PLoS medicine
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Review Meta Analysis
Elevated risk for HIV infection among men who have sex with men in low- and middle-income countries 2000-2006: a systematic review.
Recent reports of high HIV infection rates among men who have sex with men (MSM) from Asia, Africa, Latin America, and the former Soviet Union (FSU) suggest high levels of HIV transmission among MSM in low- and middle-income countries. To investigate the global epidemic of HIV among MSM and the relationship of MSM outbreaks to general populations, we conducted a comprehensive review of HIV studies among MSM in low- and middle-income countries and performed a meta-analysis of reported MSM and reproductive-age adult HIV prevalence data. ⋯ MSM have a markedly greater risk of being infected with HIV compared with general population samples from low- and middle-income countries in the Americas, Asia, and Africa. ORs for HIV infection in MSM are elevated across prevalence levels by country and decrease as general population prevalence increases, but remain 9-fold higher in medium-high prevalence settings. MSM from low- and middle-income countries are in urgent need of prevention and care, and appear to be both understudied and underserved.
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Multicenter Study
Clustered environments and randomized genes: a fundamental distinction between conventional and genetic epidemiology.
In conventional epidemiology confounding of the exposure of interest with lifestyle or socioeconomic factors, and reverse causation whereby disease status influences exposure rather than vice versa, may invalidate causal interpretations of observed associations. Conversely, genetic variants should not be related to the confounding factors that distort associations in conventional observational epidemiological studies. Furthermore, disease onset will not influence genotype. Therefore, it has been suggested that genetic variants that are known to be associated with a modifiable (nongenetic) risk factor can be used to help determine the causal effect of this modifiable risk factor on disease outcomes. This approach, mendelian randomization, is increasingly being applied within epidemiological studies. However, there is debate about the underlying premise that associations between genotypes and disease outcomes are not confounded by other risk factors. We examined the extent to which genetic variants, on the one hand, and nongenetic environmental exposures or phenotypic characteristics on the other, tend to be associated with each other, to assess the degree of confounding that would exist in conventional epidemiological studies compared with mendelian randomization studies. ⋯ These data illustrate why observational studies have produced misleading claims regarding potentially causal factors for disease. The findings demonstrate the potential power of a methodology that utilizes genetic variants as indicators of exposure level when studying environmentally modifiable risk factors.
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The catalytically active 66-kDa subunit of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) consists of DNA polymerase, connection, and ribonuclease H (RNase H) domains. Almost all known RT inhibitor resistance mutations identified to date map to the polymerase domain of the enzyme. However, the connection and RNase H domains are not routinely analysed in clinical samples and none of the genotyping assays available for patient management sequence the entire RT coding region. The British Columbia Centre for Excellence in HIV/AIDS (the Centre) genotypes clinical isolates up to codon 400 in RT, and our retrospective statistical analyses of the Centre's database have identified an N348I mutation in the RT connection domain in treatment-experienced individuals. The objective of this multidisciplinary study was to establish the in vivo relevance of this mutation and its role in drug resistance. ⋯ This study provides the first in vivo evidence that treatment with RT inhibitors can select a mutation (i.e., N348I) outside the polymerase domain of the HIV-1 RT that confers dual-class resistance. Its emergence, which can happen early during therapy, may significantly impact on a patient's response to antiretroviral therapies containing zidovudine and nevirapine. This study also provides compelling evidence for investigating the role of other mutations in the connection and RNase H domains in virological failure.
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Comparative Study
Assessment of recent HIV-1 infection by a line immunoassay for HIV-1/2 confirmation.
Knowledge of the number of recent HIV infections is important for epidemiologic surveillance. Over the past decade approaches have been developed to estimate this number by testing HIV-seropositive specimens with assays that discriminate the lower concentration and avidity of HIV antibodies in early infection. We have investigated whether this "recency" information can also be gained from an HIV confirmatory assay. ⋯ Recency information can be extracted from INNO-LIA-based confirmatory testing at no additional costs. This method should improve epidemiologic surveillance in countries that routinely use INNO-LIA for HIV confirmation.
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Oncolytic viruses hold much promise for clinical treatment of many cancers, but a lack of systemic delivery and insufficient tumor cell killing have limited their usefulness. We have previously demonstrated that vaccinia virus strains are capable of systemic delivery to tumors in mouse models, but infection of normal tissues remains an issue. We hypothesized that interferon-beta (IFN-beta) expression from an oncolytic vaccinia strain incapable of responding to this cytokine would have dual benefits as a cancer therapeutic: increased anticancer effects and enhanced virus inactivation in normal tissues. We report the construction and preclinical testing of this virus. ⋯ By combining IFN-dependent cancer selectivity with IFN-beta expression to optimize both anticancer effects and normal tissue antiviral effects, we were able to achieve, to our knowledge for the first time, tumor-specific replication, IFN-beta gene expression, and efficacy following systemic delivery in preclinical models.