Immunogenicity of personalized dendritic-cell therapy in HIV-1 infected individuals under suppressive antiretroviral treatment: interim analysis from a phase II clinical trial.

BACKGROUND: We developed a personalized Monocyte-Derived Dendritic-cell Therapy (MDDCT) for HIV-infected individuals on suppressive antiretroviral treatment and evaluated HIV-specific T-cell responses. METHODS: PBMCs were obtained from 10 HIV+ individuals enrolled in trial NCT02961829. Monocytes were differentiated into DCs using IFN-α and GM-CSF. After sequencing each patient's HIV-1 Gag and determining HLA profiles, autologous Gag peptides were selected based on the predicted individual immunogenicity and used to pulse MDDCs. Three doses of the MDDCT were administered every 15 days. To assess immunogenicity, patients' cells were stimulated in vitro with autologous peptides, and intracellular IL-2, TNF, and interferon-gamma (IFN-γ) production were measured in CD4+ and CD8+ T-cells. RESULTS: The protocol of ex-vivo treatment with IFN-α and GM-CSF was able to induce maturation of MDDCs, as well as to preserve their viability for reinfusion. MDDCT administration was associated with increased expression of IL-2 in CD4+ and CD8+ T-cells at 15 and/or 30 days after the first MDDCT administration. Moreover, intracellular TNF and IFN-γ expression was significantly increased in CD4+ T-cells. The number of candidates that increased in vitro the cytokine levels in CD4+ and CD8+ T cells upon stimulation with Gag peptides from baseline to day 15 and from baseline to day 30 and day 120 after MDDCT was significant as compared to Gag unstimulated response. This was accompanied by an increasing trend in the frequency of polyfunctional T-cells over time, which was visible when considering both cells expressing two and three out of the three cytokines examined. CONCLUSIONS: MDDC had a mature profile, and this MDDCT promoted in-vitro T-cell immune responses in HIV-infected patients undergoing long-term suppressive antiretroviral treatment. Trial registration NCT02961829: (Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure, https://www.clinicaltrials.gov/ct2/show/NCT02961829 , posted November 11th, 2016).

Potential impact of the antirheumatic agent auranofin on proviral HIV-1 DNA in individuals under intensified antiretroviral therapy: Results from a randomised clinical trial.

Antiretroviral therapy (ART) is typically composed of a combination of three antiretroviral drugs and is the treatment of choice for people with human immunodeficiency virus type 1/acquired immune deficiency syndrome (HIV-1/AIDS). However, it is unable to impact on viral reservoirs, which harbour latent HIV-1 genomes that are able to reignite the infection upon treatment suspension. The aim of this study was to provide an estimate of the safety of the disease-modifying antirheumatic agent auranofin and its impact on the HIV-1 reservoir in humans under intensified ART. For this purpose, an interim analysis was conducted of three of the six arms of the NCT02961829 clinical trial (five patients each) with: no intervention, i.e. continuation of first-line ART; intensified ART (ART + dolutegravir and maraviroc); and intensified ART plus auranofin. Auranofin treatment was found to be well tolerated. No major adverse events were detected apart from a transient decrease in CD4+ T-cell counts at Weeks 8 and 12. Auranofin decreased total viral DNA in peripheral blood mononuclear cells compared with ART-only regimens at Week 20 (P = 0.036) and induced a decrease in integrated viral DNA as quantified by Alu PCR. Despite the limited number of patient-derived sequences available in this study, phylogenetic analyses of nef sequences support the idea that auranofin may impact on the viral reservoir. [ClinicalTrials.gov ID: NCT02961829].

Short Communication: Getting Older with HIV: Increasing Frequency of Comorbidities and Polypharmacy in Brazilian HIV Patients.

Life expectancy of HIV patients has increased over time. Older HIV patients have a higher frequency of noncommunicable diseases (NCD) than general population, and require multiple treatments. The main objective is to evaluate the changes in frequency of NCD and polypharmacy in HIV patients of three referral centers in Salvador and São Paulo. We compared the frequency of NCD and use of concomitant treatments in HIV patients, >50 years, in three Brazilian referral centers (São Paulo and Salvador). Data on sociodemographic characteristics, HIV therapy, CD4 count and viral load measurements, and frequency of NCD at baseline and last medical visit were recorded. We evaluated 451 patients, 128 in Salvador and 323 in São Paulo. Mean age was 57.9 ± 6.9 years. Mean baseline CD4 count was 199 ± 169. At baseline, dyslipidemia (4.0%) was the most frequent comorbidity, but at last visit we detected a high frequency of diabetes (14.9%), dyslipidemia (26.7%), osteoporosis (6.7%), stroke (4.4%), and malignancies (3.1%). Use of concomitant drugs for treatment of NCD increased significantly between first and last visit, especially antihypertensive, lipids lowering, and diabetes drugs. Aging in HIV patients in Brazil is characterized by an increasing incidence of NCD and polypharmacy.

Quality of life, socioeconomic profile, knowledge and attitude toward sexuality from the perspectives of individuals living with Human Immunodeficiency Virus.

