Clinical and epidemiological features of mpox in a Brazilian reference center for HIV and sexually transmitted infections: A cross-sectional study.

Background: The 2022 mpox outbreak has affected disproportionately people living with HIV (PLWH) and pre-exposure prophylaxis (PrEP) users. Methods: We conducted a cross-sectional study to evaluate factors associated with laboratory diagnosis of mpox among suspected cases, and access differences between PrEP users and PLWH with confirmed diagnostic. Results: 394 mpox suspected cases were analyzed, 309 (78.4%) confirmed. Most patients with mpox were PLWH (54.4%) and 99 (32%) PrEP users. Mpox cases were likely to be between 25 and 39 years old (aOR=2.8; p=0.042), men who have sex with men/bisexual or transgender women (aOR=17.2; p< 0.001) and to have fever (aOR=4.7; p< 0.001), adenomegaly (aOR=7.2; p< 0.001) and multiple vesicular lesions (aOR=4.2; p< 0.001). Comparing PrEP users to PLWH with confirmed mpox, PrEP users had lesions predominantly with exclusive genital involvement (p=0.016); while PLWH had higher extragenital involvement (p=0.018). Conclusions: PrEP users and PLWHA were the main epidemiological groups in our cohort. Recognizing the differences between vulnerable populations can contribute to the development public policies to control mpox in settings with reduced access to vaccines.

Improving the continuum of care monitoring in Brazilian HIV healthcare services: An implementation science approach.

OBJECTIVE: To evaluate the impact of an intervention improving the continuum of care monitoring (CCM) within HIV public healthcare services in São Paulo, Brazil, and implementing a clinical monitoring system. This system identified three patient groups prioritized for additional care engagement: (1) individuals diagnosed with HIV, but not receiving treatment (the treatment gap group); (2) individuals receiving treatment for >6 months with a detectable viral load (the virologic failure group); and (3) patients lost to follow-up (LTFU). METHODS: The implementation strategies included three training sessions, covering system logistics, case discussions, and development of maintenance goals. These strategies were conducted within 30 HIV public healthcare services (May 2019 to April 2020). After each training session, professionals shared their experiences with CCM at regional meetings. Before and after the intervention, providers were invited to answer 23 items from the normalization process theory questionnaire (online) to understand contextual factors. The mean item scores were compared using the Mann-Whitney U test. The RE-AIM implementation science framework (evaluating reach, effectiveness, adoption, implementation, and maintenance) was used to evaluate the integration of the CCM. RESULTS: In the study, 47 (19.3%) of 243 patients with a treatment gap initiated treatment, 456 (49.1%) of 928 patients with virologic failure achieved suppression, and 700 of 1552 (45.1%) LTFU patients restarted treatment. Strategies for the search and reengagement of patients were developed and shared. Providers recognized the positive effects of CCM on their work and how it modified existing activities (3.7 vs. 4.4, p<0.0001, and 3.9 vs. 4.1, p<0.05); 27 (90%) centers developed plans to sustain routine CCM. CONCLUSION: Implementing CCM helped identify patients requiring more intensive attention. This intervention led to changes in providers' perceptions of CCM and care and management processes, which increased the number of patients engaged across the care continuum and improved outcomes.

An intervention for the implementation of clinical monitoring in specialized care services to people living with HIV/AIDS. / Intervenção para a implementação do monitoramento clínico em serviços especializados de atenção às pessoas vivendo com HIV/aids.

The clinical monitoring of people living with HIV/AIDS (PLWHA) contributes to identifying and managing cases of individuals who have not begun treatment (gap), those experiencing treatment failure or who have abandoned treatment. This article sought to present and discuss the development of a methodology to implement the clinical monitoring of PLWHA in the services of the Brazilian Unified National Health System (SUS). The methodology used since 2014 by the CRT-STI/AIDS-Coordination of the STI/AIDS Program, São Paulo State, Brazil, was re-structured in three meetings between June and August 2018. The new methodology retained the axes of presentation of number of users in treatment failure, gap or abandonment in the participant services, as well as the discussion of individual, social and programmatic vulnerabilities. A new axis was added which directs the discussion of the possibilities of reorganizing service care flows and management practices. Additionally, the intervention started to be carried out in health services, with the participation of a higher number of professionals from the multi-professional team, discussion of cases, workflows and processes, and regional meetings to exchange clinical monitoring experiences between services. The re-structuring of the methodology contributed to a reduction in treatment gap, a reorganization of care flows and the inclusion of clinical monitoring as a management tool in services specialized in providing care to PLWHA. This methodology can be implemented by other state programs, municipalities and services, since all have access to the same information sources used in this intervention.

