Resistencia a los inhibidores de la integrasa en niños con el virus de la inmunodeficiencia humana por transmisión vertical: primeros casos en Uruguay / Resistance to integrase inhibitors in children with vertically-transmitted human immunodeficiency virus: First cases in Uruguay

La resistencia a los antirretrovirales (ARV) es un problema de salud pública. Con el uso de inhibidores de la integrasa (INSTI) en pediatría, también comienzan a aparecer resistencias. El objetivo de esta comunicación es describir 3 casos con resistencia a los INSTI. Se describen 3 pacientes pediátricos con transmisión vertical del virus de la inmunodeficiencia humana (VIH). Iniciaron ARV de lactantes y preescolares, con mala adherencia al tratamiento, cursaron con diferentes planes secundarios a comorbilidades asociadas y fallas virológicas por resistencia. Los 3 casos clínicos describen la rápida aparición de resistencia frente a la falla virológica y el compromiso de los INSTI. La adherencia debe ser supervisada para detectar precozmente el aumento de la viremia. La falla virológica en un paciente tratado con raltegravir obliga a un rápido cambio de esquema ARV, ya que continuar utilizándolo podría favorecer nuevas mutaciones y resistencia a los INSTI de segunda generación.

Antiretroviral (ARV) drug resistance is a public health issue. Resistance has also been observed in the case of integrase strand transfer inhibitors (INSTIs) used in pediatrics. The objective of this article is to describe 3 cases of INSTI resistance. These are the cases of 3 children with vertically-transmitted human immunodeficiency virus (HIV). They were started on ARVs as infants and preschoolers, with poor treatment adherence, and had different management plans due to associated comorbidities and virological failure due to resistance. In the 3 cases, resistance developed rapidly as a result of virological failure and INSTI involvement. Treatment adherence should be monitored so that any increase in viremia can be detected early. Virological failure in a patient treated with raltegravir forces to a rapid change in ARV therapy because its continued use may favor new mutations and resistance to second-generation INSTIs.

Resistencia transmitida de VIH-1 en pacientes sin exposición a tratamiento antirretroviral: Guatemala / Transmitted HIV-1 resistance in patients without exposure to antiretroviral treatment: Guatemala / Resistência transmitida ao HIV-1 em pacientes sem exposição ao tratamento antirretroviral: Guatemala

El objetivo del estudio fue describir los niveles de resistencia transmitida de VIH-1 en adultos atendidos en Unidades de Atención Integral de Guatemala. El estudio incluyó registros de 185 pacientes adultos VIH-1 positivo, de reciente diagnóstico sin antecedente de uso de TAR, de noviembre del 2019 a noviembre del 2020. El análisis se realizó en el software DeepChek® v2.0, para la clasificación de la resistencia se siguió el algoritmo de Stanford HIVdb (v9.4 - 07/12/2022). Se encontró 18.4% (IC 95% 13.1 - 24.7%) de resistencia general a alguna familia de ARVs. Se evidenció 15.1% (IC 95% 10.3 - 21.1%) de resistencia individual a la familia de INNTR afectando principalmente a NVP y EFV; 2.2% (IC 95% 0.6 - 5.4%) de resistencia a INTR, mayormente a FTC/3TC; y 2.7% (IC 95% 0.9 - 6.2%) de resistencia intermedia y baja los IP NFV y LPV/r. Tres casos presentaron resistencia múltiple a los INTR + INNTR. Las mutaciones más frecuentemente encontradas fueron K103N (41.2%), M184V/I (8.8%) y M46I (5.9%). La elevada resistencia transmitida del VIH-1 en pacientes atendidos en distintas Unidades de Atención Integral del VIH, demuestra la importancia de analizar periódicamente la tendencia de la resistencia en personas que no han estado expuestas a ARVs, lo cual a su vez es un marcador indirecto de presencia de resistencia adquirida en el país, datos que evidencian la necesidad de acciones e intervenciones prontas y efectivas dado su impacto en la salud pública.

The objective of this study was to describe the levels of transmitted HIV-1 resistance in patients with a recent HIV diagnosis before starting ART, treated in Comprehensive Care Units in Guatemala during the years 2019 and 2020. The study included records of 185 HIV-positive adult patients, recently diagnosed with HIV without a history of ART use. The analysis was carried out in the DeepChek® v2.0 software, the Stanford HIVdb algorithm (v9.4 - 07/12/2022) was followed to classify resistance. 18.4% (95% CI 13.1 - 24.7%) of general resistance to some family of ARVs was found. There was evidence of 15.1% (95% CI 10.3 - 21.1%) of individual resistance to the NNRTI family, mainly affecting NVP and EFV; 2.2% (95% CI 0.6 - 5.4%) resistance to INTR, mostly to FTC/3TC; and 2.7% (95% CI 0.9 - 6.2%) of intermediate and low resistance IP NFV and LPV/r. Three cases presented multiple resistance to NRTIs + NNRTIs. The most frequently found mutations were K103N (41.2%), M184V/I (8.8%) and M46I (5.9%). The high transmitted resistance of HIV-1 in patients treated in different Comprehensive HIV Care Units demonstrates the importance of periodically analyzing the trend of resistance in people who have not been exposed to ARVs, which in turn is an indirect marker. of the presence of acquired resistance in the country, data that demonstrate the need for prompt and effective actions and interventions given its impact on public health.

O objetivo deste estudo foi descrever os níveis de resistência transmitida ao HIV-1 em adultos tratados em Unidades de Cuidados Integrais na Guatemala. O estudo incluiu prontuários de 185 pacientes adultos HIV-1 positivos, recentemente diagnosticados sem histórico de uso de TARV, no período de novembro de 2019 a novembro de 2020. A análise foi realizada no software DeepChek® v2.0, para classificação da resistência, O algoritmo Stanford HIVdb (v9.4 - 07/12/2022) foi seguido. Foi encontrada 18.4% (IC 95% 13.1 - 24.7%) de resistência geral a alguma família de ARVs. Houve evidência de 15.1% (IC 95% 10.3 - 21.1%) de resistência individual à família de NNRTI, afetando principalmente NVP e EFV; 2.2% (IC 95% 0.6 - 5.4%) resistência ao INTR, principalmente ao FTC/3TC; e 2.7% (IC 95% 0.9 - 6.2%) de resistência intermediária e baixa ao IP NFV e LPV/r. Três casos apresentaram resistência múltipla a NRTIs + NNRTIs. As mutações mais frequentemente encontradas foram K103N (41.2%), M184V/I (8.8%) e M46I (5.9%). A elevada resistência transmitida do HIV-1 em pacientes atendidos em diferentes Unidades de Cuidados Integrados ao HIV demonstra a importância de analisar periodicamente a tendência de resistência em pessoas que não foram expostas aos ARVs, o que por sua vez é um marcador indireto da presença de ARVs adquiridos. resistência no país, dados que demonstram a necessidade de ações e intervenções rápidas e eficazes dado o seu impacto na saúde pública.

