Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis.

BACKGROUND: The correlations of genotypic and phenotypic tests with treatment, clinical history and the significance of mutations in viruses of HIV-infected patients are used to establish resistance mutations to protease inhibitors (PIs). Emerging mutations in human immunodeficiency virus type 1 (HIV-1) protease confer resistance to PIs by inducing structural changes at the ligand interaction site. The aim of this study was to establish an in silico structural relationship between natural HIV-1 polymorphisms and unusual HIV-1 mutations that confer resistance to PIs. RESULTS: Protease sequences isolated from 151 Mexican HIV-1 patients that were naïve to, or subjected to antiretroviral therapy, were examined. We identified 41 unrelated resistance mutations with a prevalence greater than 1%. Among these mutations, nine exhibited positive selection, three were natural polymorphisms (L63S/V/H) in a codon associated with drug resistance, and six were unusual mutations (L5F, D29V, L63R/G, P79L and T91V). The D29V mutation, with a prevalence of 1.32% in the studied population, was only found in patients treated with antiretroviral drugs. Using in silico modelling, we observed that D29V formed unstable protease complexes when were docked with lopinavir, saquinavir, darunavir, tipranavir, indinavir and atazanavir. CONCLUSIONS: The structural correlation of natural polymorphisms and unusual mutations with drug resistance is useful for the identification of HIV-1 variants with potential resistance to PIs. The D29V mutation likely confers a selection advantage in viruses; however, in silico, presence of this mutation results in unstable enzyme/PI complexes, that possibly induce resistance to PIs.

Prevalence of chronic kidney disease in an adult population.

BACKGROUND AND AIMS: One strategy to prevent and manage chronic kidney disease (CKD) is to offer screening programs. The aim of this study was to determine the percentage prevalence and risk factors of CKD in a screening program performed in an adult general population. METHODS: This is a cross-sectional study. Six-hundred ten adults (73% women, age 51 ± 14 years) without previously known CKD were evaluated. Participants were subjected to a questionnaire, blood pressure measurement and anthropometry. Glomerular filtration rate estimated by CKD-EPI formula and urine tested with albuminuria dipstick. RESULTS: More than 50% of subjects reported family antecedents of diabetes mellitus (DM), hypertension and obesity, and 30% of CKD. DM was self-reported in 19% and hypertension in 29%. During screening, overweight/obesity was found in 75%; women had a higher frequency of obesity (41 vs. 34%) and high-risk abdominal waist circumference (87 vs. 75%) than men. Hypertension (both self-reported and diagnosed in screening) was more frequent in men (49%) than in women (38%). CKD was found in 14.7%: G1, 5.9%; G2, 4.5%; G3a, 2.6%; G3b, 1.1%, G4, 0.3%; and G5, 0.3%. Glomerular filtration rate was mildly/moderately reduced in 2.6%, moderately/severely reduced in 1.1%, and severely reduced in <1%. Abnormal albuminuria was found in 13%. CKD was predicted by DM, hypertension and male gender. CONCLUSIONS: A percentage CKD prevalence of 14.7% was found in this sample of an adult population, with most patients at early stages. Screening programs constitute excellent opportunities in the fight against kidney disease, particularly in populations at high risk.

Molecular epidemiology of HIV type 1 in Mexico: emergence of BG and BF intersubtype recombinants.

The molecular epidemiology of subtypes and intersubtype recombinants (IRs) of human immunodeficiency virus type 1 (HIV-1) in Mexico has not been characterized fully. Understanding its regional distribution, prevalence, adaptability, viral fitness, pathogenicity, and immunogenicity is decisive for any design of an effective HIV vaccine. The aim of this study was to describe the presence of IRs types BG and BF in a Mexican population. Protease and reverse transcriptase regions of the pol gene were sequenced using an automated sequencing system. A phylogenic tree was constructed and genetic distances were calculated using MEGA 3.1. Recombination analysis was done by bootscan using SimPlot software. Two hundred and twenty-three HIV-1-positive individuals were enrolled in the study. At baseline, the mean plasma viral load was 285,500 HIV-1 RNA copies/ml and the mean CD4 cell count was 213 cells/ml. Subtype B was found in 220 (98.6%) samples, whereas IRs were found in three patients (1.4%): two (0.9%) with BG and one (0.45%) with BF. IRs were observed in 2/124 (1.6%) samples from treated patients and in 1/99 (1.0%) from naive patients. The presence of these HIV forms at low frequency points to the need for research on the diversity, geographic distribution, and evolution of other subtypes including circulating recombinant forms and IRs to understand the molecular epidemiology and tendencies of the HIV infection in Mexico.