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IntroductionProphylactic human papillomavirus (HPV) vaccines have been shown to be highly effective in protecting women against cervical infections, high-grade abnormalities and cancer caused by the targeted HPV types. However, the evidence for their effectiveness in women living with HIV (WLWH) is less clear.MethodsWLWH and HIV-negative women who likely did (birth cohorts 1996 and later) and WLWH and HIV(−) negative who likely did not (birth cohorts before 1996) receive HPV vaccination (n=3028; 757 participants for each of the four groups). Between groups, we will compare cervicovaginal, anal and oral prevalent and 6–12 month persistent HPV6/11/16/18 infections as measured using a modified AmpFire HPV genotyping assay that tests for 15 high-risk or intermediate-risk HPV genotypes, HPV6 and HPV11. We will also compare the HPV immune response in HPV-vaccinated WLWH to HPV-vaccinated HIV-negative women using an anti-HPV16 and anti-HPV18 ELISA. Vaccination status will be confirmed through national vaccination records.AnalysisWe will calculate point prevalence and prevalence of 6–12 month persisting infections by individual HPV-type specific infections and groups of infections for each anatomic site and for each group of women. Results will be stratified by age at vaccination, age at enrolment and the number of doses (3 vs 2) as well as other factors possibly associated with HPV prevalence. Differences in endpoints between groups, overall and between subgroups, will be tested for statistical significance (p2 test. Differences in geometric mean titres and seropositivity will be tested for statistical significance using the Mann-Whitney and Fisher’s exact tests, respectively.Ethics and disseminationThe study was approved by the Albert Einstein College of Medicine Institutional Review Board and the Rwanda National Ethics Committee. Results will be disseminated through publication in peer-reviewed journals.

Introduction HIV treatment guidelines recommend that all people living with HIV (PLWH) initiate antiretroviral therapy (ART) as soon as possible after diagnosis (Treat All). As Treat All is more widely implemented, an increasing proportion of PLWH are likely to initiate ART when they are asymptomatic, and they may view the relative benefits and risks of ART differently than those initiating at more advanced disease stages. To date, patient perspectives of initiating care under Treat All in sub-Saharan Africa have not been well described. Methods From September 2018 to March 2019, we conducted individual, semi-structured, qualitative interviews with 37 patients receiving HIV care in two health centers in Kigali, Rwanda. Data were analyzed using a mixed deductive and inductive thematic analysis approach to describe perceived barriers to, facilitators of and acceptability of initiating and adhering to ART rapidly under Treat All. Results Of 37 participants, 27 were women and the median age was 31 years. Participants described feeling traumatized and overwhelmed by their HIV diagnosis, resulting in difficulty accepting their HIV status. Most were prescribed ART soon after diagnosis, yet fear of lifelong medication and severe side effects in the immediate period after initiating ART led to challenges adhering to therapy. Moreover, because many PLWH initiated ART while healthy, taking medications and attending appointments were visible signals of HIV status and highly stigmatizing. Nonetheless, many participants expressed enthusiasm for Treat All as a program that improved health as well as health equity. Conclusion For newly-diagnosed PLWH in Rwanda, initiating ART rapidly under Treat All presents logistical and emotional challenges despite the perceived benefits. Our findings suggest that optimizing early engagement in HIV care under Treat All requires early and ongoing intervention to reduce trauma and stigma, and promote both individual and community benefits of ART.

