Search

Abstract: Aims: To compare high-sensitivity C-reactive protein (hsCRP) in HIV-infected patients treated or not with antiretroviral (ARV) drugs and to correlate hsCRP levels with traditional cardiovascular risk factors and parameters of HIV infection. Methods: One hundred and seventy-one HIV-infected patients were included (129 ARV-treated and 42 ARV-naïve). Evaluations included anthropometric measurements, blood pressure, laboratory tests, ultrasonographic measurement of fat thickness and impedance analysis. Results: hsCRP levels were higher in ARV-treated compared to ARV-naïve patients (p <0.001). Seventy-two (56%) ARV-treated patients and 11 (26%) ARV-naïve patients had hsCRP concentrations >3mg/dl (high risk for cardiovascular complications) (OR 3.56; 95%CI: 1.55–8.29; p =0.001, χ 2 test). hsCRP levels correlated positively with waist measurement (p =0.004), waist-to-hip ratio (p <0.001), systolic (p =0.05) and diastolic (p =0.03) blood pressure, intra-abdominal fat thickness (p =0.02), triglycerides (p =0.001), total cholesterol (p =0.01), fasting glucose (p =0.01), and glucose (p <0.001) and insulin levels (p =0.02) measured 2h after load. No correlation was found between hsCRP levels and CD4 cell counts and HIV-viral load. Independent factors associated with hsCRP levels were therapy with current non-nucleoside reverse transcriptase inhibitors (NNRTI) (p =0.003), waist-to-hip ratio (p =0.006), fasting glucose (p =0.049) and glucose levels 2h after load (p =0.003) in multivariate analysis model 1 and current NNRTI therapy (p <0.001), protease inhibitor therapy (p =0.016) and cardiometabolic syndrome (p =0.022) in multivariate analysis model 2. Conclusion: hsCRP in HIV-infected patients is associated with traditional cardiovascular risk factors, principally in ARV-treated patients. hsCRP levels are not associated with CD4 cell counts and HIV-viral load and may constitute a marker for cardiovascular risk related to HIV infection and ARV therapy. [Copyright &y& Elsevier]

Background: In the central nervous system, HIV replication can occur relatively independent of systemic infection, and intrathecal replication of HIV-1 has been observed in patients with HIV-related and opportunistic neurological diseases. The clinical usefulness of HIV-1 RNA detection in the cerebrospinal fluid (CSF) of patients with opportunistic neurological diseases, or the effect of opportunistic diseases on CSF HIV levels in patients under HAART has not been well defined. We quantified CSF and plasma viral load in HIV-infected patients with and without different active opportunistic neurological diseases, determined the characteristics that led to a higher detection rate of HIV RNA in CSF, and compared these two compartments. Methods: A prospective study was conducted on 90 HIV-infected patients submitted to lumbar puncture as part of a work-up for suspected neurological disease. Seventy-one patients had active neurological diseases while the remaining 19 did not. Results: HIV-1 RNA was quantified in 90 CSF and 70 plasma samples. The HIV-1 RNA detection rate in CSF was higher in patients with neurological diseases, in those with a CD4 count lower than 200 cells/mm3, and in those not receiving antiretroviral therapy, as well as in patients with detectable plasma HIV-1 RNA. Median viral load was lower in CSF than in plasma in the total population, in patients without neurological diseases, and in patients with toxoplasmic encephalitis, while no significant difference between the two compartments was observed for patients with cryptococcal meningitis and HIV-associated dementia. CSF viral load was lower in patients with cryptococcal meningitis and neurotoxoplasmosis under HAART than in those not receiving HAART. Conclusion: Detection of HIV-1 RNA in CSF was more frequent in patients with neurological disease, a CD4 count lower than 200 cells/mm³ and detectable plasma HIV-1. Median HIV-1 RNA levels were generally lower in CSF than in plasma but some patients showed higher CSF levels, and no difference between these two compartments was observed in patients with cryptococcal meningitis and HIV-associated dementia, suggesting the presence of intrathecal viral replication in these patients. HAART played a role in the control of CSF HIV levels even in patients with cryptococcal meningitis and neurotoxoplasmosis in whom viral replication is potentially higher. [ABSTRACT FROM AUTHOR]

Highlights the role of the U.S. in international public health administration and policy. View that the U.S. has chosen to withdraw or abstain from several international initiatives on public health; Decision of the U.S. Food and Drug Administration (FDA) that clinical research conducted by Americans abroad are not subject to the World Medical Association's Declaration of Helsinki, which governs the rights of patients; Use of the Good Clinical Practices (GCP) guidelines by the FDA, which do not address large-scale ethical issues related to drug research; Opposition of U.S. officials to requiring the provision of aftercare medication to trial participants; Criticism for U.S. policy related to clinical research ethics.

