Characteristics of women diagnosed with mpox infection compared to men: A case series from Brazil.

BACKGROUND: Cisgender men were mostly affected during the 2022 mpox multinational outbreak, with few cases reported in women. This study compares the characteristics of individuals diagnosed with mpox infection according to gender in Rio de Janeiro. METHODS: We obtained surveillance data of mpox cases notified to Rio de Janeiro State Health Department (June 12 to December 15, 2022). We compared women (cisgender or transgender) to men (cisgender or transgender) using chi-squared, Fisher's exact, and Mood's median tests. RESULTS: A total of 1306 mpox cases were reported; 1188 (91.0%) men (99.8% cisgender, 0.2% transgender), 108 (8.3%) women (87.0% cisgender, 13.0% transgender), and 10 (0.8%) non-binary persons. Compared to men, women were more frequently older (40+years: 34.3% vs. 25.1%; p < 0.001), reported more frequent non-sexual contact with a potential mpox case (21.4% vs. 9.8%; p = 0.004), fewer sexual partnerships (10.9 vs. 54.8%; p < 0.001), less sexual contact with a potential mpox case (18.5% vs. 43.0%; p < 0.001), fewer genital lesions (31.8% vs. 57.9%; p < 0.001), fewer systemic mpox signs/symptoms (38.0% vs. 50.1%; p = 0.015) and had a lower HIV prevalence (8.3% vs. 46.3%; p < 0.001), with all cases among transgender women. Eight women were hospitalized; no deaths occurred. The highest number of cases among women were notified in epidemiological week 34, when the number of cases among men started to decrease. CONCLUSIONS: Women diagnosed with mpox presented differences in epidemiological, behavioral, and clinical characteristics compared to men. Health services should provide a comprehensive assessment that accounts for gender diversity.

Estradiol and Spironolactone Plasma Pharmacokinetics Among Brazilian Transgender Women Using HIV Pre-Exposure Prophylaxis: Analysis of Potential Interactions.

BACKGROUND AND OBJECTIVE: An important barrier to HIV prevention among transgender women (TGW) is the concern that oral pre-exposure prophylaxis (PrEP) negatively affects the efficacy of feminizing hormone therapy (FHT). We aimed to assess the impact of PrEP on FHT pharmacokinetics (PK) among TGW from Brazil. METHODS: We performed a drug-drug interaction sub-study among TGW enrolled in a daily oral PrEP demonstration study (PrEParadas, NCT03220152). Participants had a first PK assessment (PK1) 15 days after FHT (estradiol valerate 2-6 mg plus spironolactone 100-200 mg) initiation and then started PrEP (tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg). A second PK evaluation was performed 12 weeks later (PK2). Blood samples were collected prior and after the directly observed dosing (0, 0.5, 1, 2, 4, 6, 8, and 24 hours). Pharmacokinetic parameters of estradiol, spironolactone, and metabolites were estimated by non-compartmental analysis (Monolix 2021R2, Lixoft®) and compared as geometric mean ratios (GMRs, 90% confidence interval [CI]). RESULTS: Among 19 TGW who completed the substudy, median age was 26 years (interquartile range: 23-27.5). Estradiol area under the plasma concentration-time curve (AUCτ) and trough concentrations did not differ between PK1 and PK2 evaluations (GMR [90% CI]: 0.89 [0.76-1.04] and 1.06 [0.94-1.20], respectively). Spironolactone and canrenone AUCτ were statistically lower at PK2 than PK1 (0.76 [0.65-0.89] and 0.85 [0.78-0.94], respectively). Canrenone maximum concentration was also lower at PK2 than PK1 (0.82 [0.74-0.91]). CONCLUSION: Estradiol PK was not influenced by PrEP concomitant use. The small differences observed in some spironolactone and canrenone PK parameters should not prevent the concomitant use of estradiol-based FHT and PrEP. TRIAL REGISTRATION: This trial (NCT03220152) was registered on July 18, 2017.

A case report of vaccine-induced immune thrombotic thrombocytopenia (VITT) with genetic analysis.

