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BACKGROUND: Case-control studies involving test-negative (TN) and syndrome-negative (SN) controls are reliable for evaluating influenza and rotavirus vaccine effectiveness (VE) during a random vaccination process. However, there is no empirical evidence regarding the impact in real-world mass vaccination campaigns against SARS-CoV-2 using TN and SN controls. OBJECTIVE: To compare in the same population the effectiveness of SARS-CoV-2 vaccination on COVID-19-related hospitalization rates across a cohort design, TN and SN designs. METHOD: We conducted an unmatched population-based cohort, TN and SN case-control designs linking data from four data sources (public primary healthcare system, hospitalization registers, epidemiological surveillance systems and the national immunization program) in a Chilean municipality (Rancagua) between March 1, 2021 and August 31, 2021. The outcome was COVID-19-related hospitalization. To ensure sufficient sample size in the unexposed group, completion of follow-up in the cohort design, and sufficient time between vaccination and hospitalization in the case-control design, VE was estimated comparing 8-week periods for each individual. RESULTS: Among the 191,505 individuals registered in the primary healthcare system of Rancagua in Chile on March 1, 2021; 116,453 met the cohort study's inclusion criteria. Of the 9,471 hospitalizations registered during the study period in the same place, 526 were COVID-19 cases, 108 were TN controls, and 1,628 were SN controls. For any vaccine product, the age- and sex-adjusted vaccine effectiveness comparing fully and nonvaccinated individuals was 67.2 (55.7-76.3) in the cohort design, whereas it was 67.8 (44.1-81.4) and 77.9 (70.2-83.8) in the TN and SN control designs, respectively. CONCLUSION: The VE of a COVID-19 vaccination program based on age and risk groups tended to differ across the three observational study designs. The SN case-control design may be an efficient option for evaluating COVID-19 VE in real-world settings.
Subject(s)
COVID-19 Vaccines , COVID-19 , Hospitalization , Mass Vaccination , SARS-CoV-2 , Vaccine Efficacy , Humans , COVID-19/prevention & control , COVID-19/epidemiology , Chile/epidemiology , Middle Aged , Hospitalization/statistics & numerical data , Male , Female , Adult , Aged , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Case-Control Studies , Adolescent , SARS-CoV-2/immunology , Mass Vaccination/methods , Mass Vaccination/statistics & numerical data , Young Adult , Child , Child, Preschool , Infant , Cohort Studies , Immunization Programs , Aged, 80 and overABSTRACT
INTRODUCCIÓN: En las cuatro décadas de la epidemia por VIH, se han observado avances notables que han contribuido a una disminución progresiva en la incidencia de nuevas infecciones y en la mortalidad a nivel mundial. Sin embargo, no ha ocurrido lo mismo en Latinoamérica y en Chile. OBJETIVO: Esta revisión tiene como objetivo conocer la epidemiología actual a nivel global, latinoamericano y chileno. METODOLOGÍA: Se analizaron los informes epidemiológicos oficiales de infección por VIH emitidos por organismos nacionales e internacionales, más los estudios epidemiológicos nacionales. RESULTADOS: Se estima que 39 millones de personas viven con VIH en el mundo; no obstante, la mortalidad y la incidencia de nuevos casos han disminuido de forma notoria durante las últimas dos décadas, asociado a una expansión en al acceso a terapia antirretroviral en forma global. A diferencia del resto del mundo, América Latina presenta una tendencia de alza en las nuevas infecciones y Chile registra un aumento de 35% en nuevos casos durante los últimos 10 años, coincidiendo con un aumento en los flujos de migrantes que ha afectado a la región. Algunas estrategias preventivas como la profilaxis pre exposición se han implementa-do a un ritmo lento, tanto a nivel mundial, como latinoamericano. CONCLUSIONES: La epidemiología del VIH presenta características propias regionales y nacionales. En particular en Chile, diversos factores incluyendo déficit en políticas públicas de prevención y los recientes flujos migratorios han modelado nuestra actual epidemia. El desafío presente debe contemplar los esfuerzos multisectoriales para lograr los objetivos de ONUSIDA en esta década.
