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Based on the incorporation of pre-exposure prophylaxis (PrEP) as an HIV prevention strategy and considering the need to comprehend the use of medication among young people, this article analyzes narratives of gay men and transgender women from Belo Horizonte, Minas Gerais State, Brazil, participating in the PrEP1519 study. This is a qualitative research, based on the interpretative anthropology, developed by 10 in-depth interviews with PrEP users followed-up for at least three months between October and November 2019. The results showed that the drug was seen as the main motivation for participating in the study and as a strategy combined with the use of condoms, whether as additional prevention, or assuming the leading role. The medication revealed signs built by the gender performances and their relation to other medications, especially the experience of trans girls in hormonal therapy. Regarding the socialization of the use of PrEP, the narratives showed that there was no secret between the couples, which did not meant that stigmas on the association with HIV did not exist, mainly in the virtual context. In the family environment, they reported questions about the preventive function of the medication and the voluntary nature of the participation in the study. The youth's narratives revealed plural meanings of the medication and its social use, composing both the boys' and girls' performances. The signs attributed to the medication indicated that in addition to maintenance of health, the medication improves life and sexual freedom.

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.

Background: Chronic hepatitis B (CHB) affects 257 million people worldwide. However, the proportion of patients eligible for treatment in the public health system has not been established. This study describes the clinical and laboratory profiles of untreated CHB patients and estimates the eligibility rate for antiviral therapy in accordance with the Brazilian Clinical Protocol and Therapeutic Guidelines., Methods: Records of 670 CHB patients were collected from May 2012 to September 2013 in Minas Gerais. Data from each patient were analyzed by hepatitis B virus (HBV) management., Results: 461 CHB patients were treatment-naive. Of these, 23 were HBeAg-positive, 352 were HBeAg-negative, and 14 were clinically diagnosed with cirrhosis. Periodic monitoring was performed in only three patients. However, 9.3% of untreated patients met the eligibility criteria for HBV treatment., Conclusions: Few CHB patients were active carriers and eligible candidates for antiviral therapy. This study revealed inadequate pre-treatment conduct in the Brazilian public health system, emphasizing the need for regular laboratory follow-up for patients initially not eligible for treatment. Such information may indirectly subsidize the planning and improvement of actions and services related to optimal HBV management in the public sphere.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper: [All members of the WHO Access to COVID-19 Tools Accelerator Ethics and Governance Working Group declared their interests according to WHO standard procedures. None of the interests declared were found to be significant.]., (Copyright © 2022. Published by Elsevier Ltd.)

