Genome-wide association study of virologic response with efavirenz-containing or abacavir-containing regimens in AIDS clinical trials group protocols.

BACKGROUND: Efavirenz and abacavir are components of recommended first-line regimens for HIV-1 infection. We used genome-wide genotyping and clinical data to explore genetic associations with virologic failure among patients randomized to efavirenz-containing or abacavir-containing regimens in AIDS Clinical Trials Group (ACTG) protocols. PARTICIPANTS AND METHODS: Virologic response and genome-wide genotype data were available from treatment-naive patients randomized to efavirenz-containing (n=1596) or abacavir-containing (n=786) regimens in ACTG protocols 384, A5142, A5095, and A5202. RESULTS: Meta-analysis of association results across race/ethnic groups showed no genome-wide significant associations (P<5×10) with virologic response for either efavirenz or abacavir. Our sample size provided 80% power to detect a genotype relative risk of 1.8 for efavirenz and 2.4 for abacavir. Analyses focused on CYP2B genotypes that define the lowest plasma efavirenz exposure stratum did not show associations nor did analysis limited to gene sets predicted to be relevant to efavirenz and abacavir disposition. CONCLUSION: No single polymorphism is associated strongly with virologic failure with efavirenz-containing or abacavir-containing regimens. Analyses to better consider context, and that minimize confounding by nongenetic factors, may show associations not apparent here.

Constitution, Diversification and Normalisation of a Health Problem: Organising the Fight against AIDS in Switzerland (1984-2005)

The article traces the formation, diversification and normalization of the AIDS cause in Switzerland. Particular emphasis is placed on interactions between the medical field, public authorities and associative space, the latter being understood as the place where individual and collective actors compete to define the cause. The authors argue that the major phases in the structuring of the struggle, the pace of state intervention and the creation of a multi-organizational field, can only be understood if one adopts a 'configurational perspective' attentive to the manner in which, in a given context and under the effect of particular constraints, key actors strategically interact and contribute to transforming their environment and their chances of reaching their goals. This approach takes into account the changing socio-biological characteristics of those who have committed themselves to the cause. In turn, internal movement divisions about how to respond to the epidemic as well as the changing perceptions of the disease have modified the opportunities for commitment, encouraging certain individual kinds of people and excluding others.

Using STD occurence to monitor AIDS prevention : final report of the Working Group on STD Surveillance.

The overall aim of the project has been to assess the extent to which data on the frequency of occurence of STDs [Sexually transmitted diseases] might be useful in the monitoring and evaluation of AIDS prevention programmes. The objectives have been to answer the following questions: (a) Can measures of STD occurence be used as an outcome measure of AIDS/HIV preventive efforts ? In particular: -> which diseases might be useful ? -> in what ways could they be used ? (b) If measures of STD occurence can be used in this way, is existing surveillance data in Western Europe adequate for the purpose ? If not why not ? (c) What do data from existing STD surveillance systems tell us about the success or failure of AIDS prevention to date ? (d) What needs to be done in order taht STD surveillance data in the countries of Western Europe could be used for this purpose ? [Authors, p. 4]

Microenxertia ex vitro para eliminação do vírus CABMV em maracujá-azedo

O objetivo deste trabalho foi avaliar diferentes meios de cultura, utilizados sobre o ponto da enxertia, na microenxertia ex vitro para a eliminação do Cowpea aphid-borne mosaic virus (CABMV), em plantas de maracujá-azedo (Passiflora edulis Sims f. flavicarpa Deg.). Ápices caulinares, provenientes de plantas infectadas, foram microenxertados em plântulas obtidas pela germinação de sementes em substrato comercial esterilizado. Foram conduzidos experimentos com a microenxertia realizada no hipocótilo e no epicótilo, e foram utilizados cinco meios de cultura, que diferiam na concentração de fitorreguladores, aplicados no local da enxertia. O índice médio de microenxertos com folha expandida foi de 27,22 e 32,22%, quando a microenxertia foi realizada no hipocótilo e no epicótilo, respectivamente. Na microenxertia realizada no hipocótilo, não houve efeito da aplicação de meios de cultura. Na microenxertia realizada no epicótilo, o meio MS acrescido de 0,1 mg L-1 de AIB e 1 mg L-1 de BAP proporcionou 53,3% de microenxertos com folha expandida, número superior aos demais tratamentos e maior desenvolvimento das brotações. A indexação realizada pelo teste ELISA indireto, 80 a 100 dias após a microenxertia, mostrou que 93% das plantas testadas não apresentavam vírus detectável.

