Tracing of patients lost to follow-up and HIV transmission: Mathematical modelling study based on two large ART programmes in Malawi

OBJECTIVES: Treatment as prevention depends on retaining HIV-infected patients in care. We investigated the effect on HIV transmission of bringing patients lost to follow up (LTFU) back into care. DESIGN: Mathematical model. METHODS: Stochastic mathematical model of cohorts of 1000 HIV-infected patients on antiretroviral therapy (ART), based on data from two clinics in Lilongwe, Malawi. We calculated cohort viral load (CVL; sum of individual mean viral loads each year) and used a mathematical relationship between viral load and transmission probability to estimate the number of new HIV infections. We simulated four scenarios: 'no LTFU' (all patients stay in care); 'no tracing' (patients LTFU are not traced); 'immediate tracing' (after missed clinic appointment); and, 'delayed tracing' (after six months). RESULTS: About 440 of 1000 patients were LTFU over five years. CVL (million copies/ml per 1000 patients) were 3.7 (95% prediction interval [PrI] 2.9-4.9) for no LTFU, 8.6 (95% PrI 7.3-10.0) for no tracing, 7.7 (95% PrI 6.2-9.1) for immediate, and 8.0 (95% PrI 6.7-9.5) for delayed tracing. Comparing no LTFU with no tracing the number of new infections increased from 33 (95% PrI 29-38) to 54 (95% PrI 47-60) per 1000 patients. Immediate tracing prevented 3.6 (95% PrI -3.3-12.8) and delayed tracing 2.5 (95% PrI -5.8-11.1) new infections per 1000. Immediate tracing was more efficient than delayed tracing: 116 and to 142 tracing efforts, respectively, were needed to prevent one new infection. CONCLUSION: Tracing of patients LTFU enhances the preventive effect of ART, but the number of transmissions prevented is small.

Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case-control study using centralized ultrasensitive 454 pyrosequencing.

OBJECTIVES It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART. METHODS This Europe-wide case-control study included ART-naive subjects infected with drug-susceptible HIV-1 as revealed by population sequencing, who achieved virological suppression on first-line ART including one NNRTI. Cases experienced virological failure and controls were subjects from the same cohort whose viraemia remained suppressed at a matched time since initiation of ART. Blinded, centralized 454 pyrosequencing with parallel bioinformatic analysis in two laboratories was used to identify MVs in the 1%-25% frequency range. ORs of virological failure according to MV detection were estimated by logistic regression. RESULTS Two hundred and sixty samples (76 cases and 184 controls), mostly subtype B (73.5%), were used for the analysis. Identical MVs were detected in the two laboratories. 31.6% of cases and 16.8% of controls harboured pre-existing MVs. Detection of at least one MV versus no MVs was associated with an increased risk of virological failure (OR = 2.75, 95% CI = 1.35-5.60, P = 0.005); similar associations were observed for at least one MV versus no NRTI MVs (OR = 2.27, 95% CI = 0.76-6.77, P = 0.140) and at least one MV versus no NNRTI MVs (OR = 2.41, 95% CI = 1.12-5.18, P = 0.024). A dose-effect relationship between virological failure and mutational load was found. CONCLUSIONS Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART.

Collecting the Painted Netherlands: The Art Collection of Ernest of Austria in Brussels

The (art) collection of Archduke Ernest of Austria (1553-1595) is widely unknown when it comes to early-modern Habsburg collections. Ernest, younger brother of Emperor Rudolf II (b. 1552) and educated at the Madrid court, was appointed Governor-General of the Netherlands by King Philip II of Spain, his uncle, in summer 1593. Ernest relocated his court from Vienna to Brussels in early 1594 and was welcomed there with lavish festivities: the traditional Blijde Inkomst, Joyous Entry, of the new sovereign. Unfortunately, the archduke died in February 1595 after residing in Brussels for a mere thirteen months. This investigation aims to shed new light on the archduke and his short-lived collecting ambitions in the Low Countries, taking into account that he had the mercantile and artistic metropolis Antwerp in his immediate reach. I argue, that his collecting ambitions can be traced back to one specific occasion: Ernest’s Joyous Entry into Antwerp in June 1594. There the archduke received a series of six paintings of Pieter Bruegel the Elder (1525/30-1569) known as The Months (painted in 1565), hanging today in separate locations in Vienna, New York and Prague. These works of art triggered Ernest’s collecting ambitions and prompted him to focus mainly on works of art and artefacts manufactured at or traded within the Netherlands during the last eight months of his lifetime. Additionally, it will be shown that the archduke was inspired by the paintings’ motifs and therefore concentrated on acquiring works of art depicting nature and landscape scenes from the 1560s and 1590s. On the basis of the archduke’s recently published account book (Kassabuch) and of the partially published inventory of his belongings, it becomes clear that Ernest of Austria must be seen in line with the better-known Habsburg collectors and that his specific collection of “the painted Netherlands” can be linked directly to his self-fashioning as a rightful sovereign of the Low Countries.