Clinical-epidemiological characterization of women who received post-exposure HIV prophylaxis in a public hospital in Porto Alegre, Rio Grande do Sul / Caracterização clínico-epidemiológica de mulheres que receberam a profilaxia pós-exposição ao HIV em um hospital público de Porto Alegre, Rio Grande do Sul

Introduction: Prevention strategies are key to combating the epidemic of infections such as HIV and syphilis. The epidemiological scenario of Porto Alegre/RS for these infections shows the need for greater efforts in the area of prevention, seeking to characterize both the population that uses these strategies and the services involved in the care of exposed people. Objective: This study aimed to characterize the clinical and epidemiological profile of patients who received post-exposure prophylaxis (PEP) to HIV treated in a public hospital in Porto Alegre/RS. Methods: This is a retrospective, research, descriptive study based on the Clinical Protocol and Therapeutic Guidelines for PEP, updated in 2018 by the Ministry of Health. Prophylaxis request forms and medical records of patients treated were analyzed. Results: The population consisted of 87 women who received PEP from January to September 2019. There was a predominance of women aged between 20 and 29 years old (55.2%). The most frequent sexual exposure was consensual (69.0%) followed by sexual assault (31.0%). Porto Alegre was the place of residence of most patients (73.6%). The most frequently used therapeutic regimen was the combination of atazanavir, ritonavir, and tenofovir plus lamivudine. On the first visit, 8.0% of the patients showed reactive results for the treponemal syphilis test. Only 23.0% and 14.9% of patients returned for anti-HIV tests in the first and third months after exposure, respectively, and the results were non-reactive. Only 19 patients (21.8%) attended the consultations between 0 and 28 days after PEP. Conclusion: It was identified that a considerable percentage of women already had reactive serology for syphilis, most women did not return for follow-up within 28 and 90 days after the first consultation, more than half of the women were aged between 20 and 29 years old, and the most frequent sexual exposure was consensual. In this sense, efforts are needed, such as adequate counseling, adoption of interventions such as sending messages by cell phone, telephone calls, and preparation of educational materials, seeking to improve adherence to treatment and follow-up in the service, which is important given the scenario of epidemiology in Porto Alegre.Keywords: HIV. Sexually transmitted diseases. Post-exposure prophylaxis. Disease prevention

Introdução: Estratégias de prevenção são fundamentais para o combate à epidemia de infecções como o vírus da imunodeficiência humana (HIV) e sífilis. O cenário epidemiológico de Porto Alegre/RS para essas infecções mostra a necessidade de maiores esforços na área de prevenção, buscando caracterizar tanto a população que utiliza essas estratégias quanto os serviços envolvidos no atendimento das pessoas expostas. Objetivo: Caracterizar o perfil clínico-epidemiológico das pacientes que receberam a profilaxia pós-exposição (PEP) ao HIV atendidas em um hospital público de Porto Alegre/RS. Métodos: Trata-se de um estudo retrospectivo, documental, descritivo e baseado no Protocolo Clínico e Diretrizes Terapêuticas para PEP, atualizado em 2021 pelo Ministério da Saúde. Foram analisados os formulários de solicitação da profilaxia e prontuários das pacientes atendidas. Resultados: A população foi composta de 87 mulheres que receberam a PEP no período de janeiro a setembro de 2019. Predominaram mulheres com idades entre 20 e 29 anos (55,2%). A exposição sexual mais frequente foi a consentida (69,0%), seguida pela violência sexual (31,0%). Porto Alegre foi o local de residência da maioria das pacientes (73,6%). O esquema terapêutico utilizado com maior frequência foi a combinação com atazanavir, ritonavir e tenofovir associado à lamivudina. No primeiro atendimento, 8,0% das pacientes demonstraram resultados reagentes para o teste treponêmico de sífilis. Retornaram para a realização dos testes anti-HIV no primeiro e terceiro mês após a exposição apenas 23,0 e 14,9% das pacientes, respectivamente, e os resultados foram não reagentes. Apenas 19 delas (21,8%) compareceram às consultas entre zero e 28 dias posteriores à PEP. Conclusão: Foi identificado que um percentual considerável de mulheres já apresentava sorologia reagente para sífilis, a maioria das mulheres não retornou para o seguimento no período de 28 e 90 dias após o primeiro atendimento, mais da metade delas tinha idade entre 20 e 29 anos e a exposição sexual mais frequente foi a consentida. Nesse sentido, são necessários esforços como aconselhamento adequado, adoção de intervenções como o envio de mensagens pelo celular, ligações telefônicas e elaboração de materiais educativos, buscando a melhoria da adesão ao tratamento e do acompanhamento no serviço, o que é importante diante do cenário epidemiológico de Porto Alegre.Palavras-chave: HIV. Infecções sexualmente transmissíveis. Profilaxia pós-exposição. Prevenção

HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province, China, 2014-2020 / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance (HIVDR) in patients with ART failure from 2014 to 2020 in Hainan, China.@*METHODS@#A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan. We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences. Drug resistance mutations (DRMs) were analyzed using the Stanford University HIV Drug Resistance Database.@*RESULTS@#A total of 307 HIV-infected patients with ART failure were included, and 241 available pol sequences were obtained. Among 241 patients, CRF01_AE accounted for 68.88%, followed by CRF07_BC (17.00%) and eight other subtypes (14.12%). The overall prevalence of HIVDR was 61.41%, and the HIVDR against non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 59.75%, 45.64%, and 2.49%, respectively. Unemployed patients, hypoimmunity or opportunistic infections in individuals, and samples from 2017 to 2020 increased the odd ratios of HIVDR. Also, HIVDR was less likely to affect female patients. The common DRMs to NNRTIs were K103N (21.99%) and Y181C (20.33%), and M184V (28.21%) and K65R (19.09%) were the main DRMs against NRTIs.@*CONCLUSION@#The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.

Reasons, safety and efficacy analysis for conversion of HAART to TAF/FTC/BIC among HIV-infected patients / 中华医学杂志(英文版)

BACKGROUND@#This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings.@*METHODS@#We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022.@*RESULTS@#Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs . 3.40 ± 1.59 mmol/L in triglyceride ( P  = 0.014), 4.82 ± 0.74 mmol/L vs . 4.88 ± 0.72 mmol/L in total cholesterol ( P  = 0.038), 3.09 ± 0.70 mmol/L vs . 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P  <0.001), and 0.99 ± 0.11 mmol/L vs . 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P  <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P  <0.001).@*CONCLUSION@#The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.

