Evaluating the effect of direct-acting antiviral agent treatment scale-up on Hepatitis C virus prevalence among people who inject drugs in UK.

BACKGROUND: There is limited empirical work assessing the effectiveness of treatment as prevention (TasP) in reducing HCV prevalence among people who inject drugs (PWID). Here, we used survey data from the UK during 2010-2020, to evaluate the impact of direct-acting antiviral agent (DAA) treatment scale-up, which started in 2015, on HCV prevalence among PWID. METHODS: We fitted a logistic regression to time/location specific data on prevalence from the Needle Exchange Surveillance Initiative in Scotland and Unlinked Anonymous Monitoring programme in England. For each post-intervention year and location, we quantified the effect of TasP as the difference between estimated prevalence and its counterfactual (prevalence in the absence of scale-up). Progress to elimination was assessed by comparing most recent prevalence against one in 2015. RESULTS: In 2015, prevalence ranged from 0.44 to 0.71 across the 23 locations (3 Scottish, 20 English). Compared to counterfactuals, there was an absolute reduction of 46% (95% credible interval [32%,59%]) in Tayside in 2020, 35% ([24%,44%]) in Glasgow in 2019, and 25% ([10%,39%]) in the Rest of Scotland in 2020. The English sites with highest estimated absolute reductions in 2021 were South Yorkshire (45%, [29%,58%]), Thames Valley (49%, [34%,59%]) and West London (41%, [14%,59%]). Compared to 2015, there was 80% probability that prevalence had fallen by 65% in Tayside, 53% in Glasgow and 36% in the Rest of Scotland. The English sites with highest % prevalence decrease compared to 2015, achieved with probability 80%, were Chesire & Merseyside (70%), South Yorkshire (65%) and Thames Valley (71%). Higher treatment intensity was associated with higher reductions in prevalence. CONCLUSION: Conclusion. Real-world evidence showing substantial reductions in chronic HCV associated with increase of HCV treatment scale-up in the community thus supporting the effectiveness of HCV treatmen as prevention in people who inject drugs.

Hydrothiolation of Triisopropylsilyl Acetylene Sulfur Pentafluoride - Charting the Chemical Space of ß-SF5 Vinyl Sulfides.

Recently, we suggested liquid and high-boiling TIPS-CC-SF5 (TASP) as a versatile reagent to access so far elusive SF5-containing building blocks by less specialized laboratories under bench-top conditions. The synthesis of non-aromatic SF5 building blocks generally requires on-site fluorination or pentafluorosulfanylation steps employing toxic and/or gaseous reagents. Herein, we underline the versatility of this reagent by reporting a benign bench-top protocol for the synthesis of Z-configured ß-pentafluorosulfanylated vinyl sulfides in good to excellent yields (up to 99 %) with exclusive (Z)-diasteroselectivity and broad functional group tolerance. This method exploits an in-situ protodesilylation-hydrothiolation sequence. This so far uncharted class of compounds was characterized by means of NMR-spectroscopy as well as SC-XRD. Furthermore, we suggest the reaction to proceed via a kinetically controlled closed-shell reaction pathway, corroborated by in-silico experiments.

Sexual behaviour and STIs among MSM living with HIV in the PrEP era: the French ANRS PRIMO cohort study.