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., Competing Interests: Declaration of interests All authors are members of a WHO-led ACT-A Ethics and Governance Working Group set up to advise WHO on ethics and governance issues related to its role as a partner in the ACT-A. SM reports grants paid to her institution from the WHO Regional Office for Europe, UNICEF–UNDP–WB–WHO Special Program for Research and Training in Tropical Disease, and the Bill and Melinda Gates Foundation; reports paid membership with the Unitaid Proposal Review Committee; reports unpaid cochairmanship of the WHO Fair Pricing Forum; and is an unpaid member of the WHO ACT-A Governance and Ethics Working Group. JA reports paid WHO consultancy for work with the ACT-A Ethics and Governance Working Group, a paid consultancy with Wellcome, and unpaid board membership with Médecins sans Frontières Switzerland. EE declares payments, honoraria, or travel fees from Greenwall Foundation, RAND Corporation, Medical Home Network, Healthcare Financial Management Association, Ecumenical Center–UT Health, American Academy of Optometry, Associação Nacional de Hospitais Privados, National Alliance of Healthcare Purchaser Coalitions, Optum Labs, Massachusetts Association of Health Plans, District of Columbia Hospital Association, Washington University, Goldman Sachs, Brown University, The Atlantic, McKay Lab, American Society for Surgery of the Hand, Association of American Medical Colleges, American Essential Hospitals, Johns Hopkins University, National Resident Matching Program, Shore Memorial Health System, Tulane University, Oregon Health & Science University, United Health Group, Blue Cross Blue Shield, Center for Global Development, Informa, and Galien Foundation; and declares a leadership or fiduciary role in VillageMD, Oncology Analytics, Embedded Health Care, Oak HC/FT, and COVID-19 Recovery Partners. RF declares participation as a member of the WHO Strategic Advisory Group of Experts and the Immunization Working Group on COVID-19 Vaccines. GOS reports individual funding from WHO. SK is a member of the WHO Strategic Advisory Group of Experts on Immunization and the WHO SAGE Working Group on COVID-19 vaccines. JAS declares participating as a member of the WHO Technical Advisory Group on COVID-19 vaccines. MJS reports grants paid to their institution from the Canadian Institutes of Health Research (grant number #C150-2019-11), and travel fees to attend WHO and Global Research Collaboration for Infectious Disease Preparedness Global Research and Innovation Forum. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This systematic review aims to estimate the prevalence of sarcopenia in people living with HIV (PLHIV) and to assess whether there is a difference between the muscle mass of PLHIV and people living without HIV. A systematic review of randomized controlled trials, cohort studies, cross-sectional and case-control studies was carried out. PLHIV over 18 years of age and that had their muscle mass evaluated by dual-energy X-ray absorptiometry were included. Overall, 4,376 studies were found, of which 118 had their full texts evaluated. A total of 5,532 people living with HIV and 2,986 people living without HIV were identified in 41 studies. The frequency of sarcopenia defined by low muscle mass (Baumgartner's operational definition) alone was 30.3% (95%CI 24.3%, 37.1%) and the frequency of sarcopenia defined by low muscle mass with low muscle strength (EWGSOP definition) was 4.5% (95%CI 1.3%, 13.9%), p-value = 0.0006. The standardized mean differences of muscle mass between PLHIV and controls was -0.211 units of standard deviation (95%CI -0.419, -0.003). In the meta-regression analysis muscle mass mean difference was associated with BMI, CD4, percentage of subjects on ART, and study design. PLHIV have a lower muscle mass when compared to people living without HIV. This difference appears to be attenuated by higher BMI, CD4 levels, and the percentage of subjects using ART. Furthermore, the frequencies of sarcopenia assessed by the operational definition of Baumgartner and the EWGSOP are not comparable and cannot be interchanged in PLHIV., (Copyright © 2021 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

In the space of four decades, Brazil has faced two serious pandemics: human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and Coronavirus disease 2019 (COVID-19). The country's response to HIV/AIDS was coordinated by several stakeholders and recognised the importance of scientific evidence in guiding decision-making, and a network offering monitoring and antiretroviral treatment was provided through coordinated efforts by the country's universal health system. Conversely, the lack of a centrally coordinated strategy and misalignment between government ministries regarding the COVID-19 pandemic response, together with the denial of scientific evidence, promotion of ineffective treatments and insufficient vaccination efforts, have all led to the uncontrolled spread of infection, the near-total collapse of the health system and excess deaths.

Competing Interests: Competing interests: None declared.

The world is currently facing another severe pandemic, Covid-19, just four decades after the start of AIDS, and the still increasing incidence of HIV infection continues to be one of the greatest global health challenges. The way the latter was confronted is of fundamental importance for a serious discussion on global health, ethics and human rights, and this experience could and can still be applied to Covid-19. The Covid-19 pandemic has specific characteristics and these will be discussed, in relation to vaccine research and especially to the global right to equal access to products proven to be safe and effective. The article focusses primarily on issues related to Covid-19 vaccines, especially the appropriate use and limits on placebo, the right to post-trial access to placebo arm participants, and the use of an active control for subsequent Phase-3 trials after the approval of other safe and efficacious vaccines. Most importantly, it will emphasise that access to Covid-19 vaccines is a human right, which presupposes the establishment of appropriate ethical standards to ensure universal, equal, and affordable access to healthcare and to vaccines for all, and the imperative need for suspension of patents for products developed for Covid-19. It will consider the role of social determinants that contribute to the severity of Covid-19 and that must be addressed to effectively curb the current syndemic.

