Cost-effectiveness of adult circumcision in a resource-rich setting for HIV prevention among men who have sex with men

Background.  We examined the effects and cost‐effectiveness of 4 strategies of circumcision in a resource‐rich setting (Australia) in a population of men who have sex with men (MSM).

Method.  We created a dynamic mathematical transmission model and performed an economic analysis to estimate the costs, outcomes, and cost‐effectiveness of different strategies, compared with those of the status quo. Strategies included circumcision of all MSM at age 18 years, circumcision of all MSM aged 35–44 years, circumcision of all insertive MSM aged 18 years, and circumcision of all MSM aged 18 years . All costs are reported in US dollars, with a cost‐effectiveness threshold of $42,000 per quality‐adjusted life‐year.

Results.  We find that 2%–5% of human immunodeficiency virus (HIV) infections would be averted per year, with initial costs ranging from $3.6 million to $95.1 million, depending on the strategy. The number of circumcisions needed to prevent 1 HIV infection would range from 118 through 338. Circumcision of predominately insertive MSM would save $21.7 million over 25 years with a $62.2 million investment. Strategies to circumcise 100% of all MSM and to circumcise MSM aged 35–44 years would be cost‐effective; the latter would require a smaller investment. The least cost‐effective approach is circumcision of young MSM close to their sexual debut. Results are very sensitive to assumptions about the cost of circumcision, the efficacy of circumcision, sexual preferences, and behavioral disinhibition.

Conclusions.  Circumcision of adult MSM may be cost‐effective in this resource‐rich setting. However, the intervention costs are high relative to the costs spent on other HIV prevention programs.

Effectiveness of an HIV / AIDS prevention approach across three countries

The study examined the effectiveness of one community based HIV / AIDS prevention approach, Community Counselling, in PNG, India and Zambia. Results indicated the three countries differed along cultural dimensions. Differences on behaviour, attitude, knowledge and risk perceptions associated with HIV / AIDS were noted within each country that reflected exposure to the approach. The professional portfolio examines the curent situations in which cultural guidelines have been developed to assist clinicians in considering indigenous cultural differences in increasingly multicultural societies. Four case studies are presented in which aspects of these issues are identified and discussed.

HIV vaccines : brief review and discussion of future directions

This article reviews data relevant to the development of cocktail vaccines for HIV which have been designed to elicit a wide range of envelope glycoprotein-specific B- and T-cell responses.

HIV-1 down-modulates γ signaling chain of FcγR in human macrophages : a possible mechanism for inhibition of phagocytosis

HIV-1 infection impairs a number of macrophage effector functions, thereby contributing to development of opportunistic infections and the pathogenesis of AIDS. FcγR-mediated phagocytosis by human monocyte-derived macrophages (MDM) is inhibited by HIV-1 infection in vitro, and the underlying mechanism was investigated in this study. Inhibition of phagocytosis directly correlated with the multiplicity of HIV-1 infection. Expression of surface FcγRs was unaffected by HIV-1 infection, suggesting that inhibition of phagocytosis occurred during or after receptor binding. HIV-1 infection of MDM markedly inhibited tyrosine phosphorylation of the cellular proteins, which occurs following engagement of FcγRs, suggesting a defect downstream of initial receptor activation. FcγR-mediated phagocytosis in HIV-infected MDM was associated with inhibition of phosphorylation of tyrosine kinases from two different families, Hck and Syk, defective formation of Syk complexes with other tyrosine-phosphorylated proteins, and inhibition of paxillin activation. Down-modulation of protein expression but not mRNA of the γ signaling subunit of FcγR (a docking site for Syk) was observed in HIV-infected MDM. Infection of MDM with a construct of HIV-1 in which nef was replaced with the gene for the γ signaling subunit augmented FcγR-mediated phagocytosis, suggesting that down-modulation of γ-chain protein expression in HIV-infected MDM caused the defective FcγR-mediated signaling and impairment of phagocytosis. This study is the first to demonstrate a specific alteration in phagocytosis signal transduction pathway, which provides a mechanism for the observed impaired FcγR-mediated phagocytosis in HIV-infected macrophages and contributes to the understanding of how HIV-1 impairs cell-mediated immunity leading to HIV-1 disease progression.