Frequent contact with hazardous materials makes waste collection a potentially unhealthy activity. This article assesses the perception of waste management workers regarding work-related accidents in domestic and health service contexts in Brazil. Six focus groups were performed between June 2014 and August 2015. The aims of this study were to apprehend different aspects of the participants' health, workers' experiences of work-related accidents and perception of risks. Cuts and puncture injuries were reported most frequently in the line of work and were often considered as irrelevant. Immunization against hepatitis B was not common among all workers, which increases the risk of infection for those individuals. Finally, it is considered urgent to consolidate an inclusive space in which workers can have discussions on their health. [ABSTRACT FROM AUTHOR]

HIV Pre-exposure prophylaxis (PrEP) is an effective prevention tool, but there are still few studies about PrEP uptake among adolescents. We aimed to analyze the PrEP uptake process and factors associated with daily oral PrEP initiation among adolescent men who have sex with men (aMSM) and transgender women (aTGW) in Brazil. Baseline data from the first demonstration PrEP cohort study among aMSM and aTGW 15–19 years old (yo) ongoing in three large Brazilian cities (PrEP1519). After completing informed consent procedures, participants were enrolled in the cohort from February/2019 to February/2021. A socio-behavioral questionnaire was applied. Factors associated with PrEP initiation were assessed using a logistic regression model with adjusted prevalence ratios (aPR) and 95% confidence intervals (95%CI). Among recruited participants, 174 (19,2%) were aged 15–17 yo and 734 (80,8%) 18–19 yo. The rate of PrEP initiation was 78.2% and 77.4% for 15–17 yo and 18–19 yo, respectively. Factors associated with PrEP initiation were: black or mixed race (aPR 2.31; 95%CI: 1.10–4.84) among the younger adolescents 15–17 yo; experienced violence and/or discrimination due to their sexual orientation or gender identity (aPR 1.21; 95%CI: 1.01–1.46); transactional sex (aPR 1.32; 95%CI: 1.04–1.68); and having had between 2 to 5 sexual partners in the previous three months (aPR 1.39; 95%CI: 1.15–1.68) among those 18–19 yo. Unprotected receptive anal intercourse in the previous six months was associated with PrEP initiation in both age groups (aPR 1.98; 95%CI: 1.02–3.85 and aPR 1.45; 95%CI: 1.19–1.76 among 15–17 yo and 18–19 yo, respectively). The biggest challenge to promoting PrEP use for aMSM and aTGW was in the first steps of the PrEP uptake process. Once they were linked to the PrEP clinic, initiation rates were high. [ABSTRACT FROM AUTHOR]

Using baseline data from the PrEP1519 cohort, in this article we aimed to analyze: (i) the effectiveness of demand creation strategies (DCS) to enroll adolescent men who have sex with men (AMSM) and adolescent transgender women (ATGW) into an HIV combination prevention study in Brazil; (ii) the predictors of DCS for adolescents' enrollment; and (iii) the factors associated with DCS by comparing online and face-to-face strategies for enrollment. The DCS included peer recruitment (i.e., online and face-to-face) and referrals from health services and non-governmental organizations (NGOs). AMSM and ATGW who agreed to participate in the study could opt to enroll in either PrEP (PrEP arm) or to use other prevention methods (non-PrEP arm). Bivariate and multivariate analyses were conducted and logistic regression odds ratios were estimated. The DCS reached 4529 AMSM and ATGW, the majority of which were derived online (73.8%). Of this total, 935 (20.6%) enrolled to participate (76.6% in PrEP arm and 23.4% in non-PrEP arm). The effectiveness of enrolling adolescents into both arms was greater via direct referrals (235/382 and 84/382, respectively) and face-to-face peer recruitment (139/670 and 35/670, respectively) than online (328/3342). We found that a combination under DCS was required for successful enrollment in PrEP, with online strategies majorly tending to enroll adolescents of a higher socioeconomic status. Our findings reinforce the need for DCS that actively reaches out to all adolescents at the greatest risk for HIV infection, irrespective of their socioeconomic status. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article by Marcia Angell about the ethical responsibilities of researchers in developing countries which appeared in the March 30, 2000 issue.