Background: In February 2020, international controversy arose about the ethical acceptability of the WHO Malaria Vaccine Implementation Program (MVIP). Whereas some have argued that this program must be seen as research that is not in line with international ethical standards, notably regarding informed consent and local ethical review, some WHO representatives consider the MVIP as a public health implementation program that need not adhere to these standards., Methods: We performed a case analysis in light of the 2016 CIOMS International Ethical Guidelines for Health-related Research involving Humans., Findings: We argue that the MVIP has a substantial research component, and that it is prudent to therefore apply ethical norms for research involving humans, such as the CIOMS guidelines. Accordingly, we agree that the ethical requirements of informed consent and independent ethical review have not been met. In addition, we are concerned that the study might not meet CIOMS's social value requirement., Recommendations: We urge WHO to release more details about the process that led to the MVIP program and make the MVIP protocol publicly available. The full protocol should be assessed by the relevant ethics committees, new and already enrolled parents should be informed about the uncertainties under investigation and given a real opportunity to consent or refuse (continued) participation, communities should be engaged, and aspects of MVIP that require alteration in light of ethical review should be altered, if possible. Furthermore, in order to improve good ethical practices, it is necessary to engage in international debate regarding the integration of research and public health programs. Procedurally, vaccine implementation programs that combine both prevention and research should involve the wider international ethics community and ensure participation of the target populations in setting the proper conditions for launching such programs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RG is a member of the independent Bioethics Advisory Committee to Sanofi. The other authors declare no competing interests., (Published by Elsevier Ltd.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

HIV infection may be considered a chronic condition for people living with HIV with access to antiretrovirals and this has effectively increased survival. Moreover, this has also facilitated the emergence of other comorbidities increasing the risk for drug-drug interactions and polypharmacy. The profile of these interactions as well as their consequences for people living with HIV are still not completely elucidated. The objectives of this study were to describe the profile of these interactions, their prevalence and their classification according to the potential for significant or non-significant drug-drug interactions. From June 2015 to July 2016, people living with HIV on follow-up at an Infectious Diseases Referral Center in Belo Horizonte, Brazil have been investigated for the presence of drug-drug interactions. A total of 304 patients were included and the majority (75%) had less than 50 years of age, male (66.4%), and 37.8% self-defined as brown skinned. Approximately 24% were on five or more medications and half of them presented with drug-drug interactions. Patients older than 50 years had a higher frequency of antiretrovirals drug-drug interactions with other drugs compared to younger patients (p=0.002). No relationship was found between the number of drug-drug interactions and the effectiveness of antiretrovirals. As expected, the higher the number of non-HIV medications used (OR=1.129; 95%CI 1.004-1.209; p=0.04) was associated with an increase in drug-drug interactions. The high prevalence of drug-drug interactions found and the data collected should be useful to establish measures of quaternary prevention and to increase the medication security for people living with HIV., (Copyright © 2020 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

The lipid accumulation product (LAP) index is an emerging cardiovascular risk marker. We aimed to assess the accuracy of this index as a marker of cardiovascular risk in HIV-infected patients. A cross-sectional study of 133 HIV-infected patients on antiretroviral drugs and 20 non-infected controls was conducted at the outpatient clinic of a referral center of infectious and parasitic diseases. Evaluations included LAP index, homeostasis model assessment (HOMA) index, anthropometric measurements, blood pressure, glucose tolerance test, and cholesterol and triglyceride levels. Body mass index (BMI) was similar in both groups; however, waist circumference was greater in the HIV-infected patients. Triglyceride levels were significantly higher (p<0.001) and HDL cholesterol levels were lower in HIV-infected patients (p<0.001). Plasma glucose (p=0.01) and insulin (p=0.005) levels two hours after a glucose load, HOMA-IR index (p<0.001) and LAP index (p<0.001) were higher in the HIV-infected patients. A positive and significant correlation was found between HOMA-IR index and LAP (r=0.615; p<0.01), BMI (r=0.334; p<0.01) and waist circumference (r=0.452; p<0.01) in the HIV-infected patients. In male HIV-infected patients and controls, ROC curve analyses revealed that the best cut-off value of LAP to define the presence of insulin resistance was 64.8 (sensitivity 86%, specificity 77% and area under the curve 0.824). These results confirm that insulin resistance is more common in HIV-patients on antiretroviral drugs than in HIV-negative controls. A positive and significant correlation was found between the LAP index and the HOMA index, with LAP≥64.8 constituting an additional risk factor for cardiovascular disease in male HIV patients., (Copyright © 2018. Published by Elsevier Editora Ltda.)