Background Persistent infection with high-risk human papillomavirus (hrHPV) is a critical step in cervical carcinogenesis. We report on type-specific hrHPV persistence, clearance and incidence among screen-positive Rwandan women living with HIV (WLWH). Methods This was a nested analysis from a large cervical cancer screening study of ~ 5000 Rwandan WLWH. Women who tested positive for hrHPV and/or visual inspection with acetic acid were referred to colposcopy. For a subset of women (n = 298) who were ≥ 6 months delayed in receiving colposcopy, we tested their screening and colposcopy visit specimens using the AmpFire HPV genotyping assay that tests 14 hrHPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) individually. Results The mean, median (interquartile range [IQR]) and range of time between the screening and colposcopy visits were 644, 650 (490–820.5) and 197–1161 days, respectively. Mean, median (IQR) and range of age at the screening visit were 38, 37 (34–43) and 30–54 years, respectively. Two-hundred eighty-three (95.0%) had CD4 count (cells per mm3) data available at baseline with mean, median (IQR) and range of 592, 513 (346–717) and 0–7290, respectively. Two-hundred thirty-five WLWH were positive for at least one hrHPV type at the screening visit, of whom 50.2% had at least one HPV type-specific infection persist; 37.2% of all HPV infections detected at the screening visit persisted. Compared to all other HPV types in aggregate, HPV16 (vs. non-HPV16 types) (47.7%, p = 0.03) and HPV33 (vs. non-HPV33 types) (56.7%, p = 0.03) were significantly more likely, and HPV39 (vs. non-HPV39 types) (6.7%, p = 0.01), HPV51 (vs. non-HPV51 types) (15.6%, p p = 0.04) were significantly less likely, to persist. Lower CD4 counts were associated with having any persistent hrHPV infection (ptrend = 0.04) and multiple persistent hrHPV infections (ptrend = 0.04). Conclusion There is a significant proportion of WLWH with persistent hrHPV infection, emphasizing the need to vaccinate them against HPV prior to becoming sexually active.

Highlights • Resources are required to close gaps in patient knowledge & provider education. • The need to task shift from physicians to nurses & other health care workers. • Decentralized policy adaptions should be tailored to a rural-specific SSA context. • Establishment of political will to increase investments in cancer prevention. • Further study on facilitators & barriers to cancer care in national contexts., To address gaps in access to cervical cancer screening and early diagnosis of breast cancer services in Sub-Saharan African (SSA), this scoping review was conducted to explore facilitators and barriers that exist on the patient-, provider-, and system-level. An extensive literature search was conducted in accordance with scoping review methodology and the Cochrane guidelines. Our search criteria were limited to original research studies conducted in community or clinical settings in SSA within the last 10 years (2010–2020). Themes found from this review included patient knowledge and provider education, access to screening services, trust, health-related behaviors, attitudes, values, and practices, community and social values, health infrastructure, resource allocation, and political will. Identified barriers included lack of knowledge about cervical and breast cancer among patients, gaps in education and training among providers, and lack of resources and health infrastructure at the facility level and within the overall health system. Facilitators included perceived risk of cancer, support and encouragement of the provider, and utilization of novel approaches in low-resource settings by health systems. To better address individual-, provider-, and health system and facility-based facilitators and barriers to care, there is a need for political and financial investment and further research on the health service delivery in specific national health systems, especially in the context of the global campaign to eliminate cervical cancer as a public health problem.

Author(s): Murenzi, Gad; Kim, Hae-Young; Munyaneza, Athanase; Tuyisenge, Patrick; Zawadi, Thierry M; Buteera, Alex M; Adedimeji, Adebola; Mutesa, Leon; Castle, Philip E; Anastos, Kathryn; Palefsky, Joel M | Abstract: BackgroundMen who have sex with men (MSM) have a high prevalence of anal and penile human papillomavirus (HPV) infections with MSM living with HIV (MSMLH) bearing the highest rates. Data on anogenital high-risk HPV (hrHPV) among MSM in Rwanda and the associated risk factors are scant.MethodsWe recruited 350 self-identified MSM aged 18 years living in Kigali, Rwanda, with 300 recruited from the community and 50 from partner clinics. Anal and penile specimens from all participants were analyzed for hrHPV using the AmpFire platform. Logistic regression was used to calculate crude odds ratios (ORs) and adjusted ORs (aORs) with 95% confidence intervals (95% CIs) as a measure of association between various factors and anal and penile hrHPV infection prevalence.ResultsAnal hrHPV prevalence was 20.1%, was positively associated with having receptive anal sex with more partners (aOR: 9.21, 95% CI: 3.66 to 23.14), and was negatively associated with having insertive anal sex with more partners (aOR: 0.28, 95% CI: 0.12 to 0.66). Penile hrHPV prevalence was 35.0%, was negatively associated with having receptive anal sex with more partners (aOR: 0.29, 95% CI: 0.13 to 0.66), and differed significantly by HIV status, with 55.2% and 29.7% for MSMLH and HIV-negative MSM, respectively (P l 0.01).ConclusionPenile hrHPV prevalence was higher than that of anal hrHPV and it was significantly higher in Rwandan MSMLH than in HIV-negative MSM. The prevalence of anal and penile HPV infections is likely variable at different locations in Africa, according to a number of factors including HIV status and sexual practices.