Efficacy and safety profiles of dolutegravir plus lamivudine vs . bictegravir/emtricitabine/tenofovir alafenamide in therapy-naïve adults with HIV-1 / 中华医学杂志(英文版)

BACKGROUND@#Dual regimen dolutegravir (DTG) plus lamivudine (3TC) has demonstrated non-inferior efficacy compared to DTG-based three-drug regimens (3DRs), yet directly comparative data regarding the efficacy and safety of DTG + 3TC and bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for therapy-naïve people with human immunodeficiency virus (HIV)-1 (PWH) are still limited. We aimed to assess the antiviral potency and safety profiles of DTG + 3TC vs. B/F/TAF based on antiretroviral therapy (ART)-naïve PWH in China.@*METHODS@#This retrospective multicenter study enrolled PWH initiating ART with DTG + 3TC or B/F/TAF from 2020 to 2022 in Guangdong and Guangxi. We analyzed response rates based on target not detected (TND) status using intention-to-treat (ITT) analysis. Subgroups were formed based on baseline viral load (VL) (<100,000 vs . ≥100,000 copies/mL) and CD4 + cell count (<200 vs . ≥200 cell/µL). Median time to TND VL was assessed by Kaplan-Meier method. We also measured changes from baseline in CD4 + cell counts, CD4/CD8 ratio, lipid parameters, weight, creatinine (Cr), estimated glomerular filtration rate (eGFR), and drug-related adverse effects (DRAEs).@*RESULTS@#We enrolled 280 participants, including 137 (48.9%) on DTG + 3TC and 143 (51.1%) on B/F/TAF. At week 48, 96.4% (132/137) on DTG+3TC and 100% (143/143) on B/F/TAF achieved TND ( P = 0.064). At week 12, TND responses were higher with B/F/TAF (78.3% [112/143]) than DTG+3TC (30.7% [42/137]) ( P <0.001). This trend held across subgroups. B/F/TAF achieved TND faster (12 weeks) than DTG+3TC (24 weeks) ( P <0.001). No differences were seen in CD4 + cell count and CD4/CD8 ratio, except in the high-VL subgroup, where B/F/TAF showed better recovery. DRAEs were significantly lower with B/F/TAF (4.9% [7/143]) than with DTG + 3TC (13.1% [18/137]) ( P = 0.016). Lipid parameters, body weight, and Cr increased in both groups over 48 weeks, with DTG+3TC showing a more favorable effect on triglycerides, high-density lipoprotein (HDL) cholesterol, and weight gain.@*CONCLUSIONS@#In this real-life study, B/F/TAF led to a faster viral decline and fewer DRAEs compared to DTG+3TC. No significant difference was observed in the TND rate at week 48, regardless of baseline VL and CD4 + cell count. CD4 + recovery was superior for B/F/TAF in participants with high VL. The DTG + 3TC regimen had less impact on metabolic changes than B/F/TAF.

Longitudinal analysis of immune reconstitution and metabolic changes in women living with HIV: A real-world observational study / 中华医学杂志(英文版)

BACKGROUND@#Women comprise more than half of people living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) worldwide and incomplete immune recovery and metabolic abnormalities affect them deeply. Studies of HIV antiretroviral therapy (ART) have a low female representation in China. We aimed to investigate immune reconstitution and metabolic changes of female HIV-positive cohort in China longitudinally.@*METHODS@#HIV-positive women who initiated ART from January 2005 to June 2021 and were followed up regularly at least once a year were included in this study. Immunological indicators (cluster of differentiation 4 [CD4] counts and CD8 counts), viral load (VL), and metabolic indicators were collected at follow-up. All data were collected from the China Disease Prevention and Control Information System (CDPCIS). VL was tested half a year, 1 year after receiving ART, and every other year subsequently according to local policy. CD4/CD8 ratio normalization was considered as the primary outcome and defined as a value ≥1. Incidence rate and probability of CD4/CD8 ratio normalization were estimated through per 100 person-years follow-up (PYFU) and Kaplan-Meier curve, respectively. Multivariate Cox regression was used to identify independent risk factors associated with CD4/CD8 ratio normalization. We further studied the rate of dyslipidemia, hyperuricemia, diabetes, liver injury, and renal injury after ART initiation with the chi-squared tests or Fisher's exact probability tests, and a generalized estimating equation model was used to analyze factors of dyslipidemia and hyperuricemia.@*RESULTS@#A total of 494 female patients with HIV/AIDS started ART within 16 years from January 2005 to June 2021, out of which 301 women were enrolled with a median duration of ART for 4.1 years (interquartile range, 2.3-7.0 years). The overall incidence rate of CD4/CD8 ratio normalization was 8.9 (95% confidence interval [CI], 7.4-10.6) per 100 PYFU, and probabilities of CD4/CD8 normalization after initiating ART at 1 year, 2 years, 5 years, and 10 years follow-up were 11.7%, 23.2%, 44.0%, and 59.0%, respectively. Independent risk factors associated with CD4/CD8 normalization were baseline CD4 cell counts <200 cells/μL, CD8 counts >1000 cells/μL, and more than 6 months from the start of combined ART (cART) to first virological suppression. Longitudinally, the rate of hypercholesterolemia (total cholesterol [TC]) and high triglyceride (TG) showed an increasing trend, while the rate of low high-density lipoprotein cholesterol (HDL) showed a decreasing trend. The rate of hyperuricemia presented a downtrend at follow-up. Although liver and renal injury and diabetes persisted during ART, the rate was not statistically significant. Older age and protease inhibitors were independent risk factors for increase of TC and TG, and ART duration was an independent factor for elevation of TC and recovery of HDL-C.@*CONCLUSIONS@#This study showed that women were more likely to normalize CD4/CD8 ratio in comparison with findings reported in the literature even though immune reconstruction was incomplete.

A comprehensive overview on the role of phytocompounds in human immunodeficiency virus treatment / 中西医结合学报

Acquired immune deficiency syndrome (AIDS) is a worldwide epidemic caused by human immunodeficiency virus (HIV) infection. Newer medicines for eliminating the viral reservoir and eradicating the virus are urgently needed. Attempts to locate relatively safe and non-toxic medications from natural resources are ongoing now. Natural-product-based antiviral candidates have been exploited to a limited extent. However, antiviral research is inadequate to counteract for the resistant patterns. Plant-derived bioactive compounds hold promise as powerful pharmacophore scaffolds, which have shown anti-HIV potential. This review focuses on a consideration of the virus, various possible HIV-controlling methods and the recent progress in alternative natural compounds with anti-HIV activity, with a particular emphasis on recent results from natural sources of anti-HIV agents. Please cite this article as: Mandhata CP, Sahoo CR, Padhy RN. A comprehensive overview on the role of phytocompounds in human immunodeficiency virus treatment. J Integr Med. 2023; 21(4):332-353.

Beyond access to medication: the role of SUS and the characteristics of HIV care in Brazil / Para além do acesso ao medicamento: papel do SUS e perfil da assistência em HIV no Brasil

ABSTRACT OBJECTIVE To estimate the public-private composition of HIV care in Brazil and the organizational profile of the extensive network of public healthcare facilities. METHODS Data from the Qualiaids-BR Cohort were used, which gathers data from national systems of clinical and laboratory information on people aged 15 years or older with the first dispensation of antiretroviral therapy between 2015-2018, and information from SUS healthcare facilities for clinical-laboratory follow-up of HIV, produced by the Qualiaids survey. The follow-up system was defined by the number of viral load tests requested by any SUS healthcare facility: follow-up in the private system - no record; follow-up at SUS - two or more records; undefined follow-up - one record. SUS healthcare facilities were characterized as outpatient clinics, primary care and prison system, according to the respondents' self-classification in the Qualiaids survey (72.9%); for non-respondents (27.1%) the classification was based on the terms present in the names of the healthcare facilities. RESULTS During the period, 238,599 people aged 15 years or older started antiretroviral therapy in Brazil, of which 69% were followed-up at SUS, 21.7% in the private system and 9.3% had an undefined system. Among those followed-up at SUS, 93.4% received care in outpatient clinics, 5% in primary care facilities and 1% in the prison system. CONCLUSION In Brazil, antiretroviral treatment is provided exclusively by SUS, which is also responsible for clinical and laboratory follow-up for most people in outpatient clinics. The study was only possible because SUS maintains records and public information about HIV care. There is no data available for the private system.

