Virologic and immunologic effectiveness of darunavir-based salvage therapy in HIV-1-infected adults in a Brazilian clinical practice setting: results of a multicenter and retrospective cohort study

Background:Darunavir has been proven efficacious for antiretroviral-experienced HIV-1-infected patients in randomized trials. However, effectiveness of darunavir-based salvage therapy is understudied in routine care in Brazil.Methods:Retrospective cohort study of HIV-1-infected patients from three public referral centers in Belo Horizonte, who received a darunavir-based therapy between 2008 and 2010, after virologic failure. Primary endpoint was the proportion of patients with viral load <50 copies/mL at week 48. Change in CD4 cell count was also evaluated. Outcome measures were analyzed on an intent-to-treat basis applied to observational studies. Sensitivity analysis was conducted to evaluate the impact of missing data at week 48. Predictors of virologic failure were examined using rare-event, finite sample, bias-corrected logistic regression.Results:Among 108 patients, the median age was 44.2 years, and 72.2% were male. They had long-standing HIV-1 infection (median 11.6 years) and advanced disease (76.9% had an AIDS-defining event). All patients had previously received protease inhibitors and nucleoside reverse transcriptase inhibitors, 75% nonnucleoside reverse transcriptase inhibitors, and 4.6% enfuvirtide. The median length of protease inhibitor use was 8.9 years, and 90.8% of patients had prior exposure to unboosted protease inhibitor. Genotypic resistance profile showed a median of three primary protease inhibitor mutations and 10.2% had three or more darunavir resistance-associated mutations. Virologic success at week 48 was achieved by 78.7% (95% CI = 69.7&#8211;86%) of patients and mean CD4 cell count increase from baseline was 131.5 cells/&#956;L (95% CI = 103.4&#8211;159.6). In multiple logistic regression analysis, higher baseline viral load (RR = 1.04 per 10,000 copies/mL increase; 95% CI = 1.01&#8211;1.09) and higher number of darunavir resistance-associated mutations (RR = 1.23 per each; 95% CI = 0.95&#8211;1.48) were independently associated with virologic failure.Conclusion:Virologic suppression is a realistic endpoint for most treatment-experienced patients who begin a darunavir-based therapy outside the controlled conditions of a randomized trial, at routine care settings

Effects of the COVID-19 pandemic on the sexual and mental health of adolescent and adult men who have sex with men and transgender women participating in two PrEP cohort studies in Brazil: COBra study protocol

Introduction The COVID-19 pandemic and its control measures have impacted health and healthcare provision in various levels. Physical distancing measures, for instance, may affect sexual health, impacting access to HIV prevention supplies and changing sexual behaviour, as well as mental health, increasing feelings of unsafety and weakening community support ties. These effects can be worsened among socially marginalised groups, such as men who have sex with men (MSM) and transgender women (TGW). Brazil is among the countries most affected by COVID-19 in the world, where control measures have been inconsistently implemented. We aim to investigate the effects of the COVID-19 pandemic on the sexual and mental health of adolescent and adult MSM and TGW in Brazil.Methods Convergent mixed-method prospective cohort study, nested in two ongoing HIV pre-exposure prophylaxis (PrEP) cohorts in Brazil, named PrEP1519 and Combina. Participants will be invited to answer, at baseline and after 6 months, a questionnaire about the effects of the COVID-19 pandemic on sexual behaviour, HIV prevention and mental health. Data on HIV infection and sexually transmitted infections (STI) will be collected as part of routine follow-up from the cohorts. Main outcome measures (HIV infection, STI and depression symptoms) will be observed within 12 months after baseline. Sample size is estimated at 426 participants. Complementarily, 50 participants will be invited to in-depth interviews through video calls or interactive voice response, and 20 will be invited to chronicle their lives during the pandemic through digital diaries. Triangulation will be done across qualitative methods and with the quantitative data.Ethics and dissemination The study was approved by Research Ethics Committees from the Brazilian Universities coordinating the study. Findings will be published in scientific journals and presented at meetings. Informative flyers will be elaborated to communicate study findings to participants and key stakeholders