INTRODUCTION: In a context of declining condom use and high sexually transmitted infection (STI) incidence, the diffusion of "treatment as prevention" (Tasp) and more recently pre-exposure prophylaxis (PrEP) may have changed the sexual behaviour of newly diagnosed men who have sex with men (MSM) with HIV. METHODS: Six hundred and nine MSM were enrolled and followed annually between 2014 and 2021 in the ANRS PRIMO Cohort (ClinicalTrials.gov:NCT03148964) from the time of HIV seroconversion. We studied changes over calendar time in sexual behaviour before and after HIV diagnosis. Factors associated with inconsistent condom use (ICU) after HIV diagnosis, PrEP use by partner(s) and bacterial STI acquisition were studied in random-effects models. RESULTS: In the 6 months preceding HIV diagnosis, the number of sexual partners decreased from a median of 10 (IQR: 4-19) in 2014 to 6 (3-11) in 2021. After HIV diagnosis, ICU increased from 57.1% (16/28) of visits in 2014 up to 84.2% (229/272) in 2020-2021. Up to 25% (63/229) of MSM with HIV in recent years reported the use of PrEP by their partner(s) as the reason for ICU; these MSM were less frequently in a stable relationship, had a higher number of sexual partners and higher education level than those who did not report the use of PrEP by their partner(s). STI incidence after HIV diagnosis increased between 2014 and 2016 and remained high afterwards. STI risk was no longer associated with PrEP use by partners after adjustment for the number of partners and calendar period. ICU, age below 35 years, not being in a stable relationship, higher number of sexual partners were independently associated with an increased risk of STI. CONCLUSIONS: Implementation of TasP and more recently PrEP has led to major changes in the sexual behaviour of MSM with HIV. ICU has become overwhelmingly prevalent, PrEP use by the partner increasingly being the reported reason for ICU, behind TasP, which remains the main reason. Characteristics of MSM at the time of diagnosis of HIV have changed, with fewer number of sexual partners today than in 2014, which must lead to broaden the indications for PrEP prescription. STIs incidence remains high in MSM with HIV and requires improvements in screening and prevention methods such as pre- or post-exposition antibiotics or vaccines.

The Potential Role of Undetectable = Untransmittable (U = U) in Reducing HIV Stigma among Sexual Minority Men in the US.

The Undetectable = Untransmittable (U = U) message and its scientific underpinnings have been widely suggested to reduce HIV stigma. However, misunderstanding and skepticism about U = U may prevent this destigmatizing potential from being fully realized. This cross-sectional study examined associations between U = U belief (belief that someone with a sustained undetectable viral load has zero risk of sexually transmitting HIV) and HIV stigma among US sexual minority men. Differences by serostatus and effects of brief informational messaging were also explored. The survey was completed online by 106 men living with HIV and 351 HIV-negative/status-unknown men (2019-2020). Participants were 18-83 years old (M[SD] = 41[13.0]). Most were non-Hispanic White (70.0%) and gay (82.9%). Although nearly all participants (95.6%) were aware of U = U, only 41.1% believed U = U. A greater percentage of participants living with HIV (66.0%) believed U = U compared with HIV-negative/status-unknown participants (33.6%). Among participants living with HIV, U = U belief was not significantly associated with perceived, internalized, or experienced HIV stigma or with viral load prejudice (prejudice against people who have a detectable HIV viral load). Among HIV-negative/status-unknown participants, U = U belief was associated with less frequently enacted HIV discrimination, more positive feelings toward people with an undetectable viral load, and lower personal endorsement of stigmatizing beliefs. Brief informational messaging about U = U did not affect most stigma dimensions and did not favorably affect any. Interventions are needed to correct commonly held, outdated misconceptions about HIV transmission risk. Such initiatives must not only engage people living with HIV but also engage HIV-negative/status-unknown people to maximize the destigmatizing potential of U = U.

