Nyt fra tidsskrifterne

by Lauren E. Parmley, Kieran Hartsough, Oliver Eleeza, Akopon Bertin, Bockarie Sesay, Amon Njenga, Mame Toure, Ginika Egesimba, Haja Bah, Alex Bayoh, Abdulraheem Yakubu, Ellen A. B. Morrison, Susan Michaels-Strasser After a decade of civil war and the 2014–2016 West African Ebola outbreak, Sierra Leone now faces the COVID-19 pandemic with a fragile health system. As was demonstrated during Ebola, preparedness is key to limiting a health crisis’ spread and impact on health systems and ensuring continued care for vulnerable populations including people living with HIV (PLHIV). To assess COVID-19 preparedness and inform interventions to ensure continuity of HIV services at health facilities (HFs) and community service points (CSPs), we conducted site readiness assessments in Freetown, the epicenter of COVID-19 in Sierra Leone. Data were collected at nine high-volume HIV HFs and seven CSPs in April 2020, a month after COVID-19 was declared a pandemic. CSPs comprised three community drop-in centers providing HIV counseling and testing services as well as HIV prevention services (e.g., condoms and lubricants) for key and priority populations and four community-based support groups serving PLHIV. At the time of assessment, CSPs did not provide antiretroviral therapy (ART) but were considered potential sites for expansion of differentiated service delivery (DSD)—a client-centered approach to HIV care—in the context of COVID-19. Overall, 5/9 HFs had trained staff on use of personal protective equipment (PPE) and prevention of COVID-19 transmission. Most had access to masks (5/9) and gloves (7/9) for management of suspected/confirmed COVID-19 cases, and 4/9 HFs had triage procedures for isolation of suspected cases. Conversely, few CSPs had access to masks (2/7) or gloves (2/7) and no staff were trained on PPE use or COVID-19 transmission. 7/9 HFs had adequate ART stock for multi-month dispensing though few had procedures for (3/9) or had trained staff in providing DSD (2/9). Among CSPs where measures were applicable, 2/4 had procedures for DSD, 1/3 had staff trained on DSD and none had adequate ART stock. Identification of gaps in COVID-19 preparedness is a critical step in providing support for infection control and modified service delivery. Findings from this assessment highlight gaps in COVID-19 preparedness measures at sites supporting PLHIV in Sierra Leone and indicate CSPs may require intensive supervision and training to ensure HIV services are uninterrupted while minimizing COVID-19 risk, especially if used as sites to scale up DSD.

by Dani Zoorob, Shivam Shah, Danielle La Saevig, Courtney Murphy, Shaza Aouthmany, Kris Brickman Background Acute augmentation of stress and disruption of training, such as during the COVID-19 pandemic, may impact resident wellbeing. Objectives We investigated how residents in various specialties in the United States were impacted by COVID-19 on mental wellbeing and resilience levels, and the methodology for coping with the stress incurred. Methods In April 2020, the authors electronically surveyed 200 residency programs of all specialties nationally. The survey utilized two validated questionnaires to assess wellbeing and resilience, while investigating demographics and coping mechanisms. The authors used student t-test and ANOVA to quantitatively analyze the data. Results The sample consisted of 1115 respondents (with an 18% response rate). Male gender & Age >39 years were associated with more favorable average well-being indices (both p<0.01). Regarding resources, institutional support (IS) appeared favorable for resident well-being (IS 2.74, SD1.96 vs NoIS 3.71, SD2.29, p<0.01) & resilience (IS 3.72, SD0.70 vs NoIS 3.53, SD0.73, p = 0.05). The effects of mindfulness practices (MP) were not statistically significant for improvement of wellness (MP 2.87, SD 1.99 vs No MP 2.76, SD 2.15, p = 0.85) or resilience (MP 3.71, SD 0.70 vs No MP 3.72, SD 0.68, p = 0.87). Conclusions Findings highlight the critical importance of resident mental status in cases of augmented stress situations. Institutional support may contribute to promotion of resident wellbeing.

Lacticaseibacillus rhamnosus GR-1 (LGR-1) (previously classified as Lactobacillus rhamnosus GR-1) is the most researched probiotic strain for women’s health. Its various urogenital health effects, including a reduction in the recurrence of bacterial vaginosis and urinary-tract infection, are well documented. The strain has also been safely used by HIV-positive subjects, a portion of whom have reported reduced diarrhea and increased CD4 counts. Unlike most probiotic strains used for urogenital health, LGR-1 has been extensively studied for its properties, including its genomic and metabolic traits and its surface properties.

by Selamawit Woldesenbet, Tendesayi Kufa-Chakezha, Carl Lombard, Samuel Manda, Mireille Cheyip, Kassahun Ayalew, Brian Chirombo, Peter Barron, Karidia Diallo, Bharat Parekh, Adrian Puren Introduction New HIV infection during pre-conception and pregnancy is a significant contributor of mother–to–child transmission of HIV in South Africa. This study estimated HIV incidence (defined as new infection within the last one year from the time of the survey which included both new infections occurred during pregnancy or just before pregnancy) among pregnant women and described the characteristics of recently infected pregnant women at national level. Methods Between 1 October and 15 November 2017, we conducted a national cross–sectional survey among pregnant women aged 15–49 years old attending antenatal care at 1,595 public facilities. Blood specimens were collected from pregnant women and tested for HIV in a centralised laboratory. Plasma viral load and Limiting Antigen Avidity Enzyme Immunosorbent Assay (LAg) tests were further performed on HIV positive specimens to differentiate between recent and long–term infections. Recent infection was defined as infection that occurred within one year from the date of collection of blood specimen for the survey. Data on age, age of partner, and marital status were collected through interviews. Women whose specimens were classified as recent by LAg assay and with viral loads >1,000 copies/mL were considered as recently infected. The calculated proportion of HIV positive women with recent infection was adjusted for assay–specific parameters to estimate annual incidence. Survey multinomial logistic regression was used to examine factors associated with being recently infected using HIV negative women as a reference group. Age–disparate relationship was defined as having a partner 5 or more years older. Results Of 10,049 HIV positive participants with LAg and viral load data, 1.4% (136) were identified as recently infected. The annual HIV incidence was 1.5% (95% confidence interval (CI): 1.2–1.7). In multivariable analyses, being single (adjusted odds ratio, aOR: 3.4, 95% CI: 1.8–6.2) or cohabiting (aOR: 3.8, 95% CI: 1.8–7.7), compared to being married as well as being in an age–disparate relationship among young women (aOR: 3.1, 95% CI: 2.0–4.7; reference group: young women (15–24years) whose partners were not 5 years or more older) were associated with higher odds of recent infection. Conclusions Compared to previous studies among pregnant women, the incidence estimated in this study was substantially lower. However, the UNAIDS target to reduce incidence by 75% by 2020 (which is equivalent to reducing incidence to…

Particle sorting is a fundamental method in various fields of medical and biological research. However, existing sorting applications are not capable for high-throughput sorting of large-size (>100 micrometers) particles. Here, we present a novel on-chip sorting method using traveling vortices generated by on-demand microjet flows, which locally exceed laminar flow condition, allowing for high-throughput sorting (5 kilohertz) with a record-wide sorting area of 520 micrometers. Using an activation system based on fluorescence detection, the method successfully sorted 160-micrometer microbeads and purified fossil pollen (maximum dimension around 170 micrometers) from lake sediments. Radiocarbon dates of sorting-derived fossil pollen concentrates proved accurate, demonstrating the method’s ability to enhance building chronologies for paleoenvironmental records from sedimentary archives. The method is capable to cover urgent needs for high-throughput large-particle sorting in genomics, metabolomics, and regenerative medicine and opens up new opportunities for the use of pollen and other microfossils in geochronology, paleoecology, and paleoclimatology.