Intervenção para a implementação do monitoramento clínico em serviços especializados de atenção às pessoas vivendo com HIV/aids / Intervención para la implementación del monitoreo clínico en servicios especializados de atención a personas afectadas por el VIH/SIDA / An intervention for the implementation of clinical monitoring in specialized care services to people living with HIV/AIDS

O monitoramento clínico de pessoas vivendo com HIV/aids (PVHA) contribui para a identificação e gestão de caso das pessoas sem início de tratamento (gap), em falha terapêutica e em abandono de tratamento. O objetivo deste artigo é apresentar e discutir o desenvolvimento de uma metodologia para a implementação do monitoramento clínico das PVHA em serviços do Sistema Único de Saúde (SUS). A metodologia utilizada desde 2014 pelo Centro de Referência e Treinamento DST/AIDS-SP-Coordenação do Programa Estadual de IST/AIDS do Estado de São Paulo, Brasil, foi reestruturada em três reuniões, no período de junho a agosto de 2018. Foram mantidos os eixos de apresentação do número de usuários com falha terapêutica, em gap e em abandono de tratamento nos serviços participantes, e a discussão de vulnerabilidades individuais, sociais e programáticas. Foi adicionado um novo eixo que direciona a discussão das possibilidades de reorganização de fluxos assistenciais e práticas gerenciais do serviço. Adicionalmente, a intervenção passou a ser feita nos serviços de saúde, com a participação de um número maior de profissionais da equipe multiprofissional, discussão de casos, fluxos e processos de trabalho e encontros regionais para a troca de experiências em monitoramento clínico entre os serviços. A reestruturação da metodologia contribuiu para a diminuição do gap de tratamento, reorganização de fluxos assistenciais e inclusão do monitoramento clínico como ferramenta de gestão nos serviços de assistência especializada às PVHA. Essa metodologia pode ser implementada por outros programas estaduais, municípios e serviços, uma vez que todos têm acesso às mesmas fontes de informação usadas nesta intervenção.

El monitoreo clínico de personas afectadas por el VIH/SIDA (PVHA) contribuye a la identificación y gestión de caso de personas sin inicio de tratamiento (gap), con fallos en la parte terapéutica y abandono del tratamiento. El objetivo de este artículo es presentar y discutir el desarrollo de una metodología para la implementación del monitoreo clínico de las PVHA en servicios del Sistema Único de Salud (SUS). La metodología utilizada desde 2014 por el CRT-ETS/SIDA-Coordinación del Programa Estatal de ETS/SIDA del Estado de São Paulo, Brasil, fue reestructurada en tres reuniones, durante el período de junio a agosto de 2018. Se mantuvieron los ejes de presentación del número de usuarios con fallos en la parte terapéutica, gap y con abandono de tratamiento en los servicios participantes estudiados, así como la discusión de vulnerabilidades individuales, sociales y programáticas. Se añadió un nuevo eje que vertebra la discusión sobre las posibilidades de reorganización de los flujos asistenciales y prácticas de gestión del servicio. Asimismo, la intervención pasó a realizarse en los servicios de salud, con la participación de un mayor número de profesionales del equipo multiprofesional, discusión de casos, flujos y procesos de trabajo, así como encuentros regionales para el intercambio de experiencias en el monitoreo clínico entre los servicios. La reestructuración de la metodología contribuyó a la disminución del gap en el tratamiento, la reorganización de flujos asistenciales, así como la inclusión del monitoreo clínico como herramienta de gestión en los servicios de asistencia especializada a las PVHA. Esta metodología puede ser implementada en otros programas estatales, municipios y servicios, ya que todos tienen acceso a las mismas fuentes de información usadas en esta intervención.