This meta-analysis, which is based on a previously published systematic review, aims to contribute to the scientific discussion on hepatitis B virus (HBV) infection in workers who are exposed to domestic and healthcare wastes. Publications were sought which had been made available on the data used by December 2013 and updated to December 2016. The quality of the included studies was assessed according to the guidelines of Loney et al. for the critical appraisal of studies on the prevalence or incidence of a health problem. To verify the presence of heterogeneity between the papers, we used the Chi-squared test based on a Q statistic. A funnel plot was used to test for publication bias. All included studies had across-sectional study design. The association between exposure to waste and positive serology for the HBV surface antigen (HBsAg) showed a significant association [odds ratio (OR) 1.89, 95% confidence interval (CI) 1.27-2.86; p = 0.0019]. The prevalence rates of HBsAg and anti-HBc seropositivity was 0.04 (95% CI 0.03-0.05) and 0.21 (95% CI 0.14-0.28), respectively (p <0.0001). We found no evidence of publication bias. The results of this meta-analysis indicate a statistically significant association between exposure to solid waste, whether healthcare or domestic, and positive HBV infection markers. Therefore, the working conditions of waste collectors should be analyzed more closely. Immunization against HBV is recommended as the chief preventive measure for all solid waste workers.

The Brazilian response to AIDS started in 1985, with government, civil society and academic community coming together with common goals. This was strengthened with the establishment in 1988 of an universal public health system (SUS), pivotal to a comprehensive and human rights-based national STD/AIDS programme, aiming at achieving equality, integrality, inclusion and fighting prejudice and discrimination. In 1996 Brazil was a pioneer in providing treatment free-of-charge to all PLHA. This article depicts achievements and setbacks that occurred in these 30 years and the perspectives for controlling and eventually eliminating HIV/AIDS. It is fair to affirm that it is possible to defeat prejudice and discrimination and to confront the unacceptable levels of disparity, fertile ground for dissemination of HIV/AIDS and other epidemics. Tools to eliminate transmission, to adequately treat PLHA, to protect their rights, to eliminate discrimination and to end AIDS are already at hand. However, the needed changes for this to happen involve expansion of access to education, including sexual education and to quality public health care to all. It is also necessary to constant confront conservatism and to combat violence and discrimination. Brazil's track record in the confrontation of AIDS is an invaluable asset to achieve these goals.

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=69.7-86%) of patients and mean CD4 cell count increase from baseline was 131.5 cells/μL (95% CI=103.4-159.6). In multiple logistic regression analysis, higher baseline viral load (RR=1.04 per 10,000 copies/mL increase; 95% CI=1.01-1.09) and higher number of darunavir resistance-associated mutations (RR=1.23 per each; 95% CI=0.95-1.48) 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., (Copyright © 2013 Elsevier Editora Ltda. All rights reserved.)

