Switching to second-line antiretroviral therapy in resource-limited settings: comparison of programmes with and without viral load monitoring.

In high-income countries, viral load is routinely measured to detect failure of antiretroviral therapy (ART) and guide switching to second-line ART. Viral load monitoring is not generally available in resource-limited settings. We examined switching from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line regimens to protease inhibitor-based regimens in Africa, South America and Asia

Prioritising prevention strategies for patients in antiretroviral treatment programmes in resource-limited settings

Expanded access to antiretroviral therapy (ART) offers opportunities to strengthen HIV prevention in resource-limited settings. We invited 27 ART programmes from urban settings in Africa, Asia and South America to participate in a survey, with the aim to examine what preventive services had been integrated in ART programmes. Twenty-two programmes participated; eight (36%) from South Africa, two from Brazil, two from Zambia and one each from Argentina, India, Thailand, Botswana, Ivory Coast, Malawi, Morocco, Uganda and Zimbabwe and one occupational programme of a brewery company included five countries (Nigeria, Republic of Congo, Democratic Republic of Congo, Rwanda and Burundi). Twenty-one sites (96%) provided health education and social support, and 18 (82%) provided HIV testing and counselling. All sites encouraged disclosure of HIV infection to spouses and partners, but only 11 (50%) had a protocol for partner notification. Twenty-one sites (96%) supplied male condoms, seven (32%) female condoms and 20 (91%) provided prophylactic ART for the prevention of mother-to child transmission. Seven sites (33%) regularly screened for sexually transmitted infections (STI). Twelve sites (55%) were involved in activities aimed at women or adolescents, and 10 sites (46%) in activities aimed at serodiscordant couples. Stigma and discrimination, gender roles and funding constraints were perceived as the main obstacles to effective prevention in ART programmes. We conclude that preventive services in ART programmes in lower income countries focus on health education and the provision of social support and male condoms. Strategies that might be equally or more important in this setting, including partner notification, prompt diagnosis and treatment of STI and reduction of stigma in the community, have not been implemented widely

State Capacity and the Environmental Investment Gap in Authoritarian States

We construct an n-period, constrained optimization model where the authoritarian ruler maximizes expected rents subject to budget constraint of available surplus. We show that the larger state capacity is in the previous period, the worse environmental quality will be in the next period: while infrastructural investment and environmental protection increase with state capacity, the former increases at a faster rate which enlarges the gap between the two?the environmental investment gap. Given infrastructural public goods typically damage the environment, the larger this gap is the worse the environmental quality would be. This follows from rulers? optimizing logic of equating marginal returns once we assume the declining marginal productivity of factors of production of surplus. We model three types of air and water pollutants in autocracies as a function of state capacity and other relevant variables. State capacity is associated with higher levels of all three types of pollutants

Primary Antiretroviral Drug Resistance among HIV Type 1-Infected Individuals in Brazil

Infection with drug-resistant human immunodeficiency virus type 1 (HIV-1) has been documented in all countries that have surveyed for it and may result in an unfavorable response to therapy. The prevalence and characteristics of individuals with transmitted resistance to antiretroviral drugs have been scarcely described in Brazil. We performed antiretroviral resistance testing prior to initiation of therapy in 400 subjects enrolled from 20 centers in 13 Brazilian cities between March and September 2007. Genotyping was conducted using PCR-amplified HIV pol products by automated sequencing, and genotype interpretation was done according to the IAS-USA consensus. Of 400 eligible participants, 387 (95.8%) were successfully tested. Seven percent of antiretroviral-naive patients carried viruses with one or more major mutation associated with drug resistance. The prevalence of these mutations was 1.0% for protease inhibitors, 4.4% for nonnucleoside reverse transcriptase inhibitors, and 1.3% for nucleoside reverse transcriptase inhibitors. The frequency of multidrug resistance among the resistant strains was 13.6%. Among subjects infected with drug-resistant virus, the majority were infected with subtype B viruses (91%). Subjects from the city of Sao Paulo had higher transmitted resistance mutations compared to the rest of the country. Reporting a partner taking antiretroviral medications was associated with a higher chance of harboring HIV variants with major drug resistance mutations [odds ratio = 2.57 (95% confidence interval, 1.07-6.16); p = 0.014]. Resistance testing in drug-naive individuals identified 7% of subjects with mutations associated with reduced susceptibility to antiretroviral drugs. Continued surveillance of drug-resistant HIV-1 in Brazil is warranted when guidelines for HIV prophylaxis and treatment are updated. Resistance testing among drug-naive patients prior to treatment initiation should be considered, mainly directed at subjects whose partners are already on antiretroviral therapy.259861867Laboratorio Pfizer do Brasi

Primary resistance of HIV to antiretrovirals among individuals recently diagnosed at voluntary counselling and testing centres in the metropolitan region of Recife, Pernambuco