Linhagens de alface-crespa para o verão resistentes ao Meloidogyne javanica e ao vírus mosaico-da-alface

O objetivo deste trabalho foi selecionar famílias F4 de alface, oriundas do cruzamento entre as cultivares Verônica e Salinas 88, para o cultivo no verão, com relação ao tipo de folha, e à resistência ao Lettuce mosaic virus (LMV) e ao nematóide-das-galhas Meloidogyne javanica. Primeiramente, avaliaram-se a coloração da folha, tipos de borda e limbo foliares, além da tolerância ao calor no campo, em blocos ao acaso compostos pelas 15 famílias F4 previamente selecionadas, pelas cultivares parentais e pela cultivar testemunha Regina 71 (folhas lisas e tolerante ao calor), com cinco repetições e oito plantas por parcela. Na segunda etapa, as famílias foram avaliadas quanto à resistência ao LMV e ao nematóide-das-galhas, em bandejas de 128 células acondicionadas em estufa. As médias das notas atribuídas a cada família foram comparadas às médias de cada cultivar parental pelo teste de Dunnet (5%). A família AFX007B-140-21, homozigota resistente aos nematóides e ao LMV e, também, tolerante ao calor, foi a mais promissora. O cruzamento entre uma cultivar de folhas crespas e soltas com uma de folhas crespas e repolhuda, pode originar linhagens promissoras tanto de folhas crespas quanto de folhas lisas.

Deletion of the Vaccinia Virus Gene A46R, Encoding for an Inhibitor of TLR Signalling, Is an Effective Approach to Enhance the Immunogenicity in Mice of the HIV/AIDS Vaccine Candidate NYVAC-C.

Viruses have developed strategies to counteract signalling through Toll-like receptors (TLRs) that are involved in the detection of viruses and induction of proinflammatory cytokines and IFNs. Vaccinia virus (VACV) encodes A46 protein which disrupts TLR signalling by interfering with TLR: adaptor interactions. Since the innate immune response to viruses is critical to induce protective immunity, we studied whether deletion of A46R gene in a NYVAC vector expressing HIV-1 Env, Gag, Pol and Nef antigens (NYVAC-C) improves immune responses against HIV-1 antigens. This question was examined in human macrophages and in mice infected with a single A46R deletion mutant of the vaccine candidate NYVAC-C (NYVAC-C-ΔA46R). The viral gene A46R is not required for virus replication in primary chicken embryo fibroblast (CEF) cells and its deletion in NYVAC-C markedly increases TNF, IL-6 and IL-8 secretion by human macrophages. Analysis of the immune responses elicited in BALB/c mice after DNA prime/NYVAC boost immunization shows that deletion of A46R improves the magnitude of the HIV-1-specific CD4 and CD8 T cell immune responses during adaptive and memory phases, maintains the functional profile observed with the parental NYVAC-C and enhances anti-gp120 humoral response during the memory phase. These findings establish the immunological role of VACV A46R on innate immune responses of macrophages in vitro and antigen-specific T and B cell immune responses in vivo and suggest that deletion of viral inhibitors of TLR signalling is a useful approach for the improvement of poxvirus-based vaccine candidates.

A Candidate HIV/AIDS Vaccine (MVA-B) that Enhances the Magnitude and Polyfunctionality of Memory HIV-1-Specific T-Cell Responses

Background: The poxvirus vector Modified Vaccinia Virus Ankara (MVA) expressing HIV-1 Env, Gag, Pol and Nef antigens from clade B (MVA-B) is currently used as a HIV/AIDS vaccine candidate. A general strategy to try to improve the immunogenicity of poxvirus HIV-1 vaccine candidates is the deletion of known or suggested immunomodulatory vaccinia virus (VACV) genes.Methods: We have generated and characterized the innate immune sensing and the immunogenicity profile of a new HIV-1 vaccine candidate, which contains a deletion in a VACV gene.Results: We show that this VACV protein is expressed early during virus infection and localizes to the cytoplasm of infected cells. Deletion of this VACV gene from the MVA-B had no effect on virus growth kinetics; therefore this VACV protein is not essential for virus replication. The innate immune signals elicited by the MVA-B deletion mutant in human macrophages and monocyte-derived dendritic cells were characterized. In a DNA prime/MVA boost immunization protocol in mice, flow cytometry analysis revealed that the MVA-B deletion mutant enhanced the magnitude and polyfunctionality of the HIV-1-specific CD4 + and CD8 + T-cell memory immune responses, with most of the HIV-1 responses mediated by the CD8 + T-cell compartment with an effector phenotype. Significantly, while MVA-B induced preferentially Env- and Gag-specific CD8 + T-cell responses, the MVA-B deletion mutant induced more GPN-specific CD8 + T-cell responses. Furthermore, the MVA-B deletion mutant enhanced the levels of antibodies against Env in comparison with MVA-B.Conclusion: These findings revealed that this new VACV protein can be considered as an immunomodulator and that deleting this gene in MVA-B confers an immunological benefit by inducing innate immune responses and increasing the magnitude and quality of the T-cell memory immune responses to HIV-1 antigens. Our observations are relevant for the improvement of MVA vectors as HIV-1 vaccines.

