Serial evolutionary networks of within-patient HIV-1 sequences reveal patterns of evolution of X4 strains

Background The HIV virus is known for its ability to exploit numerous genetic and evolutionary mechanisms to ensure its proliferation, among them, high replication, mutation and recombination rates. Sliding MinPD, a recently introduced computational method [1], was used to investigate the patterns of evolution of serially-sampled HIV-1 sequence data from eight patients with a special focus on the emergence of X4 strains. Unlike other phylogenetic methods, Sliding MinPD combines distance-based inference with a nonparametric bootstrap procedure and automated recombination detection to reconstruct the evolutionary history of longitudinal sequence data. We present serial evolutionary networks as a longitudinal representation of the mutational pathways of a viral population in a within-host environment. The longitudinal representation of the evolutionary networks was complemented with charts of clinical markers to facilitate correlation analysis between pertinent clinical information and the evolutionary relationships. Results Analysis based on the predicted networks suggests the following:: significantly stronger recombination signals (p = 0.003) for the inferred ancestors of the X4 strains, recombination events between different lineages and recombination events between putative reservoir virus and those from a later population, an early star-like topology observed for four of the patients who died of AIDS. A significantly higher number of recombinants were predicted at sampling points that corresponded to peaks in the viral load levels (p = 0.0042). Conclusion Our results indicate that serial evolutionary networks of HIV sequences enable systematic statistical analysis of the implicit relations embedded in the topology of the structure and can greatly facilitate identification of patterns of evolution that can lead to specific hypotheses and new insights. The conclusions of applying our method to empirical HIV data support the conventional wisdom of the new generation HIV treatments, that in order to keep the virus in check, viral loads need to be suppressed to almost undetectable levels.

An evaluation of depression, self-efficacy, satisfaction with life and perceived access to medical care across stages of HIV infection

This survey was designed to identify the incidence and scope of depression, satisfaction with life, self-efficacy and perceived access to medical care for those who are infected with the HIV virus. It also determined whether or not factors such as sexual orientation, ethnicity and socioeconomic status are intervening variables with respect to mental health issues. Subjects were recruited through a purposive sample from South Florida. A total of 871 surveys were used in the analysis. The overall response rate was nearly 90%. The incidence of depression was found to be higher than 75% across all stages of HIV infection. Furthermore, the incidence of depression increased as HIV disease progressed. Satisfaction with life and for the most part, self efficacy were found to decrease slightly as HIV disease progressed. Significant variance in depression, life satisfaction and self efficacy were found across stages of HIV infection. No significant differences between groups that were HIV infected were found for depression, life satisfaction and self efficacy. The severity of depression was found to vary significantly with self efficacy, life satisfaction and access to medical care but not with socioeconomic status. Life satisfaction was found to vary significantly with socioeconomic status, depression and self efficacy but not with access to medical care. Self-efficacy was found to vary significantly with socioeconomic status, depression and life satisfaction but not with access to medical care. Gender and ethnicity were not found to be significant precedent variables in depression for HIV infected individuals. Sexual orientation was found to be a significant precedent variable for depression, life satisfaction and self efficacy.

Profilaxia da transmissão vertical do HIV

Vídeo trata da transmissão vertical do HIV que ocorre por meio da passagem do vírus da mãe para o bebê durante a gestação, o trabalho de parto, o parto propriamente dito ou a amamentação. Apresenta as formas de manejo da infecção na mãe e no bebê exposto ao HIV, a rotina laboratorial, vacinas, medicamentos e leite, com tratamento diferenciado para os bebes que nasceram de mães que não fizeram o pré-natal específico para a gravidez com a exposição ao HIV. Apresenta também um histórico da síndrome, os modos de infecção do HIV, a epidemiologia e a profilaxia, inclusive cita os manuais do Ministério da Saúde sobre o assunto.