RESUMO OBJETIVO Estimar a composição público-privada da assistência em HIV no Brasil e o perfil organizacional da extensa rede de serviços públicos. MÉTODOS Foram utilizados dados da Coorte Qualiaids-BR, que reúne dados dos sistemas nacionais de informações clínicas e laboratoriais de pessoas com 15 anos ou mais com primeira dispensação de terapia antirretroviral, entre 2015-2018, e informações dos serviços do SUS de acompanhamento clínico-laboratorial do HIV, produzidas pelo inquérito Qualiaids. O sistema de acompanhamento foi definido pelo número de exames de carga viral solicitados por algum serviço do SUS: acompanhamento no sistema privado - nenhum registro; acompanhamento no SUS - dois ou mais registros; acompanhamento indefinido - um registro. Os serviços do SUS foram caracterizados como ambulatórios, atenção básica e sistema prisional, segundo autoclassificação dos respondentes ao inquérito Qualiaids (72,9%); para os não respondentes (27,1%) a classificação baseou-se nos termos presentes nos nomes dos serviços. RESULTADOS No período, 238.599 pessoas com 15 anos ou mais iniciaram a terapia antirretroviral no Brasil, das quais, 69% receberam acompanhamento no SUS, 21,7% no sistema privado e 9,3% tiveram o sistema indefinido. Entre os acompanhados no SUS, 93,4% foram atendidos em serviços do tipo ambulatório, 5% em serviços de atenção básica e 1% no sistema prisional. CONCLUSÃO No Brasil o tratamento antirretroviral é fornecido exclusivamente pelo SUS, que também é responsável pelo acompanhamento clínico-laboratorial da terapia da maior parte das pessoas em serviços ambulatoriais. O estudo só foi possível porque o SUS mantêm registros e informações públicas acerca do acompanhamento em HIV. Não há nenhum dado disponível para o sistema privado.

Biomarcadores para el diagnóstico del síndrome de reconstitución inmune / Biomarkers for the diagnosis of immune reconstitution syndrome

Introducción: el síndrome inflamatorio de reconstitución inmune es una complicación clínica dada en algunas personas infectadas con el virus de la inmunodeficiencia humana (VIH) luego de empezar la terapia antirretroviral; se destaca por la producción de citoquinas proinflamatorias, que se han estudiado como posibles biomarcadores que puedan orientar para el diagnóstico y pronóstico de esta condición clínica. Objetivo: llevar a cabo una revisión actualizada de los avances en los biomarcadores para el diagnóstico de SIRI, resaltando la importancia de las moléculas inflamatorias y los exosomas, tanto en su patogénesis como un posible Gold estándar para la confirmación de este estado inflamatorio. Metodología: se realizó una revisión bibliográfica en bases de datos, como Science Direct, PubMed, Scopus y Medline, partiendo de los siguientes términos MeSH: síndrome inflamatorio de reconstitución, enfermedades del sistema inmune, biomarcadores, fármacos antiVIH, plasma. Conclusión: cada vez existen más avances en la identificación de moléculas que pueden servir como biomarcadores de SIRI, buscando un oportuno diagnóstico, monitoreo de la progresión clínica, mejor respuesta al tratamiento y más hallazgos sobre la fisiopatología, pero persiste la necesidad de encontrar un Gold estándar que proporcione criterios para su sospecha y confirmación.

Introduction: The inflammatory syndrome of immune reconstitution (IRIS) is a clinical complication given in some people infected with the human immunodeficiency virus (HIV), after they begin antiretroviral therapy (ART), which stands out for the production of abundant proinflammatory cytokines, which have been studied as possible biomarkers that can guide the diagnosis and prognosis of this clinical condition. Objective: Review the advances in biomarkers for the diagnosis of IRIS,and the importance of inflammatory molecules and exosomes, so their pathogenesis and as a possible Gold standard for confirmation of this inflammatory. Methodology: A bibliographic review was carried out in databases, such as Science Direct, Pubmed, Scopus and Medline based on the following MeSH terms: Inflammatory reconstitution syndrome, Immune system diseases, Biomarkers, Anti-HIV drugs, Plasma. Conclusion: There are more and more advances in the identification of various molecules that can serve as biomarkers of IRIS, seeking timely diagnosis, monitoring of clinical progression, better response to treatment and more findings on the pathophysiology of IRIS, but the urgent need to find a gold standard that provides criteria for its suspicion and confirmation persists.

Consideraciones en población transgénero respecto a la infección por VIH, terapia antiretroviral, profilaxis preexposición (PreP) e interacción con tratamiento de reafirmación de género / Considerations in the transgender population regarding HIV infection, antiretroviral therapy, pre-exposure prophylaxis (PreP) and interaction with gender reaffirmation treatment

Resumen La infección por VIH es una epidemia global (prevalencia de 0,8%). En Latinoamérica, Chile, Brasil y Uruguay son los países con mayores índices. Entre las más afectadas están la población transgénero (OR 48,8 respecto a la población general). Múltiples factores bio-psico-sociales explican estas cifras. Bajo uso del preservativo, la idea de reafirmación de género, el temor a ser reemplazadas(os) por personas cisgéneros, presencia de comercio sexual, entre otros, influyen en las mayores tasas de infección. Se han implementado medidas de prevención del VIH, pero pocas dirigidas en específico a personas transgénero. La profilaxis preexposición (PreP) parece ser una nueva alternativa de prevención en este grupo, y la integración de las unidades de apoyo en la reafirmación de género con las unidades que entregan PreP, podrían aumentar su adherencia y cobertura. En las personas transgénero con infección por VIH existe baja adherencia a terapia antirretroviral (TARV), en parte por priorización del tratamiento hormonal y miedo a que la TARV altere su proceso de hormonización. Los pocos datos existentes muestran que la hormonización no se afecta con la mayoría de la TARV, pero algunos tratamientos hormonales podrían disminuir las concentraciones plasmáticas y tisulares de ciertos antirretrovirales. Faltan estudios que evalúen la interacción entre antirretrovirales y tratamiento hormonal de reafirmación de género.