Standardized treatment regimens for chronic hepatitis B (CHB) are crucial in suppressing viral replication, disease progression and the development of complications. However, information on routine compliance with such therapeutic recommendations in medical practice is rare. Aim: To evaluate the application of Brazilian therapeutic guidelines for CHB within the scope of the Unified Health System in Minas Gerais state. Four key recommendations from the national guidelines were compared with data from treated patients: (i) eligibility to start treatment; (ii) type of treatment applied; (iii) rescue antiviral therapy; and (iv) monitoring of virological response. Most physicians (69.8%) declared to adopt these guidelines, while 10 of them were unaware. However, according to the criteria established by the guidelines, only 39.5% of treated patients should have been considered "truly" eligible to start treatment and only 67.6% of these underwent the recommended pharmacological treatment. The virological response was laboratory monitored in just over a third of patients. Rescue therapy was adequately supplanted in 41.2% of patients previously treated with lamivudine. There was low compliance with national guidelines by public service physicians in Brazil, highlighting the need to raise awareness of the importance of its adherence to expand the control of CHB. Thus, increasing the adherence of health professionals to this tool is a current challenge for health institutions and managers. [ABSTRACT FROM AUTHOR]

While the degree of COVID-19 vaccine accessibility and uptake varies at both national and global levels, increasing vaccination coverage raises questions regarding the standard of prevention that ought to apply to different settings where COVID-19 vaccine trials are hosted. A WHO Expert Group has developed guidance on the ethical implications of conducting placebo-controlled trials in the context of expanding global COVID-19 vaccine coverage. The guidance also considers alternative trial designs to placebo controlled trials in the context of prototype vaccines, modified vaccines, and next generation vaccines. [ABSTRACT FROM AUTHOR]

The Access to COVID-19 Tools Accelerator (ACT-A) is a multistakeholder initiative quickly constructed in the early months of the COVID-19 pandemic to respond to a catastrophic breakdown in global cooperation. ACT-A is now the largest international effort to achieve equitable access to COVID-19 health technologies, and its governance is a matter of broad public importance. We traced the evolution of ACT-A's governance through publicly available documents and analysed it against three principles embedded in the founding mission statement of ACT-A: participation, transparency, and accountability. We found three challenges to realising these principles. First, the roles of the various organisations in ACT-A decision making are unclear, obscuring who might be accountable to whom and for what. Second, the absence of a clearly defined decision making body; ACT-A instead has multiple centres of legally binding decision making and uneven arrangements for information transparency, inhibiting meaningful participation. Third, the nearly indiscernible role of governments in ACT-A, raising key questions about political legitimacy and channels for public accountability. With global public health and billions in public funding at stake, short-term improvements to governance arrangements can and should now be made. Efforts to strengthen pandemic preparedness for the future require attention to ethical, legitimate arrangements for governance. [ABSTRACT FROM AUTHOR]

Detection of the SARS-CoV-2 virus in stools and sewage has recently been reported, raising the hypothesis of faecal-oral transmission. If confirmed, this could have far-reaching consequences for public health and for pandemic control strategies. In this paper, we argue that a comprehensive and more nuanced analysis is required to test this hypothesis, taking into consideration both environmental dynamics and the persistence of viral infectivity. First, we examine the evidence regarding the presence of the virus in stools and sewage. Then we discuss the current framework of disease transmission through water and excreta and how the transmission of a respiratory disease fits into it. Against this background, we propose a framework to test the faecal-oral hypothesis, unpacking the different environmental routes from faeces to the mouth of a susceptible person. This framework should not be seen as a confirmation of the hypothesis but rather as an expanded view of its complexities, which could help shaping an agenda for research into a number of unanswered questions. Finally, the paper briefly discusses practical implications, based on current knowledge, for containment of the pandemic. Unlabelled Image • Presence of SARS-CoV-2 in stools and wastewater has recently been reported. • A possible faecal-oral transmission of SARS-CoV-2 has been raised. • Different routes from faeces to the mouth of a susceptible person exist. • Water, surfaces and places with vectors can be transmission routes. • A framework is proposed to help shaping a research agenda. [ABSTRACT FROM AUTHOR]

