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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 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.

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 IM by Biojector) at 0, 1 and 2 months, followed by rAd5 (10 10 PU IM 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

Treatment with indinavir has been shown to result in marked decreases in viral load and increases in CD4 cell counts in HIV-infected individuals. A randomized double-blind study to evaluate the efficacy of indinavir alone (800 mg q8h), zidovidine alone (200 mg q8h) or the combination was performed to evaluate progression to AIDS. 996 antiretroviral therapy-naive patients with CD4 cell counts of 50-250/mm3 were allocated to treatment. During the trial the protocol was amended to add lamivudine to the zidovudine-containing arms. The primary endpoint was time to development of an AIDS-defining illness or death. The study was terminated after a protocol-defined interim analysis demonstrated highly significant reductions in progression to a clinical event in the indinavir-containing arms, compared to the zidovudine arm (p

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

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.