Abstract HIV infection is a global epidemic, with a prevalence of 0.8%. In Latin America, Chile, Brazil and Uruguay are the countries with the highest rates. The transgender population is the most affected (OR of 48.8 compared to the general population). Multiple bio-psycho-social factors explain these issues. The low use of condoms for pressure from the partner, the idea of reaffirmation of gender, the fear to be replaced by a cisgender person, the presence of commercial sex, among others, influence the highest rates of infection. HIV prevention measures have been implemented, but few specifically targeted at transgender people. Pre-exposure prophylaxis (PreP) seems to be a new prevention alternative in this group, and the integration of support units in gender reaffirmation with units that deliver PreP could increase their adherence and coverage. In HIV (+) transgender people there is low adherence to antiretroviral therapy (ART), in part due to the prioritization of hormonal treatment and the fear that ART will alter their hormonalization process. The few data that exist show that hormonalization is not affected by ART, but that some hormonal treatments could lower the levels of certain antiretrovirals. More studies must be done to evaluate the interaction between antiretrovirals and gender affirming hormone therapy.

Barreiras e facilitadores do acesso de populações vulneráveis à PrEP no Brasil: Estudo ImPrEP Stakeholders / Barriers and facilitators for access to PrEP by vulnerable populations in Brazil: the ImPrEP Stakeholders Study / Barreras y facilitadores de acceso de poblaciones vulnerables a la PrEP en Brasil: Estudio ImPrEP Stakeholders

Resumo: A profilaxia pré-exposição ao HIV (PrEP) tem sido considerada uma estratégia fundamental para o controle da epidemia de HIV/aids, e desde 2018 tem sido objeto de estudo de implementação (Estudo ImPrEP Stakeholders), realizado no Brasil, no México e no Peru. Um componente qualitativo desse estudo foi desenvolvido com o objetivo de identificar os contextos sociais e estruturais que envolvem e organizam a oferta de serviços de PrEP no Brasil, as subjetividades dos atores envolvidos e as diferentes percepções que podem impactar a efetivação dessa estratégia. O presente artigo teve como foco de análise o acesso das populações vulneráveis aos serviços de PrEP, na perspectiva de gestores, profissionais de saúde, lideranças ou ativistas e usuários de PrEP. É um estudo qualitativo com o uso de metodologia compreensiva, realizado em seis capitais brasileiras, em que foram entrevistados 71 atores-chave no período de novembro de 2018 a maio de 2019. A análise foi pautada pelos modelos analíticos sobre acesso propostos por Giovanella & Fleury, McIntyre et al. e Penchansky & Thomas. Os resultados são apresentados com base em três eixos: "percepções sobre prevenção combinada e PrEP"; "disponibilidade e adequação: perfil e estrutura dos serviços no contexto do ImPrEP"; e "aceitabilidade: atitudes e práticas dos profissionais de saúde e usuários".

Abstract: HIV preexposure prophylaxis (PrEP) has been considered a fundamental strategy for controlling the HIV/AIDS epidemic, and since 2018 it has been the object of an implementation study (ImPrEP Stakeholders Study), conducted in Brazil, México, and Peru. A qualitative component of this study was developed with the objective of identifying the social and structural contexts that involve and organize the supply of PrEP services in Brazil, the stakeholders' subjectivities, and the different perceptions that can impact the strategy's implementation. The current article's focus was to analyze access by vulnerable populations to PrEP services from the perspective of managers, health professionals, leaders or activists, and users of PrEP. This was a qualitative study using a comprehensive methodology, conducted in six Brazilian state capitals, interviewing 71 key actors from November 2018 to May 2019. The analysis was based on access analysis models as proposed by Giovanella & Fleury, McIntyre et al. and Penchansky & Thomas. The results are presented along three lines: "perceptions of combined prevention and PrEP", "availability and adequacy: profile and structure of services in the context of ImPrEP", and "acceptability: attitudes and practices of health professionals and users".

Resumen: La profilaxis preexposición al VIH (PrEP) ha sido considerada una estrategia fundamental para el control de la epidemia de VIH/sida y desde 2018 ha sido objeto de estudio de implementación (Estudio ImPrEP Stakeholders), realizado en Brasil, México y Perú. Un componente cualitativo de este estudio se desarrolló con el objetivo de identificar los contextos sociales y estructurales que engloban y organizan la oferta de servicios de PrEP en Brasil, las subjetividades de los actores implicados y las diferentes percepciones que pueden impactar en hacer efectiva esa estrategia. El objetivo de este artículo es el análisis del acceso de las poblaciones vulnerables a los servicios de PrEP, desde la perspectiva de los gestores, profesionales de salud, líderes o activistas y usuarios de la PrEP. Se trata de un estudio cualitativo con uso de metodología comprensiva, realizado en seis capitales brasileñas, en las que fueron entrevistados 71 actores-clave, durante el período de noviembre de 2018 a mayo de 2019. El análisis se pautó mediante modelos analíticos sobre acceso, propuestos por Giovanella & Fleury, McIntyre et al. y Penchansky & Thomas. Los resultados se presentan a partir de tres ejes: "percepciones sobre prevención combinada y PrEP", "disponibilidad y adecuación: perfil y estructura de los servicios en el contexto de la ImPrEP" y "aceptabilidad: actitudes y prácticas de los profesionales de salud y usuarios".

Evolución virológica de pacientes con infección por VIH que inician terapia antirretroviral con carga viral basales muy alta / Virological evolution of patients with HIV infection that start antiretroviral therapy with a very high baseline viral load

INTRODUCCIÓN: Se desconoce el grado de supresión viral en pacientes con infección por VIH que inician terapia antirretroviral (TAR) con cargas virales (CV) muy altas. OBJETIVO: Conocer el porcentaje de supresión viral en pacientes con VIH que inician TAR con CV ≥ 500.000 copias/mL a 96 semanas. PACIENTES Y MÉTODO: Estudio retrospectivo. Se incluyeron pacientes que iniciaron TAR con CV ≥ 500.000 copias/mL, entre los años 2008 y 2018, estratificándose en base a escala logarítmica. Se determinó el porcentaje de supresión viral, y las variables asociadas a este desenlace. RESULTADOS: Se incluyeron 221 pacientes. La mediana de edad y CV era de 43 años y 6,0 log, respectivamente, estando la mayoría (37%) en estadio C3 al inicio de TAR. El 48,8 y 87,7% de los pacientes logró la supresión viral al año y dos años de seguimiento, respectivamente. Se observó que, a mayor edad, a mayor inmunosupresión, y a mayor CV, mayor el tiempo para lograr la indetectabilidad. Sólo se demostró fracaso virológico en tres pacientes. DISCUSIÓN: Los pacientes con infección por VIH que inician TAR con CV muy altas demoran más tiempo en lograr la supresión viral, lo cual es proporcional a la magnitud de ésta y al grado de inmunosupresión, sin que esto conlleve mayor riesgo de fracaso virológico.