Violência sexual como questão de saúde pública: importância da busca ao agressor

Apesar de predominar junto à população a idéia de que a violência sexual é praticada por pessoas desconhecidas, na realidade a maioria desses crimes é praticada por pessoa identificável pela vítima. Além de conseqüências físicas e psicológicas, também há risco em adquirir o vírus HIV. Para prevenção deste, em situação de risco, há orientação para uso da quimioprofilaxia anti-retroviral. Esse uso, por 28 dias, pode trazer efeitos adversos com intensidades variáveis. O conhecimento da sorologia anti-HIV do agressor torna-se fundamental para manter, ou suspender, com segurança, essa indicação. Este estudo descritivo, realizado no Conjunto Hospitalar de Sorocaba, teve como objetivo identificar os agressores e suas respectivas sorologias. Foi realizado a partir de fichas de notificação e os prontuários no período de julho de 2003 a dezembro de 2005. Encontraram-se 920 vítimas de violência sexual, com idades entre oito meses e 77 anos, havendo predomínio do sexo feminino (86,5 por cento). Dentre os agressores, 76 por cento foram referidos como identificáveis. Indicou-se profilaxia anti-retroviral para 24,9 por cento das vítimas. Para 80 (33,2 por cento) agressores localizados, a busca foi realizada através de contato telefônico. Encontrou-se 52,5 por cento em seus domicílios, 45 por cento em Presídio/Delegacia e 2,5 por cento no Pronto Socorro. Um agressor (1,3 por cento) apresentou sorologia positiva para HIV. As buscas encerraram-se, em sua maioria, em até seis dias (80 por cento), possibilitando a suspensão da quimioprofilaxia em 30,6 por cento dos casos. Concluiu-se que a busca ao denunciado permitiu conhecer sua sorologia anti-HIV e suspender, para um terço das vítimas, o uso da quimioprofilaxia anti-retroviral, diminuindo, com isso, a possibilidade de efeitos adversos

Modeling the Dynamics of Viral Evolution Considering Competition Within Individual Hosts and at Population Level: The Effects of Treatment

We consider two viral strains competing against each other within individual hosts (at cellular level) and at population level (for infecting hosts) by studying two cases. In the first case, the strains do not mutate into each other. In this case, we found that each individual in the population can be infected by only one strain and that co-existence in the population is possible only when the strain that has the greater basic intracellular reproduction number, R (0c) , has the smaller population number R (0p) . Treatment against the one strain shifts the population equilibrium toward the other strain in a complicated way (see Appendix B). In the second case, we assume that the strain that has the greater intracellular number R (0c) can mutate into the other strain. In this case, individual hosts can be simultaneously infected by both strains (co-existence within the host). Treatment shifts the prevalence of the two strains within the hosts, depending on the mortality induced by the treatment, which is, in turn, dependent upon the doses given to each individual. The relative proportions of the strains at the population level, under treatment, depend both on the relative proportions within the hosts (which is determined by the dosage of treatment) and on the number of individuals treated per unit time, that is, the rate of treatment. Implications for cases of real diseases are briefly discussed.

High frequency of the CCR5delta32 variant among individuals from an admixed Brazilian population with sickle cell anemia

Homozygous sickle cell disease (SCD) has a wide spectrum of clinical manifestations. In Brazil, the main cause of death of individuals with SCD is recurrent infection. The CCR5delta32 allele, which confers relative resistance to macrophage-tropic HIV virus infection, probably has reached its frequency and world distribution due to other pathogens that target macrophage in European populations. In the present investigation a relatively higher prevalence (5.1%) of the CCR5delta32 allele was identified, by PCR amplification using specific primers, in 79 SCD patients when compared to healthy controls (1.3%) with the same ethnic background (Afro-Brazilians). Based on a hypothesis that considers SCD as a chronic inflammatory condition, and since the CCR5 chemokine receptor is involved in directing a Th1-type immune response, we suggest that a Th1/Th2 balance can influence the morbidity of SCD. If the presence of the null CCR5delta32 allele results in a reduction of the chronic inflammation state present in SCD patients, this could lead to differential survival of SCD individuals who are carriers of the CCR5delta32 allele. This differential survival could be due to the development of less severe infections and consequently reduced or less severe vaso-occlusive crises.