Objectives: The aim of this study was to learn more about people diagnosed with acquired immunodeficiency syndrome (AIDS) at age 60 and above in Brazil, and to compare them with people diagnosed at a younger age., Methods: This study was based on the analysis of secondary data from the Brazilian AIDS Program. The study population consisted of people diagnosed with AIDS at age 60 and above. The comparison group was comprised of a 20% random sample of people diagnosed at age 18 to 59, frequency-matched by year of diagnosis., Results: 544,846 cases of AIDS were reported in Brazil from 1980 until June 2009. Over 90% of cases were diagnosed between 18 and 59 years of age, and 13,657 (2.5%) at age 60 and above. The first case of AIDS among the elderly was reported in 1984. The comparison group consisted of 101,528 patients. Gender proportion was similar for both groups, and the proportion of people identified with AIDS after death in the Brazilian Mortality Information System (SIM) was 4% higher among the elderly. Both groups were also similar regarding the region of residence; a markedly higher proportion lived in Southeastern Brazil. Older people were more likely to have lower education and to have contracted AIDS by heterosexual contact, and less likely to be intravenous drug users. Male to female ratio among those diagnosed with AIDS at or above age 60 decreased over the years, in the same way as observed for the whole cohort. Mortality was higher among men in both groups. CD4 category (taken closest to the date of AIDS diagnosis) was very similar in both groups., Conclusion: The characteristics of the epidemic among the elderly show similarities to the younger group considering gender distribution and CD4 category, but differ regarding educational level and exposure category. Also, the elderly were more likely not to have their AIDS condition promptly diagnosed., (Copyright © 2012 Elsevier Editora Ltda. All rights reserved.)

The purpose of this study is to estimate the survival probability of patients following their first admission for the treatment of AIDS to an infectious disease reference hospital in Belo Horizonte, Brazil, during 2005. Study subjects were monitored during a 12-month period to identify factors associated with survival probability. Late diagnosis was recorded among many of the 250 study subjects: almost half (44.8%) were diagnosed less than 30 days prior to or during their hospitalization. A high mortality rate was also detected: 39.6% of the subjects died during the 12 months of monitoring. The cumulative survival probability of the cohort group was estimated at 68.0% after 3 months and at 61.2% after 12 months. However, certain patient subgroups analyzed had even lower cumulative survival probabilities after 12 months of monitoring: if diagnosed during hospitalization, it was estimated at only 48.0% and those with no record of antiretroviral treatment had a 48.5% cumulative survival probability. Patients with severe anemia had the lowest survival probability, similar among the two lymphocyte count groups (<1000 mm(3) and ≥1000 mm(3)), the former with a 45.5% survival probability and the latter with a 46.7% one. The proportional death risk was 2.5-fold higher for men residing in other area than the capital city of the State of Minas Gerais and greater metropolitan region when compared with women residing there. The findings of this study highlight the importance of early diagnosis for predicting patient survival and reinforce the necessity of facilitating HIV diagnosis.

Finding a better first antiretroviral regimen is one of the strategies used to improve span and quality of life of HIV/AIDS patients. 891 patients were followed during 24 months or until interruption/abandonment of treatment, changing regimen or death. At the end of 6 months, 69% of the patients were still being treated with the first regimen, 54% at 12 months, 48% at 18 months and 39% at 24 months. AZT-3TC-EFV was the most prescribed regimen and with the lesser discontinuation. NNRTI regimens showed high effectiveness and durability compared to PI regimens. Irregular medication dispensation was the only risk factor for failure/interruption of treatment in multivariate analyses. Intolerance/adverse effects were mainly responsible for first regimen discontinuation, followed by abandonment/non-adherence and virologic failure. Results showed significant difference between causes of interruption of first HAART with higher percentage of intolerance/adverse effects with PI regimens and higher immunologic failure with NNRTI regimens. Even with the availability of more potent and tolerable drugs, lack of adherence to HAART and high level of adverse effects are still the most important barriers to prolonged success of treatment. This study adds relevant information about durability and effectiveness of HAART in the first decade of its use in Brazil.

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.

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.

