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.

Monitoramento da infecção pelo HIV-!: estudo da prevalência de mutações de resistência transmitida aos antirretroviarais, análise molecular e de testes sorológicos para identificação de infecção recente em pacientes no Estado de São Paulo / Monitoring of HIV-! infection: study of the prevalence of resistance mutations transmitted to antiretroviral drugs, molecular analysis and serological tests to identify recent infection in patients in the State of São Paulo

O diagnóstico laboratorial de infecção pelo HIV, assim como a identificação de subtipos virais e de mutações de resistência transmitida a drogas (TDRM, transmitted drug reisitence mutation) são importantes para o controle e monitoramento de epidemia do HIV. No presente estudo, eles foram pesquisados em amostras de sangue de indivíduos provenientes...(AU)

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.

Transmitted drug resistance among recently diagnosed adults and children in São Paulo, Brazil

Transmitted drug resistance mutations (TDRM) have been a constant threat to treatment efficacy. We evaluated TDRM in plasma RNA of 217 antiretroviral therapy-naive patients from sites in the São Paulo metropolitan area, collected from 2012 to 2014. The partial HIV-1 polymerase region was sequenced using Big Dye terminators at an ABI 3130 Genetic Analyzer. TDRM was defined according to the Stanford database calibrated population resistance (CPR v.6.0), but other drug resistance mutations (DRM) considered at the IAS list (IAS, 2014) and at the Stanford HIV Database Genotyping Resistance Interpretation (GRI-HIVdb) were also described. Out of 78% (170/217) of patients with information on the time of diagnosis, most (83%, 141/170) had been recently diagnosed, with the first positive HIV serology at a median of 58 days (IQR 18-184). Subtype B predominated (70%), followed by subtype F (10%), BF (7.5%), C (7.5%), and BC (5%). TDRMs were observed in 9.2% (20/217, CI 95% 5.9% to 13.6%), mostly (5.2%) to nonnucleoside reverse transcriptase inhibitor (NNRTI) antiretroviral class. Among children and adolescents, only a single patient showed TDRMs. Additional non-CPR mutations were observed: 11.5% (25/217) according to IAS or 4.6% (10/217) according to GRI-HIVdb. Overall, 23.5% (51/217) of the cases had one or more DRM identified. TDRM prevalence differed significantly among some sites. These trends deserve continuous and systematic surveillance, especially with the new policies of treatment as prevention being implemented in the country.

Predição do tropismo viral do HIV-1 utilizando plasma e célula em amostras de sangue de pessoas vivendo com HIV/AIDS / Prediction of HIV-1 viral tropism using plasma and cell from blood sample from people living with HV/AIDS

O HIV-1 geralmente utiliza o receptor CD4 em conjunto com um correceptor principal, CCR5 ou CXCR4, na etapa fundamental de entrada na célula hospedeira, determinando assim o tropismo viral por células que expressam estas moléculas. Diferenças no tropismo de HIV-1 têm contribuído para a compreensão da patogênese do HIV e são necessárias para suportar a decisão médica em relação ao uso de antagonistas do CCR5. O teste fenotípico de tropismo determina diretamente esta característica biológica, porém os custos e a complexidade restringem a sua utilização, sendo assim, a predição genotípica tem sido proposta como uma alternativa. O objetivo desse estudo foi padronizar e avaliar um teste de predição genotípica do tropismo. Foi adaptado para o nosso laboratório o protocolo desenvolvido pelo Centro de Excelência em HIV/Aids da Columbia Britânica (CECB)usando sequência em replicatas, avaliamos os parâmetros que possam influenciar na predição do tropismo e comparamos a predição na célula e no plasma. Produtos de PCR e plasma enviados pelo CECB foram sequenciados e analisados de forma independente no CECB e no IAL, com alta concordância. Sequências da V3 do envelope viral de 81 pacientes com consentimento informado mostraram uma correlação entre o número de ambiguidades e o menor valor de FPR, uma tendência a ter uma maior distância genética inter-sequência entre os isolados preditos como X4 e sem correlação entre o número de repetições de sequências e o menor FPR. Estudamos também diferenças na origem do material genético viral (RNA viral ou DNA pró-viral) e sua influência sobre a predição de tropismo. Em 56 amostras pareadas observou-se uma tendência na ocorrência de mais X4 em DNA pró-viral de células. Nós observamos maior distância genética entre as sequências de célula em comparação com as de plasma, e documentamos as discrepâncias na determinação do tropismo viral utilizando diferentes cut offs de uso clínico. Nosso trabalho permitiu o desenvolvimento...