Impact of multi-targeted antiretroviral treatment on gut T cell depletion and HIV reservoir seeding during acute HIV infection.

BackgroundLimited knowledge exists on early HIV events that may inform preventive and therapeutic strategies. This study aims to characterize the earliest immunologic and virologic HIV events following infection and investigates the usage of a novel therapeutic strategy.Methods and findingsWe prospectively screened 24,430 subjects in Bangkok and identified 40 AHI individuals. Thirty Thais were enrolled (8 Fiebig I, 5 Fiebig II, 15 Fiebig III, 2 Fiebig IV) of whom 15 completed 24 weeks of megaHAART (tenofovir/emtricitabine/efavirenz/raltegravir/maraviroc). Sigmoid biopsies were completed in 24/30 at baseline and 13/15 at week 24. At baseline, the median age was 29 years and 83% were MSM. Most were symptomatic (87%), and were infected with R5-tropic (77%) CRF01_AE (70%). Median CD4 was 406 cells/mm(3). HIV RNA was 5.5 log(10) copies/ml. Median total blood HIV DNA was higher in Fiebig III (550 copy/10(6) PBMC) vs. Fiebig I (8 copy/10(6) PBMC) (p = 0.01) while the median %CD4+CCR5+ gut T cells was lower in Fiebig III (19%) vs. Fiebig I (59%) (p = 0.0008). After 24 weeks of megaHAART, HIV RNA levels of <50 copies were achieved in 14/15 in blood and 13/13 in gut. Total blood HIV DNA at week 0 predicted reservoir size at week 24 (p<0.001). Total HIV DNA declined significantly and was undetectable in 3 of 15 in blood and 3 of 7 in gut. Frequency of CD4+CCR5+ gut T cells increased from 41% at baseline to 64% at week 24 (p>0.050); subjects with less than 40% at baseline had a significant increase in CD4+CCR5+ T cells from baseline to week 24 (14% vs. 71%, p = 0.02).ConclusionsGut T cell depletion and HIV reservoir seeding increases with progression of AHI. MegaHAART was associated with immune restoration and reduced reservoir size. Our findings could inform research on strategies to achieve HIV drug-free remission

Daily and Nondaily Oral Preexposure Prophylaxis in Men and Transgender Women Who Have Sex With Men: The Human Immunodeficiency Virus Prevention Trials Network 067/ADAPT Study

Background: Nondaily dosing of oral preexposure prophylaxis (PrEP) may provide equivalent coverage of sex events compared with daily dosing. Methods: At-risk men and transgender women who have sex with men were randomly assigned to 1 of 3 dosing regimens: 1 tablet daily, 1 tablet twice weekly with a postsex dose (time-driven), or 1 tablet before and after sex (event-driven), and were followed for coverage of sex events with pre- and postsex dosing measured by weekly self-report, drug concentrations, and electronic drug monitoring. Results: From July 2012 to May 2014, 357 participants were randomized. In Bangkok, the coverage of sex events was 85% for the daily arm compared with 84% for the time-driven arm (P = .79) and 74% for the event-driven arm (P = .02). In Harlem, coverage was 66%, 47% (P = .01), and 52% (P = .01) for these groups. In Bangkok, PrEP medication concentrations in blood were consistent with use of ≥2 tablets per week in >95% of visits when sex was reported in the prior week, while in Harlem, such medication concentrations occurred in 48.5% in the daily arm, 30.9% in the time-driven arm, and 16.7% in the event-driven arm (P < .0001). Creatinine elevations were more common in the daily arm (P = .050), although they were not dose limiting. Conclusions: Daily dosing recommendations increased coverage and protective drug concentrations in the Harlem cohort, while daily and nondaily regimens led to comparably favorable outcomes in Bangkok, where participants had higher levels of education and employment

Characterization of HIV seroconverters in a TDF/FTC PrEP study: HPTN 067/ADAPT

Background: HPTN 067/ADAPT evaluated tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) pre-exposure prophylaxis (PrEP) in women (South Africa) and men who have sex with men (Thailand, US). Participants received once-weekly directly observed TDF/FTC (DOT), and were then randomized to daily, time-driven, or event-driven PrEP. This report describes characterization of 12 HIV seroconversion events in this trial. Methods: HIV rapid testing was performed at study sites. Retrospective testing included: 4th generation assays; HIV RNA testing; Western blot; an HIV-1/2 discriminatory assay; resistance testing; and antiretroviral (ARV) drug testing. Results: Six of the 12 seroconverters received TDF/FTC in the DOT phase, but were not randomized (3 were acutely infected at enrollment; 2 were infected during the DOT phase; one was not randomized due to pregnancy). One of the six randomized participants had acute infection at randomization but was not diagnosed for 3–4 months because HIV rapid tests were non-reactive; continued daily PrEP use was associated with false-negative antibody tests and low HIV RNA levels. The five participants infected after randomization included four with low adherence to the PrEP regimen, and one who reported a 7-day period without dosing prior to infection. Three participants had TDF/FTC resistance (M184I, K65R), including two who received only four once-weekly TDF/FTC doses; most TDF/FTC mutations were detected by next generation sequencing only. Conclusions: In HPTN 067/ADAPT, participants who acquired HIV infection had infrequent PrEP dosing or low/suboptimal adherence. Sensitive assays improved detection of HIV infection and drug resistance. Drug resistance was observed with limited PrEP exposure