Conflicts of interest are inherent to the majority of relationships among individuals and of these with companies and institutions and, certainly, research involving human beings is no exception. In relation to clinical research, the main focus of this manuscript, conflicts of interest occur at different levels and usually permeate among them: In the pharmaceutical industry in their decisions to invest to develop new products, especially vaccines and drugs, and also in relation to marketing of these products; Among the investigators the conflicts may be related to the financial gains to participate in pharma sponsored trials, or to the expected academic career boost attained with the publication of the results of the trials and also to personal interests such as the financial support for trips to international conferences. Often the participation of host country investigators is restricted to performing phase III or IV protocols developed abroad, many times with low scientific relevance, and even lower relevance to public health; Universities or research institutes themselves also have conflicts of interest, as the sponsored projects may help increase their budgets, both directly (taxes) and indirectly (e.g., improvement of physical infrastructure of laboratories or out patient clinics); For the trial volunteers in developing countries, and Brazil is no exception despite free and universal access to its health system, participation in clinical trials is many times seen as, and can really be, an unique opportunity of receiving better health care, better treatment by the health professionals, easier access to costly lab exams and also to receiving certain medications which would otherwise be difficult to have access to. In order to handle these conflicts of interest, Brazil has a well-established and respected legal support and ethical normatization. The latter is represented by Resolution 196/96 of the Brazilian National Research Ethics Committee (CONEP). This national system was established in 1996 providing guidance to all research involving human beings and currently there are approximately 500 local research ethical committees certified by CONEP in all States of Brazil. However, there is intense international pressure mainly from the pharmaceutical industry especially to the ethical requirements emanated from the Declaration of Helsinki (DH), aiming to lower the level of ethical requirements in research to be carried out with volunteers from developing countries. Fallacious reasoning includes that the equity stated at the DH, especially the access to the best proven medical care and to the developed products to all volunteers independently of where the trial is being held, would inflate the costs of research and drive the sponsors away from the developing countries. In this line of thought, if the volunteers have not the same rights that would constitute an unacceptable double standard, or in other words, the best for the volunteers from developed countries and whatever is possible for those in developing countries. This manuscript will focus on the various levels where conflict of interest issues are more prone to happen, such as in the actions of pharmaceutical industries, their relation to health professionals, the participation of universities and research institutes, the ethical research committees and their members, including the possible pressures exerted on them by researchers, sponsors and even their institutions. Emphasis will be given to the interrelation between conflicts of interest and vulnerability, and also the causes and possible solutions to lower the risks of exploitation of volunteers in research. It will also emphasize the need to guarantee access to products that are proven efficacious to all individuals who may need them. Possible ways of empowering these volunteers will be evaluated, so that they become aware of their rights and demand for them. It will discuss the need of separating economic interests from the real needs of public health and of demystifying economic arguments used in order to justify the lowering of ethical requirements. And finally it will address the search for or the establishment of real and effective involvement of all stakeholders in an international organism really representing everyone (e.g., WHO) in order to evaluate, debate, and decrease the risks of several conflicts of interest, aiming at the establishment of research projects that can truly contribute to lower the obscene disparities of health between developed and developing countries.

Ototoxicity and antiretroviral therapy seem to be associated. The aim of this study was to evaluate this possible correlation. Evaluations were carried out on 779 medical records from HIV-infected patients who were being regularly followed up, of whom 162 were being treated with antiretroviral therapy and 122 were untreated (controls). The patients undergoing treatment were older (mean: 42 years), had had serological confirmation for longer times (80 months) and had smaller viral loads (P = 0.00). CD4+ was similar between the groups (P = 0.60). In the treated group, three cases (1.8%) of idiopathic hearing loss and two (1.3%) of otosclerosis-related hearing loss were observed, which both started after antiretroviral therapy. No statistical difference relating to idiopathic hearing loss was found between the groups. While descriptive studies consider possible ototoxicity associated with antiretroviral therapy, this possible adverse effect was not related to the antiretroviral therapy in this study. Conversely, otosclerosis might have been correlated with antiretroviral therapy. This issue deserves to be studied.

Objective: To describe bisexual men's behavior in terms of sexual identity, condom use, frequency of sexual intercourse and types of partners and to determine rates of inconsistent condom according to partner's gender., Methods: Cross-sectional study nested in a cohort of HIV-negative homosexual and bisexual men in the city of Belo Horizonte, Southeastern Brazil, followed up since 1994 (Horizonte Project). Of 1,025 subjects enrolled between 1994 and 2005, 195 volunteers who reported at admission having sexual relations with men and women during the previous six months were selected. A behavioral risk index, called Horizonte Risk Index, was estimated. It incorporates a constant assigned to each type of unprotected sexual act, adjusted for the number of sexual encounters., Results: Sexual activity with men predominated; most considered themselves as bisexual (55%) and homosexual (26%). During the six months prior to the study, median number of casual male partners (4) was higher than both casual female partners (2) and steady male or female partners (1). During vaginal sex with a steady partner, the rate of inconsistent condom use was 55%, compared to 35% and 55% in anal insertive and anal receptive sex, respectively, with steady male partners. The index was higher for those having sex with men and women compared to those having sex either exclusively with women or men (p=0.004)., Conclusions: HIV risk behavior was more frequent among men who reported sexual activity both with men and women. Bisexual men display different sexual and protective behavior according to gender and steadiness of relationships, and female steady partners had more unprotected encounters.

