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エイズと臨床研究のジャーナル

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音量 7, 問題 1 (2016)

研究論文

Comparison of Cerebrovascular Risk between Elderly Human Immunodeficiency Virus-seropositive Patients Treated with Highly Active Antiretroviral Therapy and Human Immunodeficiency Virus-seronegative Patients

Guilherme Rocha Pardi, Maria Luisa Pereira Gomes, Fernando Henrique Guimarães de Carvalho, Luis Gonzaga Silveira Filho, Luis Ronan M. Ferreira de Souza and Dalmo Correia

Introduction: The current era of AIDS is characterized by an aging of population and increase in the incidence of non-acquired immune deficiency syndrome-related diseases. The aim of the present study was to compare the cerebrovascular risk in elderly HIV(+) patients under HAART therapy with seronegative elderly.

Materials and method: This transversal study was performed between January 2011 and December 2013, and evaluated 2 groups of individuals older than 60 years. The first group included elderly HIV(+) patients who had been receiving HAART for over 1 year, and the second group included elderly HIV(−) patients. To detect cerebrovascular risk in groups, anthropometric assessments (body mass index and waist circumference), clinical evaluations (Framingham score), and laboratory assessments (carotid Doppler ultrasonography and brain magnetic resonance imaging [MRI]) were performed.

Results: The HIV(+) group included 26 patients and the HIV(−) group included 40 patients. The cerebrovascular risks based on body mass index (P=0.001), the Framingham score (P=0.02), and the presence of lesions on MRI (P=0.03) were lower in the HIV(+) group than in the HIV(−) group. Moderate to severe cerebrovascular risk according to the Framingham score was 3 times more likely among infected patients than among non-infected patients (P=0.03). Additionally, patients who had received more than 10 years of HAART had a 90% lower chance of cerebrovascular disease if they presented with a Framingham score indicating moderate to high risk than if they presented with a Framingham score indicating mild risk (P=0.03).

Conclusion: Our results suggest that the presence of HIV infection in elderly patients might increase the risk of cerebrovascular events. The risk might be low in patients who receive HAART for more than 10 years, indicating that HAART might have the potential to reduce the risk of cerebrovascular events.

研究論文

A Rapid, Self-confirming Assay for HIV: Simultaneous Detection of Anti- HIV Antibodies and Viral RNA

Zongyuan Chen, Hui Zhu, Daniel Malamud, Cheryl Barber, Yhombi Yvon Serge Ongagna, RubinaYasmin, Sayli Modak, Malvin N. Janal, William R. Abrams and Richard A. Montagna

Objective: We developed a microfluidic system to simultaneously detect host anti-HIV antibodies and viral RNA in the same specimen in order to satisfy two important diagnostic criteria, especially within resource-limited settings. First, the system can detect acute HIV infection and allow immediate confirmation of a seropositive screening result by detection of HIV RNA. It also addresses the well-known "seroconversion window" during early HIV infection when antibodies are not yet detectable and viral loads are at their highest.

Methods: We first developed and optimized two separate manual assays for the detection of host anti-HIV antibodies and viral RNA and then converted them to the microfluidic system. We optimized a commercially available serologic assay to run within the microfluidic device while we incorporated the isothermal LAMP assay to detect the presence of viral RNA. The microfluidic device and instrumentation were developed to simultaneously perform both assays without any user intervention.

Results: The finalized system consists of a disposable injection molded and film-laminated microfluidic CARD disposable device and a portable, software controlled instrument, which together can automatically perform all steps of both assays without any user intervention after the initial loading of samples and reagents. The microfluidic CARD cartridge has multiple microchannels, valves, pumps and reservoirs, which perform the immunoassay, isolates viral RNA for detection by magnetic bead based purification, and Reverse Transcriptase loop-mediated isothermal amplification (RT-LAMP). The microfluidic system was able to detect host anti-HIV antibodies and viral RNA in either a blood or saliva sample.

Conclusion: The ability to detect antibodies and simultaneously confirm a seropositive HIV-RNA result provides healthcare workers with a complete and accurate appraisal of a patient's infection status in the earliest stages of the disease and represents an important tool for the "Test and Treat" and "Treatment as Prevention" approaches for controlling the HIV epidemic.