OBJECTIVES: to analyze the quality of life of "patients" with Human Immunodeficiency Virus and relate it to their socioeconomic profile, knowledge and attitudes toward sexuality. METHOD: crosssectional and analytical study with 201 individuals who are 50 years old or older. The Targeted Quality of Life and Aging Sexual Knowledge and Attitudes Scales were applied during interviews. Multiple Linear Regression was used in data analysis. RESULTS: dimensions of quality of life more strongly compromised were disclosure worries (39.0), sexual function (45.9), and financial worries (55.6). Scores concerning knowledge and attitudes toward sexuality were 31.7 and 14.8, respectively. There was significant correlation between attitudes and the domains of overall function, health worries, medication worries, and HIV mastery. CONCLUSION: guidance concerning how the disease is transmitted, treated and how it progresses, in addition to providing social and psychological support, could minimize the negative effects of the disease on the quality of life of patients living with the Human Immunodeficiency Virus.

Quality of life, socioeconomic profile, knowledge and attitude toward sexuality from the perspectives of individuals living with Human Immunodeficiency Virus / Qualidade de vida, perfil socioeconômico, conhecimento e atitude sobre sexualidade de "pessoas que vivem" com o Vírus da Imunodeficiência Humana / Calidad de vida, perfil socioeconómico, conocimiento y actitud sobre sexualidad de "personas que viven" con el Virus de la Inmunodeficiencia Humana

Objectives: to analyze the quality of life of "patients" with Human Immunodeficiency Virus and relate it to their socioeconomic profile, knowledge and attitudes toward sexuality. Method: crosssectional and analytical study with 201 individuals who are 50 years old or older. The Targeted Quality of Life and Aging Sexual Knowledge and Attitudes Scales were applied during interviews. Multiple Linear Regression was used in data analysis. Results: dimensions of quality of life more strongly compromised were disclosure worries (39.0), sexual function (45.9), and financial worries (55.6). Scores concerning knowledge and attitudes toward sexuality were 31.7 and 14.8, respectively. There was significant correlation between attitudes and the domains of overall function, health worries, medication worries, and HIV mastery. Conclusion: guidance concerning how the disease is transmitted, treated and how it progresses, in addition to providing social and psychological support, could minimize the negative effects of the disease on the quality of life of patients living with the Human Immunodeficiency Virus. .

Objetivos : analisar a qualidade de vida dos "pacientes" com o vírus da imunodeficiência humana e relacioná-la ao perfil socioeconômico, conhecimento e atitudes sobre sexualidade. Método: estudo transversal e analítico, com 201 pessoas com 50 anos ou mais. Aplicados os instrumentos Targeted Quality of Life e Aging Sexual Knowledge and Attitudes Scale por meio de entrevistas. Para análise dos dados utilizou-se a Regressão Linear Múltipla. Resultados: as dimensões da qualidade de vida mais comprometidas foram preocupação com sigilo (39,0), atividade sexual (45,9) e preocupação financeira (55,6). Escores de conhecimentos e atitudes sobre sexualidade foram: 31,7 e 14,8, respectivamente. Houve correlação significante entre as atitudes e os domínios função geral, preocupação com saúde, preocupação com medicação e aceitação do HIV. Conclusão: orientações sobre formas de contágio, tratamento e evolução da patologia, além de suporte social e psicológico poderiam minimizar os efeitos negativos da doença sobre a qualidade de vida dos pacientes que vivem com o vírus da imunodeficiência humana. .

Objetivos: analizar la calidad de vida de "pacientes" con el virus de la inmunodeficiencia humana y relacionarla al perfil socioeconómico, al conocimiento y a las actitudes sobre sexualidad. Método: estudio transversal y analítico, en 201 personas con 50 años o más. Se aplicaron los instrumentos Targeted Quality of Life y Aging Sexual Knowledge and Attitudes Scale a través de entrevistas. Para el análisis de los datos se utilizó la Regresión Linear Múltiple. Resultados: las dimensiones de la calidad de vida más comprometidas fueron preocupación con sigilo (39,0), actividad sexual (45,9) y preocupación financiera (55,6). Los puntajes de conocimientos y actitudes sobre sexualidad fueron: 31,7 y 14,8, respectivamente. Hubo correlación significativa entre actitud y los dominios función general, preocupación con salud, preocupación con medicación y el aceptar el HIV. Conclusión: orientaciones sobre formas de contagio, obre el tratamiento y evolución de la patología, además del soporte social y psicológico podrían minimizar los efectos negativos de la enfermedad sobre la calidad de vida de los pacientes que viven con el virus de la inmunodeficiencia humana. .

DRESS Syndrome due to Nevirapine Treated with Methylprednisolone.

Nevirapine-induced DRESS syndrome is uncommon but a potentially life-threatening condition, with significant morbidity and mortality rates due to multiple-organ involvement. The authors report a case of a 47-year-old HIV-infected female patient who presented with fever, right hypochondrium pain, jaundice, and skin rash. The Nevirapine-induced DRESS syndrome was suspected based on clinical presentation and RegiSCAR scoring system. This case highlights the need for a high index of clinical suspicion among HIV-infected patients with severe skin eruption and systemic symptoms.