RESUMEN: Para reducir el estigma del VIH se ha recomendado difundir extensivamente el mensaje Indetectable = Intransmisible (U = U) y sus fundamentos científicos. Sin embargo, falta de comprensión y escepticismo acerca de U = U pueden impedir que se realice plenamente su potencial desestigmatizante. Este estudio transversal examinó las asociaciones entre la creencia U = U (creencia de que alguien con una carga viral indetectable sostenida tiene cero riesgo de transmitir sexualmente el VIH) y el estigma del VIH entre hombres de minorías sexuales estadounidenses. También se exploró si el efecto de los mensajes informativos breves dependía del estatus serológico. La encuesta fue completada en línea por 106 hombres que viven con el VIH y 351 hombres VIH negativos o de estatus desconocido (2019­2020). Los participantes tenían entre 18 y 83 años (M[DS] = 41[13,0]). La mayoría eran blancos no hispanos (70,0%) y gay (82,9%). Aunque casi todos los participantes (95,6%) sabían sobre U = U, sólo el 41,1% creían en U = U. Un mayor porcentaje de participantes con VIH (66,0%) creían que U = U en comparación con los participantes VIH negativos o de estatus desconocido (33,6%). Entre los participantes con VIH, la creencia U = U no se asoció significativamente con el estigma del VIH percibido, interiorizado o experimentado ni con el prejuicio sobre la carga viral (prejuicio contra las personas que tienen una carga viral de VIH detectable). Entre los participantes VIH negativos/con estatus desconocido, la creencia U = U se asoció con menor frecuencia de discriminación por VIH, sentimientos más positivos hacia las personas con una carga viral indetectable y menor respaldo personal a las creencias estigmatizantes. Los mensajes informativos breves sobre U = U no afectaron la mayoría de las dimensiones del estigma y no afectó favorablemente a ninguno. Se necesitan intervenciones para corregir conceptos frecuentes sobre el riesgo de transmisión del VIH que son erróneos y obsoletos. Para maximizar el potencial desestigmatizador de U = U, estas iniciativas no sólo deben involucrar a las personas que viven con el VIH, sino también a las personas VIH-negativas o de estatus desconocido.

Evaluating experiences of HIV-related stigma among people living with HIV diagnosed in different treatment eras in British Columbia, Canada.

There is mixed evidence on whether experiences of HIV-related stigma are mitigated with lived experience. We sought to examine whether people living with HIV (PLWH) with longer living experience reported varying levels of HIV-related stigma. Between January 2016-September 2018, we used purposive sampling to enrol PLWH aged ≥19 across British Columbia, Canada, where participants completed the 10-item Berger HIV Stigma Scale. We conducted bivariate analyzes examining key sociodemographic characteristics and HIV-related stigma scores. Multivariable linear regression modelled the association between year of HIV diagnosis by treatment era and HIV-related stigma scores. We enrolled 644 participants; median age at enrolment was 50 years (Q1-Q3: 42-56), with 37.4% (n = 241) diagnosed before the year 2000. The median HIV-stigma scores of all participants (19.0, Q1-Q3: 13-25, range 0-40) stratified by treatment era were: 17.0 (pre-1996), 20.0 (1996-1999), 20.0 (2000-2009), 19.0 (2010-2018) (p = 0.03). While there was a significant association at the univariate level, year of HIV diagnosis by treatment era was not associated with stigma scores after controlling for age, gender, HIV key populations, ethnicity, relationship status, social support, and ever having a mental health disorder diagnosis. This suggests that PLWH still experience HIV-related stigma today, compared to those diagnosed in earlier time periods.

Prediction, Synthesis and Evaluation of a Synthetic Peptide as an Enzyme-Linked Immunosorbent Assay (ELISA) Candidate for Screening of Bovine Antibodies against Theileria annulata.

Tick-borne diseases (TBDs) of livestock are endemic across various parts of tropical countries. Theileriosis is one such economically important TBD, caused by the Theileriidae family of organisms, which is transmitted by ticks. Theileria annulata, the causative agent of tropical theileriosis, contributes a significant loss to the dairy sector by causing anorexia, high fever, anemia, inflammatory changes in vital organs and icterus, thus, a loss in milk yield. Though vaccines are available, their protective efficacy is not absolute, and treatment is limited to early diagnosis of the causative agent. Routinely, microscopic identification of piroplasms in the erythrocytes (Giemsa-stained) of infected animals or schizonts in lymph node biopsies are practiced for diagnosis. PCR-based techniques (multiplex, uniplex, nested and real-time) have been reported to perform well in diagnosing active infection. Several attempts have been made using serological assays like Dot blot, ELISA and ICT, but the results were of variable sensitivity and specificity. Recombinant proteins like the Theileria annulata merozoite surface antigen (Tams1) and Theileria annulata surface protein (TaSP) have been explored as antigenic candidates for these assays. In the present study, we predicted an immunogenic peptide, i.e., TaSP-34, from the TaSP using various computational tools. The predicted peptide was custom synthesized. The diagnostic potential of the peptide was assessed by indirect plate ELISA to detect the bovine-IgM against Theileria annulata. Alongside, a recombinant truncated TaSP (rTaSP(tr)) was expressed and purified, which was used to compare the performance of the peptide as a diagnostic candidate. The IgM-based peptide ELISA was 100% sensitive and 92.77% specific as compared to PCR (Tams1 targeting), while 98.04% sensitivity and 97.44% specificity were observed in comparison with rTaSP(tr) ELISA. Almost perfect agreement between peptide ELISA and Tams1 PCR was observed with a Cohen's kappa coefficient (κ-value) of 0.901 and agreement of 95.31%. Further, the κ-value between the peptide ELISA and rTaSP(tr) ELISA was found to be 0.95, and the agreement was 97.65%, which shows a good correlation between the two tests. The findings suggest that the TaSP-34 peptide can be an efficient and new-generation diagnostic candidate for the diagnosis of T. annulata. Furthermore, the peptide can be synthesized commercially at a larger scale and can be a cost-effective alternative for the protein-based diagnostic candidates for T. annulata.

