Effectiveness and Safety of Direct-acting Antivirals for Treatment of Adolescents With HCV/HIV Coinfection: Real-world Data From Europe.

We evaluated the effectiveness and safety of direct-acting antivirals in adolescents with hepatitis C (HCV)/HIV coinfection using pooled individual patient-level data from 5 European cohorts. Of 122 participants in follow-up from November 2013 to August 2021, 19 were treated <18 years of age; of 15 with HCV RNA available at/after 12 weeks post-treatment, all had sustained virologic response with acceptable safety. This evidence addresses an important gap in knowledge of treatment outcomes in adolescents with HCV/HIV coinfection in real-life settings.

Development and Evaluation of an AxiomTM 60K SNP Array for Almond (Prunus dulcis).

A high-density single nucleotide polymorphism (SNP) array is essential to enable faster progress in plant breeding for new cultivar development. In this regard, we have developed an Axiom 60K almond SNP array by resequencing 81 almond accessions. For the validation of the array, a set of 210 accessions were genotyped and 82.8% of the SNPs were classified in the best recommended SNPs. The rate of missing data was between 0.4% and 2.7% for the almond accessions and less than 15.5% for the few peach and wild accessions, suggesting that this array can be used for peach and interspecific peach × almond genetic studies. The values of the two SNPs linked to the RMja (nematode resistance) and SK (bitterness) genes were consistent. We also genotyped 49 hybrids from an almond F2 progeny and could build a genetic map with a set of 1159 SNPs. Error rates, less than 1%, were evaluated by comparing replicates and by detection of departures from Mendelian inheritance in the F2 progeny. This almond array is commercially available and should be a cost-effective genotyping tool useful in the search for new genes and quantitative traits loci (QTL) involved in the control of agronomic traits.

Outcomes of etravirine-based antiretroviral treatment in treatment-experienced children and adolescents living with HIV in Europe and Thailand.

BACKGROUND: Etravirine (ETR) is approved as a component of second or third-line antiretroviral treatment (ART) for children living with HIV. We assessed the outcomes of ETR-based ART in children in routine care in Europe and Thailand. METHODS: Data on children aged <18 years at ETR start were pooled from 17 observational cohorts. Characteristics at ETR start, immunological and virological outcomes at 12 months, discontinuations, adverse events (AEs) and serious adverse events (SAEs) were described. Follow-up was censored at ETR discontinuation, death or last visit. RESULTS: 177 children ever received ETR. At ETR start, median [IQR] age was 15 [12,16] years, CD4 count 480 [287, 713] cells/mm3, 70% had exposure to ≥3 ART classes and 20% had viral load (VL) <50 copies/mL. 95% received ETR in combination with ≥1 potent drug class, mostly protease inhibitor-based regimens. Median time on ETR was 24 [7, 48] months. Amongst those on ETR at 12 months (n=141), 69% had VL<50 copies/mL. Median CD4 increase since ETR start (n=83) was 147 [16, 267] cells/mm3. Overall, 81 (46%) discontinued ETR by last follow-up. Median time to discontinuation was 23 [8, 47] months. Common reasons for discontinuation were treatment simplification (19%), treatment failure (16%) and toxicity (12%). Eight children (5%) had AEs causally associated with ETR, all dermatological/hypersensitivity reactions. Two were SAEs, both Stevens-Johnson Syndrome in children on regimens containing ETR and darunavir and were causally related to either drugs; both resolved following ART discontinuation. CONCLUSION: Children receiving ETR were predominantly highly treatment-experienced, over two-thirds were virally suppressed at 12 months.

The Association Between HIV Disclosure Status and Perceived Barriers to Care Faced by Women Living with HIV in Latin America, China, Central/Eastern Europe, and Western Europe/Canada.

Generally, women are less likely than men to disclose their HIV status. This analysis examined the relationship between HIV disclosure and (1) perceived barriers to care and (2) quality of life (QoL) for women with HIV. The ELLA (EpidemioLogical study to investigate the popuLation and disease characteristics, barriers to care, and quAlity of life for women living with HIV) study enrolled HIV-positive women aged ≥18 years. Women completed the 12-item Barriers to Care Scale (BACS) questionnaire. QoL was assessed using the Health Status Assessment. BACS and QoL were stratified by dichotomized HIV disclosure status (to anyone outside the healthcare system). Multilevel logistic regression analysis was used to identify factors associated with disclosure. Of 1945 patients enrolled from Latin America, China, Central/Eastern Europe, and Western Europe/Canada between July 2012 and September 2013, 1929 were included in the analysis (disclosed, n = 1724; nondisclosed, n = 205). Overall, 55% of patients lived with a husband/partner, 53% were employed, and 88% were receiving antiretroviral therapy. Patients who were with a serodiscordant partner were more likely to disclose (p = 0.0003). China had a disproportionately higher percentage of participants who did not disclose at all (nearly 30% vs. <15% for other regions). Mean BACS severity scores for medical/psychological service barriers and most personal resource barriers were significantly lower for the disclosed group compared with the nondisclosed group (p ≤ 0.02 for all). Compared with the disclosed group, the nondisclosed group reported statistically significantly higher (p ≤ 0.03) BACS item severity scores for 8 of the 12 potential barriers to care. The disclosed group reported better QoL. Overall, HIV nondisclosure was associated with more severe barriers to accessing healthcare by women with HIV.