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Objective: To describe the pharmacokinetics (PK), safety, and efficacy of etravirine (ETR) in HIV-infected children 1 to < 6 yrs. Design: Phase I/II, open label, multicenter, dose-finding study. Methods: Antiretroviral (ARV)-experienced children in two age cohorts (I: 2-…

Objective: To evaluate associations between hair antiretroviral (ARV) hair concentrations as an objective, cumulative adherence metric, with self-reported adherence and virologic outcomes. Design: Analysis of cohort A of the ACTG-A5288 study. These patients in resource-limited settings were failing second-line PI-based ART, but were susceptible to ≥1 NRTI and their PI, and continued taking their PI-based regimen. Methods: ARV hair concentrations participants taking 2 NRTIs with boosted atazanavir (n = 69) or lopinavir (n = 112) were analyzed at weeks 12, 24, 36 and 48 using liquid-chromatography-tandem-mass-spectrometry assays. Participants self-reported percentage of doses taken in the previous month; virologic failure (VF) was confirmed HIV-1 RNA≥1000 copies/mL at week 24 or 48. Results: From 181 participants with hair samples, (61% female median age: 39y; CD4 count: 167 cells/uL; HIV-1 RNA: 18,648 copies/mL), 91 (50%) experienced VF at either visit. At 24 weeks, median hair concentrations were 2.95 (IQR 0.49–4.60) ng/mg for atazanavir, 2.64 (IQR 0.73-7.16) for lopinavir, and 0.44 (IQR 0.11-0.76) for ritonavir. Plasma HIV-1 RNA demonstrated inverse correlations with hair levels (rs −0.46 to −0.74) at weeks 24 and 48. Weaker associations were seen with self-reported adherence (rs −0.03 to −0.24). Decreasing hair concentrations were significantly associated with VF, the hazard ratio (HR) (95%CI) for ATV, LPV and RTV were 0.69 (0.56-0.86), 0.77 (0.68–0.87), and 0.12 (0.06–0.27) respectively. Conclusions: PI hair concentrations showed stronger associations with subsequent virologic outcomes than self-reported adherence in this cohort. Hair adherence measures could identify individuals at risk of 2nd-line treatment failure in need of interventions. Correspondence to Tanakorn Apornpong, HIV-NAT, Thai Red Cross AIDS Research Centre, 104 Ratchadamri Road, Bangkok 10330 Thailand. Tel.: +662 652 3040, fax: +662 2254 7574; e-mail: tanakorn.a@hivnat.org Received 14 November, 2020 Revised 15 December, 2020 Accepted 21 December, 2020 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2021 Wolters Kluwer Health, Inc.

Objective: To evaluate the effect on anthropometric, metabolic and adipose tissue parameters of switching ART-controlled persons living with HIV (PLWH) from a protease-inhibitor regimen to raltegravir/maraviroc. Design: Substudy of ROCnRAL-ANRS157 with investigation of subcutaneous abdominal adipose tissue (SCAT) biopsy at inclusion and study end. Methods: We performed lipoaspiration of paired SCAT samples, histology on fresh/fixed samples and examined the transcriptomic profile analyzed using Illumina microarrays after RNA extraction. Statistical analyses used Wilcoxon-paired test. Results: The patients (n = 8) were mainly male (7/8), aged (mean±SEM) 54.9 ± 1.2 years, BMI 26.1 ± 1.2 kg/m2, CD4: 699 ± 56 cells/mm3, all viral load (VL)…

Objective: Previous studies indicate that transmitted/founder HIV-1 isolates are sensitive to neutralization by the transmitting donor's antibodies. This is true in at least a subset of sexual transmissions. We investigated whether this selection for neutralization-sensitive variants begins in the genital tract of the donor, prior to transmission. Design: Laboratory study. Methods: HIV-1 viruses from semen and blood of two male donors living with HIV-1 were tested for neutralization sensitivity to contemporaneous autologous antibodies. Results: In one donor, semen-derived clones (n = 10, geometric mean ID50 = 176) were 1.75 fold (95%CI 1.11–2.76, p = 0.018) more sensitive than blood-derived clones (n = 12, geometric mean ID50 = 111) to the individual's own contemporaneous neutralizing antibodies. Enhanced overall neutralization sensitivity of the semen-derived clones could not explain the difference because these semen-derived isolates showed a trend of being less sensitive to neutralization by a pool of heterologous clade-matched sera. This relative sensitivity of semen-derived clones was not observed in a second donor who did not exhibit obvious independent HIV-1 replication in the genital tract. A Bayesian analysis suggested that the set of semen sequences that we analysed originated from a blood sequence. Conclusions: In some instances, selection for neutralization sensitive variants during HIV-1 transmission begins in the genital tract of the donor and this may be driven by independent HIV-1 replication in this compartment. Thus, a shift in the selective milieu in the male genital tract allows outgrowth of neutralization-sensitive HIV-1 variants, shaping the population of isolates available for transmission to a new host. Correspondence to Jeffrey R. Dorfman, PhD, University of Cape Town, Cape Town, South Africa; e-mail: jeffrey.dorfman@uct.ac.za Received 16 June, 2020 Revised 11 March, 2021 Accepted 30 March, 2021 Copyright © 2021 Wolters Kluwer Health, Inc.