BACKGROUND: Over the course of the last four decades of global HIV epidemic, significant improvements have contributed to gradually reduce the frequency of new infections and global mortality rates. However, in Latin America particularly in Chile, new infections continue increasing. AIM: This review aims to comprehend the_epidemiology today on a worldwide, Latin American, and Chilean scale. METHODS: National epidemiology studies and official HIV reports from international and national organizations were reviewed. RESULTS: It is estimated that 39 million people live with HIV worldwide; however, mortality and the incidence of new cases have decreased markedly over the last two decades, associated with an expansion in access to antiretroviral therapy globally. In contrast to the rest of the world, Latin America shows an upward trend in new infections, with Chile registering a 35% increase in new cases over the last 10 years, coinciding with an increase in migratory flows that has occurred throughout the region. Some preventive strategies, such as pre-exposure prophylaxis, have been implemented at a slow pace, both globally and in Latin America. CONCLUSIONS: The epidemiology of HIV has regional and national characteristics. Specifically in Chile, several factors, including deficits in public prevention policies and recent migratory flows, have shaped our current epidemic. The present challenge must contemplate multisectoral efforts to achieve the UNAIDS objectives during this decade.
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Humans , HIV Infections/epidemiology , HIV Infections/prevention & control , HIV Infections/drug therapy , HIV Infections/transmission , Chile/epidemiology , Global Health , Infectious Disease Transmission, Vertical/statistics & numerical data , Anti-Retroviral Agents/therapeutic use , Latin America/epidemiologyABSTRACT
INTRODUCTION: Immune reconstitution following antiretroviral therapy (ART) initiation is crucial to prevent AIDS and non-AIDS-related comorbidities. Patients with suppressed viraemia who fail to restore cellular immunity are exposed to an increased risk of morbidity and mortality during long-term follow-up, although the underlying mechanisms remain poorly understood. We aim to describe clinical outcomes and factors associated with the worse immune recovery and all-cause mortality in people living with HIV (PLWH) from Latin America following ART initiation. METHODS: Retrospective cohort study using the CCASAnet database: PLWH ≥18 years of age at ART initiation using a three drug-based combination therapy and with medical follow-up for ≥24 months after ART initiation and undetectable viral load were included. Patients were divided into four immune recovery groups based on rounded quartiles of increase in CD4 T-cell count at 2 years of treatment (<150, [150, 250), [250, 350] and >350 cells/mm3 ). Primary outcomes included all-cause mortality, AIDS-defining events and non-communicable diseases that occurred >2 years after ART initiation. Factors associated with an increase in CD4 T-cell count at 2 years of treatment were evaluated using a cumulative probability model with a logit link. RESULTS: In our cohort of 4496 Latin American PLWH, we found that patients with the lowest CD4 increase (<150) had the lowest survival probability at 10 years of follow-up. Lower increase in CD4 count following therapy initiation (and remarkably not a lower baseline CD4 T-cell count) and older age were risk factors for all-cause mortality. We also found that older age, male sex and higher baseline CD4 T-cell count were associated with lower CD4 count increase following therapy initiation. CONCLUSIONS: Our study shows that PLWH with lower increases in CD4 count have lower survival probabilities. CD4 increase during follow-up might be a better predictor of mortality in undetectable PLWH than baseline CD4 count. Therefore, it should be included as a routine clinical variable to assess immune recovery and overall survival.