Comportamientos de riesgo en la adolescencia: paralelismos entre el uso del casco y el uso del preservativo

Un gran quantitat de problemàtiques associades a la mortalitat i morbiditat dels adolescents és poden prevenir (per exemple els accidents de circulació i el VIH). Aquests problemes de salut tenen a veure amb factors ambientals i comportamentals, i no amb factors biològics. La conducció arriscada i la pràctica de relacions sexuals sense protecció contribueixen a incrementar les taxes de malaltia en aquest col·lectiu. L'ús del preservatiu i l'ús del casc són dues conductes que salven vides. Existeix molta evidència sobre la seva efectivitat d'aquestes mesures preventives per minimitzar i/o evitar les conseqüències negatives en situacions de risc. Els resultats d'aquesta investigació posen de manifest que no tots adolescents utilitzen el casc quan circulen en ciclomotor, i el preservatiu quan mantenen relacions sexuals amb penetració. L'ús del casc i l'ús del preservatiu són conductes independents.

The impact of AIDS on income and human capital

This paper studies the impact of HIV/AIDS on per capita income and education. It explores two channels from HIV/AIDS to income that have not been sufficiently stressed by the literature: the reduction of the incentives to study due to shorter expected longevity and the reduction of productivity of experienced workers. In the model individuals live for three periods, may get infected in the second period and with some probability die of Aids before reaching the third period of their life. Parents care for the welfare of the future generations so that they will maximize lifetime utility of their dynasty. The simulations predict that the most affected countries in Sub-Saharan Africa will be in the future, on average, thirty percent poorer than they would be without AIDS. Schooling will decline in some cases by forty percent. These figures are dramatically reduced with widespread medical treatment, as it increases the survival probability and productivity of infected individuals.

The long run economic impact of AIDS

This paper studies the long-run impact of HIV/AIDS on per capita income and education. We introduce a channel from HIV/AIDS to long-run income that has been overlooked by the literature, the reduction of the incentives to study due to shorter expected longevity. We work with a continuous time overlapping generations mo deI in which life cycle features of savings and education decision play key roles. The simulations predict that the most affected countries in Sub-Saharan Africa will be in the future, on average, a quarter poorer than they would be without AIDS, due only to the direct (human capital reduction) and indirect (decline in savings and investment) effects of life-expectancy reductions. Schooling will decline on average by half. These findings are well above previous results in the literature and indicate that, as pessimistic as they may be, at least in economic terms the worst could be yet to come.

Risky business: the market for unprotected commercial sex

Each day close to 20,000 people become infected with the HIV virus worldwide; a large portion of whom are infected through unprotected sex with sex workers. While condoms are an effective defense against the transmission of HIV and other sexually transmitted infections, large numbers of sex workers are not using them with their clients. We argue that some sex workers are willing to take the risk because clients are willing to pay more to avoid using condoms. Using a panel data set from Mexico, we estimate that sex workers received a 23 percent premium for unprotected sex from clients who requested not to use a condom. However, this premium jumped to 46 percent if the sex worker was considered very attractive. These results suggest that the current policies aimed at educating sex workers about risk, empowering them and improving their access to condoms need to be complemented with interventions aimed at teaching clients about the “joy of safe sex” thereby increasing the demand for using condoms.

Obtenção de sistemas multiparticulados de isoniazida revestidos com polímero de liberação entérica

