Recurrent community-acquired pneumococcal meningitis in adults with and without identified predisposing factors.

Bacterial meningitis is still a significant public health concern, with high morbidity and mortality rates. Despite this, it is still a rare event that requires the bacterial invasion of the meninges. However, some predisposing factors can trigger recurrent episodes of meningitis. This study is aimed at determining the clinical characteristics and the molecular epidemiology of episodes of recurrent community-acquired meningitis with and without predisposing factors. For this purpose, we performed a retrospective study of our laboratory database during the period of 2010 to 2020. Additionally, using molecular tools developed in our previous works, the epidemiology of the pathogens causing these episodes was analyzed using cerebrospinal fluid samples, especially in the absence of isolated strains. We observed a total of 1,779 meningitis cases and 230 were caused by Streptococcus pneumoniae. Of those, 16 were recurrent meningitis episodes (16/1,779; 0.9%) from seven patients. Pneumococcus was the main agent responsible in these recurrent episodes and only two episodes were caused by Haemophilus influenzae. The mean age of these patients was 20 years old and three had predisposing factors which could have led to contracting meningitis. The samples presented different pneumococcal serotypes. Most of them were non-vaccine-covered serotypes and antibiotic susceptible strains. Therefore, it was demonstrated how the practical employment of molecular tools, developed for research, when applied in the routine of diagnosis, can provide important information for epidemiological surveillance. Furthermore, it was shown how pneumococcus was the leading cause of recurrent community-acquired meningitis without predisposing factors, suggesting that pneumococcal vaccination may be necessary, even in those groups of individuals considered to be less susceptible.

Lamivudine-based two-drug regimens with dolutegravir or protease inhibitor: Virological suppression in spite of previous therapy failure or renal dysfunction.

BACKGROUND: Two-Drug Regimens (2DR) have proven effective in clinical trials but real-world data, especially in resource-limited settings, is limited. OBJECTIVES: To evaluate viral suppression of lamivudine-based 2DR, with dolutegravir or ritonavir-boosted protease inhibitor (lopinavir/r, atazanavir/r or darunavir/r), among all cases regardless of selection criteria. PATIENTS AND METHODS: A retrospective study, conducted in an HIV clinic in the metropolitan area of São Paulo, Brazil. Per-protocol failure was defined as viremia above 200 copies/mL at outcome. Intention-To-Treat-Exposed (ITT-E) failure was considered for those who initiated 2DR but subsequently had either (i) Delay over 30 days in Antiretroviral Treatment (ART) dispensation, (ii) ART changed or (iii) Viremia > 200 copies/mL in the last observation using 2DR. RESULTS: Out of 278 patients initiating 2DR, 99.6% had viremia below 200 copies/mL at last observation, 97.8% below 50 copies/mL. Lamivudine resistance, either documented (M184V) or presumed (viremia > 200 copies/mL over a month using 3TC) was present in 11% of cases that showed lower suppression rates (97%), but with no significant hazard ratio to fail per ITT-E (1.24, p = 0.78). Decreased kidney function, present in 18 cases, showed of 4.69 hazard ratio (p = 0.02) per ITT-E for failure (3/18). As per protocol analysis, three failures occurred, none with renal dysfunction. CONCLUSIONS: The 2DR is feasible, with robust suppression rates, even when 3TC resistance or renal dysfunction is present, and close monitoring of these cases may guarantee long-term suppression.

Lamivudine-based two-drug regimens with dolutegravir or protease inhibitor: Virological suppression in spite of previous therapy failure or renal dysfunction

Abstract Background Two-Drug Regimens (2DR) have proven effective in clinical trials but real-world data, especially in resource-limited settings, is limited. Objectives To evaluate viral suppression of lamivudine-based 2DR, with dolutegravir or ritonavir-boosted protease inhibitor (lopinavir/r, atazanavir/r or darunavir/r), among all cases regardless of selection criteria. Patients and methods A retrospective study, conducted in an HIV clinic in the metropolitan area of São Paulo, Brazil. Per-protocol failure was defined as viremia above 200 copies/mL at outcome. Intention-To-Treat-Exposed (ITT-E) failure was considered for those who initiated 2DR but subsequently had either (i) Delay over 30 days in Antiretroviral Treatment (ART) dispensation, (ii) ART changed or (iii) Viremia > 200 copies/mL in the last observation using 2DR. Results Out of 278 patients initiating 2DR, 99.6% had viremia below 200 copies/mL at last observation, 97.8% below 50 copies/mL. Lamivudine resistance, either documented (M184V) or presumed (viremia > 200 copies/mL over a month using 3TC) was present in 11% of cases that showed lower suppression rates (97%), but with no significant hazard ratio to fail per ITT-E (1.24, p= 0.78). Decreased kidney function, present in 18 cases, showed of 4.69 hazard ratio (p= 0.02) per ITT-E for failure (3/18). As per protocol analysis, three failures occurred, none with renal dysfunction. Conclusions The 2DR is feasible, with robust suppression rates, even when 3TC resistance or renal dysfunction is present, and close monitoring of these cases may guarantee long-term suppression.