Subject(s)
Acquired Immunodeficiency Syndrome , Anti-HIV Agents , HIV Infections , Humans , Male , Retrospective Studies , Acquired Immunodeficiency Syndrome/drug therapy , Risk Factors , Drug Therapy, Combination , CD4 Lymphocyte Count , Viral Load , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly ActiveABSTRACT
Objectives: As earthquakes occur frequently in Latin America and can cause significant disruptions in HIV care, we sought to analyze patterns of HIV care for adults at Latin American clinical sites experiencing a significant earthquake within the past two decades. Study design: Retrospective clinical cohort study. Methods: Adults receiving HIV care at sites experiencing at least a "moderate intensity" (Modified Mercalli scale) earthquake in the Caribbean, Central and South America network for HIV epidemiology (CCASAnet) contributed data from 2003 to 2017. Interrupted Time Series models were fit with discontinuities at site-specific earthquake dates (Sept. 16, 2015 in Chile; Apr. 18, 2014 and Sept. 19, 2017 in Mexico; and Aug. 15, 2007 in Peru) to assess clinical visit, CD4 measure, viral load lab, and ART initiation rates 3- and 6-months after versus before earthquakes. Results: Comparing post-to pre-earthquake periods, there was a sharp drop in median visit (incidence rate ratio [IRR] = 0.79, 95% confidence interval [CI]: 0.68-0.91) and viral load lab (IRR = 0.78, 95% CI: 0.62-0.99) rates per week, using a 3-month window. CD4 measurement rates also decreased (IRR = 0.43; 95% CI: 0.37-0.51), though only using a 6-month window. Conclusions: Given that earthquakes occur frequently in Latin America, disaster preparedness plans must be more broadly implemented to avoid disruptions in HIV care and attendant poor outcomes.
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INTRODUCTION: The objective was to characterize real-world outcomes of drug-drug interactions (DDIs) between antiretrovirals (ARVs) and other drugs, including over-the-counter medications (OTC), and treatment outcomes in clinical practice. METHODS: www.clinicalcasesDDIs.com is an open-access website for healthcare providers to consult and briefly describe real-world clinical cases on DDI with ARVs. We reviewed all the clinical cases reported to the website between March 2019 and May 2023. RESULTS: A total of 139 cases were reported, mostly involving ritonavir or cobicistat (boosters; 74 cases), unboosted integrase inhibitors (InSTI; 29 cases), and non-nucleoside reverse transcriptase inhibitors (NNRTI; 23 cases). Central nervous system drugs (29 cases) and cardiovascular drugs (19 cases) were the most frequently described co-medications. Notably, OTC medications were implicated in 27 cases, including mineral supplements (11 cases), herbals (8 cases), weight loss drugs (4 cases), anabolic steroids (3 cases), and recreational drugs (1 case). OTC acted as the perpetrator drug in 21 cases, leading to loss of ARV efficacy in 17 instances (mineral supplements in 10 cases, weight loss drugs in 4 cases, herbals in 3 cases). Additionally, toxicity was reported in 4 out of 6 cases where OTC was considered the victim drug of the DDI (anabolic steroids in 3 cases, MDMA in 1 case). CONCLUSIONS: Frequent unwanted outcomes resulting from DDIs between ARVs and OTC medications underscore the importance of integrating non-prescription drugs into medication reconciliation. The real-world data available through www.clinicalcasesDDIs.com serves as a valuable resource for assessing the clinical relevance of DDIs.
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Introduction: Routine patient care data are increasingly used for biomedical research, but such "secondary use" data have known limitations, including their quality. When leveraging routine care data for observational research, developing audit protocols that can maximize informational return and minimize costs is paramount. Methods: For more than a decade, the Latin America and East Africa regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium have been auditing the observational data drawn from participating human immunodeficiency virus clinics. Since our earliest audits, where external auditors used paper forms to record audit findings from paper medical records, we have streamlined our protocols to obtain more efficient and informative audits that keep up with advancing technology while reducing travel obligations and associated costs. Results: We present five key lessons learned from conducting data audits of secondary-use data from resource-limited settings for more than 10 years and share eight recommendations for other consortia looking to implement data quality initiatives. Conclusion: After completing multiple audit cycles in both the Latin America and East Africa regions of the IeDEA consortium, we have established a rich reference for data quality in our cohorts, as well as large, audited analytical datasets that can be used to answer important clinical questions with confidence. By sharing our audit processes and how they have been adapted over time, we hope that others can develop protocols informed by our lessons learned from more than a decade of experience in these large, diverse cohorts.
