Evolutionary dynamics of HIV-1 subtype C in Brazil.

The extensive genetic diversity of HIV-1 is a major challenge for the prevention and treatment of HIV-1 infections. Subtype C accounts for most of the HIV-1 infections in the world but has been mainly localized in Southern Africa, Ethiopia and India. For elusive reasons, South Brazil harbors the largest HIV-1 subtype C epidemic in the American continent that is elsewhere dominated by subtype B. To investigate this topic, we collected clinical data and viral sequences from 2611 treatment-naïve patients diagnosed with HIV-1 in Brazil. Molecular epidemiology analysis supported 35 well-delimited transmission clusters of subtype C highlighting transmission within South Brazil but also from the South to all other Brazilian regions and internationally. Individuals infected with subtype C had lower probability to be deficient in CD4+ T cells when compared to subtype B. The HIV-1 epidemics in the South was characterized by high female-to-male infection ratios and women-to-child transmission. Our results suggest that HIV-1 subtype C probably takes advantage of longer asymptomatic periods to maximize transmission and is unlikely to outcompete subtype B in settings where the infection of women is relatively less relevant. This study contributes to elucidate factors possibly underlying the geographical distribution and expansion patterns of the most spread HIV-1 subtypes.

Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil.

The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). Since Brazil presents the largest number of people living with HIV (PLWH) in South America we aimed at understanding the dynamics of DRM in this country. We analyzed a total of 20,226 HIV-1 sequences collected from PLWH undergoing ART between 2008-2017. Results show a mild decline of DRM over the years but an increase of the K65R reverse transcriptase mutation from 2.23% to 12.11%. This increase gradually occurred following alterations in the ART regimens replacing zidovudine (AZT) with tenofovir (TDF). PLWH harboring the K65R had significantly higher viral loads than those without this mutation (p < 0.001). Among the two most prevalent HIV-1 subtypes (B and C) there was a significant (p < 0.001) association of K65R with subtype C (11.26%) when compared with subtype B (9.27%). Nonetheless, evidence for K65R transmission in Brazil was found both for C and B subtypes. Additionally, artificial neural network-based immunoinformatic predictions suggest that K65R could enhance viral recognition by HLA-B27 that has relatively low prevalence in the Brazilian population. Overall, the results suggest that tenofovir-based regimens need to be carefully monitored particularly in settings with subtype C and specific HLA profiles.

Evolutionary Genetics of Mycobacterium tuberculosis and HIV-1: "The Tortoise and the Hare".

The already enormous burden caused by Mycobacterium tuberculosis and Human Immunodeficiency Virus type 1 (HIV-1) alone is aggravated by co-infection. Despite obvious differences in the rate of evolution comparing these two human pathogens, genetic diversity plays an important role in the success of both. The extreme evolutionary dynamics of HIV-1 is in the basis of a robust capacity to evade immune responses, to generate drug-resistance and to diversify the population-level reservoir of M group viral subtypes. Compared to HIV-1 and other retroviruses, M. tuberculosis generates minute levels of genetic diversity within the host. However, emerging whole-genome sequencing data show that the M. tuberculosis complex contains at least nine human-adapted phylogenetic lineages. This level of genetic diversity results in differences in M. tuberculosis interactions with the host immune system, virulence and drug resistance propensity. In co-infected individuals, HIV-1 and M. tuberculosis are likely to co-colonize host cells. However, the evolutionary impact of the interaction between the host, the slowly evolving M. tuberculosis bacteria and the HIV-1 viral "mutant cloud" is poorly understood. These evolutionary dynamics, at the cellular niche of monocytes/macrophages, are also discussed and proposed as a relevant future research topic in the context of single-cell sequencing.

Preliminary aquatic risk assessment of imidacloprid after application in an experimental rice plot.

The potential aquatic risk of application of the neonicotinoid insecticide imidacloprid for aphid control in rice was assessed. To this end, imidacloprid was applied as Confidor(®) 200 SC at the recommended field dose of 100g a.i./ha to a Portuguese rice plot. Subsequently, fate of the test compound in water and potential effects of water samples on a battery of test species were determined. As compared to the first-tier predicted environmental concentrations (PECs) calculated using MED-Rice (around 30µg/L depending on the scenario used) and US-EPA (78µg/L) simulations, the actual peak concentration measured in the paddy water (52µg/L) was higher and lower, respectively. As was anticipated based on 50% effect concentrations (EC50 values) for Daphnia magna published in the open literature and that calculated in the present study (48h-EC50 immobility=84mg/L), no effects were observed of field water samples on daphnids. The sediment-dwelling ostracod Heterocypris incongruens, however, appeared relatively sensitive towards imidacloprid (6d-EC50 growth inhibition=0.01-0.015mg/L) and a slight effect was indeed noted in field samples taken the first week after application. Species sensitivity distributions based on published EC50 and NOEC values also revealed that other species are likely to be affected at the peak and time-weighted average imidacloprid concentrations, respectively. By applying the relative tolerance approach (i.e. by dividing the EC50 value of a certain species with that of Daphnia magna), ostracods appear to contain the most sensitive taxa to imidacloprid, followed by EPT (Ephemeroptera, Plecoptera and Trichoptera) taxa. Future field studies into (higher-tier) fate modelling of pesticides in rice paddies and effect assessment on field communities are required to ensure protection of aquatic life and wildlife (e.g. birds) from pesticide stress.