BACKGROUND: The degree of viral suppression in HIV patients who start antiretroviral therapy (ART) with very high viral loads (CV) is unknown. AIM: To know the percentage of viral suppression in HIV patients who start ART with CV ≥ 500,000 copies/mL at 96 weeks. METHOD: Retrospective study. Patients who started ART with a CV ≥ 500,000 copies/mL between 2008 and 2018 were included, stratifying on the basis of a logarithmic scale. The percentage of viral suppression and the variables associated with this outcome were determined. RESULTS: 221 patients were included. The median age and CV were 43 years and 6.0 log, respectively, with the majority (37%) being in stage C3 at the start of ART. 48.8 and 87.7% of the patients achieved viral suppression at one year and two years of follow-up, respectively. It was observed that the older the immunosuppression, and the higher CV, the longer the time to achieve undetectability. Virological failure was only demonstrated in three patients. DISCUSSION: Patients with HIV infection who start ART with very high CVs take longer to achieve viral suppression, which is proportional to the magnitude of this and the degree of immunosuppression, without this entailing a greater risk of virological failure.

Aceptabilidad a usar profilaxis pre-exposición para VIH en hombres gay y otros hombres que tienen sexo con hombres: indagación en LAMIS 2018 Chile / Acceptability of pre-exposure prophylaxis for HIV prevention among gay men and other men who have sex with men: analysis of LAMIS 2018-Chile

INTRODUCCIÓN: Chile enfrenta una reemergencia de la epidemia del VIH concentrada en hombres gay y otros HSH. La profilaxis pre exposición (PrEP) es una intervención biomédica que ha resultado ser efectiva en la prevención del VIH en el grupo de HSH. OBJETIVO: Estimar niveles de aceptabilidad del uso de PrEP en hombres gay y otros HSH participantes en estudio LAMIS 2018 - Chile, identificando características y factores asociados a la aceptabilidad del uso de PrEP. MATERIAL Y MÉTODOS: Estudio basado en datos de LAMIS-2018 Chile, encuesta transversal por internet dirigida a hombres gay, bisexual, trans y otros HSH. La submuestra de este estudio consiste en 3.976 participantes que se auto-reportaron ser VIH negativos o desconocer su estado serológico, quienes respondieron preguntas sociodemográficas, de comportamiento, sobre su aceptabilidad a usar PrEP y otros aspectos relacionados. Se realizó análisis bivariados y regresión logística multivariable para identificar los factores asociados a la aceptabilidad a usar PrEP. RESULTADOS Y DISCUSIÓN: Se identificó que 55,7% de la muestra reportó una alta aceptabilidad a usar la PrEP. La regresión logística multivariable mostró que tener relaciones sexuales sin condón (ORa = 1,67, IC 95% 1,42-1,97) y haber intentado usar PrEP (ORa = 1,99, IC 95% 1,41-1, 62) se asociaron positivamente a la aceptabilidad a usar PrEP mientras que tener una relación con pareja estable, se asoció negativamente. Se identificó una aceptabilidad a usar la PrEP relativamente alta en los participantes. No obstante, se hace necesario considerar intervenciones relacionada a aumentar el conocimiento y promover la demanda de la PrEP. Además, el presente estudio muestra la necesidad de considerar la participación de las organizaciones de la sociedad civil en su implementación, fenómenos emergentes y la pertinencia territorial.

BACKGROUND: Chile is facing a re-emergence of the HIV epidemic, concentrated among men who have sex with men (MSM). Pre-exposure prophylaxis (PrEP) is a biomedical intervention that effectively prevents HIV transmission among MSM. AIM: The study was designed to estimate acceptability of PrEP and identify factors associated with PrEP-related attitudes and behaviors among MSM using LAMIS 2018 - Chile study data. Methods: Data were taken from the LAMIS 2018 - Chile study, a cross-sectional study of gay, bisexual, transgender, and other MSM. Our subsample included 3976 participants with self-reported HIV-negative or unknown status who responded to sociodemographic questions and items related to PrEP. Bivariate analysis and multivariate logistic regression analysis were performed to identify factors associated with acceptability of PrEP. RESULTS AND DISCUSSION: A total of 55.7% of the sample reported high PrEP acceptability. Logistic regression indicated that engaging in sex without a condom (ORa = 1.67, IC 95% 1.42-1.97) and having previously used PrEP (ORa = 1.99, IC 95% 1.41-1.62) were associated with high acceptability to use PrEP, while having a stable partner was associated with low acceptability. The estimate of PrEP acceptability was relatively high among participants. However, interventions to increase awareness and promote demand for PrEP may be beneficial. Furthermore, this study demonstrates the need for non-governmental organizations to participate in such strategies and for measures that address regionally-relevant emerging phenomena.

Fractura de fémur proximal (31-A3. 2) asociada al uso de tenofovir en paciente VIH+: reporte de caso / Proximal femur fracture (31-A3. 2) associated with the use of tenofovir in an HIV-positive patient: case report

Presentamos el primer reporte de caso en paciente adulto con virus de la inmunodeficiencia humana (VIH + ) con fractura por fragilidad en fémur proximal asociada al uso de terapia antirretroviral (TARV) con fumarato de disoproxilo de tenofovir (FDT) en Chile. Actualmente, los pacientes diagnosticados con VIH inician tratamiento precoz con TARV, lo que implica mayor cantidad de años de exposición a los fármacos de la terapia. El tiempo de exposición acumulado al FDT se ha asociado a disminución de la densidad mineral ósea y falla renal progresiva, pudiendo el paciente desarrollar síndrome de Fanconi adquirido y osteomalacia, con riesgo aumentado de fractura. Presentamos el caso de un hombre de 44 años, VIH+ , evaluado en urgencia tras caída a nivel que resultó en fractura patológica del fémur proximal. Los exámenes de ingreso destacaron hipocalemia, hipocalcemia, hipofosfatemia e hipovitaminosis D. Se realizó manejo multidisciplinario, con suspensión del FDT, un cambio en la TARV, y suplementación con calcio y carga de vitamina D. Se realizó reducción cerrada y fijación con clavo cefalomedular largo, que evolucionó favorablemente con rehabilitación motora precoz; el paciente recuperó su funcionalidad previa, y se observó consolidación ósea a las 12 semanas. La aparición de dolor osteomuscular en pacientes VIH+ en TARV debe levantar alta sospecha clínica de efecto adverso a medicamento; el seguimiento de estos pacientes debe incluir el control seriado de la función renal y de los niveles séricos de calcio y fósforo. La búsqueda y sospecha de estas complicaciones permitiría una intervención precoz, mejorando la condición de los pacientes y previniendo fracturas patológicas.

We present the first case report of a human immunodeficiency virus (HIV)-positive adult patient with a fragility fracture of the proximal femur associated with antiretroviral therapy (ART) with tenofovir disoproxil fumarate (TDF) in Chile. Currently, patients diagnosed with HIV start ART early, resulting in more years of exposure to these drugs. The accumulated exposure time to TDF has been associated with a decreased bone mineral density and progressive renal failure, potentially leading to acquired Fanconi syndrome, osteomalacia, and an increased risk of fracture. We present a case of a 44-year-old, HIV-positive man assessed at the emergency room after a fall from standing height which resulted in a proximal femoral pathological fracture. Laboratory findings at admission revealed hypokalemia, hypocalcemia, hypophosphatemia, and hypovitaminosis D. Multidisciplinary management was performed, with TDF discontinuation, ART change, and supplementation with calcium and vitamin D. Closed reduction and fixation with a long cephalomedullary nail was successful, with early motor rehabilitation, functional recovery, and bone consolidation at 12 weeks. Musculoskeletal pain in HIV-positive patients on ART must raise the clinical suspicion of an adverse drug effect; the follow-up of these subjects must include serial monitoring of renal function and serum calcium and phosphorus levels. Screening and suspicion of such complications would enable an early intervention, improving the patients' condition and preventing pathological fractures.