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Introduction: Severe acute respiratory syndrome virus 2 (SARS-CoV-2) has caused over million deaths worldwide, with more than 61,000 deaths in Chile. The Chilean government has implemented a vaccination program against SARS-CoV-2, with over 17.7 million people receiving a complete vaccination scheme. The final target is 18 million individuals. The most common vaccines used in Chile are CoronaVac (Sinovac) and BNT162b2 (Pfizer-Biotech). Given the global need for vaccine boosters to combat the impact of emerging virus variants, studying the immune response to SARS-CoV-2 is crucial. In this study, we characterize the humoral immune response in inoculated volunteers from Chile who received vaccination schemes consisting of two doses of CoronaVac [CoronaVac (2x)], two doses of CoronaVac plus one dose of BNT162b2 [CoronaVac (2x) + BNT162b2 (1x)], and three doses of BNT162b2 [BNT162b2 (3x)]. Methods: We recruited 469 participants from Clínica Dávila in Santiago and the Health Center Víctor Manuel Fernández in the city of Concepción, Chile. Additionally, we included participants who had recovered from COVID-19 but were not vaccinated (RCN). We analyzed antibodies, including anti-N, anti-S1-RBD, and neutralizing antibodies against SARS-CoV-2. Results: We found that antibodies against the SARS-CoV-2 nucleoprotein were significantly higher in the CoronaVac (2x) and RCN groups compared to the CoronaVac (2x) + BNT162b2 (1x) or BNT162b2 (3x) groups. However, the CoronaVac (2x) + BNT162b2 (1x) and BNT162b2 (3x) groups exhibited a higher concentration of S1-RBD antibodies than the CoronaVac (2x) group and RCN group. There were no significant differences in S1-RBD antibody titers between the CoronaVac (2x) + BNT162b2 (1x) and BNT162b2 (3x) groups. Finally, the group immunized with BNT162b2 (3x) had higher levels of neutralizing antibodies compared to the RCN group, as well as the CoronaVac (2x) and CoronaVac (2x) + BNT162b2 (1x) groups. Discussion: These findings suggest that vaccination induces the secretion of antibodies against SARS-CoV-2, and a booster dose of BNT162b2 is necessary to generate a protective immune response. In the current state of the pandemic, these data support the Ministry of Health of the Government of Chile's decision to promote heterologous vaccination as they indicate that a significant portion of the Chilean population has neutralizing antibodies against SARS-CoV-2.
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COVID-19 , Vaccines , Humans , Immunity, Humoral , SARS-CoV-2 , BNT162 Vaccine , Chile , COVID-19/prevention & control , Vaccination , Antibodies, NeutralizingABSTRACT
ABSTRACTGlobally the community of people with HIV is ageing, and some of these have increasingly complex care needs, with a known excess of non-HIV related comorbidities and related issues including consequent polypharmacy. At the 2022 International AIDS Conference in Montréal, Canada, the "Silver Zone" was created in the Global Village as a safe space for older people with HIV. As part of the Silver Zone activities, a session discussing global models of care for in this group was held. HIV treatment providers and advocates from diverse resource settings and with a diversity of expertise were invited to share their experience, reflections, and ideas, and this consensus statement was formed based on these discussions. Different approaches to care emerged, based on local needs and resources, and it became clear that issues of complexity and frailty need not be age limited. Despite clear regional differences, some common themes became apparent, and a consensus was established on basic principles that may be considered in diverse settings. These are discussed here, with agreement on necessary proximal steps to develop bespoke person-centred care models.
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HIV Infections , Humans , Aged , HIV Infections/drug therapy , Silver , Aging , Patient-Centered Care , PolypharmacyABSTRACT
Introduction: Booster doses of SARS-CoV-2 vaccines improve seroconversion rates in solid organ transplant recipients (SOTRs) but the impact of homologous and heterologous booster doses in neutralizing antibody (NAb) titers and their ability to interfere with the variant of concern Omicron are not well studied. Methods: We designed a prospective, open-label, observational clinical cohort study. 45 participants received two doses of BNT162b2 or CoronaVac (21-day or 28-day intervals, respectively) followed by a first and second booster with BNT162b2 (5-month apart each) and we analyzed the neutralizing antibody titers against SARSCoV-2 D614G (B.1 lineage) and Omicron (BA.1 lineage). Results: Our results show that SOTRs receiving an initial two-dose scheme of CoronaVac or BNT162b2 generate lower NAbs titers against the ancestral variant of SARS-CoV-2 when compared with healthy controls. Although these NAb titers were further decreased against the SARS-CoV-2 Omicron, a single BNT162b2 booster in both groups was sufficient to increase NAb titers against the variant of concern. More importantly, this effect was only observed in those participants responding to the first two shots but not in those not responding to the initial vaccination scheme. Discussion: The data provided here demonstrate the importance of monitoring antibody responses in immunocompromised subjects when planning booster vaccination programs in this risk group.