Granulocyte-macrophage colony-stimulating factor augments phagocytosis of mycobacterium avium complex by human immunodeficiency virus type 1-infected monocytes/macrophages in vitro and in vivo

The role of human immunodeficiency virus type 1 (HIV-1) infection on the ability of human monocytes/macrophages to phagocytose Mycobacterium avium complex (MAC) in vivo and in vitro and the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on this function were investigated. By use of a flow cytometric assay to quantify phagocytosis, HIV-1 infection was found to impair the ability of monocyte-derived macrophages to phagocytose MAC in vitro, whereas GM-CSF significantly improved this defect. Phagocytosis was not altered by exposure to a mutant form of GM-CSF (E21R) binding only to the α chain of the GM-CSF receptor, suggesting that signaling by GM-CSF that leads to augmentation of phagocytosis is via the β chain of the receptor. In a patient with AIDS and disseminated multidrug-resistant MAC infection, GM-CSF treatment improved phagocytosis of MAC by peripheral blood monocytes and reduced bacteremia. These results imply that GM-CSF therapy may be useful in restoring antimycobacterial function by human monocytes/macrophages.

Establishment of HIV-1 latency in resting CD4+ T cells depends on chemokine-induced changes in the actin cytoskeleton

Eradication of HIV-1 with highly active antiretroviral therapy (HAART) is not possible due to the persistence of long-lived, latently infected resting memory CD4+ T cells. We now show that HIV-1 latency can be established in resting CD4+ T cells infected with HIV-1 after exposure to ligands for CCR7 (CCL19), CXCR3 (CXCL9 and CXCL10), and CCR6 (CCL20) but not in unactivated CD4+ T cells. The mechanism did not involve cell activation or significant changes in gene expression, but was associated with rapid dephosphorylation of cofilin and changes in filamentous actin. Incubation with chemokine before infection led to efficient HIV-1 nuclear localization and integration and this was inhibited by the actin stabilizer jasplakinolide. We propose a unique pathway for establishment of latency by direct HIV-1 infection of resting CD4+ T cells during normal chemokine-directed recirculation of CD4+ T cells between blood and tissue.

Expression and purification of soluble recombinant full length HIV-1 Pr55(Gag) protein in Escherichia coli

The HIV-1 Gag precursor protein, Pr55(Gag), is a multi-domain polyprotein that drives HIV-1 assembly. The morphological features of HIV-1 suggested Pr55(Gag) assumes a variety of different conformations during virion assembly and maturation, yet structural determination of HIV-1 Pr55(Gag) has not been possible due to an inability to express and to isolate large amounts of full-length recombinant Pr55(Gag) for biophysical and biochemical analyses. This challenge is further complicated by HIV-1 Gag's natural propensity to multimerize for the formation of viral particle (with ∼2500 Gag molecules per virion), and this has led Pr55(Gag) to aggregate and be expressed as inclusion bodies in a number of in vitro protein expression systems. This study reported the production of a recombinant form of HIV-1 Pr55(Gag) using a bacterial heterologous expression system. Recombinant HIV-1 Pr55(Gag) was expressed with a C-terminal His×6 tag, and purified using a combination of immobilized metal affinity chromatography and size exclusion chromatography. This procedure resulted in the production of milligram quantities of high purity HIV-1 Pr55(Gag) that has a mobility that resembles a trimer in solution using size exclusion chromatography analysis. The high quantity and purity of the full length HIV Gag will be suitable for structural and functional studies to further understand the process of viral assembly, maturation and the development of inhibitors to interfere with the process.

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013

BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets. FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action. FUNDING: Bill & Melinda Gates Foundation.