Detection of human feces pecovirus in newly diagnosed HIV patients in Brazil.

Circular single stranded DNA viruses (CRESS DNA) encoding a homologous replication-associated protein (REP) have been identified in most of eukaryotic groups. It is not clear yet the role in human diseases or details of the life cycle of these viruses. Recently, much interest has been raised in the evolutionary history of CRESS DNA owing to the increasing number of new sequences obtained by Next-Generation Sequencing (NGS) in distinct host species. In this study we describe two full-length CRESS DNA genomes obtained of two newly diagnosed HIV patients from São Paulo State, Brazil. The initial BLASTx search indicated that both sequences (named SP-FFB/2020 and SP-MJMS/2020) are highly similar (98%) to a previous CRESS DNA sequence detected in human fecal sample from Peru in 2016 and designated as pecovirus (Peruvian stool-associated circo-like virus). This study reported for the first time the Human feces pecovirus in the feces of two newly diagnosed HIV patients in Brazil. Our comparative analysis showed that although pecoviruses in South America share an identical genome structure they diverge and form distinct clades. Thus, we suggest the circulation of different species of pecoviruses in Latin America. Nevertheless, further studies must be done to examine the pathogenicity of this virus.

Impact of covid-19 on people living with HIV-1: care and prevention indicators at a local and nationwide level, Santo André, Brazil.

The world has been dealing with Aids for forty years, covid-19 accentuated societal inequalities and promoted a rupture in care and prevention, including for people living with HIV. We compiled official HIV indicators, analyzed the impact of covid-19 in Brazil, at São Paulo State (SP), and compared it to the municipality of Santo André (in the state of São Paulo), which adopted linkage/retention strategies to mitigate the impact of covid-19. From 2019 to 2020, suppression/adhesion rates remained stable. The number of new treatments decreased both in Brazil (-19.75%) and São Paulo (-16.44%), but not in Santo André, where 80% of new patients started treatment within 30 days from their first TCD4 test (70% in São Paulo and 64% in Brazil). However, PrEP dispensing increased during this period. The distribution of 2,820 HIV self-tests in Santo André lead to only one documented new HIV diagnosis linked to care. Synergistic strategies to swiftly diagnose and connect new cases, ensuring retention as well as rescuing missing patients deserve priority in the fight against HIV, especially in times of covid-19.

Recent HIV infections: evaluation of a simple identification score for newly diagnosed patients.

OBJECTIVE: Recognize incident infection to better characterize the groups that fuel HIV epidemic. We propose a simple score to identify recent infections among newly diagnosed patients as a HIV surveillance tool. METHODS: Newly diagnosed patients were defined as recent infections when a negative serological test in the previous year was available. Laboratory tests, such as the avidity index (Bio-Rad, according to the CEPHIA protocol), chemiluminescent intensity (CMIA, architect, Abbott), and the nucleotide ambiguity index of partial pol sequences were used as proxies of recency. A simple score based on clinical symptoms of acute retroviral syndrome during the previous year, CD4+ T cell count, and viral load at admission was tested to assess the predictive power, using receiver operating characteristic (ROC) curves, to identify recent cases of infection. RESULTS: We evaluated 204 recently diagnosed patients who were admitted to the Ambulatório de Referência em Moléstias Infecciosas de Santo André (Santo André Reference Infectious Diseases Outpatient Clinic), in the metropolitan region of São Paulo, Brazil, recruited between 2011 and 2018. An HIV-negative test in the year prior to enrollment was documented in 37% of participants. The proportion of cases classified as recent infections (less than one year), according to the laboratory proxies were: 37% (67/181) for an avidity index < 40%, 22% (30/137) for a CMIA < 200, and 68% (124/181) for an ambiguity index < 0.5%. Using different combinations of recency definitions, our score showed an area under the ROC curve from 0.66 to 0.87 to predict recency. CONCLUSIONS: Using data from patients' interviews and routine laboratory tests at admission, a simple score may provide information on HIV recency and thus, a proxy for HIV incidence to guide public policies. This simple for the Brazilian public health system and other low- and middle-income countries.