研究論文

Prevalence and Risk Factors for Self-reported Sexually Transmitted Infections among Adults in the Diepsloot Informal Settlement, Johannesburg, South Africa

Tariro J Basera, Simbarashe Takuva, Keith Muloongo, Ndumiso Tshuma and Peter S Nyasulu

Background: Sexually transmitted infections (STIs) are a significant cause of morbidity among sexually active adults with multiple consequences including enhancing HIV transmission.

Objective: To determine the prevalence of self-reported sexually transmitted infections and associated risk factors among adults in Diepsloot informal settlement, Johannesburg, South Africa.

Design: This is a cross sectional study involving secondary analysis of data collected in a survey among adults living in Diepsloot in 2013. Data from 3953 respondents was analysed. Univariable and multivariable logistic regression modelling was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of the association between selfreported STI status and socio-demographic and clinical characteristics.

Results: Of the 3953 participants, 2481 (62.8%) were female. Self-reported prevalence of STIs was 20.4% (n=808). Among the study participants, 815 (25.9%) people were HIV positive and of these 19.9% reported an STI. Being single [Odds Ratio (OR) 1.82, (95% CI 1.08, 3.05)], prior exposure to gender based violence or sexual assault (OR 2.25, 95% CI 1.39, 3.63), alcohol use (OR 1.50, 95% CI 1.04, 2.16), and having not utilised healthcare services in the past 2 years (OR 2.30, 95% CI 1.44, 3.68) were associated with increased odds of self-reporting an STI. HIV negative status was associated with reduced odds of self-reporting an STI (OR = 0.26, 95% CI 0.14, 0.50)

Conclusion: The estimated prevalence of self-reported STIs among adults aged 20 to 82 years in Diepsloot, indicates a substantial burden of STIs in this population. The close connection between HIV status, history of gender based violence/sexual assault and utilisation of healthcare services underscore the need to scale up behavioural interventions coupled with targeted screening of at risk populations to simultaneously reduce the occurrence of genderbased violence and prevent the transmission of STIs including HIV.

研究論文

Antiretroviral Treatment-Associated Hepatotoxicity and Anemia in Patients Receiving Stavudine or Zidovudine Containing Regimens in Sub- Saharan African Settings

Dieter Wenderlein, Paola Scarcella, Ines Zimba, Richard Luhanga, Sandro Mancinelli, Maria Cristina Marazzi, Ersilia Buonomo, Stefano Orlando, Leonardo Palombi and Giuseppe Liotta

Objective: Purpose of this study was to assess the prevalence and risk factors associated with development of hepatotoxicity and anemia following initiation of antiretroviral treatment (ART) containing stavudine (d4T) or zidovudine (AZT) in the first year of treatment in the African setting.

Method: We evaluated aspartate aminotransferase and haemoglobin levels at baseline and at 1, 2, 3, 6, 9 and 12 months following ART initiation among 10,537 HIV-1 infected, ART-naïve, non-pregnant adults in Mozambique and Malawi. The Cox proportional hazards model was used to assess risk factors for hepatotoxicity and anaemia in the first year following ART initiation.

Results: The prevalence of ART-associated hepatotoxicity grades 1-2 declined in the first 3 months of ART from 13.5% to 10.8%, and grades 3-4 from 2.0% to 0.2% from month 1 to month 6. The prevalence of hepatotoxicity grades 1-2 peaked at month 6 due to the use of d4T (overall 14.2%; d4T-arm: 16.2%, AZT-arm: 5.8%). Anemia grades 1-2 and 3-4 declined from month 1 (13.3%, 3.2% respectively) to month 12 (3.0%, 0.5%, respectively).

Risk factors for hepatotoxicity grades 1-2 included d4T use, an elevated VL pre-ART and female sex, and for anemia grade 1-2 and 3-4 AZT use, female sex and malaria. A high pre-ART VL was associated with the onset of severe anaemia. Not being malnourished was protective against mild hepatotoxicity and anemia. The ART-related mortality observed in the cohort was low (0.017%).

Conclusion: In African settings the risk of untreated HIV outweighs the risk of anemia and hepatotoxicity mediated by ART. The prevalence of ART mediated hepatotoxicity declines in the first 3 to 6 months of treatment, and that of anemia declines in the first 12 months of ART. Patients with a poor health status at the start of ART are at highest risk of developing ART-associated hepatotoxicity and anemia.

