Highly pathogenic adapted HIV-1 strains limit host immunity and dictate rapid disease progression.

OBJECTIVE: The study of HIV-1 rapid progressors has been limited to specific case reports. Nevertheless, identification and characterization of the viral and host factors involved in rapid progression are crucial when attempting to uncover the correlates of rapid disease outcome. DESIGN: We carried out comparative functional analyses in rapid progressors (n = 46) and standard progressors (n = 46) early after HIV-1 seroconversion (≤1 year). The viral traits tested were viral replicative capacity, co-receptor usage, and genomic variation. Host CD8 T-cell responses, humoral activity, and HLA immunogenetic markers were also determined. RESULTS: Our data demonstrate an unusual convergence of highly pathogenic HIV-1 strains in rapid progressors. Compared with standard progressors, rapid progressor viral strains show higher in-vitro replicative capacity (81.5 vs. 67.9%; P = 0.025) and greater X4/DM co-receptor usage (26.3 vs. 2.8%; P = 0.006) in early infection. Limited or absent functional HIV-1 CD8 T-cell responses and neutralizing activity were measured in rapid progressors. Moreover, the increase in common HLA allele-restricted CD8 T-cell escape mutations in rapid progressors acts as a signature of uncontrolled HIV-1 replication and early impairment of adaptive cellular responses. CONCLUSION: Our data support a dominant role for viral factors in rapid progressors. Robust HIV-1 replication and intrinsic viral properties limit host adaptive immune responses, thus driving rapid disease progression.

Rapid and accurate G M1-gangliosidosis diagnosis using a parentage testing microsatellite

The G M1-gangliosidosis is an autosomal recessive lysosomal storage disease caused by structural defects of the beta-galactosidase gene (GLB1) which lead to a severe phenotypical impairment in homozygous individuals, whereas heterozygous carriers remain clinically normal. Currently employed DNA parentage tests include the analysis of microsatellites, which also have a diagnostic predictive value. The aim of this study was to provide a reliable tool for genotyping the canine GLB1 which can be effectively integrated in parentage testing investigations. For this purpose the association between the GLB1 gene and the AHT K253 microsatellite was analyzed in 30 Alaskan huskies (11 GLB1+/+, 17 GLB1+/- and 2 GLB1-/- dogs). The 143 bp AHT K253 microsatellite allele was identified only in GLB1+/- and GLB1-/- animals and was in strong linkage disequilibrium with the causative mutation for G M1-gangliosidosis, a 19 bp duplication within exon 15 of the GLB1 gene. The results of the present study revealed a 100% concordance between the previous established genotypes and those obtained after the analysis of the AHT K253 microsatellite. Thus, the genotype of the AHT K253 microsatellite, which is routinely determined during dog parentage testing, has a high predictive value for the G M1-gangliosidosis carrier status.

Privacy-preserving genomic testing in the clinic: a model using HIV treatment

PURPOSE The implementation of genomic-based medicine is hindered by unresolved questions regarding data privacy and delivery of interpreted results to health-care practitioners. We used DNA-based prediction of HIV-related outcomes as a model to explore critical issues in clinical genomics. METHODS We genotyped 4,149 markers in HIV-positive individuals. Variants allowed for prediction of 17 traits relevant to HIV medical care, inference of patient ancestry, and imputation of human leukocyte antigen (HLA) types. Genetic data were processed under a privacy-preserving framework using homomorphic encryption, and clinical reports describing potentially actionable results were delivered to health-care providers. RESULTS A total of 230 patients were included in the study. We demonstrated the feasibility of encrypting a large number of genetic markers, inferring patient ancestry, computing monogenic and polygenic trait risks, and reporting results under privacy-preserving conditions. The average execution time of a multimarker test on encrypted data was 865 ms on a standard computer. The proportion of tests returning potentially actionable genetic results ranged from 0 to 54%. CONCLUSIONS The model of implementation presented herein informs on strategies to deliver genomic test results for clinical care. Data encryption to ensure privacy helps to build patient trust, a key requirement on the road to genomic-based medicine.Genet Med advance online publication 14 January 2016Genetics in Medicine (2016); doi:10.1038/gim.2015.167.