Background: There has recently been an increase in HIV infection rates among men who have sex with men (MSM). This study aimed at investigating risk factors associated with incident HIV infection in a MSM cohort–Project Horizonte, Belo Horizonte, Minas Gerais, Brazil. Methodology: This is a nested case-control study in an ongoing open cohort of homosexual and bisexual men, carried out in 1994–2010, during which 1,085 volunteers were enrolled. Each HIV seroconverted volunteer (case) was compared with three randomly selected HIV negative controls, matched by admission date and age (±3 years). During follow-up, 93 volunteers seroconverted and were compared with 279 controls. Principal Findings: The risk factors associated with HIV seroconversion were: contact with partner’s blood during sexual relations (OR 3.7; 95% CI 1.2–11.6), attendance at gay saunas in search for sexual partners (OR 2.6; 95% CI 1.3–5.4), occasional intake of alcohol when flirting and engaging in sexual activity (OR 2.5; 95% CI 1.3–5.1), inconsistent use of condoms in receptive anal sex (OR 2.4; 95% CI 1.1–5.4), little interest to look up information about AIDS (OR 2.6; 95% CI 1.0–6.7) particularly in newspapers (OR 3.4; 95% CI 1.4–8.1). Conclusions: This study shows that MSM are still engaging in risk behavior, such as unprotected anal intercourse, despite taking part in a cohort study on various preventive measures. New preventive strategies in touch with the epidemic’s development and the specificities of this particular population are needed. [ABSTRACT FROM AUTHOR]

Abstract: Background: Human immunodeficiency virus type 1 (HIV-1) subtype B predominates in Brazil, but in the southern region subtype C is the most frequent, followed by subtypes B, F1 and recombinant forms. In southern Brazil, these subtypes co-circulate in subjects with homogeneous demographic and clinical features, enabling a better understanding of the role of HIV-1 subtypes on the characteristics of infection. Objectives: To evaluate the prevalence of different HIV-1 subtypes in subjects with recent diagnosis for HIV infection in the extreme south of Brazil, and to study their association with demographic, behavioral, clinical and laboratorial characteristics. Study design: We have determined the genetic sequence of viral protease and reverse transcriptase (polymerase, connection and RNase H domains) isolated from studied subjects. Viral subtype was inferred by comparison with reference HIV sequences, and recombination was determined with Simplot analysis. The association of HIV-1 subtypes with studied characteristics was evaluated by chi-square, Fisher''s exact, Student''s t and Kruskal–Wallis tests. Results: Two hundred and forty-five HIV isolates were molecularly characterized, and the association with variables was studied for 233 (95.1%) patients. Of those, 46.8% followed AIDS defining criteria. HIV-1C was responsible for 56.3% of infections, and was associated with heterosexual transmission (p =0.001) and with higher CD4+ T-cell counts (p =0.02). Conclusions: The molecular epidemiology of HIV-1 in the southernmost Brazil is currently steady with predominance of HIV-1C. This is the first study showing a robust association of the infection by this subtype and heterosexual transmission in the state of Rio Grande do Sul, Brazil. [Copyright &y& Elsevier]

Abstract: Background: Major and accessory drug resistance mutations have been recently characterized in the C-terminal RT subdomains of HIV-1, connection and RNase H. However, their presence in treatment-naïve patients infected with HIV-1 non-B subtypes remains largely unknown. Objectives: To characterize the patterns of primary resistance at the C-terminal RT subdomains of HIV-1 infecting subjects in the southern region of Brazil, where HIV-1 subtypes B and C co-circulate. Study design: Plasma viral RNA was extracted from patients recently diagnosed for HIV infection (2005–2008). The protease and reverse transcriptase regions were PCR-amplified and sequenced. Infecting HIV subtypes were assigned by phylogenetic inference and drug resistance mutations were determined following the IAS consensus and recent reports on C-terminal RT mutations. Results: The major mutation to NNRTI T369I/V was found in 1.8% of patients, while A376S was present in another 8.3%. In the RNase H domain, the compensatory mutation D488E was more frequently observed in subtype C than in subtype B (p =0.038), while the inverse was observed for mutation Q547K (p <0.001). The calculated codon genetic barrier showed that 22% of subtype B isolates, but no subtype C, carried T360, requiring two transitions to change into the resistance mutation 360V. Conclusions: Major resistance-conferring mutations to NNRTI were detected in 10% of RT connection domain viral sequences from treatment-naïve subjects. We showed for the first time that the presence of specific polymorphisms can constrain the acquisition of definite resistance mutations in the connection and RNase H subdomains of HIV-1 RT. [Copyright &y& Elsevier]