Objectives: People living with HIV are exposed to a higher risk of coronary artery disease (CAD) compared to the general population. Epicardial fat may play a unique role in promoting coronary atherosclerosis. We measured epicardial fat in participants living with HIV and controls and investigated its association with coronary plaque volume and low attenuation plaque, a marker of plaque vulnerability. Design: This is a cross sectional study, nested in the Canadian HIV and Aging Cohort Study, a large prospective cohort actively following participants with HIV and controls. Participants with low/intermediate cardiovascular risk without symptoms/history of CAD were invited to undergo cardiac computed tomography (CT). Methods: Volume of epicardial fat, coronary plaque and low attenuation component of the plaque were measured. Association between epicardial fat, coronary plaque volume and low attenuation component was tested using adjusted regression analysis. Results: A total of 169 participants with HIV and 81 controls underwent cardiac CT. Participants with HIV had a greater epicardial fat volume compared to controls (p = 0.019). In participants with HIV, epicardial fat volume was positively associated with duration of non-nucleoside reverse transcriptase inhibitors (NNRTI) (β=2.19, p = 0.004). After adjustment for cardiovascular risk factors, epicardial fat volume was positively associated to non-calcified plaque volume (OR = 1.09, p = 0.028) and to the low attenuation plaque component portion (β=0.38, p = 0.026). Conclusion: The association of epicardial fat volume to non-calcified plaque volume and to low attenuation component plaque may suggest a potential mechanism by which epicardial fat could be a silent driver of CAD in the HIV population. Correspondence to Carl Chartrand-Lefebvre, MD, MSc, Radiology Department, CHUM (University of Montreal Medical Center), 1051, Sanguinet street, Montréal (Québec) H2X 0C1. Tel: +514 890 8450; e-mail: chartrandlef@videotron.ca. Received 22 October, 2020 Revised 15 February, 2021 Accepted 16 March, 2021 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2021 Wolters Kluwer Health, Inc.

In this randomized, single-center, open-label, 96-week, superiority, controlled trial of 50 HIV-infected patients with HIV-RNA…

Objectives: Gaps between recommended and actual levels of HIV preexposure prophylaxis (PrEP) use remain among men who have sex with men (MSM). Interventions can address these gaps, but it is unknown how public health initiatives should invest prevention funds into these interventions to maximize their population impact. Design: We used a stochastic network-based HIV transmission model for MSM in the Atlanta area paired with an economic budget optimization model. Methods: The model simulated MSM participating in up to three real-world PrEP cascade interventions designed to improve initiation, adherence, or persistence. The primary outcome was infections averted over 10 years. The budget optimization model identified the investment combination under different budgets that maximized this outcome given intervention costs from a payer perspective. Results: From the base 15% PrEP coverage level, the three interventions could increase coverage to 27%, resulting in 12.3% of infections averted over 10 years. Uptake of each intervention was interdependent: maximal use of the adherence and persistence interventions depended on new PrEP users generated by the initiation intervention. As the budget increased, optimal investment involved a mixture of the initiation and persistence interventions, but not the adherence intervention. If adherence intervention costs were halved, the optimal investment was roughly equal across interventions. Conclusions: Investments into the PrEP cascade through initiatives should account for the interactions of the interventions as they are collectively deployed. Given current intervention efficacy estimates, the total population impact of each intervention may be improved with greater total budgets or reduced intervention costs. Correspondence to Samuel M. Jenness, Emory University, 1520 Clifton Road, Atlanta, GA 30323; e-mail: samuel.m.jenness@emory.edu. Received 4 January, 2021 Revised 21 March, 2021 Accepted 31 March, 2021 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2021 Wolters Kluwer Health, Inc.

Objective: The objective of this study was to compare HIV-negative cisgender women (CGW) with MSM for mucosal tissue differences in pharmacokinetics, HIV infectivity and cell phenotype. Design: A substudy of HPTN 069/ACTG A5305, 48-week study of three oral candidate preexposure prophylaxis regimens: maraviroc, maraviroc/emtricitabine and maraviroc/tenofovir disoproxil fumarate (TDF) compared with a TDF/emtricitabine control group. Methods: Plasma, peripheral blood mononuclear cells and cervical and colorectal tissue biopsies were collected at Baseline (no drug), Week 24 and 48 (on drug), and Week 49 (1-week postdrug). Drug concentrations were assessed in all matrices. HIV infectivity was assessed using tissue biopsy ‘explants’ challenged with HIV ex vivo followed by HIV p24 measurement. Flow cytometry evaluated colorectal cell phenotype. Results: Thirty-seven CGW and 54 MSM participated. CGW's colorectal explant p24 was higher than MSM before (0.31 log10, P = 0.046), during (1.01-1.19 log10, P = 0.016) and one week after (0.61 log10, P = 0.011) study drug dosing. Pooling regimens, cervical explant p24 did not differ among visits. CGW had higher plasma maraviroc and colorectal tissue tenofovir diphosphate and lower colorectal tissue emtricitabine (all P …

Treatment with tenofovir disoproxil fumarate (TDF) has been associated with hypophosphatemia mainly due to injury of the renal proximal tubulus. Studies on the impact of tenfovir alafenamid (TAF) on phosphate homeostasis in PLHIV are limited. Prompted by a patient with phosphate wasting under tenofovir but no other evidence for tubular dysfunction, a retrospective cohort analysis with 102 people living with HIV (PLHIV) revealed that hypophosphatemia remained largely unchanged after switching from TDF to TAF. Correspondence to Professor Georg M.N. Behrens, Department for Rheumatology and Clinical Immunology, Hannover Medical School, Carl-Neuberg-Straße 1, D - 30625 Hannover, Germany. Tel.: +49 511 532 5337; fax: +49 511 532 5324; e-mail: behrens.georg@mh-hannover.de Received 11 March, 2021 Accepted 28 March, 2021 Copyright © 2021 Wolters Kluwer Health, Inc.

Objective: People with HIV (PWH) experience increased prevalence of obstructive lung disease (OLD), regardless of greater observed smoking behaviors. We investigated whether the effect of incident OLD on mortality differed by HIV and HIV viral suppression among persons who inject drugs (PWID) and report smoking history. Design: ALIVE is a longitudinal, observational cohort study of HIV-positive and seronegative PWID. This analysis included participants who had at least one spirometry measure to assess OLD between 2007 and 2016, excluding those who never smoked (5%, n = 62) or had baseline OLD (17%, n = 269). Methods: Incident OLD occurred when the first pre-bronchodilator FEV1/FVC…

The Coronavirus disease 2019 (COVID-19) pandemic continues with 122.5 million cases and over 2.7 million deaths reported by the World Health Organization on the 23rd of March 2021(WHO, 2021). The virus has more impact onimmunocompromised patients such as cancer patients (Belsky, 2021, Jindal, 2020), stem cell transplant patients (Belsky, 2021, Sahu, 2020), HIV patients (Patel, 2021), solid organ transplant recipients (Belsky, 2021) including heart transplant patients (Marcondes-Braga, 2021). We present a case of COVID-19-related post-myocarditis state on MRI late after initial infection in a HT recipient.

An amendment to this paper has been published and can be accessed via the original article.

Journal of Medical Virology, Accepted Article.