Are the World AIDS Conferences guilty of gender bias? Evidence from trends in the monitoring of WAC scientific discourse from 1989 to 2012

Background : The issue of gender is acknowledged as a key issue for the AIDS epidemic. World AIDS Conferences (WAC) have constituted a major discursive space for the epidemic. We sought to establish the balance regarding gender in the AIDS scientific discourse by following its development in the published proceedings of WAC. Fifteen successive WAC 1989-2012 served to establish a "barometer" of scientific interest in heterosexual and homo/bisexual men and women throughout the epidemic. It was hypothesised that, as in other domains of Sexual and Reproductive Health, heterosexual men would be "forgotten" partners. Method : Abstracts from each conference were entered in electronic form into an Access database. Queries were created to generate five categories of interest and to monitor their annual frequency. All abstract titles including the term "men" or "women" were identified. Collections of synonyms were systematically and iteratively developed in order to classify further abstracts according to whether they included terms referring to "homo/bisexual" or "heterosexual". Reference to "Mother to Child Transmission" (MTCT) was also flagged. Results : The category including "men", but without additional reference to "homo-bisexuel" (i.e. referring to men in general and/or to heterosexual men) consistently appears four times less often than the equivalent category for women. Excluding abstracts on women and MTCT has little impact on this difference. Abstracts including reference to both "men" and "homo-bisexual" emerge as the secondmost frequent category; presence of the equivalent category for women is minimal. Conclusion : The hypothesised absence of heterosexual men in the AIDS discourse was confirmed. Although the relative presence of homo-bisexual men and women as a focal subject may be explained by epidemiological data, this is not so in the case of heterosexual men and women. This imbalance has consequences for HIV prevention.

APOBEC3G genetic variants and their influence on the progression to AIDS.

The cytosine deaminase APOBEC3G, in the absence of the human immunodeficiency virus type 1 (HIV-1) accessory gene HIV-1 viral infectivity factor (vif), inhibits viral replication by introducing G-->A hypermutation in the newly synthesized HIV-1 DNA negative strand. We tested the hypothesis that genetic variants of APOBEC3G may modify HIV-1 transmission and disease progression. Single nucleotide polymorphisms were identified in the promoter region (three), introns (two), and exons (two). Genotypes were determined for 3,073 study participants enrolled in six HIV-AIDS prospective cohorts. One codon-changing variant, H186R in exon 4, was polymorphic in African Americans (AA) (f = 37%) and rare in European Americans (f < 3%) or Europeans (f = 5%). For AA, the variant allele 186R was strongly associated with decline in CD4 T cells (CD4 slope on square root scale: -1.86, P = 0.009), The 186R allele was also associated with accelerated progression to AIDS-defining conditions in AA. The in vitro antiviral activity of the 186R enzyme was not inferior to that of the common H186 variant. These studies suggest that there may be a modifying role of variants of APOBEC3G on HIV-1 disease progression that warrants further investigation.

Measuring discrepancies between knowledge, preoccupation and fear of aids in populations.

A simple tool to quantify discrepancies between knowledge, preoccupation and fear regarding hiv and aids is presented. This tool is based on standard questions available in health surveys. Some results using recent Swiss data are presented, and the method is discussed.

SIDA: l'information comme outil de prévention. [AIDS: information as a means to prevention].

Objective information for the groups exposed to the disease and the public in general is the only step that is currently possible in the prevention of AIDS. A certain number of information and support actions have been developed as a consequence of the appearance of AIDS in Switzerland. The AIDS information hot-line at the CHUV is one of these actions with the aim of orienting the information according to demand and examining the utility of this means, we made a prospective evaluation of the calls (between 23 October 1985-inception of the line and 31 March 1986). Out of a total of 535 calls, 317 requests for appointments (tests, consultation) or written documentation, and 218 (41%) were transferred to the doctor; 39% of the calls came from people who were directly concerned (ill, with a positive test, exposed groups), 11% from health professionals, and 47% from the general public. 56% of the calls were concerned with transmission of the disease (sexual, blood, indirect), 22% with the meaning of the detection test, 22% referred to the symptoms of the disease. According to the doctor's estimate, although the standard of knowledge is satisfactory in 55% of the cases, a considerable number of false ideas, that generate irrational fear, still persist. This hot-line thus provides a sympathetic ear and individual support, particularly for the exposed groups, rather than information about the disease. The existence of this action, therefore, appears justified, but must be integrated into a global strategy of information promotion.