Unlabelled: Sensorineural hearing loss (SNHL) related to chronic suppurative otitis media (CSOM) was studied to clarify the involvement of cholesteatomas in this context., Aim: to evaluate SNHL related to CSOM and its association with cholesteatomas, disease duration and patients ages., Methods: Retrospective analysis of 115 patients with CSOM with and without cholesteatoma submitted to surgical treatment. Inclusion criteria were active unilateral disease, normal contralateral ear and age below 60 years., Results: The average age was 26.3 years, 58 males and 57 females. The duration of ear disease was, in average, 12.4 years. The average threshold of hearing was 40 dB in CSOM ear and 22 dB in the normal contralateral ear (P=0.002). CSOM with cholesteatoma occurred in 78 of 115 cases. In the abnormal ear, SNHL was seen in 15 cases, being 6 cases of profound loss, that correlated with adjusted-age (P=0.003) and absence of cholesteatoma (P=0.01), but not with disease duration (P=0.458)., Conclusion: SNHL occurred in 13% of the patients with CSOM, and was correlated with older age, but not with the presence of cholesteatoma or longer duration of ear disease.

Introduction: The Brazilian AIDS Programme success is recognized worldwide, due to its integrated approach of prevention, respect for human rights and to free of charge universal access to state of the art antiretrovirals., Current Situation: As of 2006, 180,000 people living with AIDS are on HAART with 17 drugs available, receiving medical and laboratory care through the public health system. Costs for ART drugs reached US$ 400 million in 2006 and will increase steeply if the current trends are maintained: uptake of approximately 20,000 new patients/year and the need for more expensive, patent-protected second and third line drugs., Discussion: We discuss the strengths and weaknesses of the programme, budgetary pressures, the need for more intense preventive efforts, for boosting local production of new drugs, for more investment in research and development and the issue of voluntary and compulsory licensing. There are many hurdles in pursuing long-term sustainability, which depends on country driven initiatives and international collaboration and participation., Conclusion: We conclude that the Brazilian experience demonstrated the capability of a developing country to treat people with equity, independently of race, gender or economic power and that this equality "seed" has already spread to other countries. Internally this experience must be used to tackle other endemic diseases, such as leprosy, malaria, dengue and leishmania. The Brazilian political will has been proven but, once again, there will be the need for concerted action by civil society, researchers, health professionals, people living with HIV/AIDS and the government to convince the world that health needs should not be treated as commercial issues, and that progress in research and development must be shared throughout the world if we expect to survive as a civilization.

The aims of this study were to describe anthropometric data and glycemic and lipidic profiles of HIV-infected patients treated or not with antiretrovirals (ARV) drugs, and to assess association between these drugs and body composition changes, lipid and glucose homeostasis disturbances. There were 176 patients included (133 ARV-treated patients and 43 ARV-naïve). The patients were submitted to clinical evaluation, laboratorial analysis, ultrasonographic measurements, bioelectrical impedance analysis and skin folds thickness measurements. The ARV-treated group showed higher waist-to-hip ratio (p= 0.0002), higher intra-abdominal fat thickness measured by ultrasonography (p= 0.003) and lower bicipital (p= 0.01) and tricipital (p= 0.0002) skin folds. This group also showed higher triglyceride (p= 0.0002), total cholesterol (p= 0.00007), HDL cholesterol (p= 0.009), glucose measurements one hour (p= 0.01) and two hours (p= 0.001) after dextrose load, higher levels of fasting insulin (p= 0.03) and higher HOMAR index (p= 0.02). The antiretroviral drugs are associated with increased visceral fat and decreased peripheral fat pads. Beside that, these drugs are associated with atherogenic lipid profile and insulin resistance, two independent risk predictors of cardiovascular disease.