Abstract Background Existing evidence showed that Human Immunodeficiency Virus counselling and testing uptake among Ethiopian youths is low, and factors contributing to it are not well studied. Therefore, this study aims to assess the status of uptake and identify its determinants using the 2016 Ethiopia Demographic and Health Survey data. Method Data of 10,903 Ethiopian youths were extracted from the 2016 Ethiopian Demographic and Health Survey. The association between the response variable and the predictors was modeled by multilevel binary logistic regression, whereas adjusted odds ratio and confidence intervals were used to measure associations and their statistical significance. The variation in the uptake of counselling and testing of HIV across regions of Ethiopia was quantified by intra-class correlation. Result The current study revealed that, overall, 34.9% (95% CI: 33.5, 36.2%) Ethiopian youths were ever tested for human immunodeficiency virus. Results show that about 9% of the variation in the probability of being tested for the disease was due to the regional variations. Moreover, having moderate and comprehensive HIV knowledge, being rich, having risky sexual behaviour, having a better educational level, having professional work, being married, owning of mobile, and having access to media were positively associated with human immunodeficiency virus voluntary counselling and testing uptake. On the other hand, being male, following protestant religion, following Muslim religion, and following other religions than orthodox religion were negatively associated with the uptake of human immunodeficiency virus counselling and testing. Conclusion Voluntary human immunodeficiency virus counselling and testing uptake among Ethiopian youths is very low and varies across the regions which might hamper the ambitious plan of Ethiopia to end the disease as a public health threat by 2030. Emphasis should be given to promoting the youths’ HIV-related knowledge through community-based education, encouraging and empowering the youths to participate in professional works by giving due focus to poor youths, and promoting mass media utilization to better achieve the plan.

Objective Youth represent a population disparately impacted by the HIV epidemic. With most new HIV diagnoses occurring among adolescents and young adults, novel approaches to address this disparity are necessary. The objective of the current study was to describe the Youth to Telehealth and Text to Improve Engagement in Care (Y2TEC) intervention, which aims to fill this gap. The Y2TEC intervention (trial registration NCT03681145) offers an innovative approach to improve HIV treatment engagement among youth living with HIV by focusing on treatment barriers related to mental health and substance use. This allows for a holistic approach to providing culturally informed intervention strategies for this population. Participants and setting The Y2TEC intervention was developed for youth with HIV in the large metropolitan area of the San Francisco Bay Area. The Y2TEC intervention was developed based on formative interdisciplinary research and is grounded in the information–motivation–behavioural skills model. Results The intervention includes 12 sessions each lasting 20–30 minutes, which are delivered through videoconferencing and accompanying bidirectional text messaging. The intervention sessions are individualised, with session dosage in each major content area determined by participant’s level of acuity. Conclusions The Y2TEC intervention is well positioned to help decrease HIV-related disparities in youth living with HIV through its innovative use of video-counselling technologies and an integrated focus on HIV, mental health and substance use.

by Agajie Likie Bogale, Tilahun Teklehaymanot, Jemal Haidar Ali, Getnet Mitike Kassie Background To establish successful strategies and increasing the utilization of preventive services, there is a need to explore the extent to which the general female population is aware and use the service for cervical cancer-screening among women infected with HIV in Africa. Available evidences in this regard are controversial and non-conclusive on this potential issue and therefore, we estimated the pooled effect of the proportion of knowledge, attitude and practice of HIV infected African women towards cervical cancer screening to generate evidence for improved prevention strategies. Methods We applied a systematic review and meta-analysis of studies conducted in Africa and reported the proportion of knowledge, attitude and practice towards cervical cancer screening. We searched electronic databases: PubMed/Medline, SCOPUS, ScienceDirect, Web of science, Cumulative Index of Nursing and allied Health Sciences (CINAHL) and Google scholar databases to retrieve papers published in English language till August 2020. We used random-effects model to estimate the pooled effect, and funnel plot to assess publication bias. The registration number of this review study protocol is CRD42020210879. Results In this review, we included eight published papers comprising 2,186 participants. The estimated pooled proportion of knowledge of the participants was 43.0% (95%CI:23.0–64.0) while the pooled estimates of attitudes and practices were 38.0% (95%CI: 1.0–77.0) and 41.0% (95%CI: 4.0–77.0), respectively. The proportion of the outcome variables were extremely heterogeneous across the studies with I2> 98%). Conclusion The pooled estimates of knowledge, attitude and practice were lower than other middle income countries calls for further activities to enhance the uptake of the services and establish successful strategies.

by Sozinho Acácio, Tacilta Nhampossa, Llorenç Quintò, Delfino Vubil, Marcelino Garrine, Quique Bassat, Tamer Farag, Sandra Panchalingam, James P. Nataro, Karen L. Kotloff, Myron M. Levine, Sharon M. Tennant, Pedro L. Alonso, Inácio Mandomando Background Rotavirus vaccines have been adopted in African countries since 2009, including Mozambique (2015). Disease burden data are needed to evaluate the impact of rotavirus vaccine. We report the burden of rotavirus-associated diarrhea in Mozambique from the Global Enteric Multicenter Study (GEMS) before vaccine introduction. Methods A case-control study (GEMS), was conducted in Manhiça district, recruiting children aged 0–59 months with moderate-to-severe diarrhea (MSD) and less-severe-diarrhea (LSD) between December 2007 and November 2012; including 1–3 matched (age, sex and neighborhood) healthy community controls. Clinical and epidemiological data and stool samples (for laboratory investigation) were collected. Association of rotavirus with MSD or LSD was determined by conditional logistic regression and adjusted attributable fractions (AF) calculated, and risk factors for rotavirus diarrhea assessed. Results Overall 915 cases and 1,977 controls for MSD, and 431 cases and 430 controls for LSD were enrolled. Rotavirus positivity was 44% (217/495) for cases and 15% (160/1046) of controls, with AF = 34.9% (95% CI: 32.85–37.06) and adjusted Odds Ratio (aOR) of 6.4 p< 0.0001 in infants with MSD compared to 30% (46/155) in cases and 14% (22/154) in controls yielding AF = 18.7%, (95% CI: 12.02–25.39) and aOR = 2.8, p = 0.0011 in infants with LSD. The proportion of children with rotavirus was 32% (21/66) among HIV-positive children and 23% (128/566) among HIV-negative ones for MSD. Presence of animals in the compound (OR = 1.9; p = 0.0151) and giving stored water to the child (OR = 2.0, p = 0.0483) were risk factors for MSD; while animals in the compound (OR = 2.37, p = 0.007); not having routine access to water on a daily basis (OR = 1.53, p = 0.015) and washing hands before cooking (OR = 1.76, p = 0.0197) were risk factors for LSD. Conclusion The implementation of vaccination against rotavirus may likely result in a significant reduction of rotavirus-associated diarrhea, suggesting the need for monitoring of vaccine impact.