Suscetibilidade de cercas-vivas, quebra-ventos e plantas invasoras ao vírus da leprose e sua transmissão para laranjeiras por Brevipalpus phoenicis (Geijskes) (Acari: Tenuipalpidae)

Objetivou-se avaliar a potencialidade de algumas plantas freqüentes em pomares cítricos de hospedar o vírus da leprose, transmitido por Brevipalpus phoenicis (Geijskes). Foram utilizadas as seguintes plantas: Hibiscus sp. L., Malvaviscus mollis DC., Grevillea robusta A. Cunn., Mimosa caesalpiniaefolia Benth., Bixa orellana L., Commelina benghalensis L., Bidens pilosa L., Sida cordifolia L. e Ageratum conyzoides L.. Duas criações-estoque do ácaro foram realizadas, sendo uma sobre frutos com sintomas de leprose e outra sobre frutos sem sintomas. De cada planta hospedeira do ácaro, escolheram-se duas folhas, delimitando-se na face inferior de cada planta uma área, que recebeu ácaros criados sobre frutos com lesões de leprose, que aí permaneceram durante sete dias. Os ácaros foram em seguida transferidos para mudas cítricas das variedades Natal e Valência e mantidos em casa de vegetação. As folhas das diferentes espécies vegetais sobre as quais os ácaros estavam anteriormente, foram destacadas e conservadas em placas de Petri, sobre algodão e papel-filtro umedecido. Ácaros criados sobre frutos sem lesões de leprose foram mantidos por três dias sobre essas folhas e, posteriormente, transferidos para novas mudas cítricas, que também foram subseqüentemente mantidas em uma casa de vegetação. Após 60 dias, quantificou-se o número de lesões de leprose nas mudas cítricas. Os resultados evidenciaram que o ácaro não perdeu a capacidade de transmissão do vírus para mudas cítricas após acesso alimentar por sete dias sobre qualquer uma das plantas intermediárias consideradas no estudo. Ácaros provenientes de frutos sem lesões de leprose adquiriram o vírus da leprose e o transmitiram a mudas cítricas quando tiveram acesso alimentar a C. benghalensis, A. conyzoides, B. pilosa, S. cordifolia e B. orellana, onde, anteriormente, ácaros criados sobre frutos com lesões de leprose permaneceram por sete dias. Estes resultados evidenciam a potencialidade de estas plantas serem depositárias e fonte de transmissão do vírus para plantas cítricas suscetíveis.

Manejo cultural do maracujazeiro-amarelo em ciclo anual visando à convivência com o vírus do endurecimento dos frutos: um estudo de caso

Este estudo de caso teve por objetivo analisar a qualidade dos frutos e a produtividade em t/ha de maracujá-amarelo, em dois ciclos anuais, plantados, respectivamente, nos dias 04-10-04 (1º plantio) e 20-08-05 (2º plantio). As mudas da seleção Afruvec foram formadas em tubetes no interior de estufa com tela antiafídeo. O pomar, nos dois ciclos produtivos, foi irrigado por gotejamento, adotando-se uma densidade de 1.600 plantas/ha. O 1º plantio foi erradicado no dia 13-07-05, em função de o pomar apresentar a totalidade das plantas com sintomas típicos do vírus do endurecimento dos frutos (PWV) nas folhas e frutos. No 1º e no 2º plantios, os sintomas tiveram início no dia 26-01-05 e no dia 04-01-06, respectivamente. Não houve necessidade de eliminação de plantas em ambos os plantios, já que o início dos sintomas de PWV ocorreu quando as plantas se encontravam em pleno florescimento. Pelos resultados, pode-se concluir que o manejo adotado regionalmente, com plantio em ciclo anual, permitiu uma ampliação do período de colheita, decorrente da antecipação de plantio no 2º ano; uma produtividade de 16,94 kg/planta e 18,39 kg/planta, no 1º e 2º anos, respectivamente; um aumento da rentabilidade na safra de 2006 em função: da maior produção, melhor cotação dos frutos para mesa e indústria, e aproveitamento dos investimentos realizados no 1º ano. As técnicas empregadas promoveram uma eficiente redução do potencial de inóculo regional, favorecendo uma sustentabilidade na produção.