostitutes working in Buenos Aires. As we previously mentioned for other risk groups, we found an association between HTLV-I/II and HIV-1 infection in this particular group. Although we did not find any significant difference between HIV-1 seropositivity and the variables analyzed through the questionnaire, the prevalence of HIV-1 infection was higher in prostitutes working in mask brothels ('sauna or massage houses') as compared with hotel or street prostitutes.

PIP: Serum samples from 237 female prostitutes of mean age 25 years recruited from 16 different Buenos Aires locations of differing economic status were studied to determine the prevalence of HIV-1 and HTLV-I/II in the subpopulation. The participants, aged 17-39 years, also provided data on their sex behavior, health, and socioeconomic conditions. The presence of HIV-1 and HTLV-I/II antibodies was assessed using ELISA and particle agglutination, respectively, with positive results confirmed by immunofluorescence assay (IFA). HIV-1-seropositive samples were also tested for p24 antigen. VDRL for syphilis performed upon all samples found 13.2% to have serological evidence of infection. All women had been treated for frequently occurring sexually transmitted diseases. 15 women tested seropositive for infection with HIV-1. Two HIV-1 seropositive prostitutes were also positive for HTLV-I/II antibodies and HIV p24-Ag. PCR for HTLV-I/II was not performed, but titration by IFA suggests HTLV-I. The study's serologic results indicate a relatively high prevalence of HIV-1 infection among prostitutes working in Buenos Aires. The prevalence of HIV-1 infection was higher among prostitutes working in mask brothels such as saunas and massage houses than among hotel and street prostitutes.

Presence of neutralizing antibodies to heterologous human immunodeficiency virus type 1 isolates in sera of infected individuals is not predictive of rate of disease progression.

These studies were undertaken to examine whether the presence of human immunodeficiency virus type 1 (HIV-1)-neutralizing antibodies in sera of infected individuals would alter the rate of disease progression. HIV-1-infected individuals (n = 87) were initially examined for neutralizing activity in vitro against both laboratory and tissue culture-adapted clinical heterologous HIV-1 isolates. The neutralizing activities of sera were determined by a 90% or greater reduction in HIV-1 p24 levels in vitro. In a cross-sectional analysis of all infected individuals, we observed that sera from asymptomatic individuals neutralized a significantly greater number of heterologous HIV-1 isolates than sera from symptomatic patients. Patients who could be followed up longitudinally (n = 24) were then studied to determine the impact of neutralizing antibodies on the rate of disease progression. We observed no significant difference between the numbers of HIV-1 isolates neutralized in vitro by sera from patients who remained clinically stable and by those from patients who progressed rapidly. Our data indicated that the presence or absence of neutralizing antibodies to heterologous HIV-1 isolates was not associated with the rate of disease progression.

Serologic evaluation of human immunodeficiency virus type 1-infected individuals from Argentina and the United States indicates a similar distribution of subgroup B isolates.

Utilizing peptides based on the V3 region of gp120, we undertook a serologic examination of human immunodeficiency virus type 1 (HIV-1)-infected individuals from Argentina to determine if prevalent HIV-1 isolates could be identified in this population. Our findings suggest that a similar pool of HIV-1 subgroup B isolates exists in both Argentina and the United States.

PIP: This study examined serum specimens from HIV-1 infected individuals from Argentina (n = 50) and the United States (n = 38) for antibody reactivity to a panel of V3-based synthetic peptides. Serum specimens were further analyzed for the ability to neutralize laboratory and clinical isolates of HIV-1 in vitro. Patterns of antibody reactivity to these V3 peptides, together with neutralizing activity, indicated that infected individuals from both Argentina and the US have been exposed to HIV-1 isolates belonging to subgroup B. Serum specimens from the United States (37 males and 1 female) were obtained from military personnel and their dependents. Of these patients, 35 were asymptomatic and 3 were symptomatic. Specimens from Argentina were obtained from HIV-1-infected individuals examined in Buenos Aires, Argentina (37 males and 13 females). Half of the infected individuals from Argentina were symptomatic. Serum specimens were screened for antibody reactivity to HIV-1 gp160 synthetic peptides by an enzyme-linked immunosorbent assay. Examination of V3 peptide recognition indicated that a higher percentage of Argentinean serum specimens reacted with peptide RP189 than serum specimens from the United States (34% and 5%, respectively). A higher percentage of serum specimens from the United States reacted with peptide RP135 (LAI) than was observed with serum specimens from Argentina (47% vs. 16%, respectively). Neutralization assays again indicated a similar pattern of antibody reactivity with serum specimens from infected individuals from Argentina and the United States. Nucleotide sequence analysis of clinical isolates has demonstrated that the HIV-1 subgroup B is predominant in the United States. Serologic reactivity to V3-based peptides in this study suggests that isolates commonly found in the US (i.e., MN, SF2, and NY-5) are also frequently observed in Argentina. These results suggest that there is similar distribution of HIV-1 subgroup B isolates among infected individuals from Argentina and the United States.

HTLV type I and HTLV type II infection among Indians and natives from Argentina.

Endemic foci for HTLV-II infection have been identified in several Amerindian populations. To determine HTLV-I and/or HTLV-II infection among Amerindians living in Argentina we studied 454 sera or plasmas from Indians and natives from different areas of our country. All samples were tested by the particle agglutination technique, and positive reactions were confirmed by the immunofluorescence assay (IFA). IFA titration was used to differentiate HTLV-I and HTLV-II antibodies. Twenty-three of 222 samples (10.4%) were found positive among the Tobas Indians; 22 samples were typed as HTLV-II and 1 as HTLV-I. Antibodies for HTLV-I were found in the serum and CSF of three natives from Salta with a TSP diagnosis. No positive samples were found among 96 Mapuche Indians and 133 natives from San Luis. Our results indicate that HTLV-II is endemic among the Tobas Indians. In this study, infection by these retroviruses in Argentinian Amerindians seems to have a marked geographic distribution.