Suchergebnisse

Sanger genotypic drug resistance assays currently used for routine HIV management often miss low‐frequency drug‐resistant HIV variants, potentially posing patients at risk of antiretroviral treatment failure. Next‐generation sequencing (NGS) technologies allow detection of such minority variants down to approximately 0.5%–1% frequency. They also facilitate interrogating "other" HIV genomic regions like Gag or the RT connection domain, which modulate HIV resistance and are not usually addressed in routine care. Due to the capacity and scalability of NGS platforms, it is even feasible to envision full HIV genome sequencing to inform treatment design at relatively low cost and workload. Although the equipment for NGS remains rather expensive and accurate analysis of NGS still requires comprehensive bioinformatics support, even these barriers are being reduced. The steadfast evolution of NGS platforms is dramatically reducing the cost of genotyping. Open‐source and commercial bioinformatic solutions are automatizing and streamlining analyses and NGS drug resistance data interpretation to the extent that lab technicians without bioinformatics knowledge will soon be able to generate reliable estimates of drug resistance from NGS data on their own. However, despite such impressive advances, the main question remains open: do we need NGS for HIV management? In this presentation, we will review the evidence supporting (or not) NGS for HIV clinical management. We will argue that, on one hand, detection of minority variants may further improve the outcomes of first‐line efavirenz or nevirapine‐based ART, may help design more effective salvage ART regimens, and may improve clinical outcomes to CCR5 antagonists. On the other hand, although well‐powered studies are generally lacking, detection of minority variants does not seem to modify the outcomes of first‐line ART including higher genetic barrier drugs such as second‐generation NNRTIs, protease or integrase inhibitors. We will then discuss the relationship between minority variants and ART adherence and will end by summarizing the main challenges faced by NGS to reach routine HIV clinical management.

IT HAS BEEN A LONG-STANDING AND WIDELY ACCEPTED HYPOTHESIS THAT ECONOMIC EVENTS PLAY AN IMPORTANT ROLE IN THE RESULTS OF ELECTIONS. THIS PAPER AIMS AT FURTHER TESTING THE HYPOTHESIS THAT ECONOMIC ISSUES HAVE A ROLE IN THE SHAPING OF VOTERS PREFERENCES. TO DO SO, THE AUTHORS HAVE USED DATA FROM THE PRESIDENTIAL REFERNDUM HELD IN CHILE ON 5 OCTOBER, 1988. THE REFERENDUM PRESENTED TWO OPTIONS: THE OPTION YES IMPLIED THE CONTINUATION OF GENERAL AUGUSTO PINOCHET AS PRESIDENT OF CHILE FOR AN EIGHT YEAR PERIOD; THE OPTION NO IMPLIED AN OPEN GENERAL ELECTIONS TO BE HELD IN DEVEMBER OF 1989. THE PAPER CONCLUDES THAT EVEN THOUGH ECONOMIC VARIABLES ARE A KEY FACTOR IN VOTER'S PREFERENCES AND ELECTORAL RESULTS, THERE IS NO POSSIBILITY FOR GOVERNMENTS TO MANIPULATE THESE VARIABLES AND BENEFIT FROM OPPORTUNISITC BEHAVIORS.