Introduction Aiming to reach UNAIDS 90‐90‐90 targets, nearly all sub‐Saharan African countries have expanded antiretroviral therapy (ART) to all people living with HIV (PLWH) (Treat All). Few published data exist on viral load testing and viral suppression under Treat All in this region. We assessed proportions of patients with available viral load test results and who were virally suppressed, as well as factors associated with viral suppression, among PLWH in 10 Rwandan health centres after Treat All implementation. Methods Cross‐sectional study during 2018 of adults (≥15 years) engaged in HIV care at 10 Rwandan health centres. Outcomes were being on ART (available ART initiation date in the study database, with no ART discontinuation prior to 1 January 2018), retained on ART (≥2 post‐ART health centre visits ≥90 days apart during 2018), available viral load test results (viral load measured in 2018 and available in study database) and virally suppressed (most recent 2018 viral load 49 years (adjusted prevalence ratio (aPR): 0.83, 95% CI 0.76 to 0.90 and those with pre‐ART CD4 counts of

Purpose: Cervical cancer screening reduces cervical cancer incidence and mortality. In Rwanda, cervical cancer screening is conducted predominately at primary health care centers. However, a significant number of age-eligible women who have not undergone screening present at primary health care centers with cervical cancer. The aim of our paper is to understand barriers and facilitators of cervical cancer screening from providers' perspectives. Methods: We selected the ten top- and ten bottom-performing health centers for cervical cancer screening in the past five years within Rwanda. We identified three health care providers at each health center as key informants to be interviewed. A thematic analysis was conducted. Results: We interviewed 33 providers. Providers consistently reported barriers for women to attend cervical cancer screening included: 1) women not seeking cervical cancer screening service while asymptomatic; 2) never having given birth at a health facility; 3) too busy with daily responsibilities to seek care; 4) being unfamiliar with gynecological service procedures; and 5) feeling uncomfortable with undergoing a pelvic exam and exposing their genitals. Reported facilitators to screening women included, health education activities, and providing multiple health services at the health center Services, such as family planning and child vaccination that attract women, which makes it easier for health care providers to provide them with educational information and offer them screening. Conclusion: Health care providers reported patients with limited health-seeking behaviors as a barrier to cancer screening services but felt that educational sessions facilitated uptake among eligible women. Use of mass media to disseminate information on cervical cancer screening and prevention may encourage women to come to the clinic, at which time they may receive the education they need to undergo screening. Cervical cancer screening policies should evaluate and address existing health-seeking behaviors within their target population in order to achieve effective coverage. Citation Format: Charles Ingabire, Amanda Pierz, Josephine Gasana, Francine Umwiza, Laura Drown, Athanase Munyaneza, Lydia Businge, Gallican Kubwimana, Gad Murenzi, François Uwinkindi, Alma Adler, Philip Castle, Thomas C. Randall. “Women Are Reluctant to Make Long Journeys to Seek Screening Services While They Do Not Have Any Pain:” Providers' Experience on Cervical Cancer Screening in Primary Health Care Centers in Rwanda [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 95.