Club drug use and unprotected anal intercourse among HIV-seronegative men who have sex with men seeking HIV/STD testing at a local STD clinic in Houston

Objective. To explore (1) the association between "club drug" use and unprotected anal intercourse (UAI) and (2) the association between binge drug use and UAI among HIV seronegative men who have sex with men (MSM) seeking HIV/STD testing at a local clinic in Houston. ^ Study design. A sub-sample of 297 HIV seronegative MSM from a cross-sectional study of drug and sexual behavior in Houston was conducted in 2006. Patients who were seeking HIV/STD testing at a local MSM-identified STD clinic were recruited for an anonymous computer-assisted interview. Analysis of identified secondary data consisted of self-reported information about demographic characteristics, use of drugs, and sexual behaviors. ^ Results. With new and casual sex partners, there was a strong and statistically significant association between use of "club drugs" and UAI. No association between binge drug use and UAI was evident. Men aware of HIV seropositivity or unaware of the HIV serostatus of their primary partner were less likely to report UAI. ^ Conclusion. These data suggest that in the Houston area, HIV-negative MSM club drug users, particularly multiple drug users, are at higher risk of UAI than comparable MSMs who do not use club drugs. Episode-level data regarding binge use of these and other drugs, and UAI should be collected in future studies to explore their relationship. The 'new partner' category should be added to sex partner types to measure sex and drug use behaviors in future studies.^ Keywords. HIV-negative MSM; club drugs; unprotected anal intercourse; binge drug use. ^

Impacts of an HIV counseling and testing initiative -- results from an experimental intervention in a large firm in South Africa

We have run experimental interventions to promote HIV tests in a large firm in South Africa. We combined HIV tests with existing medical check programs to increase the uptake. In the foregoing survey we undertook previously, it was suggested that fears and stigma of HIV/AIDS were the primary reasons given by the employees for not taking the test. To counter these, we implemented randomized interventions. We find substantial heterogeneity in responses by ethnicity. Africans and Colored rejected the tests most often. Supportive information increased the uptake by 6 to 16% points. A tradeoff in targeting resulting in stigmatizing the targeted and a reduction of exclusion error is discussed.

Evidence for rapid disappearance of initially expanded HIV-specific CD8+ T cell clones during primary HIV infection

Down-regulation of the initial burst of viremia during primary HIV infection is thought to be mediated predominantly by HIV-specific cytotoxic T lymphocytes, and the appearance of this response is associated with major perturbations of the T cell receptor repertoire. Changes in the T cell receptor repertoire of virus-specific cytotoxic T lymphocytes were analyzed in patients with primary infection to understand the failure of the cellular immune response to control viral spread and replication. This analysis demonstrated that a significant number of HIV-specific T cell clones involved in the primary immune response rapidly disappeared. The disappearance was not the result of mutations in the virus epitopes recognized by these clones. Evidence is provided that phenomena such as high-dose tolerance or clonal exhaustion might be involved in the disappearance of these monoclonally expanded HIV-specific cytotoxic T cell clones. These findings should provide insights into how HIV, and possibly other viruses, elude the host immune response during primary infection.

Recombination leads to the rapid emergence of HIV-1 dually resistant mutants under selective drug pressure.

The potential contribution of recombination to the development of HIV-1 resistance to multiple drugs was investigated. Two distinct viruses, one highly resistant to a protease inhibitor (SC-52151) and the other highly resistant to zidovudine, were used to coinfect T lymphoblastoid cells in culture. The viral genotypes could be distinguished by four mutations conferring drug resistance to each drug and by other sequence differences specific for each parental virus. Progeny virions recovered from mixed infection were passaged in the presence and absence of both zidovudine and SC-52151. Dually resistant mutants emerged rapidly under selective conditions, and these viruses were genetic recombinants. These results emphasize that genetic recombination could contribute to high-level multiple-drug resistance and that this process must be considered in chemotherapeutic strategies for HIV infection.

Rapid testing of oilseeds for oil quantity and iodine number of oil /

Caption title.