Antiretroviral treatment simplification with darunavir/ritonavir or lopinavir/ritonavir monotherapy maintains sustained HIV viremia suppression in clinical trials. However, data about the efficacy of this strategy in routine clinical practice is still limited, and no direct comparison between darunavir/ritonavir and lopinavir/ritonavir has been performed to date. We retrospectively studied all HIV‐1‐infected subjects who initiated monotherapy with darunavir/ritonavir or lopinavir/ritonavir while having plasma VL<50 c/mL, and had at least 1 subsequent follow‐up visit in our clinic. When two consecutive PI‐monotherapy regimens were used, each regimen was considered separately. The primary endpoint was the percentage of patients who maintained virological suppression (HIV‐1 VL <50 c/mL) through follow‐up. Virological failure was defined as at least two consecutive HIV‐1 VL >50 c/mL. We also evaluated other reasons for treatment discontinuation. Analyses were performed considering all regimens (full dataset analysis) either as "on treatment" or as "treatment switch equals failure". Five hundred and seventy‐three PI‐monotherapy regimens corresponding to 520 subjects were included, 262 with darunavir/ritonavir and 311 with lopinavir/ritonavir. Medians (IQR) follow‐up were 50 (26.3–107.6) and 85.6 (36.9–179.1) weeks for subjects on darunavir/ritonavir and lopinavir/ritonavir, respectively (p<0.001). Overall, 67 (11.7%) subjects experienced virological failure, 23 (8.7%) were on darunavir/ritonavir and 42 (13.5%) were on lopinavir/ritonavir (p=0.796). Two hundred and three (77.5%) patients on darunavir/ritonavir and 154 (49.5%) on lopinavir/ritonavir maintained virological suppression in the "treatment switch equals failure" (p=0.002). Other reasons for treatment discontinuation were gastrointestinal toxicity and dyslipidemia in 7.2% and 5.9% of cases, respectively. Gastrointestinal toxicities and dyslipidemia leading to treatment discontinuation were more frequent in patients on lopinavir/ritonavir (10.6% and 10.3%, respectively) than in patients on darunavir/ritonavir (3.1% and 0.8%, respectively). Monotherapy with darunavir/ritonavir or lopinavir/ritonavir as simplification strategy appears to be effective and safe in subjects with virological suppression in clinical practice. Virological efficacy seems to be similar between regimens. However, rates of discontinuation due to toxicities were higher in subjects on lopinavir/ritonavir than darunavir/ritonavir.

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

Human immunodeficiency virus type 1 (HIV-1) was discovered in the early 1980s when the virus had already established a pandemic. For at least three decades the epidemic in the Western World has been dominated by subtype B infections, as part of a sub-epidemic that traveled from Africa through Haiti to United States. However, the pattern of the subsequent spread still remains poorly understood. Here we analyze a large dataset of globally representative HIV-1 subtype B strains to map their spread around the world over the last 50 years and describe significant spread patterns. We show that subtype B travelled from North America to Western Europe in different occasions, while Central/Eastern Europe remained isolated for the most part of the early epidemic. Looking with more detail in European countries we see that the United Kingdom, France and Switzerland exchanged viral isolates with non-European countries than with European ones. The observed pattern is likely to mirror geopolitical landmarks in the post-World War II era, namely the rise and the fall of the Iron Curtain and the European colonialism. In conclusion, HIV-1 spread through specific migration routes which are consistent with geopolitical factors that affected human activities during the last 50 years, such as migration, tourism and trade. Our findings support the argument that epidemic control policies should be global and incorporate political and socioeconomic factors.

Human immunodeficiency virus type 1 (HIV-1) was discovered in the early 1980s when the virus had already established a pandemic. For at least three decades the epidemic in the Western World has been dominated by subtype B infections, as part of a sub-epidemic that traveled from Africa through Haiti to United States. However, the pattern of the subsequent spread still remains poorly understood. Here we analyze a large dataset of globally representative HIV-1 subtype B strains to map their spread around the world over the last 50. years and describe significant spread patterns. We show that subtype B travelled from North America to Western Europe in different occasions, while Central/Eastern Europe remained isolated for the most part of the early epidemic. Looking with more detail in European countries we see that the United Kingdom, France and Switzerland exchanged viral isolates with non-European countries than with European ones. The observed pattern is likely to mirror geopolitical landmarks in the post-World War II era, namely the rise and the fall of the Iron Curtain and the European colonialism. In conclusion, HIV-1 spread through specific migration routes which are consistent with geopolitical factors that affected human activities during the last 50. years, such as migration, tourism and trade. Our findings support the argument that epidemic control policies should be global and incorporate political and socioeconomic factors. . . .