総説

HIV-1 Capsid as a Target for Antiviral Therapy

Zhiqing Zhang, Feng Zhang, Chao Yang, Jialong Qi, Shuangquan Gao, Shaowei Li, Ying Gu and Ningshao Xia

Highly active anti-retroviral therapy (HAART) is the mainstay anti-HIV-1 therapy as it prolongs survival and switches HIV-1 infection from a fatal disease to a chronic yet manageable one. Unfortunately, drug toxicity and the emergence of drug-resistant mutant strains in patients undergoing long-term therapy have meant that there is still a continual need for novel drugs that target alternative molecules in the HIV-1 life cycle. The HIV-1 Gag precursor protein is a multidomain polyprotein that is proteolytically cleaved into the main, mature capsid protein; CA. CA has multifaceted roles during HIV-1 morphogenesis and is thus regarded as a promising target for future antiviral intervention. In this review, we describe the advances made in our understanding of the HIV-1 capsid structure and the key interactions involved during core assembly, and discuss how this and future knowledge will provide important structural insight for antiviral design.

総説

The Challenge of Malignancies in HIV-1, Beyond Immune Activation and Back to Decreased Immune Surveillance

Daniel O Griffin

The HIV-1 epidemic continues around the world, but also in the United States where we continue to see approximately 50,000 new diagnosis of HIV-1 infection each year. It is estimated that there are currently more than 1.2 million individuals in the United States living with HIV-1 infection, with 12.8% unaware of their infection. Effective therapy for HIV-1 is allowing infected individuals to have greater life expectancies. We now have an older aging population infected with HIV-1, reaching ages where diseases such as malignancy are increased in incidence. Even compared to age matched peers there is clearly an excess of malignancies affecting the HIV-1-infected population. Malignancies are now the most common cause of death for patients in the United States living with HIV-1 infection. B-cell malignancies are the most common malignancy accounting for death in HIV-1 infected patients in the United States. It is not clear that all that we have come to understand regarding B-cell lymphomas applies to the lymphomas developing in the HIV-1-infected population. It is particularly important to understand the factors leading to and molecular disturbances involved in these lymphomas developing in the HIV-1-infected population as they appear to be increasing in frequency and characterized by aggressive courses with short median survival times. Although much attention has focused on the chronic immune activation hypothesis of cancer in HIV-1 infection, this article explores the possible contribution of decreased immune surveillance and exposure to highly active antiretroviral medications to the development of B-cell lymphomas in HIV-1-infected patients.

研究論文

The Influence of HIV, HCV and Inhibitors on the Quality of Life and Behavior of the Disease in Patients with Haemophilia: An Observational Study

Ana Torres-Ortuño, Rubén Cuesta-Barriuso and Joaquín Nieto-Munuera

Background: Inhibitors are the main complication in the treatment of haemophilia. A high percentage of adult patients were infected in past decades by HIV and HCV through factor concentrates. This study compared the quality of life of patients with hemophilia (QoL) and illness behavior in adult patients with haemophilia according to the development of inhibitors and HIV or HCV co-infection.

Method: This is an observational clinical study. 69 adult patients with haemophilia participated. We used A36 Hemophilia-QoL and IBQ questionnaires to measure the QoL and illness behavior, respectively. The dependent variables were type and severity of haemophilia, type of treatment, development of inhibitors, HIV and HCV infection, or both.

Results: We observed significant differences in the perception of QoL and illness behavior in patients according to the development of inhibitor and coinfection with HIV-HCV. We obtained four groups: the first and second group, which comprise 67% of the sample, exhibit behavior patterns indicating good adaptation to the disease and good QoL. The other two groups, which comprise 33% of the sample show behavior that is not well adapted to the disease, and poor quality of life.

Conclusion: The development of inhibitors itself does not influence the quality of life and illness behavior in patients with haemophilia. Patients infected with HIV or HCV do not have a worse illness behavior compared to those uninfected. The development of inhibitors and HIV-HCV co-infection has a negative impact on quality of life and illness behavior in patients with haemophilia.

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