Navigating the Viral Divide: Sexual and Gender Minority Community Perspectives on Treatment as Prevention.

Since it was established that HIV-positive individuals who maintain an undetectable viral load are unable to sexually transmit HIV (U=U), treatment as prevention (TasP) has become an important biomedical HIV prevention option. Many have remained optimistic that TasP, combined with pre-exposure prophylaxis (PrEP), will help close the "viral divide" between those living with and without HIV. This qualitative interview study of 62 sexual and gender minority (SGM) individuals of mixed serostatuses explored community perspectives regarding TasP, including the meaning of undetectability and how U=U impacts understandings of serodifference. Five key themes emerged from interviews: (1) undetectable does not equal HIV-negative, (2) PrEP is more promoted than TasP, (3) TasP increases openness to serodifferent sex, (4) rejection of TasP absolutism, and (5) the importance of layering prevention strategies. These findings suggest that while TasP is helping to bridge the viral divide, serostatus distinctions remain prevalent and important to many SGM individuals.

Improving HIV testing, linkage, and retention in care among South African men through U=U messaging: A study protocol for two sequential hybrid type 1 effectiveness- implementation randomized controlled trials.

BACKGROUND: Increasing HIV testing and treatment coverage among people living with HIV (PLHIV) is essential for achieving global AIDS epidemic control. However, compared to women, cis-gender heterosexual men living with HIV are significantly less likely to know their HIV status, initiate anti-retroviral therapy (ART) and achieve viral suppression. This is particularly true in South Africa, where men are also at increased risk of mortality resulting from AIDS-related illnesses. While there is growing knowledge of Treatment as Prevention or the concept Undetectable=Untransmittable (U=U) among PLHIV in Western and high-income countries, the reach and penetration of the U=U message in sub-Saharan Africa remains limited, and few studies have evaluated the impact of accessible and relatable U=U messages on ART initiation and adherence. To address these gaps, rigorous evaluations of interventions that incorporate U=U messages are needed, especially among men in high prevalence settings. METHODS: Building on our U=U messages that we previously developed for men using behavioral economics insights and a human-centered design, we will conduct two sequential hybrid type 1 effectiveness-implementation trials to evaluate the impact of U=U messages on men's uptake of community-based HIV testing and ART initiation (Trial 1), and retention in care and achievement of viral suppression (Trial 2). A cluster randomized trial will be implemented for Trial 1, with HIV testing service site-days randomized to U=U or standard-of-care (SoC) messages inviting men to test for HIV. An individual-level randomized control trial will be implemented for Trial 2, with men initiating ART at six government clinics randomized to receive U=U counselling or SoC treatment adherence messaging. We will incorporate a multi-method evaluation to inform future implementation of U=U messaging interventions. The study will be conducted in the Buffalo City Metro Health District of the Eastern Cape Province and in the Cape Town Metro Health District in the Western Cape Province in South Africa. DISCUSSION: These trials are the first to rigorously evaluate the impact of U=U messaging on HIV testing uptake, ART initiation and achievement of viral suppression among African men. If effective, these messaging interventions can shape global HIV testing, treatment and adherence counselling guidelines and practices.