Determining the prevalence and type of antiretroviral (ARV) resistance among ARV-naïve individuals is important to assess the potential responses of these individuals to first-line regimens. The prevalence of primary resistance and the occurrence of recent infections among individuals with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) were identified among recently diagnosed patients at five sexually transmitted disease/AIDS testing and counselling centres in the metropolitan region of Recife (RMR), Pernambuco, Brazil, between 2007-2009. One-hundred and eight samples were analysed using the Calypte® BED assay. Males predominated (56%), as did patients aged 31-50 years. Twenty-three percent presented evidence of a recent HIV infection. The median CD4+ T lymphocyte count was 408 cells/mm³ and the median viral load was 3.683 copies/mL. The prevalence of primary resistance was 4.6% (confidence interval 95% = 1-8.2%) based on criteria that excluded common polymorphisms in accordance with the surveillance drug resistance mutation criteria. The prevalence of resistance to non-nucleoside reverse transcriptase, nucleoside/nucleotide reverse transcriptase and protease inhibitors were 3.8%, 1.5% and 0.8%, respectively. Fifty-seven percent of strains were from clade B, 37.7% were clade F and 3.1% were clade C; there were no statistically significant differences with respect to resistance between clades. Recent infection tended to be more common in men (p = 0.06) and in municipalities in the south of the RMR (Jaboatão dos Guararapes and Cabo de Santo Agostinho) (p = 0.046). The high prevalence of recent infection and the high prevalence of non-B strains in this poor Brazilian region merit further attention.Laboratório Central de Saúde Pública de Pernambuco Setor de VirologiaUniversidade Federal de Pernambuco Programa de Pós-Graduação em Medicina TropicalFiocruz Centro de Pesquisa Aggeu MagalhãesCentro de Testagem e Aconselhamento Herbert de SouzaUniversidade Federal de São Paulo (UNIFESP) Laboratório de RetrovirologiaUNIFESP, Laboratório de RetrovirologiaSciEL

International Nonregimes: A Research Agenda1

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146934/1/j.1468-2486.2007.00672.x.pd

Interaction-Dependent PCR: Identification of Ligand−Target Pairs from Libraries of Ligands and Libraries of Targets in a Single Solution-Phase Experiment

Interaction-dependent PCR (IDPCR) is a solution-phase method to identify binding partners from combined libraries of small-molecule ligands and targets in a single experiment. Binding between DNA-linked targets and DNA-linked ligands induces formation of an extendable duplex. Extension links codes that identify the ligand and target into one selectively amplifiable DNA molecule. In a model selection, IDPCR resulted in the enrichment of DNA encoding all five known protein−ligand pairs out of 67 599 possible sequences.Chemistry and Chemical Biolog

Effect of blood glucose level on standardized uptake value (SUV) in F-18- FDG PET-scan : a systematic review and meta-analysis of 20,807 individual SUV measurements

Objectives To evaluate the effect of pre-scan blood glucose levels (BGL) on standardized uptake value (SUV) in F-18-FDG-PET scan. Methods A literature review was performed in the MEDLINE, Embase, and Cochrane library databases. Multivariate regression analysis was performed on individual datum to investigate the correlation of BGL with SUVmax and SUVmean adjusting for sex, age, body mass index (BMI), diabetes mellitus diagnosis, F-18-FDG injected dose, and time interval. The ANOVA test was done to evaluate differences in SUVmax or SUVmean among five different BGL groups (200 mg/dl). Results Individual data for a total of 20,807 SUVmax and SUVmean measurements from 29 studies with 8380 patients was included in the analysis. Increased BGL is significantly correlated with decreased SUVmax and SUVmean in brain (p <0.001, p <0.001,) and muscle (p <0.001, p <0.001) and increased SUVmax and SUVmean in liver (p = 0.001, p = 0004) and blood pool (p=0.008, p200 mg/dl had significantly lower SUVmax. Conclusion If BGL is lower than 200mg/dl no interventions are needed for lowering BGL, unless the liver is the organ of interest. Future studies are needed to evaluate sensitivity and specificity of FDG-PET scan in diagnosis of malignant lesions in hyperglycemia.Peer reviewe

The impact of the nelfinavir resistance-conferring mutation D30N on the susceptibility of HIV-1 subtype B to other protease inhibitors

The human immunodeficiency virus type 1 (HIV-1) protease mutation D30N is exclusively selected by the protease inhibitor (PI) nelfinavir and confers resistance to this drug. We demonstrate that D30N increases the susceptibility to saquinavir (SQV) and amprenavir in HIV-1 subtype B isolates and that the N88D mutation in a D30N background neutralizes this effect. D30N also suppresses indinavir (IDV) resistance caused by the M46I mutation. Interestingly, in patients with viruses originally containing the D30N mutation who were treated with IDV or SQV, the virus either reversed this mutation or acquired N88D, suggesting an antagonistic effect of D30N upon exposure to these PIs. These findings can improve direct salvage drug treatment in resource limited countries where subtype B is epidemiologically important and extend the value of first and second line PIs in these populations