Switching from efavirenz to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide reduces central nervous system symptoms in people living with HIV / 中华医学杂志(英文版)

BACKGROUND@#Central nervous system (CNS) symptoms after efavirenz (EFV) treatment in people living with human immunodeficiency virus (HIV) could persist and impact their quality of life. We assessed the impact of EFV-based regimen replacement with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF), which is considered an alternative option for subjects who do not tolerate EFV. Most specifically, we assessed the safety and the efficacy of E/C/F/TAF and its effects on the participants' neuropsychiatric toxicity symptoms in a real-life setting.@*METHODS@#A prospective cohort study was conducted among virologic suppressed HIV-positive participants receiving EFV-based regimens with ongoing CNS toxicity ≥ grade 2. The participants were switched to single-pill combination regimens E/C/F/TAF and followed up for 48 weeks. The neuropsychiatric toxicity symptoms were measured using a CNS side effects questionnaire, as well as the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. The primary outcome measure was the proportion of participants experiencing grade 2 or higher CNS toxicity after EFV switch off at weeks 12, 24, and 48. Secondary endpoints included virologic and immunological responses and the effect on fasting lipids at week 48 after switch.@*RESULTS@#One hundred ninety-six participants (96.9% men, median age: 37.5 years, median: 3.7 years on prior EFV-containing regimens) were included in the study. Significant improvements in anxiety and sleep disturbance symptoms were observed at 12, 24, and 48 weeks after switching to E/C/F/TAF (P < 0.05). No significant change in depression symptom scores was observed. At 48 weeks after switch, HIV viral load <50 copies/mL was maintained in all of the participants, median fasting lipid levels were moderately increased (total cholesterol [TC]: 8.2 mg/dL, low-density lipoprotein cholesterol [LDL-C]: 8.5 mg/dL, high-density lipoprotein cholesterol [HDL-C]: 2.9 mg/dL, and triglyceride (TG): 1.6 mg/dL, and the TC:HDL-C ratio remained stable.@*CONCLUSIONS@#The single-pill combination regimens E/C/F/TAF is safe and well tolerated. This study reveals that switching from EFV to E/C/F/TAF significantly reduces neuropsychiatric toxicity symptoms in people living with HIV with grade 2 or higher CNS complaints.

Survival of HIV/AIDS patients treated under ART follow-up at the University hospital, northwest Ethiopia

INTRODUCTION@#The survival of HIV/AIDS patients on antiretroviral therapy (ART) is determined by a number of factors, including economic, demographic, behavioral, and institutional factors. Understanding the survival time and its trend is crucial to developing policies that will result in changes. The aim of this study was to compare the survival estimates of different subgroups and look into the predictors of HIV/AIDS patient survival.@*METHODS@#A retrospective cohort study of HIV/AIDS patients receiving ART at the University of Gondar teaching hospital was carried out. To compare the survival of various groups, a Kaplan-Meier survival analysis was performed. The Cox proportional hazards model was used to identify factors influencing HIV/AIDS patient survival rates.@*RESULTS@#In the current study, 5.91% of the 354 HIV/AIDS patients under ART follow-up were uncensored or died. Age (HR = 1.051) and lack of formal education (HR = 5.032) were associated with lower survival rate, whereas family size of one to two (HR = 0.167), three to four (HR = 0.120), no alcoholic consumption (HR = 0.294), no smoking and chat use (HR = 0.101), baseline weight (HR = 0.920), current weight (HR = 0.928), baseline CD4 cell count (HR = 0.990), baseline hemoglobin (HR = 0.800), and no TB diseases were associated with longer survival rate.@*CONCLUSIONS@#Fewer deaths were reported in a study area due to high patient adherence, compared to previous similar studies. Age, educational status, family size, alcohol consumption, tobacco and chat usage, baseline and current weight, baseline CD4 cell count, baseline hemoglobin, and tuberculosis (TB) diseases were all significant predictors of survival of HIV/AIDS patients.

Immune recovery after antiretroviral therapy initiation: a challenge for people living with HIV in Brazil / Recuperação imunológica após o início da terapia antirretroviral: um desafio para pessoas vivendo com HIV no Brasil / Recuperación inmunológica tras el inicio de una terapia antirretroviral: un desafío para la gente que vive con VIH en Brasil

Immune recovery reflects health conditions. Our goal was to estimate the time it takes to achieve immune recovery and its associated factors, in people living with HIV (PLHIV), after antiretroviral therapy (ART) initiation. A historical cohort study was performed among PLHIV (> 18 years-old) in Minas Gerais State, Brazil, using data from healthcare databases. Patients initiating ART between 2009-2018, with T-CD4+ lymphocytes and viral load recorded before and after antiretroviral therapy were included. The outcome is achievement of immune recovery, defined as the first T-CD4+ > 500 cells/µL after ART initiation. Explanatory variables were age, gender, place of residence, year of ART initiation, baseline viral load and T-CD4+, viral load status, and adherence to ART at follow-up. Descriptive analysis, cumulative, and person-time incidences of immune recovery were estimated. Median-time to immune recovery was estimated using Kaplan-Meier method. Factors associated with immune recovery were assessed by Cox regression. Among 26,430 PLHIV, 8,014 (30%) were eligible. Most were male (67%), mean age 38.7 years, resided in non-central region, median-baseline T-CD4+ = 228 cells/µL (< 200 cells/µL = 43%) and viral load median-baseline = 4.7 log10 copies/mL (detectable viral load = 99%). Follow-up time = 15,872 person-years. Cumulative and incidence rate were 58% (95%CI: 57-58) (n = 4,678) and 29.47 cases/100 person-years, respectively. Median-time to immune recovery was of 22.8 months (95%CI: 21.9-24.0). Women living with HIV, younger than 38 years of age, with T-CD4+ baseline > 200 cells/µL, detectable viral load (baseline), antiretroviral therapy-adherence and undetectable viral load (follow-up) were independently associated with immune recovery. Time to immune recovery remains long and depends on early treatment and antiretroviral therapy-adherence.