The emergence of the rare syndrome called vaccine-induced immune thrombocytopenia and thrombosis (VITT) after adenoviral vector vaccines, including ChAdOx1 nCov-19, raises concern about one's predisposing risk factors. Here we report the case of a 56-year-old white man who developed VITT leading to death within 9 days of symptom onset. He presented with superior sagittal sinus thrombosis, right frontal intraparenchymal hematoma, frontoparietal subarachnoid and massive ventricular hemorrhage, and right lower extremity arterial and venous thrombosis. His laboratory results showed elevated D-dimer, C-reactive protein, tissue factor, P-selectin (CD62p), and positive anti-platelet factor 4. The patient's plasma promoted higher CD62p expression in healthy donors' platelets than the controls. Genetic investigation on coagulation, thrombophilia, inflammation, and type I interferon-related genes was performed. From rare variants in European or African genomic databases, 68 single-nucleotide polymorphisms (SNPs) in one allele and 11 in two alleles from common SNPs were found in the patient genome. This report highlights the possible relationship between VITT and genetic variants. Additional investigations regarding the genetic predisposition of VITT are needed.

Perspectives on Adherence From the ACTG 5360 MINMON Trial: A Minimum Monitoring Approach With 12 Weeks of Sofosbuvir/Velpatasvir in Chronic Hepatitis C Treatment.

BACKGROUND: With the advent of efficacious oral direct-acting antivirals (DAAs) for hepatitis C virus (HCV), identification of characteristics associated with adherence is critical to treatment success. We examined correlates of sub-optimal adherence to HCV therapy in a single-arm, multinational, clinical trial. METHODS: ACTG A5360 enrolled HCV treatment-naive persons without decompensated cirrhosis from 5 countries. All participants received a 12-weeks course of sofosbuvir/velpatasvir at entry. In-person visits occurred at initiation and week 24, sustained virologic response (SVR) assessment. Adherence at week 4 was collected remotely and was dichotomized optimal (100%, no missed doses) versus sub-optimal (<100%). Correlates of sub-optimal adherence were explored using logistic regression. RESULTS: In total, 400 participants enrolled; 399 initiated treatment; 395/397 (99%) reported completing at week 24. Median age was 47 years with 35% female. Among the 368 reporting optimal adherence at week 4 SVR was 96.5% (95% confidence interval [CI] [94.1%, 97.9%]) vs 77.8% (95% CI [59.2%, 89.4%]) P value < .001. In the multivariate model age <30 years and being a US participant were independently associated with early sub-optimal adherence. Participants <30 years were 7.1 times more likely to have early sub-optimal adherence compared to their older counterparts. CONCLUSIONS: Self-reported optimal adherence at week 4 was associated with SVR. Early self-reported adherence could be used to identify those at higher risk of treatment failure and may benefit from additional support. Younger individuals <30 years may also be prioritized for additional adherence support. Clinical Trials Registration. NCT03512210.

Low PrEP adherence despite high retention among transgender women in Brazil: the PrEParadas study.

INTRODUCTION: We aimed to evaluate daily oral pre-exposure prophylaxis (PrEP) uptake, retention, and adherence and predictors of study non-attendance and low PrEP adherence in a Brazilian trans-specific 48-week study (PrEParadas). METHODS: We enrolled transgender women (TGW) engaging in high-risk sexual behaviours between August 2017 and December 2018. PrEP adherence was based on tenofovir diphosphate concentrations in dried blood spots (DBS). We used random effects logistic regression models and ordinal models to estimate the odds of having a missed visit and of low PrEP adherence, respectively. Multivariable models were adjusted for variables with p-value<0.10 in the univariate analysis. RESULTS: From the 271 eligible, 130 participants were enrolled in the study (PrEP uptake: 48%), out of which 111 (85.4%) were retained at 48 weeks. Multivariable model for study non-attendance included study visit, age, main sexual partner and stimulant use. The odds of missing a visit increased after the week 24. Participants aged 18-24 (adjusted odds ratio [aOR] = 8.76, 95% CI: 2.09-36.7) and 25-34 years (aOR = 6.79, 95% CI: 1.72-26.8) compared to TGW aged 35+ years had significantly higher odds of having a missed visit. The odds of a missed visit were higher among participants reporting stimulant use (aOR = 4.99, 95% CI: 1.37-18.1) compared to no stimulant use. DBS levels at week 48 showed that 42 (38.5%), 14 (12.8%) and 53 (48.6%) of 109 participants had low, moderate and high PrEP adherence. Multivariable model for low PrEP adherence included study visit, age, schooling, race/colour, housing, binge drinking, stimulant use, feminizing hormone therapy (FHT) use and received text message. Low PrEP adherence was significantly higher among participants with less years of schooling (aOR = 6.71, 95% CI: 1.30-34.5) and had a borderline association with Black colour/race (aOR = 6.72, 95% CI: 0.94-47.8). Participants using the FHT available at the site had decreased odds of low PrEP adherence (aOR = 0.38, 95% CI: 0.16-0.88). No participant seroconverted over the course of the study. CONCLUSIONS: Although high PrEP retention can be achieved in a gender-affirming setting, PrEP adherence may be an important challenge faced among TGW due to social disparities. The scale-up of prevention tools like PrEP will have to address systemic social determinants as these stand as important barriers for TGW's access to health services.