by Lin Chen, Mingyu Luo, Yun Xu, Yan Xia, Xin Zhou, Wanjun Chen, Hui Wang, Tingting Jiang, Weiyong Chen, Yan Luo, Qiaoqin Ma, Jianmin Jiang, Xiaohong Pan To analyze the results of HIV screening and the HIV-positive rate based on different HIV detection strategies in Zhejiang Province, China. Data were downloaded from the AIDS Prevention and Control Information System on May 1, 2019. HIV screening, prevalence, and incidence data were analyzed from 2008 to 2018. The incidence of HIV was calculated from the results of BED testing. SPSS software (ver. 19.0) was used for the analysis. The number of people screened for HIV increased by 229.7% from 2008 to 2018, while the incidence of HIV increased from 1.14‱ (2010) to 1.67‱ (2018), peak by 2015 (2.28‱). The proportion of people screened for HIV in medical institutions increased from 62.0% in 2008 to 67.1% in 2018, while of all positive tests, 47.9% were conducted at medical institutions in 2008, which increased to 63.2% in 2018. VCT and STD clinic attendees, who had only 4.5% of all those undergoing HIV tests, accounted for 23.7% of all HIV positive in 2018. The rate of HIV-positive people and incidence of HIV both increased in Zhejiang Province between 2008 and 2015. The most effective strategy for detecting HIV new cases is screening visitors to VCT and STD clinics.

AbstractBackgroundThere are limited data on individual human immunodeficiency virus (HIV) viral load (VL) trajectories at the population-level after the introduction of universal test and treat (UTT) in sub-Saharan Africa.MethodsHuman immunodeficiency virus VLs were assessed among HIV-positive participants through 3 population-based surveys in 4 Ugandan fishing communities surveyed between November 2011 and August 2017. The unit of analysis was a visit-pair (2 consecutive person-visits), which were categorized as exhibiting durable VL suppression, new/renewed VL suppression, viral rebound, or persistent viremia. Adjusted relative risks (adjRRs) and 95% confidence intervals (CIs) of persistent viremia were estimated using multivariate Poisson regression.ResultsThere were 1346 HIV-positive participants (n = 1883 visit-pairs). The population-level prevalence of durable VL suppression increased from 29.7% to 67.9% during UTT rollout, viral rebound declined from 4.4% to 2.7%, and persistent viremia declined from 20.8% to 13.3%. Younger age (15–29 vs 40–49 years; adjRR = 1.80; 95% CI = 1.19–2.71), male sex (adjRR = 2.09, 95% CI = 1.47–2.95), never being married (vs currently married; adjRR = 1.88, 95% CI = 1.34–2.62), and recent migration to the community (vs long-term resident; adjRR = 1.91, 95% CI = 1.34–2.73) were factors associated with persistent viremia.ConclusionsDespite increases in durable VL suppression during roll out of UTT in hyperendemic communities, a substantial fraction of the population, whose risk profile tended to be younger, male, and mobile, remained persistently viremic.

AbstractBackground We investigated whether higher-intensity exercise provided greater decrease in markers of inflammation, and whether responses differed by HIV serostatus.MethodsPeople with HIV (PWH; n = 32) and controls (n = 37) aged 50–75 years completed 12 weeks moderate-intensity exercise, then were randomized to moderate- or high-intensity exercise for 12 additional weeks (n = 27 and 29, respectively). Inflammation biomarkers were measured at 0, 12, 24 weeks. Mixed and multiple regression models were adjusted for baseline inflammation, age, and body mass index.ResultsBaseline tumor necrosis factor-α (TNF-α), soluble TNF receptor 2 (sTNFR2), and soluble CD14 (sCD14) were significantly higher among PWH than controls (P < .04). From week 0–12, changes in interleukin-6 (IL-6), TNF-α, and sTNFR1 were not significantly different by HIV serostatus. We found no significant interaction between HIV serostatus/exercise intensity on week 12–24 changes in IL-6, TNF-α, and sTNFR1. Among high-intensity exercisers, PWH and controls had significant increases in sCD14 (P ≤ .003), controls significant increases in IL-10 (P = .01), and PWH nonsignificant decrease in highly sensitive C-reactive protein (P = .07). Other markers were not significantly different by serostatus or intensity.ConclusionsModerate and high-intensity exercise elicited similar effects on inflammation among PWH and controls, with additional beneficial effects seen among high-intensity exercisers. Increase in sCD14 and attenuated IL-10 increase (PWH only) merit further study.Clinical Trials RegistrationNCT02404792.

AbstractBackgroundImmune reconstitution inflammatory syndrome (IRIS) is a common cause of morbidity among people with human immunodeficiency virus (PWH) who initiate antiretroviral therapy (ART) with severe lymphopenia. Easily accessible tools that reliably predict emergence and elucidate pathogenesis of IRIS are needed to facilitate improved clinical management.MethodsPlasma levels of biomarkers were measured before ART initiation in a large multinational cohort of ART-naive PWH with severe immunosuppression (CD4+ count <100 cells/mm3) in United States, Kenya, and Thailand. We performed a series of multiparametric analyses of inflammatory and clinical biomarkers and developed a composite score merging relevant biomarkers for use in a prediction model.ResultsWe identified a distinct baseline inflammatory profile and changes in inflammatory networks among biomarkers in participants who subsequently developed mycobacterial or viral IRIS. We also developed a composite score incorporating biomarkers associated with IRIS (interleukin-6 [IL-6], IL-10, IL-27, sCD14, interferon-γ, tumor necrosis factor-α, hyaluronic acid, D-dimer, body mass index, and hemoglobin) that accurately predicted mycobacterial IRIS and death in this cohort.ConclusionsSystemic inflammatory profiles in PWH with severe immunosuppression are predictive of IRIS. Composite scores for the prediction of mycobacterial IRIS and death could be useful for risk stratification in PWH and lymphopenia initiating ART.Clinical Trials Registration NCT00286767.

AbstractCryptococcal antigen (CrAg) detection could direct the timely initiation of antifungal therapy. We searched MEDLINE and Embase for studies where CrAg detection in serum/cerebrospinal fluid (CSF) and CSF fungal culture were done on adults living with human immunodeficiency virus (HIV) who had suspected cryptococcal meningitis (CM). With Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2), we evaluated the risk of bias in 11 included studies with 3600 participants, and used a random-effects meta-analysis to obtain summary sensitivity and specificity of serum and CSF CrAg, as well as agreement between CSF CrAg and CSF culture. Summary sensitivity and specificity of serum CrAg were 99.7% (97.4–100) and 94.1% (88.3–98.1), respectively, and summary sensitivity and specificity of CSF CrAg were 98.8% (96.2–99.6) and 99.3% (96.7–99.9), respectively. Agreement between CSF CrAg and CSF culture was 98% (97–99). In adults living with HIV who have CM symptoms, serum CrAg negativity may rule out CM, while positivity should prompt induction antifungal therapy if lumbar puncture is not feasible. In a first episode of CM, CSF CrAg positivity is diagnostic.