SARS-CoV-2 testing among patients and healthcare professionals in an HIV outpatient clinic in Brazil.

The COVID-19 pandemic in Brazil has been marked by high infection and death rates. The immune response generated by current vaccination might be influenced by previous natural infection, and baseline estimates may help in the evaluation of vaccine-induced serological response. We evaluated previous SARS-CoV-2 testing (RT-PCR), and performed rapid diagnostic tests (RDT) and high throughput electrochemiluminescence immunoassay (ECLIA) before vaccination among people living with HIV (PLWH), users of antiretroviral prophylaxis (PrEP/PEP), and healthcare professionals in an HIV outpatient clinic (HCP-HC). RDT was positive in 25.7% (95% CI: 19-33%) overall, 31.3% (95% CI : 18-45%) among PLWH, 23.7% (95% CI : 14-34%) in PrEP/PEP users and 21.4% (95% CI : 05-28%) in HCP-HC (p=0.548). Diagnostic RT-PCR testing was very limited, even for symptomatic individuals, and whereas all HCP-HC had one test perfomed, only 35% of the patients (PREP/PEP/PLWH) were tested (p<0.0001). Adequate monitoring of post-vaccination humoral response and breakthrough infections including those in asymptomatic cases are warranted, especially in immunologically compromised individuals.

A simple algorithm for selecting cases to investigate acute and early HIV infections in low- and middle-income countries.

We documented the outcome of an over 10-year (2011-2021) effort to diagnose acute and early HIV infections (AEHI) in an Infectious Diseases Outpatient Clinic with limited resources. Of a total of 132, 119 HIV-RNA tests were performed from 2017 to 2020, 12 cases were identified, using a simple algorithm: risk exposure of 6 weeks or less before the visit and/or symptoms compatible with acute retroviral syndrome 7-30 days after exposure and/or undetermined 3rd generation rapid diagnostic test or serology. AEHI diagnoses varied from 2.4% among asymptomatic to 25% for undetermined serology cases using this simple screening applicable to different settings.

SARS-CoV-2 testing among patients and healthcare professionals in an HIV outpatient clinic in Brazil

ABSTRACT The COVID-19 pandemic in Brazil has been marked by high infection and death rates. The immune response generated by current vaccination might be influenced by previous natural infection, and baseline estimates may help in the evaluation of vaccine-induced serological response. We evaluated previous SARS-CoV-2 testing (RT-PCR), and performed rapid diagnostic tests (RDT) and high throughput electrochemiluminescence immunoassay (ECLIA) before vaccination among people living with HIV (PLWH), users of antiretroviral prophylaxis (PrEP/PEP), and healthcare professionals in an HIV outpatient clinic (HCP-HC). RDT was positive in 25.7% (95% CI: 19-33%) overall, 31.3% (95% CI : 18-45%) among PLWH, 23.7% (95% CI : 14-34%) in PrEP/PEP users and 21.4% (95% CI : 05-28%) in HCP-HC (p=0.548). Diagnostic RT-PCR testing was very limited, even for symptomatic individuals, and whereas all HCP-HC had one test perfomed, only 35% of the patients (PREP/PEP/PLWH) were tested (p<0.0001). Adequate monitoring of post-vaccination humoral response and breakthrough infections including those in asymptomatic cases are warranted, especially in immunologically compromised individuals.

Impact of covid-19 on people living with HIV-1: care and prevention indicators at a local and nationwide level, Santo André, Brazil

ABSTRACT The world has been dealing with Aids for forty years, covid-19 accentuated societal inequalities and promoted a rupture in care and prevention, including for people living with HIV. We compiled official HIV indicators, analyzed the impact of covid-19 in Brazil, at São Paulo State (SP), and compared it to the municipality of Santo André (in the state of São Paulo), which adopted linkage/retention strategies to mitigate the impact of covid-19. From 2019 to 2020, suppression/adhesion rates remained stable. The number of new treatments decreased both in Brazil (-19.75%) and São Paulo (-16.44%), but not in Santo André, where 80% of new patients started treatment within 30 days from their first TCD4 test (70% in São Paulo and 64% in Brazil). However, PrEP dispensing increased during this period. The distribution of 2,820 HIV self-tests in Santo André lead to only one documented new HIV diagnosis linked to care. Synergistic strategies to swiftly diagnose and connect new cases, ensuring retention as well as rescuing missing patients deserve priority in the fight against HIV, especially in times of covid-19.