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.)

We assessed the performance of HIV-1 genotyping tests in rescue therapy. Patients were divided into two groups: group 1 (genotyped), included those switching to new antiretroviral drugs based on HIV-1 genotyping data, and group 2 (standard of care -SOC), comprised those in rescue therapy who had not used this test. This was an open and non-randomized study, with 74 patients, followed up for a mean period of 12 months, from February 2002 to May 2003. The groups differed in the duration of antiretroviral use, experience with diverse drug classes (non-nucleoside reverse transcriptase inhibitors and protease inhibitors) and viral load <2.6 log10 copies/mL at any time during treatment. In 23 patients (group 1), the switch in antiretroviral (ARV) regimen was based on genotyping data; this test was not used for 51 patients (group 2). Two CD4 + lymphocyte counts and viral load counts were made for each patient during the study. Data from the pharmacy where patients received antiretroviral agents, medical charts, and direct interviews with patients to assess compliance to treatment, were analyzed. In the genotyped group, the average drop in viral load was 2.8 log10, compared with a 1.5 log10 difference in group 2; the difference was significant in the first assessment performed six months after switching (p=0.001). Considering the patients with viral load < 2.6 log10 (400 copies/mL) after switching, the patients in group 1 had a better performance in the first assessment (73.9% versus 31.1% in groups 1 and 2, respectively); this difference was significant (p=0.001). In multivariate analysis, the variables associated with a greater drop in viral load in the first assessment were the patients whose switching was based on genotyping (group 1), those with a past history of viral load < 2.6 log10 and correct use of antiretroviral agents. In conclusion, the genotyping test and adherence were found to be independent factors for success in the management of patients who failed treatment.

Human Ehrlichia chaffeensis infections have been reported in North America, Asia and Europe, but only recently have human cases been reported in Brazil. Nine new human cases of E. chaffeensis infection diagnosed on a clinical and serological basis are reported. Serological tests were performed with indoor slides prepared with CDC stock DH-82 cells infected with E. chaffeensis (Arkansas strain). All but two patients were adults. Seven patients were male and two female. The fever duration varied from 4 to 120 days with a median of 6 days. All patients recalled previous tick attack. IgM was detected in four cases. Influenza like syndrome was the most frequent clinical form affecting five patients. Two patients had fever of unknown origin (FUO), one patient had blood culture-negative endocarditis and one had encephalitis. All patients except one recovered. Two patients were correctly treated. One patient with FUO had AIDS and unexplained pancytopenia. The occurrence of human ehrlichiosis by E. chaffeensis remains to be proved in Brazil; the cases reported here highlight the possibility of such disease occurrence in Brazil.

Rickettsial diseases except those belonging to spotted fever group rickettsioses are poorly studied in South America particularly in Brazil where few epidemiological reports have been published. We describe a serosurvey for Rickettsia rickettsii, R. typhi, Coxiella burnetii, Bartonella henselae, B. quintana, and Ehrlichia chaffeensis in 437 healthy people from a Brazilian rural community. The serum samples were tested by indirected micro-immunoflourescence technique and a cutoff titer of 1:64 was used. The seroprevalence rates for R. rickettsii, R. typhi, C. burnetii, B. henselae, B. quintana, and E. chaffeensis were respectively 1.6% (7 samples); 1.1% (5 samples); 3.9% (17 samples); 13.7% (60 samples); 12.8% (56 samples), and 10.5% (46 samples). Frequent multiple/cross-reactivity was observed in this study. Age over 40 years old, urban profession, and rural residence were significantly associated with some but not all infections rate. Low seropositivity rates for R. rickettsii, R. typhi, and C. burnetii contrasted with higher rates of seropositivity for B. quintana, B. henselae, and E. chaffeensis. These results show that all tested rickettsial species or antigenically closely related possible exist in this particular region.