AbstractBackgroundPersons living with human immunodeficiency virus (HIV) are at elevated risk of developing the malignant diseases that require allogeneic stem cell transplantation (ASCT). Recent data suggest that these individuals are also at an elevated risk of certain complications post-ASCT. This risk may result from preexisting HIV-related factors affecting dynamics of immune reconstitution post-ASCT. However, to date, there has been little work describing the dynamics of immune reconstitution post-ASCT in persons with HIV and none comparing these data to controls without HIV.MethodsWe assessed T-cell reconstitution in 6 ASCT with HIV recipients (HIV+ASCT) compared to a control population of 21 ASCT without HIV recipients. In a subset of HIV+ASCT recipients we performed additional flow cytometry profiling of CD8+ T-cell subsets and antigen specificity of reconstituting CD4+ and CD8+ T cells.ResultsWe observe no difference in post-ASCT CD4+ T cells between HIV+ASCT and HIV-negative ASCT recipients, despite much lower pre-ASCT CD4+ T-cell counts in the HIV+ASCT group. In contrast, we observed significantly higher CD8+ T-cell numbers in the HIV+ASCT group post-ASCT. The reconstituting CD8+ T-cells were predominantly CD45RO+, whereas homing markers and antigen specificity of these cells varied between participants.ConclusionThis study represents the most extensive characterization of immune-reconstitution post-ASCT in persons with HIV, and the first to our knowledge to compare these data to ASCT controls without HIV. The results indicate that immune reconstitution in this group can be affected by preexisting HIV infection and post-ASCT antigen exposure.

Abstract Background Previous studies have reported that presence and severity of Buruli ulcer (BU) may reflect the underlying immunosuppression in HIV infected individuals by causing increased incidence of multiple, larger and ulcerated lesions. We report cases of BU-HIV coinfection and the accompanying programmatic challenges encountered in central Ghana. Methods Patients with PCR confirmed BU in central Ghana who were HIV positive were identified and their BU01 forms were retrieved and reviewed in further detail. A combined 16S rRNA reverse transcriptase / IS2404 qPCR assay was used to assess the Mycobacterium ulcerans load. The characteristics of coinfected patients (BU+HIV+) were compared with a group of matched controls. Results The prevalence of HIV in this BU cohort was 2.4% (compared to national HIV prevalence of 1.7%). Eight of 9 BU+HIV+ patients had a single lesion and ulcers were the most common lesion type. The lesions presented were predominantly category II (5/9) followed by category I lesions. The median (IQR) time to healing was 14 (8–28) weeks in the BU+HIV+ compared to 28 (12–33) weeks in the control BU+HIV− group (p = 0.360). Only one BU+HIV+ developed a paradoxical reaction at week 16 but the lesion healed completely at week 20. The median bacterial load (16SrRNA) of BU+HIV+ patients was 750 copies /ml (95% CI 0–398,000) versus 500 copies/ml (95% CI 0–126,855,500) in BU+HIV− group. Similarly, the median count using the IS2404 assay was 500 copies/ml (95% CI 0–500) for BU+HIV+ patients versus 500 copies/ml (95% CI 500–31,000) for BU+HIV− patients. BU+HIV− patients mounted a significantly higher interferon-γ response compared to the BU+HIV+ co-infected patients with respective median (range) responses of [1687(81.11–4399) pg/ml] versus [137.5(4.436–1406) pg/ml, p = 0.03]. There were challenges with the integration of HIV and BU care in this cohort. Conclusion The prevalence of HIV in the BU+ infected population was not significantly increased when compared to the prevalence of HIV in the general population. There was no clear relationship between BU lesion severity and HIV viral load or CD4 counts. Efforts should be made to encourage the integration of care of patients with BU-HIV coinfection.

Journal Name: The American Journal of Tropical Medicine and HygieneVolume: 104Issue: 4Pages: 1222-1224…

by Aminu Abba Yusuf, Baba Maiyaki Musa, Najibah Aliyu Galadanci, Musa Babashani, Aminu Zakari Mohammed, Donna J. Ingles, Agnes B. Fogo, C. William Wester, Muktar Hassan Aliyu Background HIV-positive persons of African descent are disproportionately affected by chronic kidney disease (CKD). Deterioration to end-stage kidney disease (ESKD) also occurs in this population at a higher frequency. There remains a lot to learn about the genetic susceptibility to CKD in HIV positive patients, and the pathophysiology of progression to ESKD. Objectives We will conduct an exploratory genotype-phenotype study in HIV-positive persons with CKD in Aminu Kano Teaching Hospital, Nigeria, to determine blood-based differential gene expression biomarkers in different kidney risk groups according to the KDIGO 2012 criteria. Methods We will consecutively screen 150 HIV-positive adults (≥18 years of age) attending the HIV clinic of Aminu Kano Teaching Hospital, Kano, Nigeria, for CKD based on proteinuria and elevation of estimated glomerular filtration rate. Among these, two separate groups of 16 eligible participants each (n = 32) will be selected in the four (4) KDIGO 2012 kidney risk categories. The groups will be matched for age, sex, viral suppression level and antiretroviral (ARV) regimen. In the first group (n = 16), we will determine differential gene expression markers in peripheral blood mononuclear cells using mRNA-sequencing (RNA-Seq). We will validate the differential expression markers in the second group (n = 16) using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Using a systems-based approach, we will construct, visualize and analyze gene-gene interaction networks to determine the potential biological roles of identified differential expression markers based on published literature and publicly available databases. Results Our exploratory study will provide valuable information on the potential roles of differential expression biomarkers in the pathophysiology of HIV-associated kidney disease by identifying novel biomarkers in different risk categories of CKD in a sub-Saharan African population. The results of this study will provide the basis for population-based genome-wide association studies to guide future personalized medicine approaches. Conclusion Validated biomarkers can be potential targets for the development of stage-specific therapeutic interventions, an essential paradigm in precision medicine.

