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.

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.

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.

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.

Undiagnosed acute HIV infection identified through RNA testing of pooled serum samples obtained during a dengue outbreak in São Paulo, Brazil

Abstract INTRODUCTION: Improving HIV diagnostics and treatment is necessary to end the AIDS epidemic. Pooled plasma can be used to identify patients with acute HIV disease, even before serological tests. During dengue outbreaks, patients having symptoms common to other acute viral diseases might seek medical care. METHODS: We evaluated HIV RNA in pooled seronegative dengue samples. RESULTS: After excluding individuals with a known HIV diagnosis, an HIV-1 prevalence of 0.73% [95% confidence interval (CI) 0.23-1.76; 4/546 samples] was found. CONCLUSIONS: Promoting strategies to diagnose these individuals and provide them with medical treatment might be instrumental for controlling the HIV epidemic.

Diagnóstico da infecção pelo HIV-1: proposta de um algoritmo para identificação de infecção aguda / Diagnosis of HIV-1 infection: proposal of an algorithm for the identification of acute infection

A epidemia de AIDS em nosso País apresenta relativa estabilidade, concentrada em populações de maior vulnerabilidade, porém informações são em geral relacionadas à fase avançada da doença. Nosso estudo procura contribuir com informações sobre casos incidentes de infeção pelo HIV-1, através de um algoritmo que favorece a identificação de casos em fase aguda da doença. Esse algoritmo, com critérios clínicos e laboratoriais, permitiu o recrutamento consecutivo de 99 pacientes em um universo de cerca de 300 casos novos incorporados ao SAE do Município de Santo André, no período de outubro de 2011 a novembro de 2014. Nesses pacientes recém diagnosticados foram analisadas características clínicas, epidemiológicas e aspectos moleculares do HIV-1. Alguns aspectos clínicos e laboratoriais foram avaliados em adicionais 154 casos incorporados nesta época, assim como algumas características do HIV-1 identificadas em teste de genotipagem no período entre 2001 e 2014, em pacientes do mesmo SAE, que permitiram contextualizar a coorte. Entre os 99 pacientes... O algoritmo proposto identificou 5 casos em 8 suspeitos de infecção aguda. A genotipagem pré-tratamento avaliou...Na coorte foi identificado ainda, por estudo clínico e epidemiológico, confirmado por associação filogenética, uma possível transmissão do HIV-1 por procedimento de manicure (Matsuda et al., 2014b).

The AIDS epidemic in our country shows a relative stability, concentrated in the most vulnerable populations, but the limited information is generally related to the advanced stage of the disease. Our study aims to contribute with information on incident cases of HIV-1 infection. In a universe of about 300 new cases incorporated into the Santo André AIDS Program from Oct/2011 to Nov/2014, 99 patients were recruited consecutively. The study evaluated patients admitted after a recent diagnostic through the usual demand for follow-up and from an active case finding, using clinical laboratory algorithm that aimed to identify patients with acute infection. Available clinical and laboratory data from 154 additional cases incorporated in the service during this period and molecular data from HIV-1 genotypic tests from patients of this service in the period of 2001-2012, allowed to contextualize the cohort findings. Among the 99 patients studied ...The proposed algorithm has identified 5/8 cases of suspected acute infection. Pretreatment genotyping, evaluated...In the cohort, we identified, based in epidemiological clinical and subsequent phylogeny a possible transmission of HIV-1 for manicure procedure (Matsuda et al., 2014b).