A recuperação imunológica reflete condições de saúde. Nosso objetivo foi estimar o tempo até a recuperação imunológica e fatores associados em pessoas vivendo com HIV (PVHIV) após de iniciar a terapia antirretroviral (TARV). Foi conduzida uma coorte histórica de PVHIV (> 18 anos) no Estado de Minas Gerais, Brasil, usando bancos de serviços públicos de saúde. Foram incluídos pacientes que iniciaram a TARV entre 2009 e 2018, com linfócitos T-CD4+ e carga viral registrados antes e depois do início da TARV. O desfecho foi a recuperação imunológica, definida como a primeira contagem de T-CD4+ > 500 cel/µL após o início da TARV. As variáveis explanatórias foram idade, sexo, local de residência, ano de início de TARV, carga viral basal, T-CD4+ na linha de base e carga viral e adesão à TARV no seguimento. Foi realizada uma análise descritiva com estimativa de incidência acumulada e taxa de incidência (pessoa-ano). O tempo mediano até a recuperação imunológica foi estimado pelo método Kaplan-Meier. Fatores associados à recuperação imune foram avaliados por meio de regressão de Cox. Entre as 26.430 PVHIV, 8.014 (30%) foram elegíveis. A maioria era do sexo masculino (67%), com média de idade = 38,7 anos, residência em regiões fora da região metropolitana, mediana de T-CD4+ baseline = 228 células/µL (< 200 células/µL = 43%) e mediana de carga viral baseline = 4,7 log10 cópias/mL (carga viral detectável = 99%). Tempo de seguimento = 15.872 pessoas-ano. A incidência acumulativa e a taxa de incidência foram foram 58% (IC95%: 57-58) (n = 4.678) e 29,47 casos/100 pessoas-ano, respectivamente. Tempo mediano até recuperação imune = 22,8 meses (IC95%: 21,9-24,0). Os fatores independentemente associados com recuperação imunológica foram sexo feminino, idade < 38 anos, T-CD4+ basal > 200 células/µL, carga viral detectável (linha de base), adesão à TARV e carga viral indetectável (no seguimento). O tempo até a recuperação imunológica ainda é longo e impactado pelo tratamento precoce e da adesão à TARV.

La recuperación inmunológica refleja condiciones de salud. Nuestra meta fue estimar el tiempo y los factores asociados a la recuperación inmunológica en personas que viven con VIH (PVVIH), tras iniciar una terapia antirretroviral (TAR). Se realizó sobre una cohorte histórica entre PVVIH (> 18 años de edad) en Minas Gerais, Brasil, usando datos de las bases de datos del sistema de salud. Se incluyeron a pacientes que comenzaron una TAR entre 2009-2018, con T-CD4+ linfocitos y carga viral, registrada antes/después de TAR. El resultado fue el logro de recuperación inmunológica, definida como la primera T-CD4+ > 500 células/µL tras la iniciación TAR. Las variables explicatorias fueron: edad, género, lugar de residencia, año de iniciación TAR, base de referencia de carga viral, base de referencia de T-CD4+ y estatus de la carga viral y adherencia al TAR en el seguimiento. Se estimó: análisis descriptivo, acumulativo e incidencias persona-tiempo de recuperación inmunológica. La media de tiempo para la recuperación inmunológica se estimó usando el método Kaplan-Meier. Los factores asociados con la recuperación inmunológica se evaluaron mediante la regresión de Cox. Entre las 26.430 PVVIH, 8.014 (30%) fueron elegibles. La mayoría eran hombres (67%), media de edad = 38,7 años, residentes en una región no central, media de base de referencia T-CD4+ = 228 células/µL (< 200 células/µL = 43%) y carga viral media de base de referencia = 4,7 log10 copias/mL (carga viral detectable = 99%). El tiempo de seguimiento = 15.872 persona-años. La tasa acumulativa y de incidencia fue 58% (95%CI: 57-58) (n = 4.678) y 29,47 casos/100 persona-años, respectivamente. El tiempo de media para la recuperación inmunológica = 22,8 meses (95%CI: 21,9-24,0). Género femenino, PVVIH < 38 años de edad, T-CD4+ base de referencia > 200 células/µL, carga viral detectable (base de referencia), adherencia al TAR e carga viral indetectable (seguimiento) estuvieron independientemente asociadas con la recuperación inmunológica. El tiempo para la recuperación inmunológica sigue siendo largo y depende de un tratamiento temprano y de adherencia a la TAR.

Virologic success under antiretroviral therapy among people living with HIV/AIDS in the state of Paraná, Brazil / Avaliação do sucesso virológico da terapia antirretroviral em pessoas vivendo com HIV/AIDS no estado do Paraná, Brasil

ABSTRACT Objective: To characterize the sociodemographic profile of the population undergoing antiretroviral treatment in the state of Paraná, Brazil, to investigate the proportion of people undergoing treatment among all those diagnosed, and to analyze the proportion of patients with suppressed viral load in different regions of the state. Methods: Observational descriptive and analytical study carried out with information referring to the period from January 2018 to January 2019. Data were obtained from the Sistema Informatizado de Monitoramento Clínico das Pessoas Vivendo com HIV/AIDS [Computerized System for Clinical Monitoring of People Living with HIV/AIDS] and Sistema de Controle Logístico de Medicamentos[Drug Supply Control System]. The proportion of people on antiretroviral treatment in the state and the proportion of patients with viral load ≤1,000 copies/mL and ≤50 copies/mL were calculated. The results were compared with the corresponding parameters of the World Health Organization goal 90-90-90. Results: The state of Paraná managed to reach the second and third parameters of the 90-90-90 goal of the World Health Organization. Among those diagnosed, 93.12% were on antiretroviral treatment, and 90.0% of them had a viral load below 50 copies of viral RNA/mL of blood, indicating virologic success. Conclusion: The health policy aimed at the population living with HIV/AIDS, and the health services available in Paraná have been successful in parameters relevant to the control of the epidemic. However, it is necessary to ensure the diagnosis of people infected with HIV in the population.

RESUMO Objetivo: Caracterizar o perfil sociodemográfico da população em tratamento antirretroviral no estado do Paraná, investigar a proporção de pessoas em tratamento entre todos os diagnosticados e analisar a proporção de pacientes com carga viral suprimida nas diferentes regiões do estado. Métodos: Estudo observacional descritivo e analítico realizado com informações referentes ao período de janeiro de 2018 a janeiro de 2019. Os dados foram obtidos do Sistema Informatizado de Monitoramento Clínico das Pessoas Vivendo com HIV/AIDS e do Sistema de Controle Logístico de Medicamentos. Foram calculadas as proporções de pessoas em tratamento antirretroviral no estado e de pacientes com carga viral ≤1.000 cópias/mL e ≤50 cópias/mL. Os resultados foram comparados com os parâmetros correspondentes da meta 90-90-90 da Organização Mundial da Saúde. Resultados: O estado do Paraná alcançou o segundo e o terceiro parâmetros da meta 90-90-90 da Organização Mundial da Saúde. Entre os diagnosticados, 93,12% encontravam-se em tratamento antirretroviral, e 90,0% destes apresentavam carga viral abaixo 50 cópias do RNA viral/mL de sangue, indicando sucesso virológico. Conclusão: A política de saúde voltada à população vivendo com HIV/AIDS e os serviços de saúde disponibilizados no Paraná têm obtido êxito em parâmetros relevantes para o controle da epidemia. Entretanto, é necessário assegurar o diagnóstico das pessoas infectadas por HIV na população.