Developmental reprogramming of myometrial stem cells by endocrine disruptor linking to risk of uterine fibroids.

BACKGROUND: The stage, when tissues and organs are growing, is very vulnerable to environmental influences, but it's not clear how exposure during this time causes changes to the epigenome and increases the risk of hormone-related illnesses like uterine fibroids (UFs). METHODS: Developmental reprogramming of myometrial stem cells (MMSCs), the putative origin from which UFs originate, was investigated in vitro and in the Eker rat model by RNA-seq, ChIP-seq, RRBS, gain/loss of function analysis, and luciferase activity assays. RESULTS: When exposed to the endocrine-disrupting chemical (EDC) diethylstilbestrol during Eker rat development, MMSCs undergo a reprogramming of their estrogen-responsive transcriptome. The reprogrammed genes in MMSCs are known as estrogen-responsive genes (ERGs) and are activated by mixed lineage leukemia protein-1 (MLL1) and DNA hypo-methylation mechanisms. Additionally, we observed a notable elevation in the expression of ERGs in MMSCs from Eker rats exposed to natural steroids after developmental exposure to EDC, thereby augmenting estrogen activity. CONCLUSION: Our studies identify epigenetic mechanisms of MLL1/DNA hypo-methylation-mediated MMSC reprogramming. EDC exposure epigenetically targets MMSCs and leads to persistent changes in the expression of a subset of ERGs, imparting a hormonal imprint on the ERGs, resulting in a "hyper-estrogenic" phenotype, and increasing the hormone-dependent risk of UFs.

Long-term follow-up and novel variant in Suleiman-El-Hattab syndrome: Expanding the genotypic and clinical spectrum of a rare neurodevelopmental disorder.

Suleiman-El-Hattab syndrome (SULEHS, OMIM #618950) is an autosomal recessive multisystem developmental disorder characterized by distinctive facial appearance, global developmental delay/intellectual disability, poor expressive speech and happy demeanor. SULEHS is an ultra-rare disorder associated with biallelic loss-of-function variants of the TASP1 gene, and up-to-date, seven patients from five families have been reported in the literature. Loss of TASP1 function has been reported to alter H3K4 histone modifications and expression of TFIIA and HOX transcription factors in the SULEHS phenotype. In this report, a new patient molecularly diagnosed with SULEHS by a novel homozygous c.404-2A > G variant in the TASP1 gene is presented with the long-term follow-up. Although the majority of the patient's clinical characteristics were similar to those of previously reported SULEHS patients, this study was the first to describe some additional anomalies, such as cystic hygroma, increased nuchal thickness, coarctation of the aorta, pulmonary stenosis, pulmonary sequestration anomaly, chronic constipation, encephalomalacia, and aggressive behavior. Because of the remarkable similarities between the clinical features of Baraitser-Winter syndrome (BRWS) and the patient, BRWS was considered the most likely diagnosis before the molecular diagnosis. Network analysis also supported that the interaction of the SULEHS-associated TASP1 gene with the BRWS-associated ACTB and ACTG1 genes through common intermediate molecules. Overall, despite the existence of differences in clinical features, inheritance patterns, and underlying pathophysiology between BRWS and SULEHS, both diseases could be considered in the differential diagnosis due to the high clinical similarities, including the dysmorphic features, growth parameters, neurodevelopmental phenotype, neurological problems, and multisystem involvement. Additionally, this report could contribute to a better understanding of the genotypic and clinical features of SULEHS by describing a novel pathogenic variant and new clinical features, such as prenatal manifestations.

Biomedical bargains: Negotiating "safe sex" on antiretroviral treatment in rural South Africa.