A minimal monitoring approach for the treatment of hepatitis C virus infection (ACTG A5360 [MINMON]): a phase 4, open-label, single-arm trial.

BACKGROUND: Despite widespread availability of direct-acting antivirals including generic formulations, limited progress has been made in the global adoption of hepatitis C virus (HCV) treatment. Barriers to treatment scale-up include availability and access to diagnostic and monitoring tests, health-care infrastructure, and requirement for frequent visits during treatment. METHODS: ACTG A5360 was a phase 4, open-label, single-arm trial across 38 sites in Brazil, South Africa, Thailand, Uganda, and the USA. Key inclusion criteria were age of 18 years or older, evidence of active HCV infection (HCV RNA >1000 IU/mL) and HCV treatment-naive; patients with compensated cirrhosis and HIV/HCV co-infection were included but their enrolment was capped. All participants received a fixed dose combination of oral sofosbuvir (400 mg) and velpatasvir (100 mg) once daily for 12 weeks. The minimal monitoring (MINMON) approach consisted of four components: (1) there was no pre-treatment genotyping; (2) the entire treatment course (84 tablets) was dispensed at entry; (3) there were no scheduled visits or laboratory monitoring; and (4) there were two points of remote contact, at week 4 for adherence and week 22, to schedule outcome assessment at week 24 (-2 weeks to +4 weeks). Participants who missed the week 24 window could return for a visit to assess treatment response any time before week 72. Unplanned visits for any reason were permissible before the week 24 visit. The primary efficacy outcome was sustained virological response (SVR), defined as HCV RNA less than the lower limit of quantification measured at least 22 weeks post-treatment initiation; the primary safety outcome was serious adverse events. The primary efficacy analysis included all participants who initiated treatment, using a missing=failure approach. The primary safety analysis included all participants who initiated treatment and had at least one post-treatment assessment. This trial is registered at ClinicalTrials.gov, NCT03512210. FINDINGS: Between Oct 22, 2018, and July 19, 2019, 400 participants were enrolled across all 38 sites; 399 initiated treatment. At the SVR assessment visit, 355 (89%) of 397 participants reported taking 100% of the trial medication during the 12-week treatment period; two patients did not have any follow-up visits after the entry visit and were excluded from the safety analyses. Overall, 379 of the 399 who initiated treatment had an SVR (95·0%, 95% CI 92·4-96·7). 14 (4%) of 397 participants reported serious adverse events between treatment initiation and week 28; none were treatment related or led to treatment discontinuation or death. 15 (4%) of 399 participants had unplanned visits; none were related to treatment. INTERPRETATION: In this diverse global population of people with HCV, the MINMON approach with sofosbuvir-velpatasvir treatment was safe and achieved SVR comparable to standard monitoring observed in real-world data. Coupled with innovative case finding strategies, this strategy could be crucial to the global HCV elimination agenda. FUNDING: US National Institutes of Health and Gilead Sciences.

Standard dose raltegravir or efavirenz-based antiretroviral treatment for patients co-infected with HIV and tuberculosis (ANRS 12 300 Reflate TB 2): an open-label, non-inferiority, randomised, phase 3 trial.