Known for thousands of years, tuberculosis (TB) is the leading cause of mortality by a single infectious disease due to lack of patient adherence to available treatment regimens, the rising of multidrug resistant strains of TB (MDR-TB) and co-infection with HIV virus. Isoniazid and rifampicin are the most powerful bactericidal agents against M. tuberculosis. Because of that, this couple of drugs becomes unanimity in anti-TB treatment around the world. However, the rifampicin in acidic conditions in the stomach can be degraded rapidly, especially in the presence of isoniazid, which reduces the amount of available drug for absorption, as well as its bioavailability, contributing to the growing resistance to tuberculostatic drugs. Rifampicin is well absorbed in the stomach because of its high solubility between pH 1 and 2 and the gastric absorption of isoniazid is considered poor, therefore it is mostly intestinal. This work has as objective the development of gastro-resistant multiple-systems (granules and pellets) of isoniazid aiming to prevent the contact with rifampicin, with consequent degradation in acid stomach and modulate the release of isoniazid in the intestine. Granules of isoniazid were obtained by wet method using both alcoholic and aqueous solutions of PVP K-30 as aggregating and binder agent, at proportions of 5, 8 and 10%. The influence of the excipients (starch, cellulose or filler default) on the physical and technological properties of the granules was investigated. The pellets were produced by extrusionesferonization technique using isoniazid and microcrystalline cellulose MC 101 (at the proportion of 85:15) and aqueous solution of 1% Methocel as platelet. The pellets presented advantages over granular, such as: higher apparent density, smaller difference between apparent and compaction densities, smoother surface and, especially, smaller friability, and then were coated with an organic solution of Acrycoat L 100 ® in a fluidized bed. Different percentages of coating (15, 25 and 50%) were applied to the pellets which had their behavior evaluated in vitro by dissolution in acidic and basic medium. Rifampicin dissolution in the presence of uncoated and coated isoniazid pellets was evaluated too. The results indicate that the gastro resistance was only achieved with the greatest amount of coating and isoniazid is released successfully in basic step. The amount of rifampicin in the dissolution medium when the isoniazid pellets were not coated was lower than in the presence of enteric release pellets. Therefore, the polymer Acrycoat L 100 ® was efficient for coating with gastro-resistant function and can solve the problem of low bioavailability of rifampicin and help to reduce its dosage

Manifestações otorrinolaringológicas em crianças com AIDS

Introduction: The study of otolaryngologic manifestations in children HIV + can lead to early diagnosis of AIDS, allowing specific treatment, responsible by reduced morbidity and mortality. Objectives: Detect the otolaryngologic manifestations in children with AIDS and alert to the importance of the early diagnosis. Study design: Clinical prospective. Material and method: We evaluated 22 children with AIDS assisted at Faculdade de Medicina de Botucatu (São Paulo, Brasil). The medical records were reviewed and the children were submitted to otolaryngologic and hearing acuity exams. Results: We evaluated 12 boys and 10 girls, whose ages ranged from 8 months to 12 years. In B and C clinical classification were included 18 children who were using anti-retroviral medicaments. Physical examination mainly indicated cervical lymphadenopathy (18 cases), paleness of the nasal mucous membrane with abundant mucous secretion over the nasal epithelium (15 cases) and retraction of tympanic membranes (seven cases). The main otolaryngologic diagnoses were: rhinosinusitis (16 cases), oral candidiasis (13 cases), inadequate eustachian tube function (seven cases) and recurrent tonsillar infections (six cases). Conductive hearing loss were detected in 4 children. No child presented sensorineural hearing loss. Conclusions: The main otolaryngologic manifestations presented by the children with HIV virus were rhinosinusitis, oral candidiasis, inadequate eustachian tube function and recurrent tonsillar infections. The allergic aspect of the nasal mucous membrane and the cervical lymphadenopathy were frequent signs and could alert the otolaryngologyst to AIDS during the exam.

Synthesis and cytotoxicity of a ruthenium nitrosyl nitric oxide donor with isonicotinic acid and a cell penetrating peptide

The syntheses and properties of trans-[Ru(NH3) 4(L)(NO)](BF4)3 (L = isonicotinic acid (inaH) (I) or ina-Tat48-60 (II)) are described. Tat48-60, a cell penetrating peptide fragment of the Tat regulatory protein of the HIV virus, was linked to the ruthenium nitrosyl through inaH. I and II release NO after reduction forming trans-[Ru(NH3)4(L)(H2O)]3 +. The IC50 values against B16-F10 melanoma cells of I and II (21 μmol L- 1 and 23 μmol L- 1, respectively) are close to that of the commercially available cisplatin (33 μmol L- 1) and smaller than similar complexes. The cytotoxicity is assigned to the NO released from I and II. © 2012 Elsevier B.V.

Desenvolvimento e caracterização de dispersão sólida com propriedade mucoadesiva para liberação de zidovudina

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