The clinical monitoring of people living with HIV/AIDS (PLWHA) contributes to identifying and managing cases of individuals who have not begun treatment (gap), those experiencing treatment failure or who have abandoned treatment. This article sought to present and discuss the development of a methodology to implement the clinical monitoring of PLWHA in the services of the Brazilian Unified National Health System (SUS). The methodology used since 2014 by the CRT-STI/AIDS-Coordination of the STI/AIDS Program, São Paulo State, Brazil, was re-structured in three meetings between June and August 2018. The new methodology retained the axes of presentation of number of users in treatment failure, gap or abandonment in the participant services, as well as the discussion of individual, social and programmatic vulnerabilities. A new axis was added which directs the discussion of the possibilities of reorganizing service care flows and management practices. Additionally, the intervention started to be carried out in health services, with the participation of a higher number of professionals from the multi-professional team, discussion of cases, workflows and processes, and regional meetings to exchange clinical monitoring experiences between services. The re-structuring of the methodology contributed to a reduction in treatment gap, a reorganization of care flows and the inclusion of clinical monitoring as a management tool in services specialized in providing care to PLWHA. This methodology can be implemented by other state programs, municipalities and services, since all have access to the same information sources used in this intervention.

[Comprehensiveness and healthcare technologies: a narrative on conceptual contributions to the construction of the comprehensiveness principle in the Brazilian Unified National Health System]. / Integralidade e tecnologias de atenção à saúde: uma narrativa sobre contribuições conceituais à construção do princípio da integralidade no SUS.

Comprehensiveness is the most challenging principle for building health reform in the Brazilian Unified National Health System (SUS). This study aims to identify critical moments in the conceptual debate on comprehensiveness and its contributions to reflection on healthcare technologies in the SUS. The essay addresses some conceptual constructs that approach comprehensiveness as an underlying principle in health programs and actions at various levels and in various dimensions of the healthcare organization - from intersubjective interactions to the organization of regional networks. The study was based on a non-systematic literature review on comprehensiveness and related themes in the Brazilian public health field in the last five decades. The study proposed a chronology/typology spanning the 1960s to the 2010s, divided into four significant periods or categories. The narrative is not intended to be exhaustive, but to build a comprehensive reference base capable of contributing to analyses, assessments, and debates on healthcare organization in the SUS according to the comprehensiveness principle.

Integralidade e tecnologias de atenção à saúde: uma narrativa sobre contribuições conceituais à construção do princípio da integralidade no SUS / Comprehensiveness and healthcare technologies: a narrative on conceptual contributions to the construction of the comprehensiveness principle in the Brazilian Unified National Health System / Integralidad y tecnologías de atención a la salud: una narrativa sobre contribuciones conceptuales a la construcción del principio de la integralidad en el Sistema Único de Salud brasileño

Resumo: Dentre os princípios do SUS, o de integralidade talvez seja o mais desafiador na construção da Reforma Sanitária. É objetivo deste estudo identificar momentos críticos do debate conceitual em torno da integralidade e suas contribuições para a reflexão acerca de tecnologias de atenção à saúde no âmbito do SUS. O ensaio percorre algumas construções conceituais que se aproximam da questão da integralidade como princípio norteador de programas e ações de saúde em diversos planos e dimensões da organização da atenção à saúde - das interações intersubjetivas à organização de redes regionais. O estudo se baseou em revisão não sistemática da literatura sobre o tema da integralidade e afins na produção do campo da Saúde Coletiva brasileira nas últimas cinco décadas. Propõe-se uma cronologia/tipologia que se estende dos anos 1960 à década de 2010, dividindo-a em quatro períodos/categorias julgados significativos. A narrativa não pretende ser exaustiva, mas construir uma referência compreensiva capaz de contribuir para análises, avaliações e debates acerca da organização da atenção à saúde no SUS conforme o princípio da integralidade.

Abstract: Comprehensiveness is the most challenging principle for building health reform in the Brazilian Unified National Health System (SUS). This study aims to identify critical moments in the conceptual debate on comprehensiveness and its contributions to reflection on healthcare technologies in the SUS. The essay addresses some conceptual constructs that approach comprehensiveness as an underlying principle in health programs and actions at various levels and in various dimensions of the healthcare organization - from intersubjective interactions to the organization of regional networks. The study was based on a non-systematic literature review on comprehensiveness and related themes in the Brazilian public health field in the last five decades. The study proposed a chronology/typology spanning the 1960s to the 2010s, divided into four significant periods or categories. The narrative is not intended to be exhaustive, but to build a comprehensive reference base capable of contributing to analyses, assessments, and debates on healthcare organization in the SUS according to the comprehensiveness principle.