Objective: This study examined interactions between simian immunodeficiency virus (SIV), chronic binge alcohol (CBA), and antiretroviral therapy (ART) on growth factor signaling, neuroinflammatory markers, viral loads (VL), and CD4 counts. Design: Adult male rhesus macaques were administered CBA (13–14 g EtOH/kg/week) or sucrose (SUC) three months prior to SIVmac251 infection until study endpoint. At viral setpoint, a subset of CBA/SIV+ and SUC/SIV+ macaques were randomized to receive daily ART (PMPA 20 mg/kg, FTC, 30 mg/kg). Frontal cortex (FC) and basal ganglia (BG) were collected for gene and protein expression. Methods: Relationships between brain and plasma VL or CD4 counts were determined using linear regression. Effects of SIV, CBA, and ART on markers of neuroinflammation and brain-derived neurotropic factor (BDNF) signaling were determined by ANOVA and linear regression. Results: SIV increased FC and BG neuroinflammatory and glial cell gene expression (CX3CR1, B2 M), and reduced FC AKT phosphorylation. CBA decreased FC and BG TrkB phosphorylation, and increased TrkB-FL and SLC1A3 expression in FC and BG, respectively. ART suppressed plasma and brain VL, reduced neuroinflammatory gene expression in FC (IBA1, CX3CR1, and GFAP), and BG (CD74 and CD11ß), and did not restore FC or BG BDNF signaling deficits. Conclusions: Results show ART-mediated reduction in VL and neuroinflammatory gene expression, irrespective of CBA administration. ART did not attenuate SIV- and CBA-mediated BDNF signaling deficits, suggesting these deficits, despite effective neuroinflammation suppression, may explain CBA- and SIV-associated neurocognitive deficits. Therapeutics targeting growth factor signaling may be important adjuvants in treating HIV-associated neurocognitive decline. Correspondence to Dr. Patricia E. Molina, Department of Physiology, LSUHSC, 1901 Perdido Street, P7-3, New Orleans, LA 70112. Tel.: 504-568-6187; e-mail: pmolin@lsuhsc.edu Received 13 August, 2020 Revised 9 March, 2021 Accepted 16 March, 2021 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2021 Wolters Kluwer Health, Inc.

Objectives: To study the impact of late presentation (CD4 0.4 and >1) multiple T-cell marker recovery (MTMR): CD4+ >500 cells/μL plus CD4% >29% plus CD4/CD8 >1), and treatment discontinuation due to adverse events (TDAE) at 48 weeks from ART initiation. Results: Of 8,002 participants, 48.7% were LP. Of them 45.8% initiated ART with a NNRTI- (mostly TDF/FTC/EFV), 33.9% with a PI- (mostly TDF/FTC+boosted DRV) and 20.3% with an INI-based regimen (mostly ABC/3TC/DTG). At 48 weeks, LP had similar VS, but worse IR, than non-LP with no difference on TDAE. LP initiating with NNRTI- based regimens were more likely to achieve VS than those starting with INI-based, due to the higher chance of achieving VS observed with TDF/FTC/RPV compared to ABC/3TC/DTG. Initial treatment with NNRTI- or PI-based showed similar IR than the INI-based regimens, which showed lower rates of TDAE than NNRTI- and PI-based regimens. Conclusions: Despite safety and effectiveness of initial ART in terms of VS, LP may not experience complete IR. In LP, effectiveness and safety depends on both the class and the specific first-line ART regimen. Correspondence to Marta Rava, PhD, Instituto de Salud Carlos III, Avda. Monforte de Lemos 5, 28029 Madrid. Tel.: +(0034) 91 82 22869; e-mail: mrava@isciii.es Received 26 November, 2020 Revised 2 March, 2021 Accepted 8 March, 2021 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2021 Wolters Kluwer Health, Inc.

Objective: Abnormal deposition of the antimicrobial peptide amyloid beta (Aβ) is a characteristic of Alzheimer's Disease (AD). The objective of this study was to elucidate risk factors for brain Aβ in a cohort enriched for human immunodeficiency virus (HIV) and other neurotropic pathogens. Design: Cross-sectional cohort study. Methods: We examined autopsy brains of 257 donors with a mean age of 52.8 years; 62% were male; and 194 were HIV+ and 63 HIV-. Hyperphosphorylated tau (p-tau) and Aβ were identified in frontal and temporal regions by immunohistochemistry. APOE genotyping was performed. Clinical and neuropathological predictors for Aβ were identified in univariate analyses, and then tested in multivariate regressions. Results: Cortical Aβ was identified in 32% of the sample, and active brain infection in 27%. Increased odds of Aβ were seen with increasing age and having an APOE ε4 allele; for the overall sample, HIV+ status was protective and brain infection was not a predictor. Within the HIV+ population, predictors for Aβ were duration of HIV disease and APOE alleles, but not age. When HIV disease duration and other HIV parameters were introduced into models for the entire sample, HIV disease duration was equivalent to age as a predictor of Aβ. Conclusion: We hypothesize that dual aspects of immune suppression and stimulation in HIV, and beneficial survivor effects in older HIV+ individuals, account for HIV+ status decreasing, and HIV duration increasing, odds of Aβ. Importantly, with HIV, disease duration replaces age as an independent risk for Aβ, suggesting HIV-associated accelerated brain senescence. Correspondence to Susan Morgello, MD, Department of Neurology, Box 1137, Mount Sinai Medical Center, NY NY 10029. Tel: +1 212 241 9118; fax: +1 212 241 2972; e-mail: susan.morgello@mssm.edu Received 3 February, 2021 Revised 4 March, 2021 Accepted 17 March, 2021 Copyright © 2021 Wolters Kluwer Health, Inc.

Objectives: To evaluate the prevalence of low vitamin D levels among well-treated pregnant women living with HIV (WLWH) on combination antiretroviral therapy in Denmark, to identify risk factors of low vitamin D levels, and to assess the association between vitamin D status and birth outcomes. Design: Nationwide cohort study. Methods: All WLWH in Denmark giving birth from 2000–2018 with a vitamin D measurement during pregnancy were identified. Risk factors for low vitamin D (deficiency or insufficiency) were assessed using log-binomial regression models, both univariate and adjusted for maternal and HIV factors. The association between vitamin D status and birth outcomes was assessed using linear regression models for continues outcomes and log-binomial models for binary outcomes. Results: Among 208 WLWH, the prevalence of vitamin D deficiency was 13%, insufficiency 34%, and sufficiency 53%. Being of African origin (RR 2.68, p = 0.01), Asian origin (RR 3.38, p = 50 copies/mL (RR 1.43, p = 0.04) was associated with an increased risk of low vitamin D level. WLWH with vitamin D deficiency had an increased risk of preterm birth (RR 2.66, p = 0.03) and giving birth to small for gestational age (SGA) children (RR 6.83, p = 0.02) compared to WLWH with sufficient vitamin D level. Conclusion: Low vitamin D level was prevalent among well-treated pregnant WLWH in Denmark, especially among women of African or Asian origin, and women with detectable viral loads. Vitamin D deficiency was associated with an increased risk of preterm birth and SGA. Correspondence to Nina Weis, Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark, Kettegaard alle 30, 2650 Hvidovre, Denmark. E-mail: nina.weis@regionh.dk Received 22 September, 2020 Revised 14 March, 2021 Accepted 22 March, 2021 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2021 Wolters Kluwer Health, Inc.