Wide-scale availability of antiretroviral treatment (ART) has transformed the global landscape for HIV prevention, shifting emphasis away from a strictly behavioral focus on changing sexual practices towards a biomedical approach. Successful ART management is measured by an undetectable viral load, which helps maintain overall health and prevent onward viral transmission. The latter utility of ART, however, must be understood in the context of its implementation. In South Africa, ART has become easily accessible - yet ART knowledge spreads unevenly, while counseling advice and normative expectations and experiences of gender and aging interact to inform sexual practices. As ART enters the sexual lives of middle-aged and older people living with HIV (MOPLH), a population growing rapidly, how has it informed sexual decisions and negotiations? Drawing on in-depth interviews with MOPLH on ART, corroborated with focus group discussions and national ART-related policies and guidelines, we find that for MOPLH, sexual decisions increasingly feature compliance with biomedical directives and concern for ART efficacy. Seeking consensus regarding the biological risks of sex on ART becomes an important feature of sexual negotiations, and anticipated disagreements can pre-empt sexual relationships altogether. We introduce the concept of biomedical bargains to explain what happens when disagreements arise, and the terms of sex are negotiated using competing interpretations of biomedical information. For both men and women, ostensibly gender-neutral biomedical discourses provide new discursive resources and strategies for sexual decisions and negotiations, yet biomedical bargains are still embedded in gender dynamics-women invoke the dangers of jeopardizing treatment efficacy and longevity to insist on condoms or justify abstinence, while men utilize biomedical arguments in an effort to render condomless sex safe. While the full therapeutic benefits of ART are critical for the efficacy and equity of HIV programs, they will nonetheless always affect, and be affected by, social life.

Barriers to Treatment as Prevention Adoption Among Sexual and Gender Minority Individuals Who Have Sex with Men in the United States.

The discovery that people with an undetectable HIV viral load are unable to transmit the virus to sex partners (U = U) has ushered in a new era in HIV care. As a result of this discovery, treatment as prevention (TasP) has become a powerful tool toward ending the epidemic. However, despite its sound scientific basis, many communities affected by HIV face barriers toward adopting TasP as a complete HIV prevention strategy. In addition, most research to date has only focused on TasP in the context of committed monogamous partnerships. To identify barriers to TasP adoption among some of those most affected by HIV, we conducted in-depth qualitative interviews with 62 sexual and gender minority individuals of varying serostatuses. Participants were identified from the results of an online survey, where those who indicated at least some awareness of TasP were invited to partake in a follow-up interview. Interviews were thematically coded to identify emergent themes relating to TasP adoption. Seven primary barriers emerged from data analysis pertaining to TasP science, internalized beliefs about HIV safety, and interactional dynamics between partners: (1) unfamiliarity with TasP science, (2) perceived limitations of TasP science, (3) difficulty changing understanding of "safe sex," (4) unwillingness to rely on partners' reports of being undetectable, (5) persistent HIV stigma, (6) less difficulty finding serosimilar partners, and (7) difficulty incorporating TasP into casual encounters. Together, these barriers confirm the existing findings about TasP adoption, and extend the literature by identifying barriers beyond a lack of education and outside of monogamous contexts.

Psychosocial factors involved in the very infrequent use of HIV testing among French MSM: a cross-sectional study.

BACKGROUND: Among men who have sex with men (MSM) in France, the average time between infection and testing is too long, leading to late diagnosis. A better understanding of very infrequent HIV testing (VIT; i.e. have not tested for at least 6 years) could help reach unknowingly long-infected MSM. Thus, we aim to identify psychosocial factors associated with VIT among MSM in France. METHODS: We conducted a multivariate regression on the data collected via a cross-sectional survey among 315 MSM. RESULTS: 11.1% (n = 35) had VIT. Being over 50, not knowing about the existence of HIV self-testing, having predominantly heterosexual friends, and the level of belief in the effectiveness of treatment as prevention were significantly associated with VIT. CONCLUSION: We call for the development, at the same time, of programs that operate at the individual, institutional and societal levels. In particular, we recommend diversifying the modes of promotion and access to prevention tools, especially for MSM over 50 years old or with little or no connection to the gay community.

Sequence polymorphisms in a Theileria annulata surface protein (TaSP) known to augment the immunity induced by live attenuated cell line vaccine.