Recent HIV infections: evaluation of a simple identification score for newly diagnosed patients

ABSTRACT OBJECTIVE Recognize incident infection to better characterize the groups that fuel HIV epidemic. We propose a simple score to identify recent infections among newly diagnosed patients as a HIV surveillance tool. METHODS Newly diagnosed patients were defined as recent infections when a negative serological test in the previous year was available. Laboratory tests, such as the avidity index (Bio-Rad, according to the CEPHIA protocol), chemiluminescent intensity (CMIA, architect, Abbott), and the nucleotide ambiguity index of partial pol sequences were used as proxies of recency. A simple score based on clinical symptoms of acute retroviral syndrome during the previous year, CD4+ T cell count, and viral load at admission was tested to assess the predictive power, using receiver operating characteristic (ROC) curves, to identify recent cases of infection. RESULTS We evaluated 204 recently diagnosed patients who were admitted to the Ambulatório de Referência em Moléstias Infecciosas de Santo André (Santo André Reference Infectious Diseases Outpatient Clinic), in the metropolitan region of São Paulo, Brazil, recruited between 2011 and 2018. An HIV-negative test in the year prior to enrollment was documented in 37% of participants. The proportion of cases classified as recent infections (less than one year), according to the laboratory proxies were: 37% (67/181) for an avidity index < 40%, 22% (30/137) for a CMIA < 200, and 68% (124/181) for an ambiguity index < 0.5%. Using different combinations of recency definitions, our score showed an area under the ROC curve from 0.66 to 0.87 to predict recency. CONCLUSIONS Using data from patients' interviews and routine laboratory tests at admission, a simple score may provide information on HIV recency and thus, a proxy for HIV incidence to guide public policies. This simple for the Brazilian public health system and other low- and middle-income countries.

Field evaluation of COVID-19 antigen tests versus RNA based detection: Potential lower sensitivity compensated by immediate results, technical simplicity, and low cost.

One year into the coronavirus disease 2019 (COVID-19) pandemic, diagnostic strategies, although central for contact tracing and other preventive measures, are still limited. To meet the global demand, lower cost and faster antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection are a convenient alternative to the gold standard reverse transcription-polymerase chain reaction (RT-PCR) assay. We tested laboratory-based RT-PCR RNA detection and two rapid antigen detection (RAD) tests, based on the immunochromatography test for nucleocapsid protein of SARS-CoV-2 (COVID-19 Ag ECO Test, ECO Diagnóstica, and Panbio COVID-19 Ag Rapid Test Abbott). Paired collection and testing were done in a small prospective open study in three clinical services in São Paulo, constituted of mostly symptomatic volunteers at collection (97%, 109/112) for a median of 4 days (interquartile range: 3-6), ranging from 1 to 30. Among the 108 paired RT-PCR/RAD tests, results were concordant in 96.4% (101/108). The test's performance was comparable, with an overall sensitivity of 87% and a specificity of 96%. These observations add to other data that suggest that antigen tests may provide reasonable sensitivity and specificity and deserve a role to improve testing strategies, especially in resource-limited settings.

Field evaluation of COVID­19 antigen tests versus RNA based detection: Potential lower sensitivity compensated by immediate results, technical simplicity, and low cost

One year into the coronavirus disease 2019 (COVID­19) pandemic, diagnosticstrategies, although central for contact tracing and other preventive measures, arestill limited. To meet the global demand, lower cost and faster antigen tests forsevere acute respiratory syndrome coronavirus 2 (SARS­CoV­2) detection are aconvenient alternative to the gold standard reverse transcription­polymerase chainreaction (RT­PCR) assay. We tested laboratory­based RT­PCR RNA detection andtwo rapid antigen detection (RAD) tests, based on the immunochromatography testfor nucleocapsid protein of SARS­CoV­2 (COVID­19 Ag ECO Test, ECO Diagnóstica,and Panbio COVID­19 Ag Rapid Test Abbott). Paired collection and testing weredone in a small prospective open study in three clinical services in São Paulo,constituted of mostly symptomatic volunteers at collection (97%, 109/112) for amedian of 4 days (interquartile range: 3­6), ranging from 1 to 30. Among the108 paired RT­PCR/RAD tests, results were concordant in 96.4% (101/108). Thetest's performance was comparable, with an overall sensitivity of 87% and aspecificity of 96%. These observations add to other data that suggest that antigentests may provide reasonable sensitivity and specificity and deserve a role toimprove testing strategies, especially in resource­limited settings.

