A Phylogenetic Analysis of Human Immunodeficiency Virus Type 1 Sequences in Kiev: Findings Among Key Populations.

Background: The human immunodeficiency virus (HIV) epidemic in Ukraine has been driven by a rapid rise among people who inject drugs, but recent studies have shown an increase through sexual transmission. Methods: Protease and reverse transcriptase sequences from 876 new HIV diagnoses (April 2013-March 2015) in Kiev were linked to demographic data. We constructed phylogenetic trees for 794 subtype A1 and 64 subtype B sequences and identified factors associated with transmission clustering. Clusters were defined as ≥2 sequences, ≥80% local branch support, and maximum genetic distance of all sequence pairs in the cluster ≤2.5%. Recent infection was determined through the limiting antigen avidity enzyme immunoassay. Sequences were analyzed for transmitted drug resistance mutations. Results: Thirty percent of subtype A1 and 66% of subtype B sequences clustered. Large clusters (maximum 11 sequences) contained mixed risk groups. In univariate analysis, clustering was significantly associated with subtype B compared to A1 (odds ratio [OR], 4.38 [95% confidence interval {CI}, 2.56-7.50]); risk group (OR, 5.65 [95% CI, 3.27-9.75]) for men who have sex with men compared to heterosexual males; recent, compared to long-standing, infection (OR, 2.72 [95% CI, 1.64-4.52]); reported sex work contact (OR, 1.93 [95% CI, 1.07-3.47]); and younger age groups compared with age ≥36 years (OR, 1.83 [95% CI, 1.10-3.05] for age ≤25 years). Females were associated with lower odds of clustering than heterosexual males (OR, 0.49 [95% CI, .31-.77]). In multivariate analysis, risk group, subtype, and age group were independently associated with clustering (P < .001, P = .007, and P = .033, respectively). Eighteen sequences (2.1%) indicated evidence of transmitted drug resistance. Conclusions: Our findings suggest high levels of transmission and bridging between risk groups.

Synthesis of the antimalarial drug FR900098 utilizing the nitroso-ene reaction.

The antimalarial drug FR900098 was prepared from diethyl allylphosphonate involving the nitroso-ene reaction with nitrosocarbonyl methane as the key step followed by hydrogenation and dealkylation. The utilization of dibenzyl allylphosphonate as the starting compound allows one-step hydrogenation with dealkylation, which simplifies the preparative scheme further.

HIV Incidence Estimates Using the Limiting Antigen Avidity EIA Assay at Testing Sites in Kiev City, Ukraine: 2013-2014.

OBJECTIVE: To estimate HIV incidence and highlight the characteristics of persons at greatest risk of HIV in the Ukraine capital, Kiev. METHOD: Residual samples from newly-diagnosed persons attending the Kiev City AIDS Centre were tested for evidence of recent HIV infection using an avidity assay. Questions on possible risk factors for HIV acquisition and testing history were introduced. All persons (≥16yrs) presenting for an HIV test April'13-March'14 were included. Rates per 100,000 population were calculated using region-specific denominators. RESULTS: During the study period 6370 individuals tested for HIV. Of the 467 individuals newly-diagnosed with HIV, 21 had insufficient samples for LAg testing. Of the remaining 446, 39 (8.7%) were classified as recent with an avidity index <1.5ODn, 10 were reclassified as long-standing as their viral load was <1000 copies/mL, resulting in 29 (6.5%) recent HIV infections. The only independent predictor for a recent infection was probable route of exposure, with MSM more likely to present with a recent infection compared with heterosexual contact [Odds Ratio 8.86; 95%CI 2.65-29.60]. We estimated HIV incidence at 21.5 per 100,000 population, corresponding to 466 new infections. Using population estimates for MSM and PWID, incidence was estimated to be between 2289.6 and 6868.7/100,000 MSM, and 350.4 for PWID. CONCLUSION: A high proportion of persons newly-infected remain undiagnosed, with MSM disproportionally affected with one in four newly-HIV-diagnosed and one in three recently-HIV-infected. Our findings should be used for targeted public health interventions and health promotion.

HIV Testing and Diagnosis Rates in Kiev, Ukraine: April 2013-March 2014.

OBJECTIVE: Data from Ukraine on risk factors for HIV acquisition are limited. We describe the characteristics of individuals testing for HIV in the main testing centres of the Ukrainian capital Kiev, including HIV risk factors, testing rates, and positivity rates. METHODS: As part of a larger study to estimate HIV incidence within Kiev City, we included questions on possible risk factors for HIV acquisition and testing history to existing systems in 4 infectious disease clinics. Data were provided by the person requesting an HIV test using a handheld electronic tablet. All persons (≥16 yrs) presenting for an HIV test April 2013-March 2014 were included. Rates per 100,000 were calculated using region-specific denominators for Kiev. RESULTS: During the study period 6370 individuals tested for HIV, equivalent to a testing rate of 293.2 per 100,000. Of these, 467 (7.8%) were HIV-positive, with the highest proportion positive among 31-35 year olds (11.2%), males (9.4%), people who inject drugs (PWID) (17.9%) and men who have sex with men (MSM) (24.1%). Using published population size estimates of MSM, diagnosis rates for MSM ranged from 490.6 to 1548.3/100,000. A higher proportion of heterosexual women compared to heterosexual men reported contact with PWID, (16% vs. 4.7%) suggesting a bridging in risk between PWID and their sexual partners. CONCLUSION: Collection of HIV risk factor information in Kiev, essential for the purposes of developing effective HIV prevention and response tools, is feasible. The high percentage of MSM among those testing positive for HIV, may indicate a significant level of undisclosed sex between men in national figures.

H-coupled electron transfer in alkane C-h activations with halogen electrophiles.

The mechanisms for the reactions of isobutane and adamantane with polyhalogen electrophiles (HHal(2)(+), Hal(3)(+), Hal(5)(+), and Hal(7)(+), Hal = Cl, Br, or I) were studied computationally at the MP2 and B3LYP levels of theory with the 6-31G (C, H, Cl, Br) and 3-21G (I) basis sets, as well as experimentally for adamantane halogenations in Br(2), Br(2)/HBr, and I(+)Cl(-)/CCl(4). The transition structures for the activation step display almost linear C...H...Hal interactions and are characterized by significant charge transfer to the electrophile; the hydrocarbon moieties resemble the respective radical cation structures. The regiospecificities for polar halogenations of the 3-degree C-H bonds of adamantane, the high experimental kinetic isotope effects (k(H)/k(D) = 3-4), the rate accelerations in the presence of Lewis and proton (HBr) acids, and the high kinetic orders for halogen (7.5 for Br(2)) can only be understood in terms of an H-coupled electron-transfer mechanism. The three centered-two electron (3c-2e) electrophilic mechanistic concept based on the attack of the electrophile on a C-H bond does not apply; electrophilic 3c-2e interactions dominate the C-H activations only with nonoxidizing electrophiles such as carbocations. This was shown by a comparative computational analysis of the electrophilic and H-coupled electron-transfer activation mechanisms for the isobutane reaction with an ambident electrophile, the allyl cation, at the above levels of theory.