Rapid testing for group B streptococcus during labour: a test accuracy study with evaluation of acceptability and cost-effectiveness

OBJECTIVE: To determine the accuracy, acceptability and cost-effectiveness of polymerase chain reaction (PCR) and optical immunoassay (OIA) rapid tests for maternal group B streptococcal (GBS) colonisation at labour. DESIGN: A test accuracy study was used to determine the accuracy of rapid tests for GBS colonisation of women in labour. Acceptability of testing to participants was evaluated through a questionnaire administered after delivery, and acceptability to staff through focus groups. A decision-analytic model was constructed to assess the cost-effectiveness of various screening strategies. SETTING: Two large obstetric units in the UK. PARTICIPANTS: Women booked for delivery at the participating units other than those electing for a Caesarean delivery. INTERVENTIONS: Vaginal and rectal swabs were obtained at the onset of labour and the results of vaginal and rectal PCR and OIA (index) tests were compared with the reference standard of enriched culture of combined vaginal and rectal swabs. MAIN OUTCOME MEASURES: The accuracy of the index tests, the relative accuracies of tests on vaginal and rectal swabs and whether test accuracy varied according to the presence or absence of maternal risk factors. RESULTS: PCR was significantly more accurate than OIA for the detection of maternal GBS colonisation. Combined vaginal or rectal swab index tests were more sensitive than either test considered individually [combined swab sensitivity for PCR 84% (95% CI 79-88%); vaginal swab 58% (52-64%); rectal swab 71% (66-76%)]. The highest sensitivity for PCR came at the cost of lower specificity [combined specificity 87% (95% CI 85-89%); vaginal swab 92% (90-94%); rectal swab 92% (90-93%)]. The sensitivity and specificity of rapid tests varied according to the presence or absence of maternal risk factors, but not consistently. PCR results were determinants of neonatal GBS colonisation, but maternal risk factors were not. Overall levels of acceptability for rapid testing amongst participants were high. Vaginal swabs were more acceptable than rectal swabs. South Asian women were least likely to have participated in the study and were less happy with the sampling procedure and with the prospect of rapid testing as part of routine care. Midwives were generally positive towards rapid testing but had concerns that it might lead to overtreatment and unnecessary interference in births. Modelling analysis revealed that the most cost-effective strategy was to provide routine intravenous antibiotic prophylaxis (IAP) to all women without screening. Removing this strategy, which is unlikely to be acceptable to most women and midwives, resulted in screening, based on a culture test at 35-37 weeks' gestation, with the provision of antibiotics to all women who screened positive being most cost-effective, assuming that all women in premature labour would receive IAP. The results were sensitive to very small increases in costs and changes in other assumptions. Screening using a rapid test was not cost-effective based on its current sensitivity, specificity and cost. CONCLUSIONS: Neither rapid test was sufficiently accurate to recommend it for routine use in clinical practice. IAP directed by screening with enriched culture at 35-37 weeks' gestation is likely to be the most acceptable cost-effective strategy, although it is premature to suggest the implementation of this strategy at present.

Evaluating New Matrix Pooled Testing Methods for Detecting HIV Treatment Failure with and without Covariate Information

Thesis (Master's)--University of Washington, 2016-08

Adaptation and validation into Portuguese language of the HIV Antibody Testing Attitude Scale

Objective. To culturally adapt and validate a version in European Portuguese language of the HIV Antibody Testing Attitude Scale. Methods. Study conducting a methodological investigation for the adaptation and validation of an attitude measurement instrument. The instrument translation and back-translation were performed. Then, a pre-test was conducted. The study used a sample of 317 subjects from the academic community - students, professors and other professionals - who were contacted in the campus. Ethical principles were observed. Results. Three analyses were conducted using the method of principal component analysis (PCA) with five, four and three factors. A three-factor solution was achieved, which presents 50.82% variance. In the analysis of inter-item correlation, values between -0.018 and 0.749 were observed. Internal consistency shows Cronbach’s alpha coefficients of 0.860 overall and between 0.865 and 0.659 in the three factors. Conclusion. The instrument version shows psychometric properties that allow its use in Portuguese-speaking countries.