Polymorphism in Gag Gene Cleavage Sites of HIV-1 Non-B Subtype and Virological Outcome of a First-Line Lopinavir/Ritonavir Single Drug Regimen

Virological failure on a boosted-protease inhibitor (PI/r) first-line triple combination is usually not associated with the detection of resistance mutations in the protease gene. Thus, other resistance pathways are being investigated. First-line PI/r monotherapy is the best model to investigate in vivo if the presence of mutations in the cleavage sites (CS) of gag gene prior to any antiretroviral treatment might influence PI/r efficacy. 83 patients were assigned to initiate antiretroviral treatment with first-line lopinavir/r monotherapy in the randomised Monark trial. We compared baseline sequence of gag CS between patients harbouring B or non-B HIV-1 subtype, and between those who achieved viral suppression and those who experienced virological failure while on LPV/r monotherapy up to Week 96. Baseline sequence of gag CS was available for 82/83 isolates; 81/82 carried at least one substitution in gag CS compared to HXB2 sequence. At baseline, non-B subtype isolates were significantly more likely to harbour mutations in gag CS than B subtype isolates (p<0.0001). Twenty-three patients experienced virological failure while on lopinavir/r monotherapy. The presence of more than two substitutions in p2/NC site at baseline significantly predicted virological failure (p = 0.0479), non-B subtype isolates being more likely to harbour more than two substitutions in this specific site. In conclusion, gag cleavage site was highly polymorphic in antiretroviral-naive patients harbouring a non-B HIV-1 strain. We show that pre-therapy mutations in gag cleavage site sequence were significantly associated with the virological outcome of a first-line LPV/r single drug regimen in the Monark trial

Calibration of PRECIS in employing future scenarios in Bangladesh

Providing Regional Climates for Impacts Studies (PRECIS) is a regional climate model, which is used for the simulation of regional-scale climatology at high resolution (i.e. 50-km horizontal resolution). The calibration of rainfall and temperature simulated by PRECIS is performed in Bangladesh with the surface observational data from the Bangladesh Meteorological Department (BMD) for the period 1961-1990. The Climate Research Unit (CRU) data is also used for understanding the performance of the model. The results for the period 1961-1990 are used as a reference to find the variation of PRECIS-projected rainfall and temperature in 2071, in and around Bangladesh, as an example. Analyses are performed using the following two methods: (1) grid-to-grid and (2) point-to-point analyses. It is found that grid-to-grid analysis provides overestimation of PRECIS in Bangladesh because of downscaling of observed data when gridded from asymmetric low-density data network of BMD. On the other hand, model data extracted at observational sites provide better performance of PRECIS. The model overestimates rainfall in dry and pre-monsoon periods, whereas it underestimates it in the monsoon period. Overall, PRECIS is found to be able to estimate about 92 of surface rainfall. Model performance in estimating rainfall increases substantially with the increase in the length of time series of datasets. Systematic cold bias is found in simulating the annual scale of the surface temperature. In the annual scale, the model underestimates temperature of about 0.61 °C that varies within a range of + 1.45°C to - 3.89°C in different months. This analysis reveals that rainfall and temperature will be increased in Bangladesh in 2071. On the basis of the analyses, look-up tables for rainfall and temperature were prepared in a bid to calibrate PRECIS simulation results for Bangladesh. The look-up tables proposed in this analysis can be employed in the application of the projected rainfall and temperature in different sectors of the country. These look-up tables are useful only for the calibration of PRECIS simulation results for future climate projection for Bangladesh