Acute HIV infection detection and immediate treatment estimated to reduce transmission by 89% among men who have sex with men in Bangkok

Published 28 June 2017Introduction: Antiretroviral treatment (ART) reduces HIV transmission. Despite increased ART coverage, incidence remains high among men who have sex with men (MSM) in many places. Acute HIV infection (AHI) is characterized by high viral replication and increased infectiousness. We estimated the feasible reduction in transmission by targeting MSM with AHI for early ART. Methods: We recruited a cohort of 88 MSM with AHI in Bangkok, Thailand, who initiated ART immediately. A risk calculator based on viral load and reported behaviour, calibrated to Thai epidemiological data, was applied to estimate the number of onwards transmissions. This was compared with the expected number without early interventions. Results: Forty of the MSM were in 4th-generation AHI stages 1 and 2 (4thG stage 1, HIV nucleic acid testing (NAT)+/4thG immunoassay (IA)-/3rdG IA–; 4thG stage 2, NAT+/4thG IA+/3rdG IA–) while 48 tested positive on third-generation IA but had negative or indeterminate western blot (4thG stage 3). Mean plasma HIV RNA was 5.62 log¹⁰ copies/ml. Any condomless sex in the four months preceding the study was reported by 83.7%, but decreased to 21.2% by 24 weeks on ART. After ART, 48/ 88 (54.6%) attained HIV RNA <50 copies/ml by week 8, increasing to 78/87 (89.7%), and 64/66 (97%) at weeks 24 and 48, respectively. The estimated number of onwards transmissions in the first year of infection would have been 27.3 (95% credible interval: 21.7–35.3) with no intervention, 8.3 (6.4–11.2) with post-diagnosis behaviour change only, 5.9 (4.4–7.9) with viral load reduction only and 3.1 (2.4–4.3) with both. The latter was associated with an 88.7% (83.8–91.1%) reduction in transmission. Conclusions: Disproportionate HIV transmission occurs during AHI. Diagnosis of AHI with early ART initiation can substantially reduce onwards transmission.Eugène D.M.B. Kroon, Nittaya Phanuphak, Andrew J. Shattock, James L.K. Fletcher, Suteeraporn Pinyakorn, Nitiya Chomchey, Siriwat Akapirat, Mark S. de Souza, Merlin L. Robb, Jerome H. Kim, Frits van Griensven, Jintanat Ananworanich, and David P. Wilson on behalf of the RV254/SEARCH 010 Study Grou

Visual Arts as the Means of Implementing the Artistic and Creative Potential of Preschool Children

Пріоритетним завданням дошкільної освіти в Україні є розвиток творчої особистості дитини. Дослідження психолог ів та педагогів довели, що для розвитку і реалізації творчого потенціалу дитини необхідно використовувати оптимальні умови й засоби. Творчість дітей засобами образотворчого мистецтва є процесом природним та високоефективним. Науковцями визначено базові складові творчого потенціалу особистості, засади та систему умов, необхідних для художньо-творчого розвитку. На основі цих визначень ми розробили і впровадили педагогічну роботу, спрямовану на розвиток та реалізацію художньо-творчого потенціалу дошкільників засобами образотворчого мистецтва.According to the National doctrine of education development in Ukraine, the professional pedagogical studies must be personality oriented. The future teacher must be trained not only as a subject teacher, but also a professional teacher capable to communicate and interact with pupils and adults. A future educator has to know that pedagogical expedience of his activity is at first the result of his mastering the psychological and pedagogical knowledge, secondly, investigation of the rational use of his potential individuality in the process of pedagogical interactivity. The main feature of professional training of future teachers has to be his social orientation, the orientation to meaningful values. Certainly the aesthetic and artistic values have to be socially meaningful features created by humanity. In general great attention is paid to the aesthetic and artistic education of students and to the deep acquaintance of future teachers with the peculiarities of aesthetic and artistic education of children, especially in preschool age, by facilities of different types of art (musical, graphic, theatrical, choreographic and others like that). In the curricula of higher educational pedagogical establishments a lot of time is given to study the subjects of aesthetic cycle. The teachers of higher educational establishments, who worked out the programs of certain courses, determine their proper purpose and task. Among the other types of art the graphic one has unique possibilities to the decision of tasks both of artistic and personality development, public and spiritual growth of the young generation. In preschool age the depicting activity is one of the most accessible and emotionally keen. Great role belongs to the art, to its influence in drafting the valued orientation of a person. Forming the valued options of a person, bringing them up to the greatest values – public ideals is a component part of the public destination of art. In full it carries out when incarnated public values become meaningful for a person, determine character of his vital functions. In psychological-pedagogical literature the development of a capacity for the aesthetic beautiful estimation of the phenomenon of reality is determined as one of the most important problems of aesthetic art education. The followers of such point of view consider the grounds, that a person’s forming consists of forming of his relations as facilities of intercommunication with reality, as facilities of existence. Each of relationships with reality becomes the subject of certain pedagogical influence