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are potent and well tolerated. In Brazil, the first-generation NNRTI efavirenz is included in the majority of first-line antiretroviral treatment regimens. In this study, we evaluated the effectiveness of etravirine, a new second-generation NNRTI, among patients failing antiretroviral regimens containing first-generation NNRTIs. We assessed single resistance mutations to etravirine as well as complex resistance mutations profile and discuss the potential of introducing etravirine as salvage therapy. [ABSTRACT FROM AUTHOR]

Abstract: Chemokines are chemoattractant cytokines involved in the immune response of a wide variety of diseases. There are few studies assessing their role in opportunistic infections in HIV-infected patients. In this study, we measured CC and CXC chemokines in cerebrospinal fluid (CSF) samples obtained from 40 HIV-infected patients with or without opportunistic infections of the central nervous system (CNS). CSF samples were also analyzed for quantification of total protein, cell count and HIV-1 RNA. HIV+ patients with cryptococcal meningitis had higher levels of CCL2, CCL3, CCL5, CXCL9 and CXCL10 when compared to patients without opportunistic neurological infections. Furthermore, HIV+ patients with associated cryptococcal meningitis had higher levels of CCL3, CXCL9 and CXCL10 when compared to HIV+ patients with associated toxoplasmic encephalitis. CCL3 and CXCL9 levels were positively correlated with CSF HIV-1 RNA levels, CSF protein concentration, and CSF cell count. CXCL10 level was correlated with the CSF viral load and the CSF cell count and CCL5 level was correlated with the CSF cell count. In conclusion, the profile of chemokines in CSF of HIV patients may differ according to the modality of the presented opportunistic infection and according to other biological markers, such as viral load in CSF. These differences are probably related to different patterns of neuroinflammatory responses displayed by patients with different opportunistic neurological infections. [Copyright &y& Elsevier]

Aims: To compare the intra-abdominal fat thickness measured by ultrasound between HIV-infected patients treated or not with antiretroviral drugs and to correlate these visceral adiposity measurements to other parameters of cardiovascular risks. Methods: In a transversal observational study, 160 HIV-infected patients were recruited and divided in two groups, i.e., 123 antiretroviral (ARV)-treated and 37 ARV-naïve patients. These patients were submitted to anthropometric determinations, laboratorial analysis, ultrasonographic measurements of subcutaneous and intra- abdominal fat thickness and to tetrapolar bioelectrical impedance analysis in order to measure the body composition. Results: In the patients treated with highly active antiretroviral therapy (HAART) the intra-abdominal fat pad was significantly thicker than that of the untreated group (69 ± 21 mm, n = 123 vs. 60 ± 18 mm, n = 37; p = 0.03 Student’s t test). The intra-abdominal fat thickness correlated significantly with plasma triglyceride, total cholesterol, fasting glucose, glucose measurements 2 h after dextrose load, fasting insulin, HOMA-IR index, systolic and diastolic blood pressures, weight, BMI, WHR and caliper-measured total fat percentage. Conclusion: The results showed that antiretroviral therapy is associated with increased ultrasonographic measurements of visceral adiposity. Our data demonstrated a strong correlation between intra-abdominal fat thickness and independent risk factors of cardiovascular disease: atherogenic lipid profile and insulin resistance. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Describes the design and data collection methods of the Project Horizonte, an open cohort of homosexual and bisexual HIV-1 negative men and a component of the Minas Gerais AIDS Vaccine Program of the Federal University of Minas Gerais in Brazil. Objectives of the project; Blood collection and laboratory tests; Project Horizonte HIV infection incidence rates; Characteristics of single-visit participants versus participants