Atenção ao usuário em um centro de referência HIV/Aids: perspectiva de profissionais e usuários

We study the health care focused on care in an intercessor and dialogical relationship with the User, which involves the construction of therapeutic projects essential to the quality of the treatment of the user in health services, and it is necessary individual and collective actions. It is intended to acknowledge and analyze the perception of social subjects, users and professionals on the treatment given to a user of a Specialized Outpatient Service (Serviço Ambulatorial Especializado SAE) in STD/HIV/AIDS state reference in Natal, RN. The study is structured in a transdisciplinary vision of science and knowledge, theoretical and methodological principles that give meaning to the expression of the institutional features of care and health care reconnecting them to the social context. As a research strategy we seek the expressions of 56 subjects of social research, which agreed to participate in the sample, from a symbolic map of the attention, coupled with the techniques of observation and semi-structured interview. For the analysis of the results, five categories of analysis were established: the meaning of the service, care perception, process of communication and interaction, treatment perception and organization and evaluation of the service. It is argued that the attention and care are developed in a technical health care assistance to the disease, focusing on attention based on treatment, on diagnostic and drug therapy of antiretroviral drugs, reflecting the traditional biomedical paradigm of attention to the disease. This is also the mode of organization of practical actions in daily SAE: the therapy proves to be fragmented in several specialties, vertical and feeds the same model, generating tension and overload for professionals; showing impersonal care focused on structured and informative technology, unrelated to an interactive dialogic. From the speech of the subjects, the SAE is understood as the place of confrontation with the disease, but also enables greater elaboration of the illness by meeting their peers. Living with HIV and AIDS is living with concern, apprehension and fear, but mainly with the stigma, prejudice and exclusion, which require that the disease is kept in secret. There is a movement of forces and power, expressed in the knowledge-power of those who dominate the technical and administrative capabilities, devices that concentrate the maintenance of the medicalization of care, rapid consultations and with little attention, making it difficult to interact with and listen to, combined with structural failures, organizational and inadequate management of the service. We conclude that there are dimensions that are not considered in the internal dynamics of the care service multiple forms, characterized by care conflicting models, marked by individual interventions related to the disease. The subject is not considered together with his speech as technical discourse is imposed and care production based on material technology is observed

Darunavir: A Critical Review of Its Properties, Use and Drug Interactions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Medidas contraceptivas e de proteção da transmissão do HIV por mulheres com HIV/Aids

OBJETIVO: Atualmente, entre as mulheres, a relação sexual é a forma de transmissão que mais tem contribuído para a feminização da epidemia de HIV/Aids. Na busca constante de se estabelecer padrões mais adequados de orientação para saúde, investigou-se o uso de medidas contraceptivas, que também sirvam de proteção da transmissão do HIV, entre mulheres portadoras de HIV/Aids. MÉTODOS: Estudo exploratório desenvolvido em um serviço público ambulatorial de um hospital universitário, referência aos portadores de HIV/Aids da região centro-sul do Estado de São Paulo, no período de cinco meses (2000 a 2001). Foram estudadas 73 mulheres portadoras da infecção pelo HIV, ou com Aids. Os dados foram obtidos por meio de um formulário que investigava a caracterização sociodemográfica, as formas de anticoncepção utilizada e a situação sorológica do parceiro sexual. Os dados foram analisados descritivamente e os conteúdos das respostas abertas, agrupados em temas. Foi aplicado o teste exato de Fisher para análise de algumas variáveis, em nível de 5%. Para a análise de conteúdo utilizou-se a proposta de Bardin. RESULTADOS: A maioria das mulheres estava em fase de vida reprodutiva, eram casadas e foram contaminadas quase exclusivamente por meio da relação heterossexual. Entre elas, 35,4% referiam parceiro sexual discordante quanto à sorologia anti-HIV, e 13,7% utilizavam formas inadequadas de anticoncepção que também não protegiam da transmissão do HIV. CONCLUSÕES: Os resultados alertam para a necessidade de ações educativas continuadas quanto a experiências sexuais mais seguras entre portadoras de HIV/Aids, para que elas possam discutir com seus parceiros outras formas de exercerem sua sexualidade, sendo capazes de estabelecer opção contraceptiva mais consciente, de maneira a zelar pela sua saúde, do parceiro e até do concepto.