Subject(s)
COVID-19 , Organ Transplantation , Humans , Antibodies, Neutralizing , BNT162 Vaccine , Cohort Studies , COVID-19 Vaccines , Organ Transplantation/adverse effects , Prospective Studies , SARS-CoV-2ABSTRACT
Immune performance following antiretroviral therapy initiation varies among patients. Despite achieving viral undetectability, a subgroup of patients fails to restore CD4+ T-cell counts during follow-up, which exposes them to non-AIDS defining comorbidities and increased mortality. Unfortunately, its mechanisms are incompletely understood, and no specific treatment is available. In this review, we address some of the pathophysiological aspects of the poor immune response from a translational perspective, with emphasis in the interaction between gut microbiome, intestinal epithelial dysfunction, and immune system, and we also discuss some studies attempting to improve immune performance by intervening in this vicious cycle.
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HIV Infections , Humans , HIV Infections/drug therapy , CD4 Lymphocyte Count , Dysbiosis , CD4-Positive T-Lymphocytes , Comorbidity , Antiretroviral Therapy, Highly ActiveABSTRACT
BACKGROUND: Between May and November, 2022, global outbreaks of human monkeypox virus infection have been reported in more than 78 000 people worldwide, predominantly in men who have sex with men. We describe the epidemiological and clinical characteristics of monkeypox virus infection in cisgender (cis) and transgender (trans) women and non-binary individuals assigned female sex at birth to improve identification and understanding of risk factors. METHODS: International collaborators in geographical locations with high numbers of diagnoses of monkeypox virus infection were approached and invited to contribute data on women and non-binary individuals with confirmed monkeypox virus infection. Contributing centres completed deidentified structured case-report spreadsheets, adapted and developed by participating clinicians, to include variables of interest relevant to women and non-binary individuals assigned female at birth. We describe the epidemiology and clinical course observed in the reported infections. FINDINGS: Collaborators reported data for a total of 136 individuals with monkeypox virus infection who presented between May 11 and Oct 4, 2022, across 15 countries. Overall median age was 34 years (IQR 28-40; range 19-84). The cohort comprised 62 trans women, 69 cis women, and five non-binary individuals (who were, because of small numbers, grouped with cis women to form a category of people assigned female at birth for the purpose of comparison). 121 (89%) of 136 individuals reported sex with men. 37 (27%) of all individuals were living with HIV, with a higher proportion among trans women (31 [50%] of 62) than among cis women and non-binary individuals (six [8%] of 74). Sexual transmission was suspected in 55 (89%) trans women (with the remainder having an unknown route of transmission) and 45 (61%) cis women and non-binary individuals; non-sexual routes of transmission (including household and occupational exposures) were reported only in cis women and non-binary individuals. 25 (34%) of 74 cis women and non-binary individuals submitted to the case series were initially misdiagnosed. Overall, among individuals with available data, rash was described in 124 (93%) of 134 individuals and described as anogenital in 95 (74%) of 129 and as vesiculopustular in 105 (87%) of 121. Median number of lesions was ten (IQR 5-24; range 1-200). Mucosal lesions involving the vagina, anus, or oropharynx or eye occurred in 65 (55%) of 119 individuals with available data. Vaginal and anal sex were associated with lesions at those sites. Monkeypox virus DNA was detected by PCR from vaginal swab samples in all 14 samples tested. 17 (13%) individuals were hospitalised, predominantly for bacterial superinfection of lesions and pain management. 33 (24%) individuals were treated with tecovirimat and six (4%) received post-exposure vaccinations. No deaths were reported. INTERPRETATION: The clinical features of monkeypox in women and non-binary individuals were similar to those described in men, including the presence of anal and genital lesions with prominent mucosal involvement. Anatomically, anogenital lesions were reflective of sexual practices: vulvovaginal lesions predominated in cis women and non-binary individuals and anorectal features predominated in trans women. The prevalence of HIV co-infection in the cohort was high. FUNDING: None.