Associations of hormonal contraceptive use with measures of HIV disease progression and antiretroviral therapy effectiveness.

OBJECTIVE: To examine the associations between hormonal contraceptive use and measures of HIV disease progression and antiretroviral treatment (ART) effectiveness. STUDY DESIGN: A prospective cohort study of women with prevalent HIV infection in St. Petersburg, Russia, was conducted. After contraceptive counseling, participants chose to use combined oral contraceptives (COCs), depot-medroxyprogesterone acetate (DMPA), a copper intrauterine device (IUD) or male condoms for pregnancy prevention. Among participants not using ART at enrollment, we used multivariate Cox regression to assess the association between current (time-varying) contraceptive use and disease progression, measured by the primary composite outcome of CD4 decline to <350 cells/mm(3), ART initiation or death. Among participants using ART at enrollment, we used linear mixed models to estimate the predicted mean CD4 change at select time points by contraceptive method. RESULTS: During a total of 5233 months follow-up among participants not using ART with enrollment CD4 ≥350 cells/mm(3) (n=315), 97 experienced disease progression. Neither current use of COCs [adjusted hazard ratio (aHR) 0.91, 95% confidence interval (CI) 0.56-1.48] nor DMPA (aHR 1.28, 95% CI 0.71-2.31) was associated with a statistically significant increased risk for disease progression compared with use of nonhormonal methods (IUD or condoms). Among participants using ART at enrollment (n=77), we found no statistically significant differences in the predicted mean changes in CD4 cell count comparing current use of COCs (p=.1) or DMPA (p=.3) with nonhormonal methods. CONCLUSION: Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection. IMPLICATIONS: Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection.

Barriers to access to care reported by women living with HIV across 27 countries.

Increased access to successful antiretroviral therapy (ART) is necessary in order to achieve an AIDS-free generation. Importantly, slightly over half of the people living with HIV are women. Small studies have described many barriers to accessing treatment and care among women living with HIV. This cross-sectional, non-interventional, epidemiological study assessed the prevalence of barriers to accessing care for women living with HIV across 27 countries, divided into four global regions. HIV-positive women attending routine clinical visits were offered the opportunity to participate in the study. Data describing the study sites and demographic characteristics of the participating women were collected. Participating women filled out questionnaires including the Barriers to Care Scale (BACS) questionnaire, on which they reported the extent to which they found each of the 12 potential barriers to accessing health care problematic. A total of 1931 women living with HIV were included in the study: 760 from Western Europe and Canada (WEC), 532 from Central and Eastern Europe (CEE), 519 from Latin America (LA), and 120 from China. The mean age of participating women was 40.1 ± 11.4 years. A total of 88.2% were currently taking ART. A total of 81.8% obtained HIV treatment under a government health plan. The most prevalent barrier to care was community HIV/AIDS stigma. Community HIV/AIDS knowledge, lack of supportive/understanding work environments, lack of employment opportunities, and personal financial resources were also highly prevalent barriers to accessing care. These findings indicate that, more than 30 years after the start of the AIDS epidemic, stigma is still a major issue for women living with HIV. Continued efforts are needed to improve community education on HIV/AIDS in order to maximize access to health care among women living with HIV.

Reduced HIV symptoms and improved health-related quality of life correlate with better access to care for HIV-1 infected women: the ELLA study.