BACKGROUND: In patients co-infected with HIV and tuberculosis, antiretroviral therapy options are limited due to drug-drug interactions with rifampicin. A previous phase 2 trial indicated that raltegravir 400 mg twice a day or efavirenz 600 mg once a day might have similar virological efficacy in patients given rifampicin. In this phase 3 trial, we assessed the non-inferiority of raltegravir to efavirenz. METHODS: We did a multicentre, open-label, non-inferiority, randomised, phase 3 trial at six sites in Côte d'Ivoire, Brazil, France, Mozambique, and Vietnam. We included antiretroviral therapy (ART)-naive adults (aged ≥18 years) with confirmed HIV-1 infection and bacteriologically confirmed or clinically diagnosed tuberculosis who had initiated rifampicin-containing tuberculosis treatment within the past 8 weeks. Using computerised random numbers, we randomly assigned participants (1:1; stratified by country) to receive raltegravir 400 mg twice daily or efavirenz 600 mg once daily, both in combination with tenofovir and lamivudine. The primary outcome was the proportion of patients with virological suppression at week 48 (defined as plasma HIV RNA concentration <50 copies per mL). The prespecified non-inferiority margin was 12%. The primary outcome was assessed in the intention-to-treat population, which included all randomly assigned patients (excluding two patients with HIV-2 infection and one patient with HIV-1 RNA concentration of <50 copies per mL at inclusion), and the on-treatment population, which included all patients in the intention-to-treat population who initiated treatment and were continuing allocated treatment at week 48, and patients who had discontinued allocated treatment due to death or virological failure. Safety was assessed in all patients who received at least one dose of the assigned treatment regimen. This study is registered with ClinicalTrials.gov, NCT02273765. FINDINGS: Between Sept 28, 2015, and Jan 5, 2018, 460 participants were randomly assigned to raltegravir (n=230) or efavirenz (n=230), of whom 457 patients (230 patients in the raltegravir group; 227 patients in the efavirenz group) were included in the intention-to-treat analysis and 410 (206 patients in the raltegravir group; 204 patients in the efavirenz group) in the on-treatment analysis. At baseline, the median CD4 count was 103 cells per µL and median plasma HIV RNA concentration was 5·5 log10 copies per mL (IQR 5·0-5·8). 310 (68%) of 457 participants had bacteriologically-confirmed tuberculosis. In the intention-to-treat population, at week 48, 140 (61%) of 230 participants in the raltegravir group and 150 (66%) of 227 patients in the efavirenz had achieved virological suppression (between-group difference -5·2% [95% CI -14·0 to 3·6]), thus raltegravir did not meet the predefined criterion for non-inferiority. The most frequent adverse events were HIV-associated non-AIDS illnesses (eight [3%] of 229 patients in the raltegravir group; 21 [9%] of 230 patients in the efavirenz group) and AIDS-defining illnesses (ten [4%] patients in the raltegravir group; 13 [6%] patients in the efavirenz group). 58 (25%) of 229 patients in raltegravir group and 66 (29%) of 230 patients in the efavirenz group had grade 3 or 4 adverse events. 26 (6%) of 457 patients died during follow-up: 14 in the efavirenz group and 12 in the raltegravir group. INTERPRETATION: In patients with HIV given tuberculosis treatment, non-inferiority of raltegravir compared with efavirenz was not shown. Raltegravir was well tolerated and could be considered as an option, but only in selected patients. FUNDING: National French Agency for AIDS Research, Ministry of Health in Brazil, Merck. TRANSLATIONS: For the Portuguese and French translations of the abstract see Supplementary Materials section.

Clinical and Virologic Outcomes After Changes in First Antiretroviral Regimen at 7 Sites in the Caribbean, Central and South America Network.

BACKGROUND: HIV-infected persons in resource-limited settings may experience high rates of antiretroviral therapy (ART) change, particularly because of toxicity or other nonfailure reasons. Few reports address patient outcomes after these modifications. METHODS: HIV-infected adults from the 7 Caribbean, Central and South America network clinical cohorts who modified >1 drug from the first ART regimen (ART-1) for any reason thereby starting a second regimen (ART-2) were included. We assessed cumulative incidence of, and factors associated with, death, virologic failure (VF), and regimen change after starting ART-2. RESULTS: Five thousand five hundred sixty-five ART-naive highly active ART initiators started ART-2 after a median of 9.8 months on ART-1; 39% changed to ART-2 because of toxicity and 11% because of failure. Median follow-up after starting ART-2 was 2.9 years; 45% subsequently modified ART-2. Cumulative incidences of death at 1, 3, and 5 years after starting ART-2 were 5.1%, 8.4%, and 10.5%, respectively. In adjusted analyses, death was associated with older age, clinical AIDS, lower CD4 at ART-2 start, earlier calendar year, and starting ART-2 because of toxicity (adjusted hazard ratio = 1.5 vs. failure, 95% confidence interval: 1.0 to 2.1). Cumulative incidences of VF after 1, 3, and 5 years were 9%, 19%, and 25%. In adjusted analyses, VF was associated with younger age, earlier calendar year, lower CD4 at the start of ART-2, and starting ART-2 because of failure (adjusted hazard ratio = 2.1 vs. toxicity, 95% confidence interval: 1.5 to 2.8). CONCLUSIONS: Among patients modifying the first ART regimen, risks of subsequent modifications, mortality, and virologic failure were high. Access to improved antiretrovirals in the region is needed to improve initial treatment success.