Subject(s)
Mpox (monkeypox) , Sexual and Gender Minorities , Infant, Newborn , Male , Humans , Female , Adult , Monkeypox virus , Mpox (monkeypox)/diagnosis , Mpox (monkeypox)/epidemiology , Homosexuality, Male , Disease OutbreaksABSTRACT
Long-acting injectable antiretroviral therapy (LA ART) has been found to be non-inferior to daily oral ART in phase 3 clinical trials and is poised to soon enter routine clinical care. This treatment modality has the potential to address many barriers to daily oral ART adherence among people living with human immunodeficiency virus (HIV) and for HIV Pre-Exposure prevention. Data from the Patient Reported Outcomes (PROs) showed high rates of satisfaction, acceptability, tolerability and preference for the LA regimen, compared with the daily oral treatment. Once LA ART is available, access and uptake will be limited because of current knowledge gaps in the use of these agents and multiple challenges many specific to low-income and middle-income countries, where the epidemic is most concentrated and HIV prevention and treatment options are limited. These gaps will lead to multiple systems-level and individual-level barriers to implementation. Anticipating and addressing these gaps and barriers will help fulfill the promise of these agents against the pandemic.
Subject(s)
Anti-HIV Agents , HIV Infections , Humans , Developing Countries , Anti-HIV Agents/therapeutic use , Anti-Retroviral Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/prevention & control , PovertyABSTRACT
Peer support interventions for people living with HIV and AIDS (PLWHA) are effective, but their associated time and material costs for the recipient and the health system make them reachable for only a small proportion of PLWHA. Internet-based interventions are an effective alternative for delivering psychosocial interventions for PLWHA as they are more accessible. Currently, no reviews are focusing on internet-based interventions with peer support components. This scoping review aims to map the existing literature on psychosocial interventions for PLWHA based on peer support and delivered through the internet. We conducted a systematic scoping review of academic literature following methodological guidelines for scoping reviews, and 28 articles met our criteria. We summarized the main characteristics of the digital peer support interventions for PLWHA and how they implemented peer support in a virtual environment. Overall the reported outcomes appeared promising, but more robust evidence is needed.
Subject(s)
HIV Infections , Internet-Based Intervention , HIV Infections/psychology , HIV Infections/therapy , HumansABSTRACT
OBJECTIVES: The aim of this study was to describe the incidence, clinical characteristics, and risk factors of late-onset opportunistic infections (LOI) in people who live with HIV (PWLHA) within the Caribbean, Central and South America network for HIV epidemiology. METHODS: We performed a retrospective cohort study including treatment-naive PWLHA enrolled at seven sites (Argentina, Brazil, Chile, Peru, Mexico, and two sites in Honduras). Follow-up began at 6 months after treatment started. Outcomes were LOI, loss to follow-up, and death. We used a Cox proportional hazards model and a competing risks model to evaluate risk factors. RESULTS: A total of 10,583 patients were included. Median follow up was at 5.4 years. LOI occurred in 895 (8.4%) patients. Median time to opportunistic infection was 2.1 years. The most common infections were tuberculosis (39%), esophageal candidiasis (10%), and Pneumocystis jirovecii (P. jirovecii) pneumonia (10%). Death occurred in 576 (5.4%) patients, and 3021 (28.5%) patients were lost to follow-up. A protease inhibitor-based regimen (hazard ratio 1.25), AIDS-defining events during the first 6 months of antiretroviral-treatment (hazard ratio 2.12), starting antiretroviral-treatment in earlier years (hazard ratio 1.52 for 2005 vs 2010), and treatment switch (hazard ratio 1.31) were associated with a higher risk of LOI. CONCLUSION: LOI occurred in nearly one in 10 patients. People with risk factors could benefit from closer follow-up.
