Immunological Evolution of a Cohort of HIV-2 Infected Patients: Peculiarities of an Underestimated Infection.

Background: Human Immunodeficiency Virus type 2 (HIV-2) affects a minority of patients in Italy; nevertheless, the increasing migratory flow from higher prevalence areas led to the spread of this virus into our Country. We evaluate clinical, viro-immunological, and therapeutic characteristics of patients with HIV-2 infection and HIV-1/HIV-2 dual-infection and the early treatment impact on overall survival and incidence of AIDS events. Methods: We retrospectively analyzed all HIV-2, and HIV-1/HIV-2 positive patients followed in a large Italian clinic from January 1987 to December 2020. We recorded demographic, viro-immunological, clinical, and therapeutic data. We performed a descriptive analysis followed by a longitudinal analysis to explore the factors associated with the CD4+ lymphocyte trend; lastly, we studied the possible predictors of death and AIDS in our cohort in a multivariable model. Results: 32 subjects were enrolled, 17 (53%) HIV-2 infected and 15 (46.8%) HIV-1/HIV-2 dual-infected; 12 patients were lost to follow up, while 3 died. We found a lack of HIV-2 viremia in 12/32 subjects (37.5%). Most of the patients at baseline had a good viro-immunological profile with HIV-2 RNA <200 copies/ml and CD4+ lymphocyte >200 cell/mcl. We found a CD4+ lymphocyte improvement over time, both in the absolute number (ß 472.61, 95%CI 383.05-562.18, p<0.001) and in percentage (ß 25.28, 95%CI 21.91 - 28.66, p<0.001). Nevertheless, subjects taking cART had CD4+ lymphocyte percentage increase over time, and this trend appeared significantly better than those who did not receive therapy. Lastly, in the multivariable model CD4+, T-cell count increase was negatively associated with AIDS (HR 0.34 95%CI 0.13-0.91, p=0.032). Conclusion: We found a higher prevalence of HIV-1/2 dual infection than in previous observations. Subjects with HIV-2 infection showed a favorable immunological condition at diagnosis, and the benefits of cART in those who received treatment are undiscussed. Moreover, our data suggest a different disease course based on age at diagnosis, as in HIV-1 infections. We encourage starting cART at diagnosis in HIV-2 patients, regardless of CD4+ lymphocyte, because even in the new cART era, CD4+ lymphocyte decrease remains the strongest predictor of death and AIDS also in this population.

Evaluation of boosted and unboosted atazanavir plasma concentration in HIV infected patients.

OBJECTIVES: The aim of the study was to identify variables that can influence atazanavir plasma concentration. METHODS: We retrospectively analysed atazanavir trough concentration of HIV infected patients who performed therapeutic drug monitoring between October 2007 and July 2011. Qualitative variables were compared with X(2) test while continuous ones with Mann-Whitney and Student's t-test. A linear regression model was used to investigate factors influencing atazanavir plasma concentration. Therefore, we analysed the impact of cirrhosis on atazanavir pharmacokinetic variability. RESULTS: 255 plasma samples from 179 patients were analysed. At the univariate analysis female gender (+144.4 ng/mL; p=0.05) and tenofovir (+196.8 ng/mL; p=0.002) were associated with higher atazanavir concentrations. The multivariate model confirmed these two variables (+164.6 ng/mL; p=0.02 and +150.4 ng/mL; p=0.01) as independently associated with higher atazanavir trough concentration. The analysis of cirrhotic population showed an influence of tenofovir (-255.9 ng/mL; p=0.01), increased AST (+95.3 ng/mL; p=0.09), ALT (+67.9 ng/mL; p=0.07) and creatinine (+517.2 ng/mL; p=0.04). The multivariate model confirm that tenofovir was associated with lower atazanavir trough concentration (-284.1 ng/mL; p=0.005) while AST values significantly increased atazanavir concentrations (+114.5 ng/mL; p=0.03). DISCUSSION: Atazanavir is a safe and manageable drug. Our results suggest that female patients tend to have higher atazanavir plasma concentration, while the effect of tenofovir needs to be better clarified.

Thermal plasticity in Drosophila melanogaster: a comparison of geographic populations.

BACKGROUND: Populations of Drosophila melanogaster show differences in many morphometrical traits according to their geographic origin. Despite the widespread occurrence of these differences in more than one Drosophila species, the actual selective mechanisms controlling the genetic basis of such variation are not fully understood. Thermal selection is considered to be the most likely cause explaining these differences. RESULTS: In our work, we investigated several life history traits (body size, duration of development, preadult survival, longevity and productivity) in two tropical and two temperate natural populations of D. melanogaster recently collected, and in a temperate population maintained for twelve years at the constant temperature of 18 degrees C in the laboratory. In order to characterise the plasticity of these life history traits, the populations were grown at 12, 18, 28 and 31.2 degrees C. Productivity was the fitness trait that showed clearly adaptive differences between latitudinal populations: tropical flies did better in the heat but worse in the cold environments with respect to temperate flies. Differences for the plasticity of other life history traits investigated between tropical and temperate populations were also found. The differences were particularly evident at stressful temperatures (12 and 31.2 degrees C). CONCLUSION: Our results evidence a better cold tolerance in temperate populations that seems to have been evolved during the colonisation of temperate countries by D. melanogaster Afrotropical ancestors, and support the hypothesis of an adaptive response of plasticity to the experienced environment.