Resumen: Entre los principios del Sistema Único de Salud brasileño (SUS), el de integralidad tal vez sea el que más desafíos supone de todos los presentes en la construcción de la Reforma Sanitaria. El objetivo de este estudio es identificar momentos críticos del debate conceptual, en torno a la integralidad y sus contribuciones, para la reflexión acerca de tecnologías de atención a la salud en el ámbito del SUS. El ensayo recorre algunas construcciones conceptuales que se aproximan a la cuestión de la integralidad, como un principio director de programas y acciones de salud en diversos planos y dimensiones de la organización de la atención a la salud, desde las interacciones intersubjetivas, a la organización de redes regionales. El estudio se basó en una revisión no sistemática de la literatura sobre el tema de la integralidad y cuestiones afines en la producción del campo de la Salud Colectiva brasileña durante las últimas cinco décadas. Se propone una cronología/tipología que se extiende desde los años 60 a la década de 2010, dividiéndola en cuatro períodos/categorías considerados como significativos. La narrativa no pretende ser exhaustiva, sino construir una referencia comprensiva capaz de contribuir a análisis, evaluaciones y debates, a cerca de la organización de la atención a la salud en el SUS, según el principio de la integralidad.

The HIV-Brazil cohort study: design, methods and participant characteristics.

BACKGROUND: The HIV-Brazil Cohort Study was established to analyze the effectiveness of combination antiretroviral therapy (cART) and the impact of this treatment on morbidity, quality of life (QOL) and mortality. The study design, patients' profiles and characteristics of cART initiation between 2003 and 2010 were described. METHODOLOGY/PRINCIPAL FINDINGS: Since 2003, the HIV-Brazil Cohort has been following HIV-infected adults receiving cART at 26 public health care facilities, using routine clinical care data and self-reported QOL questionnaires. When not otherwise available, data are obtained from national information systems. The main outcomes of interest are diseases related or unrelated to HIV; suppression of viral replication; adverse events; virological, clinical and immunological failures; changes in the cART; and mortality. For the 5,061 patients who started cART between 2003 and 2010, the median follow-up time was 4.1 years (IQR 2.2-5.9 years) with an 83.4% retention rate. Patient profiles were characterized by a predominance of men (male/female ratio 1.7∶1), with a mean age of 36.9 years (SD 9.9 years); 55.2% had been infected with HIV via heterosexual contact. The majority of patients (53.4%) initiated cART with a CD4+ T-cell count ≤200 cells/mm3. The medications most often used in the various treatment regimens were efavirenz (59.7%) and lopinavir/ritonavir (18.2%). The proportion of individuals achieving viral suppression within the first 12 months of cART use was 77.4% (95% CI 76.1-78.6). Nearly half (45.4%) of the patients presented HIV-related clinical manifestations after starting cART, and the AIDS mortality rate was 13.9 per 1,000 person-years. CONCLUSIONS/SIGNIFICANCE: Results from cART use in the daily practice of health services remain relatively unknown in low- and middle-income countries, and studies with the characteristics of the HIV-Brazil Cohort contribute to minimizing these shortcomings, given its scope and patient profile, which is similar to that of the AIDS epidemic in the country.

Safety and immunogenicity of an HIV-1 gag DNA vaccine with or without IL-12 and/or IL-15 plasmid cytokine adjuvant in healthy, HIV-1 uninfected adults.

BACKGROUND: DNA vaccines are a promising approach to vaccination since they circumvent the problem of vector-induced immunity. DNA plasmid cytokine adjuvants have been shown to augment immune responses in small animals and in macaques. METHODOLOGY/PRINCIPAL FINDINGS: We performed two first in human HIV vaccine trials in the US, Brazil and Thailand of an RNA-optimized truncated HIV-1 gag gene (p37) DNA derived from strain HXB2 administered either alone or in combination with dose-escalation of IL-12 or IL-15 plasmid cytokine adjuvants. Vaccinations with both the HIV immunogen and cytokine adjuvant were generally well-tolerated and no significant vaccine-related adverse events were identified. A small number of subjects developed asymptomatic low titer antibodies to IL-12 or IL-15. Cellular immunogenicity following 3 and 4 vaccinations was poor, with response rates to gag of 4.9%/8.7% among vaccinees receiving gag DNA alone, 0%/11.5% among those receiving gag DNA+IL-15, and no responders among those receiving DNA+high dose (1500 ug) IL-12 DNA. However, after three doses, 44.4% (4/9) of vaccinees receiving gag DNA and intermediate dose (500 ug) of IL-12 DNA demonstrated a detectable cellular immune response. CONCLUSIONS/SIGNIFICANCE: This combination of HIV gag DNA with plasmid cytokine adjuvants was well tolerated. There were minimal responses to HIV gag DNA alone, and no apparent augmentation with either IL-12 or IL-15 plasmid cytokine adjuvants. Despite the promise of DNA vaccines, newer formulations or methods of delivery will be required to increase their immunogenicity. TRIAL REGISTRATION: Clinicaltrials.gov NCT00115960 NCT00111605.