Subject(s)
HIV Infections , Opportunistic Infections , Brazil , CD4 Lymphocyte Count , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Latin America/epidemiology , Opportunistic Infections/epidemiology , Opportunistic Infections/etiology , Retrospective Studies , Risk FactorsABSTRACT
Background: Clinical outcomes are rarely studied in virologically suppressed people living with HIV (PWH) and incomplete CD4 recovery. To explore whether time living with severe immunosuppression predict clinical outcomes better than baseline or time updated CD4, we estimated the association between cumulative percentage of time with CD4 <200 cells/µL during viral suppression (VS) (%tCD4<200), and mortality and comorbidities during 2000-2019. Methods: In a retrospective cohort analysis, we followed PWH initiating ART in Latin America from first VS (HIV-RNA<200 copies/µL) to death, virological failure or loss to follow-up. We fit Cox models to estimate risk of death and/or AIDS-defining and serious non-AIDS-defining events (ADE and SNADE -cancer, cardiovascular, liver, and renal diseases) by %tCD4<200 (continuous variable). We predicted survival probabilities for each event and calculated risks of hypothetical cases of different %tCD4<200. Findings: In 8,369 patients with 34·9 months of follow-up (median, IQR: 16·7, 69·1), 4,274 (51%) started ART with CD4<200 cells/µL. Median %tCD4<200 was 0% (IQR: 0, 15%). We identified 195 (2·3%) deaths and 584 (7·2%) patients with ADE/SNADE. For an increased %tCD4<200 of 15% (e.g., 15% vs. 0%), the adjusted relative hazard (aHR) of death was 1·27 (95% confidence interval [CI]: 1·19 - 1·35), of ADE/SNADE was 1·13 (95%CI: 1·09 - 1·17), of SNADE was 0·96 (95%CI: 0·89 - 1·02) and of death/ADE/SNADE was 1·11 (95%CI: 1·07 - 1·14). Estimates were similar after adjusting for time updated CD4 count. Interpretation: In virologically suppressed PWH, increased time living with severe immunosuppression had an increased risk of death and ADE/SNADE in this Latin American cohort, independently of time updated CD4 count. Funding: This work was supported by the NIH-funded Caribbean, Central and South America network for HIV epidemiology (CCASAnet, U01AI069923), a member cohort of the International Epidemiologic Databases to Evaluate AIDS (leDEA). This award is funded by the following institutes: Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD), National Cancer Institute (NCI), National Institute Of Allergy And Infectious Diseases (NIAID), National Institute Of Mental Health (NIMH), the National Heart, Lung, and Blood Institute (NHLBI), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the Fogarty International Center (FIC). Specific funding was provided from the Fogarty International Center (FIC) for lead author, Yanink Caro-Vega, for the Fogarty-IeDEA Mentorship Program (FIMP).
ABSTRACT
SARS-CoV-2 variant Lambda was dominant in several South American countries, including Chile. To ascertain the efficacy of local vaccination efforts, we used pseudotyped viruses to characterize the neutralization capacity of antibodies elicited by CoronaVac (n = 53) and BNT162b2 (n = 56) in healthcare workers from Clínica Santa María and the Faculty of Medicine at Universidad de Chile, as well as in convalescent plasma from individuals infected during the first wave visiting the Hospital Clínico at Pontificia Universidad Católica (n = 30). We observed that BNT162b2 elicits higher neutralizing antibody titres than CoronaVac, with differences ranging from 7.4-fold for the ancestral spike (Wuhan-Hu-1) to 8.2-fold for the Lambda spike and 13-fold for the Delta spike. Compared with the ancestral virus, neutralization against D614G, Alpha, Gamma, Lambda and Delta variants was reduced by between 0.93- and 4.22-fold for CoronaVac, 1.04- and 2.38-fold for BNT162b2, and 1.26- and 2.67-fold for convalescent plasma. Comparative analyses among the spike structures of the different variants suggest that mutations in the spike protein from the Lambda variant, including the 246-252 deletion in an antigenic supersite at the N-terminal domain loop and L452Q/F490S within the receptor-binding domain, may account for immune escape. Interestingly, analyses using pseudotyped and whole viruses showed increased entry rates into HEK293T-ACE2 cells, but reduced replication rates in Vero-E6 cells for the Lambda variant when compared with the Alpha, Gamma and Delta variants. Our data show that inactivated virus and messenger RNA vaccines elicit different levels of neutralizing antibodies with different potency to neutralize SARS-CoV-2 variants, including the variant of interest Lambda.