Monitoramento da infecção pelo HIV-1: diagnóstico da infecção aguda e proposta de um algoritmo para identificação de casos recentes / Monitoring of HIV-1 infection: diagnosis of acute infection and proposal of an algorithm to identify recent cases

O tratamento antirretroviral eficaz tornou a aids uma doença crônica manejável, porém, passados quase quarenta anos, a epidemia se sustenta. Entender quem são os indivíduos responsáveis pelos novos casos (infecção incidente), que apresentam maior transmissibilidade, vinculá-los rapidamente no tratamento e mantê-los com adesão é importante estratégia para quebra da cadeia de transmissão (indetectável=intransmissível). Nosso estudo procurou identificar casos recentes e avaliar a factibilidade de se reconhecer estes casos, não somente na admissão no serviço, para priorizar esta vinculação, mas também, para fins de vigilância epidemiológica, propondo uma pontuação de identificação, sem custo adicional ao SUS, combinando parâmetros laboratoriais e clínicos (e.g. sintomas suspeitos de SRA no último ano, CD4 e carga viral no diagnóstico). Amostras de uma coorte de 204 pacientes (2011-2017) foram avaliadas em testes de estimativa de tempo de infecção [índice de avidez (Bio-rad, protocolo CEPHIA), CMIA (architect) e índice de ambiguidade da sequência pol. Nestes a proporção de casos recentes foi de 26,3% (CMIA<250 RLU), 56% (índice de avidez<80%) e 68,5% (ambiguidade<0,5%) sugerindo que novas infecções são responsáveis por cerca de metade dos casos. Os valores do índice de avidez e da CMIA, índice de avidez e do índice de ambiguidade, mostraram-se correlacionados (Spearman, p<0,005), sugerindo terem boa comparabilidade. A pontuação foi testada quanto ao seu poder preditivo (curva ROC) para diferentes definições de identificação da infecção recente. A pontuação de melhor poder discriminativo foi quatorze, com sensibilidade de 66-80% e especificidade de 75-84%, com área sobre a curva de 0,77-0,87. Entre os 204, destacamos 7 casos de infecção na fase aguda entre 47 suspeitos, diagnosticados por biologia molecular, e adicionais 3/546 casos com sintomas compatíveis com SRA, testados e negativos para dengue na epidemia de 2015. A resistência primária mostrou-se baixa (6%) e houve elevada supressão viral (95%). Nesta coorte, o uso de teste molecular e da sorologia de 4ª geração, foram importantes na identificação de casos agudos, porém necessitam de estudos de custo efetividade para sua incorporação de forma mais ampla.

Prevalence of HIV-1 transmitted drug resistance and viral suppression among recently diagnosed adults in São Paulo, Brazil.

HIV-1 transmitted drug resistance (TDR) mutations may reduce the efficacy of antiretroviral therapy (ART), but pre-treatment testing to determine the virus genotype can improve the efficacy of ART. Unfortunately, issues related to cost and logistics of pre-treatment testing limit its use in resource-limited settings. We studied 596 ART-naive individuals who were newly diagnosed from 2014 to 2016 in São Paulo, Brazil, to evaluate TDR and virological outcome after 48 weeks of genotype-guided therapy. One or more TDR (based on the WHO surveillance list) was observed in 10.9% (CI 95%, 8.6-13.6) of the sequences, the most common of which was the K103 N mutation, which confers resistance to first-generation drugs of the non-nucleoside reverse transcriptase inhibitor (NNRTI) antiretroviral drug class. Dual-class (1%, 6/596) and triple-class (0.34%, 2/596) resistance were uncommon. After 48 weeks of treatment with ART, infection was suppressed to below 200 copies/mL in most patients (95%), with full suppression (RNA target not detected) in 65%. The following characteristics at patient enrollment were independently associated with a lack of full suppression: CD4 T cell counts below 500 cells/µL, viremia above 100,000 copies/mL, older age, and TDR to NNRTI. The rates of resistance were intermediate, but genotype-guided therapy resulted in high rates of viral suppression. The observed resistance profile should not be an obstacle to the use of the dolutegravir-based regimen now recommended in Brazil, but genotype testing may be warranted before initiating first-generation NNRTI-based regimens.