INTRODUCTION: Global HIV-1 prevalence is 35.3 million [1]; women comprise >50% of those infected. The majority of women may lack regular care and only one-fourth are virologically suppressed [2]. ELLA is a cross-sectional, non-interventional study conducted across Europe, Latin America, Canada and Asia that describes barriers to care for HIV-infected women and associations with disease stage, symptoms and health-related quality of life (HRQoL). METHODS: HIV-infected women eligible for ELLA (≥18 years) completed: Barrier to Care Scale (BACS) comprising 12 items in four domains (Index range 0-12, Overall range 1-4, greater=more barriers, Overall score ≥2 considered severe); AIDS Clinical Trials Group (ACTG) Health Status Assessment comprising 21 items assessing 9 HRQoL domains (range 0-100, greater=better); and ACTG Symptom Distress Module comprising 20 symptoms rated on bother (range 0-4, greater=more bother). Healthcare providers documented medical history and HIV clinical data. Correlations of BACS response and last reported VL/CD4 count with HIV symptoms and HRQoL were analyzed. Spearman rank order was used to test correlations with statistical significance set at p<0.05. RESULTS: Enrollment: 1931 women from 30 countries; mean age 40 years (16.9% >50 years); 47.7% education <12 years; 36% unemployed; 82.9% urban residence. HIV was acquired heterosexually in 83.0%; 88.2% of subjects were on ART; 57.5% had VL<50 c/ml; mean CD4 was 540.5 c/µL. Mean [SD] BACS Index and Overall scores were 6.19 [3.47] (N=1818) and 2.09 [0.71] (N=1922), respectively. Stigma was a prominent barrier. Lower (better) BACS Index and Overall scores correlated with better HRQoL on all nine domains (p<0.0001). Lower VL and greater CD4 count were both correlated with better HRQoL for eight of nine domains (p<0.04, p≤0.0002, respectively) excepting pain. Lower BACS Index and Overall scores correlated with fewer symptom count and less symptom bother (p<0.0001). Fewer symptom count and less symptom bother correlated with better HRQoL on all nine domains (p<0.0001). While greater CD4 count correlated with fewer HIV symptoms and less bother (p<0.0001), VL did not significantly correlate with either. CONCLUSIONS: In HIV-infected women, reduced barriers to care correlated with fewer symptoms, less symptom bother and better HRQoL. Improved HRQoL may be mediated by greater CD4 counts and fewer symptoms. Better access to care may improve HRQoL outcomes in this population.

Olfactory neuron-specific expression of A30P α-synuclein exacerbates dopamine deficiency and hyperactivity in a novel conditional model of early Parkinson's disease stages.

Mutations in the N-terminus of the gene encoding α-synuclein (α-syn) are linked to autosomal dominantly inherited Parkinson's disease (PD). The vast majority of PD patients develop neuropsychiatric symptoms preceding motor impairments. During this premotor stage, synucleinopathy is first detectable in the olfactory bulb (OB) and brain stem nuclei; however its impact on interconnected brain regions and related symptoms is still less far understood. Using a novel conditional transgenic mouse model, displaying region-specific expression of human mutant α-syn, we evaluated effect and reversibility of olfactory synucleinopathy. Our data showed that induction of mutant A30P α-syn expression increased transgenic deposition into somatodendritic compartment of dopaminergic neurons, without generating fibrillar inclusions. We found reversibly reduced levels of dopamine and metabolites in the OB, suggesting an impact of A30P α-syn on olfactory neurotransmitter content. We further showed that mutant A30P expression led to neurodegenerative changes on an ultrastructural level and a behaviorally hyperactive response correlated with novelty, odor processing and stress associated with an increased dopaminergic tone in midbrain regions. Our present data indicate that mutant (A30P) α-syn is directly implicated in reduction of dopamine signaling in OB interneurons, which mediates further alterations in brain regions without transgenic expression leading functionally to a hyperactive response. These modulations of neurotransmission may underlie in part some of the early neuropsychiatric symptoms in PD preceding dysfunction of the nigrostriatal dopaminergic system.

Determinants of contraceptive choice among women with HIV.

OBJECTIVE: To examine factors associated with contraceptive choice among HIV-infected women. DESIGN: Data for this cross-sectional analysis were derived from baseline visits of 435 participants in an ongoing prospective study of contraception among HIV-infected women in Russia. Participants enrolled in one of four groups: combined oral contraceptives (COCs) along with condoms, depot medroxyprogesterone acetate (DMPA) along with condoms, copper intrauterine device (IUD) along with condoms, or condoms alone. METHODS: After contraceptive counseling and assessment of medical eligibility to use study methods, participants selected a method. Standardized interviews were used to collect demographic, reproductive and behavioral information. RESULTS: Most women were eligible to use COCs (89%) and DMPA (94%); 87% of nonpostpartum women were eligible to use the IUD. The method chosen by most women was condoms alone (47%), followed by COCs along with condoms (29%), DMPA along with condoms (20%) and IUD along with condoms (4%). In multivariable analyses, independent predictors of choosing a method highly effective during typical use (COCs, DMPA, or IUD) along with condoms included having at least two births (prevalence ratio = 1.4), postpartum enrollment (prevalence ratio = 1.3), desiring (prevalence ratio = 1.4), or uncertainty about desiring (prevalence ratio = 1.3) a future pregnancy, prior oral contraceptive use (prevalence ratio = 1.3), recent injection drug use (prevalence ratio = 1.3) and never (prevalence ratio = 2.3) or sometimes (prevalence ratio = 1.9) using condoms in the last year. CONCLUSION: Among HIV-infected women, several characteristics that may place women at greater risk for unintended pregnancy and its adverse consequences were associated with choice of highly effective contraceptive methods. These findings may aid in the development of interventions to increase use of effective contraception among HIV-infected women.