Theileria annulata is a tick-borne protozoan causing tropical theileriosis in cattle. The use of attenuated cell line vaccines in combination with subunit vaccines has been relatively successful as a control method, as exemplified by a recent study in which immunization with a local cell line followed by booster vaccinations with recombinant T. annulata surface protein (TaSP) resulted in 100% protection upon field challenge in Sudan. However, these findings cannot be directly extrapolated to other countries as culture-attenuated live vaccines are generated using local strains and no systematic evaluation of genotype differences between countries has been undertaken. In this study, we sequenced the TaSP gene from T. annulata cell lines and field isolates from Tunisia (n = 28) and compared them to genotypes from Sudan (n = 25) and Morocco (n = 1; AJ316259.1). Our analyses revealed 20 unique TaSP genotypes in the Tunisian samples, which were all novel but similar to genotypes found in Asia. The impact of these polymorphisms on the ability of the TaSP antigen to boost the immunity engendered by live cell line vaccines, especially in Tunisia where studies with TaSP have not been conducted, remains to be examined. Interestingly, phylogenetic analyses of publicly available TaSP sequences resolved the sequences into two clusters with no correlation to the geographical origin of the isolates. The availability of candidate vaccines that were recently attenuated using local strains from Sudan, Tunisia, Egypt and Morocco should be exploited to generate a comprehensive catalogue of genetic variation across this regional collection of attenuated live vaccines.

Healthcare and treatment experiences among people diagnosed with HIV before and after a province-wide treatment as prevention initiative in British Columbia, Canada.

INTRODUCTION: In 2010, the Canadian province of British Columbia (BC) initiated the Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) program to improve HIV testing, linkage to care, and treatment uptake, thereby operationalizing the HIV Treatment as Prevention (TasP) framework at the population-level. In this analysis, we evaluated self-reported HIV care experiences and therapeutic outcomes among people diagnosed with HIV prior to and after implementation of this provincial program. METHODS: A cross-sectional analysis was performed on the baseline data of a cohort of people living with HIV (PLWH) (19 years and older) in the province of BC sampled from July 2016 to September 2018. All participants consented to linking their survey data to the provincial HIV treatment registry. Individuals diagnosed with HIV from January 1 2000-December 31 2009 were classified as pre-intervention and those diagnosed January 1 2010-December 31 2018 as post-intervention cohorts. Bivariate analyses were run using Chi-square and Wilcoxon Rank Sum tests. Cox proportional hazards regression model demonstrates time to antiretroviral therapy (ART) initiation (from HIV baseline) and virological suppression (2 consecutive plasma viral load measurements < 200 copies/ml). RESULTS: Of the 325 participants included in this analysis, 198 (61%) were diagnosed with HIV in the pre-intervention era and 127 (39%) in the post-intervention era. A higher proportion of participants in post-intervention era were diagnosed at walk-in clinics (45% vs. 39%) and hospitals (21% vs. 11%) (vs pre-intervention) (p = 0.042). Post-intervention participants had initiated ART with less advanced HIV disease (CD4 count 410 vs. 270 cells/ul; p = 0.001) and were less likely to experience treatment interruptions at any point in the 5 years after HIV diagnosis (17% vs. 48%; p < 0.001). The post-intervention cohort had significantly more timely ART initiation (aHR: 5.97, 95%CI 4.47, 7.97) and virologic suppression (aHR: 2.03, 95%CI 1.58, 2.60) following diagnosis, after controlling for confounders. CONCLUSIONS: We found favourable treatment experiences and more timely ART initiation and virologic suppression after a targeted TasP provincial program. Our results illustrate the importance of accessible low-barrier HIV testing and treatment in tackling the HIV epidemic.

Imaging Histamine H3 Receptors with Positron Emission Tomography.