Purpose: In Rwanda, cancer prevalence and death have not been accurately documented up to 2018. In response, Rwanda, through the Ministry of Health and supported by Albert Einstein College of Medicine with funding from the U.S. National Cancer Institute, established a National Cancer Registry (NCR) in July 2018 to collect national cancer data. We aimed to determine the number of cancers by type, the distribution of cancers in the Rwandan population, and cancer trends over the last ten years in Rwanda. Methods: Registry data were collected over a ten-year period (2009-2018) from public and private health institutions and the National Institute of Statistics. Cancers were coded using the third edition of the International Classification of Diseases for Oncology (ICD-O3). Data entry and analysis were performed using CanReg5 system and IARCcrg quality control. The National Institute of Statistics of Rwanda provided an estimate of the country's population census for 2012 by age and sex, and the annual population was estimated assuming constant rates of change within age-sex groups. Results: Over ten years (2009-2018), a total of 18,562 cancers were registered; 11,034 (59%) in women and 7,528 (41%) in men. Breast and cervical cancers were most common among women [n=2283 (21%) and n=2330 (21%), respectively] while prostate and stomach cancers were most common among men [n=976 (13%) and n=772 (10%), respectively]. Most cases were diagnosed in women aged 50-54 (n=1381) and 45-49 (n=1189) and men aged 60-64 (n=794) and 55-59 (n=756). Cancers diagnosed in Rwanda increased from 759 cases in 2009 to 2,862 cases in 2018. Conclusion: In Rwanda, Cancers are more common in women and are diagnosed at an earlier age in women than in men. There has been a significant increase in documented cancers over 10 years, potentially related to significant improvements in diagnostic capacity within the Rwandan health system. Citation Format: Lydia Businge, Francois Uwinkindi, Marc Hagenimana, Gad Murenzi, Gallican Kubwimana, Francoise Musabyimana, Charles Ingabire, Athanase Munyaneza, Cecile Ingabire, Thomas C Randall, Kathryn Anastos, Philip E Castle. Cancer Update in Rwanda (2009-2018) [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 86.

IntroductionCurrent HIV guidelines recommend differentiated service delivery (DSD) models that allow for fewer health centre visits for clinically stable people living with HIV (PLHIV). Newly diagnosed PLHIV may require more intensive care early in their treatment course, yet frequent appointments can be burdensome to patients and health systems. Determining the optimal parameters for defining clinical stability and transitioning to less frequent appointments could decrease patient burden and health system costs. The objectives of this pilot study are to explore the feasibility and acceptability of (1) reducing the time to DSD from 12 to 6 months after antiretroviral therapy (ART) initiation,and (2) reducing the number of suppressed viral loads required to enter DSD from two to one.Methods and analysesThe present study is a pilot, unblinded trial taking place in three health facilities in Kigali, Rwanda. Current Rwandan guidelines require PLHIV to be on ART for ≥12 months with two consecutive suppressed viral loads in order to transition to less frequent appointments. We will randomise 90 participants to one of three arms: entry into DSD at 6 months after one suppressed viral load (n=30), entry into DSD at 6 months after two suppressed viral loads (n=30) or current standard of care (n=30). We will measure feasibility and acceptability of this intervention; clinical outcomes include viral suppression at 12 months (primary outcome) and appointment attendance (secondary outcome).Ethics and disseminationThis clinical trial was approved by the institutional review board of Albert Einstein College of Medicine and by the Rwanda National Ethics Committee. Findings will be disseminated through conferences and peer-reviewed publications, as well as meetings with stakeholders.Trial registration numberNCT04567693.