Avaliação de serviços de assistência ambulatorial em aids, Brasil: estudo comparativo 2001/2007

OBJETIVO: Avaliar os serviços do Sistema Único de Saúde brasileiro de assistência ambulatorial a adultos vivendo com aids em 2007 e comparar com a avaliação de 2001. MÉTODOS: Os 636 serviços cadastrados no Ministério da Saúde em 2007 foram convidados a responder a um questionário previamente validado (Questionário Qualiaids) com 107 questões de múltipla escolha sobre a organização da assistência prestada. Analisaram-se as frequências das respostas de 2007 comparando-as com as obtidas em 2001 na forma de variação percentual (VP). RESULTADOS: Responderam o questionário 504 (79,2%) serviços. Cerca de 100,0% dos respondentes relataram ter pelo menos um médico, suprimento sem falhas de antirretrovirais e de exames CD4 e carga viral. Vários aspectos mostraram melhor desempenho em 2007 comparados a 2001: registro de número de faltas à consulta médica (de 18,3 para 27,0%, VP: 47,5%), agendamento de consulta em menos de 15 dias no início da terapia antirretroviral (de 55,3 para 66,2%, VP: 19,7%) e participação organizada do usuário (de 5,9 para 16,7%, VP: 183,1%). Houve manutenção de dificuldades: pequena variação na disponibilidade de exames especializados em até 15 dias, como endoscopia (31,9 para 34,5%, VP: 8,1%), e a piora de indicadores como tempo ideal de acesso a consultas especializadas (55,9 para 34,5% em cardiologia, VP negativa de 38,3%). O tempo médio despendido nas consultas médicas de seguimento manteve-se baixo: 15 minutos ou menos (52,5 para 49,5%, VP negativa de 5,8%). CONCLUSÕES: A avaliação de 2007 mostrou que os serviços contam com os recursos essenciais para a assistência ambulatorial. Houve melhoras em muitos aspectos em relação a 2001, mas persistem desafios. Pouco tempo dedicado à consulta médica pode estar vinculado ao número insuficiente de médicos e/ou à baixa capacidade de escuta e diálogo. A acessibilidade prejudicada a consultas especializadas mostra a dificuldade das infraestruturas locais do Sistema Único de Saúde.

HIV attitudes and practices among professors in a Brazilian dental school.

Although there is considerable published research on Acquired Immunodeficiency Syndrome (AIDS), individual biases persist because of lack of information regarding HIV virus transmission. As a result, both infected patients and health care professionals suffer. The objective of this study was to determine if there is prejudice among university professors at the School of Dentistry at Aracatuba's Sao Paulo State University (FOA-UNESP) concerning HIV-positive patients or HIV-positive health care professionals. Out of the seventy-seven professors who responded to the questionnaire, 62.3 percent (forty-eight) stated that they advise their students not to refuse to treat a patient with HIV. Although 96.2 percent (fifty-two) of the fifty-four professors who treat patients have reported that they treat patients who are HIV-positive, only 65.3 percent of them were aware of infection control precautions, and only 32.7 percent reported that they would treat an HIV-positive patient like any other patient. There is also prejudice regarding HIV-positive professionals because only 48.1 percent (thirty-seven) of the professors responded that they would be willing to be treated by an infected professional. It can be concluded that there is prejudice among some of the FOA-UNESP university professors regarding individuals who are HIV-positive.

The β-chemokines MIP-1α and RANTES and lipoprotein metabolism in HIV-infected Brazilian patients

HIV patients are predisposed to the development of hypertriglyceridemia and hypercholesterolemia as a result of both viral infection and HIV infection therapy, especially the protease inhibitors. Chemokines and cytokines are present at sites of inflammation and can influence the nature of the inflammatory response in atherosclerosis. We investigated the correlation between biochemical variables and β-chemokines (MIP-1α and RANTES) and the apolipoprotein E genotype in HIV-infected individuals. The apolipoproteins were measured by nephelometry. Triglycerides and total cholesterol were determined by standard enzymatic procedures. The β-chemokines were detected by ELISA. The genetic category of CCR5 and apolipoprotein E were determined by PCR amplification and restriction enzymes. Immunological and virological profiles were assessed by TCD4 + and TCD8 + lymphocyte counts and viral load quantification. Positive correlations were found between apo E and CD8 + (p = 0.035), apo E and viral load (p = 0.018), MIP-1α and triglycerides (p = 0.039) and MIP-1α and VLDL (p = 0.040). Negative correlations were found between viral load and CD4 + (p = 0.05) and RANTES and CD4 + (p = 0.029). The β-chemokine levels may influence lipid metabolism in HIV-infected individuals. © 2005 by The Brazilian Journal of Infectious Diseases and Contexto Publishing. All rights reserved.