Positron emission tomography (PET) provides a unique tool to study the biochemistry of the human brain in vivo. By using PET probes that are binding selectively to certain receptor subtypes, brain PET allows the quantification of receptor levels in various brain areas of human subjects. This approach has the potential to reveal abnormal receptor expressions that may contribute to the physiopathology of some psychiatric and neurological disorders. This approach also has the potential to assist in the drug development process by determining receptor occupancy in vivo allowing selection of proper drug dosage to produce therapeutic effects. Several PET tracers have been developed for histamine H3 receptors (H3R). However, despite the potential of PET to elucidate the role of H3R in vivo, only limited work has been conducted so far. This article reviews the work that has been done in this area. Notably, we will cover the limitations of the first-generation PET radioligand for H3R and present the advantages of novel radioligands that promise an explosion of clinical PET research on the role of H3R in vivo.

Merging care and prevention: preventive properties of antiretroviral drugs and HIV chronification in the case of Switzerland.

Medication is closely involved in the subjective experience of chronic diseases, but also in the chronification process of illnesses which is described in this paper in the specific case of HIV. The development of antiretroviral drugs (ARVs) and the progressive recognition of their potential dual use as treatment as prevention (TasP) and pre-exposure prophylaxis (PrEP) reshape the experience of HIV and its transmission. Acknowledging the importance of a socioanthropological approach to drugs, this paper highlights how therapeutic strategies of treatment and prevention currently shape the process of HIV chronification and its experience for people concerned with ARVs in Switzerland, whether they are seropositive patients on lifelong treatment or seronegative people affected by the preventive properties of drugs.

Sexual and Relationship Benefits of a Safer Conception Intervention Among Men with HIV Who Seek to Have Children with Serodifferent Partners in Uganda.

Many men with HIV (MWH) in Uganda desire children, yet seldom receive reproductive counseling related to HIV care. Because men are under engaged in safer conception programming, they miss opportunities to reap the benefits of these programs. The objective of this sub-analysis was to explore the relationship and intimacy benefits of integrating safer conception counseling and strategies into HIV care, an emergent theme from exit interviews with men who participated in a pilot safer conception program and their partners. Twenty interviews were conducted with MWH who desired a child in the next year with an HIV-uninfected/status unknown female partner, and separate interviews were conducted with female partners (n = 20); of the 40 interviews, 28 were completed by both members of a couple. Interviews explored experiences participating in The Healthy Families program, which offered MWH safer conception counseling and access to specific strategies. Data were analyzed using thematic analysis. Three major subthemes or "pathways" to the relationship and intimacy benefits associated with participation in the program emerged: (1) improved dyadic communication; (2) joint decision-making and power equity in the context of reproduction; and (3) increased sexual and relational intimacy, driven by reduced fear of HIV transmission and relationship dissolution. These data suggest that the intervention not only helped couples realize their reproductive goals; it also improved relationship dynamics and facilitated intimacy, strengthening partnerships and reducing fears of separation. Directly addressing these benefits with MWH and their partners may increase engagement with HIV prevention strategies for conception.

HIV Serostatus Disclosure Among Men Who Have Sex with Men in China in the Era of U=U and PrEP.

Given the recent evidence on "Undetectable = Untransmittable" (U=U) and pre-exposure prophylaxis (PrEP), the present study aimed to investigate HIV disclosure behaviors and their associations with sexual risk behaviors and U=U and PrEP awareness among men who have sex with men (MSM) in China. A cross-sectional survey was conducted among 689 MSM recruited through a gay-friendly non-governmental organization located in Chengdu, China in 2018-2019. Information was collected by a structured self-administrated questionnaire. The enrolled sample included 554 (80.4%) participants who were HIV-negative and 135 (19.6%) participants with an unknown HIV status. In terms of disclosure, 41.4% of participants informed all partners about their HIV status all the time (informing behavior), while 30.4% asked all partners about their HIV status all the time (asking behavior). Only one-fifth knew about U=U, but this was not statistically associated with either informing or asking behavior. Half (50.5%) had heard of PrEP but this was not statistically associated with either informing or asking behavior. Common barriers to informing and asking behaviors were lower risk perception of HIV infection, a history of sexually transmitted infections, engagement in receptive sex, and a history of sex with casual partners. We found that both U=U and PrEP awareness and HIV serostatus disclosure were infrequent and not associated in this study of Chinese MSM. These data indicate huge information gaps among MSM in China.