A phase IIA randomized clinical trial of a multiclade HIV-1 DNA prime followed by a multiclade rAd5 HIV-1 vaccine boost in healthy adults (HVTN204).

BACKGROUND: The safety and immunogenicity of a vaccine regimen consisting of a 6-plasmid HIV-1 DNA prime (envA, envB, envC, gagB, polB, nefB) boosted by a recombinant adenovirus serotype-5 (rAd5) HIV-1 with matching inserts was evaluated in HIV-seronegative participants from South Africa, United States, Latin America and the Caribbean. METHODS: 480 participants were evenly randomized to receive either: DNA (4 mg i.m. by Biojector) at 0, 1 and 2 months, followed by rAd5 (10(10) PU i.m. by needle/syringe) at 6 months; or placebo. Participants were monitored for reactogenicity and adverse events throughout the 12-month study. Peak and duration of HIV-specific humoral and cellular immune responses were evaluated after the prime and boost. RESULTS: The vaccine was well tolerated and safe. T-cell responses, detected by interferon-γ (IFN-γ) ELISpot to global potential T-cell epitopes (PTEs) were observed in 70.8% (136/192) of vaccine recipients overall, most frequently to Gag (54.7%) and to Env (54.2%). In U.S. vaccine recipients T-cell responses were less frequent in Ad5 sero-positive versus sero-negative vaccine recipients (62.5% versus 85.7% respectively, p = 0.035). The frequency of HIV-specific CD4+ and CD8+ T-cell responses detected by intracellular cytokine staining were similar (41.8% and 47.2% respectively) and most secreted ≥2 cytokines. The vaccine induced a high frequency (83.7%-94.6%) of binding antibody responses to consensus Group M, and Clades A, B and C gp140 Env oligomers. Antibody responses to Gag were elicited in 46% of vaccine recipients. CONCLUSION: The vaccine regimen was well-tolerated and induced polyfunctional CD4+ and CD8+ T-cells and multi-clade anti-Env binding antibodies. TRIAL REGISTRATION: ClinicalTrials.gov NCT00125970.

A phase I trial of preventive HIV vaccination with heterologous poxviral-vectors containing matching HIV-1 inserts in healthy HIV-uninfected subjects.

We evaluated replication-defective poxvirus vectors (modified vaccinia Ankara [MVA] and fowlpox [FPV]) in a homologous and heterologous vector prime-boost vaccination regimen containing matching HIV inserts (MVA-HIV and FPV-HIV) given at months 0, 1, 3, 5 and 7 in 150 healthy HIV-negative vaccinia-naïve participants. FPV-HIV alone was poorly immunogenic, while the high dose (10(9)pfu/2 ml) of MVA-HIV alone elicited maximal responses after two injections: CD4+ and CD8+ T-cell responses in 26/55 (47.3%) and 5/60 (8.3%) of participants, respectively, and IFN-γ ELISpot responses in 28/62 (45.2%). The infrequent CD8+ T-cell responses following MVA-HIV priming were boosted only by the heterologous (FPV-HIV) construct in 14/27 (51.9%) of participants post 4th vaccination. Alternatively, HIV envelope-specific binding antibodies were demonstrated in approximately two-thirds of recipients of the homologous boosting regimen, but in less than 20% of subjects after the heterologous vector boost. Thus, a heterologous poxvirus vector prime-boost regimen can induce HIV-specific CD8+ T-cell and CD4+ T-cell responses, which may be an important feature of an optimal regimen for preventive HIV vaccination.