Objective: The lack of available biomarkers for diagnosing and predicting different stages of liver disease with a non-invasive strategy is currently one of the main challenges that clinicians are facing. Recent evidence indicates that the plasma levels of specific microRNAs (miRNAs) may be significantly altered in patients with liver injury, including those with human immunodeficiency virus type 1 (HIV-1) infections. Design/methods: Large-scale deep sequencing analysis of small RNA expression was performed on plasma samples from 46 patients with HIV-1/hepatitis C virus (HCV) co-infections that did not exhibit liver fibrosis at the time of sampling. Results: A total of 1065 different miRNAs were identified. After a mean of 10.3 years, 26 of the 46 patients developed liver fibrosis (stage F2–4) and 20 remained without signs of liver fibrosis (stage F0–1). We identified a signature of seven miRNAs: 100–5p, 192–5p, 99a-5p, 122–5p, 125b-2–3p, 1246, and 194–5p, which were highly correlated with progression to liver fibrosis. These seven miRNAs detected liver fibrosis progression with an area under the curve (AUC) of 0.910–0.806. Two miRNAs, 100–5p and 192–5p, which displayed the best AUC values, yielded a sensitivity of 88% and a specificity of 85% for detecting liver fibrosis progression. Conclusions: Our results demonstrated that circulating miRNA levels had potential in predicting liver fibrosis progression before the clinical detection of liver fibrosis or significant clinical signs, such as elevated liver transaminases or platelets. Thus, our results might facilitate predictions of liver injury progression in patients with HIV-1-infections. Correspondence to Miguel Angel Martinez, Fundació irsiCaixa, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain. Tel: +34 934656374; fax: +34 934653968; e-mail: mmartinez@irsicaixa.es Received 12 November, 2020 Revised 12 March, 2021 Accepted 16 March, 2021 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2021 Wolters Kluwer Health, Inc.

Abstract Background Hepatitis C virus reinfections in HIV-positive men-who-have-sex-with-men (MSM) challenge the effectiveness of antiviral treatment. To fight this problem, an adapted sexual risk reduction intervention was implemented within a hepatitis C treatment trial. Following this, the current study had two aims and describes 1) how the program was received by participants; and 2) their responses to the program regarding sexual risk taking. Based on the participants’ input, we hoped to judge the intervention’s potential for scale-up. Methods Seventeen participants who received the sexual risk reduction intervention in addition to hepatitis C treatment were recruited for semi-structured interviews six to 12 months post-intervention. We evaluated the responses via reflexive thematic analysis and applied the concept of sense-making. Results Giving hepatitis C a place and living without it again illustrates how participants received the program and how their experiences were altered by the impact of sense-making. Based on their responses, we allocated participants to three groups: 1. Avoid risks: get rid of hepatitis C for life. For these men, hepatitis C remained a life-threatening disease: they actively modified their risk behavior and felt supported by the intervention in maintaining their behavioral changes. 2. Minimize risks: live as long as possible without hepatitis C. In contrast to group 1, these men saw hepatitis C as a manageable disease. The intervention facilitated reflection on risks and how to develop behavioral changes that suited them individually. 3. Accept risks; live with the risk of hepatitis C. These men perceived behavioral changes as much more difficult than “easy” medical treatment. They expected to either undergo repeated rounds of treatment or stay HCV re-infected. Conclusion These results illustrate the diversity of men’s responses and their decisions regarding sexual risk behavior after participating in a combination of antiviral treatment and a sexual risk reduction intervention. Two major aspects were identified: 1) Teachable moments, particularly at the time of diagnosis/treatment, could offer an opportunity to develop openness for behavioral change; 2) adapting sexual risk reduction interventions to sense-making patterns could help to improve its effectiveness. Support for reducing infection risk and raising awareness of preventative measures are additional benefits. Trial registration Clinical Trial Number: NCT02785666, 30.05.2016.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Introduction Housing instability and homelessness are significant barriers to medical treatment for people living with HIV/AIDS. For these individuals, lack of stable housing and stigma is associated with insufficient access to care, poor adherence to medication and higher cost burdens to the healthcare system. This protocol reports on the efforts to evaluate Sanctum V.1.0, a hospice and transitional care home for adults with HIV/AIDS in Saskatoon, Saskatchewan, Canada. The current project was developed out of a need to identify how Sanctum V.1.0 produces varying programme outcomes to assist in endeavours to replicate the programme in other geographic locations. Methods and analysis A realist evaluation will be conducted to explore how and why Sanctum V.1.0 is successful or unsuccessful, in which circumstances and for whom. Rather than explore the degree to which a programme is effective, realist evaluations seek to uncover mechanisms that explain processual links between programme inputs and outcomes. The completed first phase of the project involved the development of an initial realist programme theory. Phases 2 and 3 will consist of methods to test, refine and validate the initial theory using various data sources. Ethics and dissemination Ethics approval was obtained from the institutional review board at the University of Saskatchewan on 2 July 2020. Results will be disseminated according to stakeholders’ desires.

Introduction Individuals recruited into clinical trials for life-threatening illnesses are particularly vulnerable. This is especially true in low-income settings. The decision to enrol may be influenced by existing inequalities, poor healthcare infrastructure and fear of death. Where patients are confused or unconscious the responsibility for this decision falls to relatives. This qualitative study is nested in the ongoing AMBIsome Therapy Induction OptimisatioN (AMBITION) Trial. AMBITION is recruiting participants from five countries in sub-Saharan Africa and is trialling a novel treatment approach for HIV-associated cryptococcal meningitis, an infection known to affect brain function. We aim to learn from the experiences of participants, relatives and researchers involved in AMBITION. Methods and analysis We will collect data through in-depth interviews with trial participants and the next of kin of participants who were confused at enrolment and therefore provided surrogate consent. Data will be collected in Gaborone, Botswana; Kampala, Uganda and Harare, Zimbabwe. Interviews will follow a narrative approach including participatory drawing of participation timelines. This will be supplemented by direct observation of the research process at each of the three recruiting hospitals. Interviews will also take place with researchers from the African and European institutions that form the partnership through which the trial is administered. Interviews will be transcribed verbatim, translated (if necessary) and organised thematically for narrative analysis. Ethics and dissemination This study has been approved by the Health Research Development Committee, Gaborone (Reference: HPDME:13/18/1); Makerere School of Health Sciences Institutional Review Board, Kampala (Reference: 2019–061); University of Zimbabwe Joint Research Ethics Committee, Harare (Reference: 219/19), and the London School of Hygiene and Tropical Medicine (Reference: 17957). Study findings will be shared with research participants from the sites, key stakeholders at each research institution and ministries of health to help inform the development and implementation of future trials. The findings of this study will be published in journals and presented at academic meetings. Trial registration Registered at www.clinicaltrials.gov:NCT04296292.