Development of a device useful to reproducibly produce large quantities of viable and uniform stem cell spheroids with controlled diameters

Three-dimensional cellular aggregates can mimic the natural microenvironment of tissues and organs and obtaining them through controlled and reproducible processes is mandatory for scaling up and implementing drug cytotoxicity and efficacy tests, as well as tissue engineering protocols. The purpose of this work was to develop and evaluate the performance of a device with two different geometries fabricated by additive manufacturing. The methodology was based on casting a microwell array insert using a non-adhesive hydrogel to obtain highly regular microcavities to standardize spheroid formation and morphology. Spheroids of dental pulp stem cells, bone marrow stromal cells and embryonic stem cells showing high cell viability and average diameters of around 253, 220, and 500 μm, respectively, were produced using the device with the geometry considered most adequate. The cell aggregates showed sphericity indexes above 0.9 and regular surfaces (solidity index higher than 0.96). Around 1000 spheroids could be produced in a standard six-well plate. Overall, these results show that this method facilitates obtaining a large number of uniform, viable spheroids with pre-specified average diameters and through a low-cost and reproducible process for a myriad of applications

Comparison of diagnostic performance of RT-qPCR, RT-LAMP and IgM/IgG rapid tests for detection of SARS-CoV-2 among healthcare workers in Brazil

Background: COVID-19 has become a major public health problem after the outbreak caused by SARS-CoV-2 virus. Great efforts to contain COVID-19 transmission have been applied worldwide. In this context, accurate and fast diagnosis is essential. Methods: In this prospective study, we evaluated the clinical performance of three different RNA-based molecular tests – RT-qPCR (Charité protocol), RT-qPCR (CDC (USA) protocol) and RT-LAMP – and one rapid test for detecting anti-SARS-CoV-2 IgM and IgG antibodies. Results: Our results demonstrate that RT-qPCR using the CDC (USA) protocol is the most accurate diagnostic test among those evaluated, while oro-nasopharyngeal swabs are the most appropriate biological sample. RT-LAMP was the RNA-based molecular test with lowest sensitivity while the serological test presented the lowest sensitivity among all evaluated tests, indicating that the latter test is not a good predictor of disease in the first days after symptoms onset. Additionally, we observed higher viral load in individuals who reported more than 3 symptoms at the baseline. Nevertheless, viral load had not impacted the probability of testing positive for SARS-CoV-2. Conclusion: Our data indicates that RT-qPCR using the CDC (USA) protocol in oro-nasopharyngeal swabs samples should be the method of choice to diagnosis COVID-19

Virologic and Immunologic Effectiveness at 48 Weeks of Darunavir–Ritonavir-Based Regimens in Treatment-Experienced Persons Living with HIV-1 Infection in Clinical Practice

Introduction: Published data addressing the effectiveness of darunavir–ritonavir (DRV/r)-based therapy for multiexperienced patients in developing countries are scarce. This study evaluated the 48-week virologic and immunologic effectiveness of salvage therapy based on DRV/r for the treatment of multidrug-experienced HIV-1-infected adults in Brazil. Materials and Methods: A multicenter retrospective cohort study was carried out with multidrug-experienced adults who were on a failing antiretroviral therapy and started a DRV/r-based salvage therapy between 2008 and 2010. The primary effectiveness end point was the proportion of patients with virologic success (plasma HIV-1 RNA <50 copies/mL at week 48). Results: At 48 weeks, 73% of the patients had HIV-RNA <50 copies/mL and a mean increase of 108 CD4 cells/mm 3 . Higher baseline viral load, lower baseline CD4 count, younger age, and 3 or more DRV/r-associated resistance mutations were significantly predictive of virologic failure. Concomitant use of raltegravir was strongly associated with virologic success. Conclusion: The use of DRV/r-based regimens for salvage therapy is an effective strategy in the clinical care setting of a developing country