IntroductionThe optimal method(s) for screening HIV-infected women, especially for those living in sub-Saharan Africa, for cervical precancer and early cancer has yet to be established.Methods and analysisA convenience sample of >5000 Rwandan women, ages 30–54 years and living with HIV infection, is being consented and enroled into a cross-sectional study of cervical cancer screening strategies. Participants are completing an administered short risk factor questionnaire and being screened for high-risk human papillomavirus (hrHPV) using the Xpert HPV assay (Cepheid, Sunnyvale, California, USA), unaided visual inspection after acetic acid (VIA) and aided VIA using the Enhanced Visual Assessment (EVA) system (Mobile ODT, Tel Aviv, Israel). Women positive for hrHPV and/or by unaided VIA undergo colposcopy, which includes the collection of two cervical specimens prior to undergoing a four-quadrant microbiopsy protocol. The colposcopy-collected specimens are being tested by dual immunocytochemical staining for p16INK4aand Ki-67 (CINtec PLUS Cytology, Ventana, Tucson, Arizona, USA) and for E6 or E7 oncoprotein for 8 hrHPV genotypes (HPV16, 18, 31, 33, 35, 45, 52 and 58) using the next-generation AV Avantage hrHPV E6/E7 test (Arbor Vita Corporation, Freemont, California, USA). Women with a local pathology diagnosis of cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+) or pathology review diagnosis of CIN grade three or more severe (CIN3+) will receive treatment. Clinical performance and cost-effectiveness (eg, sensitivity, specificity and predictive values) of different screening strategies and algorithms will be evaluated.Ethics and disseminationThe protocol was approved by local and institutional review boards for human subjects research. At the completion of the study, results will be disseminated to the scientific community through peer-reviewed publication and to the Rwandan stakeholders through an external advisory panel.

The interactions between different glucosidic anthocyanins (pelargonin, cyanin, delphinin, malvin and petunin) and some organic compounds (lactic, galacturonic, tannic, phenolic and sinapic acids; pyrogallol, furfural, pectin, cellulose, hydrolitic lignin) which are present in food-stuffs were investigated at pH 3.0-4.3 and 25 °C. The interactions were monitored by means of u.v.-VIS spectra and their different behaviours were highlighted by following changes in absorbance over a range of wavelengths (delta lambda and delta A). Significant effects on absorbance were detected and are discussed in terms of the phenomenon of co-pigmentation.

The use of diazaphosphole derivatives generated in situ or the PCl3/hydrazone combination can be applied in a novel efficient one-pot procedure for the synthesis at room temperature of the title six-, seven- and eight-membered rings using always high concentration of the reagents (0.2–0.5M). N-alkenyl derivatives of 1,2-diazaheterocycles such as 8 (perhydro-pyridazine-3,6-diones), 9 (perhydro-1,2-diazepin-3,7-diones), 10 (perhydro-1,2-diazocin-3,8-diones) and 11 (1,2-dihydro-pyridazine-3,6-diones) were obtained by reaction of PCl3, ketone methylhydrazones and succinic, glutaric, adipic and maleic acids respectively. Changing the order of addition of reagents, or their simultaneous addition, gave identical results. In all the procedures the yields were good. The exclusive or prevalent formation of the E isomer was always observed. The E-configuration of the exocyclic double bond was deduced from some NOE experiments carried out on a E,Z mixture obtained by isomerization of the E isomer. Mechanism for the reaction is also proposed.

The use of diazaphosphole derivatives generated in situ or the PCl3/hydrazone combination can be applied in a novel efficient one-pot procedure for the synthesis at room temperature of the title six-, seven- and eight-membered rings using always high concentration of the reagents (0.2–0.5M). N-alkenyl derivatives of 1,2-diazaheterocycles such as 8 (perhydro-pyridazine-3,6-diones), 9 (perhydro-1,2-diazepin-3,7-diones), 10 (perhydro-1,2-diazocin-3,8-diones) and 11 (1,2-dihydro-pyridazine-3,6-diones) were obtained by reaction of PCl3, ketone methylhydrazones and succinic, glutaric, adipic and maleic acids respectively. Changing the order of addition of reagents, or their simultaneous addition, gave identical results. In all the procedures the yields were good. The exclusive or prevalent formation of the E isomer was always observed. The E-configuration of the exocyclic double bond was deduced from some NOE experiments carried out on a E,Z mixture obtained by isomerization of the E isomer. Mechanism for the reaction is also proposed.