Anal Cancers in Previously Screened Versus Unscreened Patients: Tumor Stage and Treatment Outcomes.

BACKGROUND: Targeted screening programs for patients at high risk for anal squamous-cell carcinoma have been proposed; however, the evidence in support of screening remains unclear. OBJECTIVE: This study aimed to determine whether screening high-risk patients (predominantly those living with HIV) detected squamous-cell carcinoma at an earlier stage compared to the routine practice of not screening. DESIGN: This is a cohort study. SETTINGS: This study was conducted at a quaternary care center in Canada. PATIENTS: Included patients were at least 18 years old with a pathologic diagnosis of invasive anal squamous-cell carcinoma between 2002 and 2022. INTERVENTIONS: Patients diagnosed through a high-risk screening program were compared to those who did not undergo screening. MAIN OUTCOME MEASURES: The primary outcome was clinical stage at presentation, categorized as T1N0M0 vs other. Secondary outcomes included treatments received, treatment failure, and overall survival. RESULTS: A total of 612 patients with anal squamous-cell carcinoma were included, with 26 of those patients diagnosed through a screening program. Patients with screen-detected cancers had greater odds of presenting with T1N0M0 tumors compared to unscreened patients (18 [69.2%] vs 84 [14.3%]; adjusted OR 9.95; 95% CI, 3.95-25.08). A propensity score-matched sensitivity analysis found similar results (OR 11.13; 95% CI, 4.67-26.52). Screened patients had greater odds of treatment with wide local excision alone, as opposed to any combination of chemotherapy, radiation therapy, and surgery (3 [12.5%] vs 18 [3.2%]; OR 4.38; 95% CI, 1.20-16.04). There were no statistically significant differences in treatment failure or overall survival between groups. LIMITATIONS: The small number of screened patients limits the power of the analysis. CONCLUSIONS: Screening for anal squamous-cell carcinoma among high-risk populations detects cancers at an earlier stage. Patients with screen-detected cancers also had a greater likelihood of being candidates for wide local excision alone, which may have spared them the morbidity associated with chemoradiotherapy or abdominoperineal resection. See Video Abstract. CNCERES DE ANO EN PACIENTES PREVIAMENTE DETECTADOS POR CRIBADO VERSUS NO DETECTADOS ESTADIO DEL TUMOR Y RESULTADOS DEL TRATAMIENTO: ANTECEDENTES:Se han propuesto programas de cribado dirigidos a pacientes con alto riesgo de carcinoma anal de células escamosas; sin embargo, la evidencia a favor de la detección sigue sin estar clara.OBJETIVO:Este estudio tuvo como objetivo determinar si el cribado de pacientes de alto riesgo (predominantemente aquellos que viven con el VIH) detectó el carcinoma de células escamosas en una etapa más temprana en comparación con la práctica habitual de no cribado.DISEÑO:Este es un estudio de cohortes.CONFIGURACIÓN:Este estudio se realizó en un centro de atención cuaternaria en Canadá.PACIENTES:Los pacientes incluidos tenían al menos 18 años con un diagnóstico patológico de carcinoma de células escamosas anal invasivo entre 2002 y 2022.INTERVENCIONES:Los pacientes diagnosticados mediante un programa de cribado de alto riesgo se compararon con aquellos que no se sometieron a cribado.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue el estadio clínico en la presentación, categorizado como T1N0M0 versus otro. Los resultados secundarios incluyeron los tratamientos recibidos, el fracaso del tratamiento y la supervivencia general.RESULTADOS:Se incluyeron un total de 612 pacientes con carcinoma anal de células escamosas, con 26 de esos pacientes diagnosticados a través de un programa de cribado. Los pacientes con cánceres detectados mediante cribado tenían mayores probabilidades de presentar tumores T1N0M0 en comparación con los pacientes no cribados (18 [69.2%] frente a 84 [14.3%]; razón de probabilidad ajustada 9.95; intervalo de confianza del 95 % 3.95 -25.08). Un análisis de sensibilidad emparejado por puntaje de propensión encontró resultados similares (odds ratio 11.13; intervalo de confianza del 95% 4.67 -26.52; p < 0.001). Los pacientes examinados tenían mayores probabilidades de recibir tratamiento con escisión local amplia sola, en comparación con cualquier combinación de quimioterapia, radiación y cirugía (3 [12.5%] frente a 18 [3.2%]; razón de probabilidad 4.38; intervalo de confianza del 95 % 1.20 -16.04). No hubo diferencias estadísticamente significativas en el fracaso del tratamiento o la supervivencia global entre los grupos.LIMITACIONES:El pequeño número de pacientes evaluados limita el poder del análisis.CONCLUSIONES:La detección del carcinoma anal de células escamosas entre las poblaciones de alto riesgo detecta los cánceres en una etapa más temprana. Los pacientes con cánceres detectados mediante cribado también tenían una mayor probabilidad de ser candidatos para una escisión local amplia sola, lo que puede haberles evitado la morbilidad asociada con la quimiorradioterapia o la resección abdominoperineal. (Traducción --Dr. Aurian Garcia Gonzalez ).

Routinized Syphilis Screening Among Men Living With Human Immunodeficiency Virus: A Stepped Wedge Cluster Randomized Controlled Trial.

BACKGROUND: We implemented an opt-out clinic-based intervention pairing syphilis tests with routine human immunodeficiency virus (HIV) viral load testing. The primary objective was to determine the degree to which this intervention increased the detection of early syphilis. METHODS: The Enhanced Syphilis Screening Among HIV-Positive Men (ESSAHM) Trial was a stepped wedge cluster-randomized controlled trial involving 4 urban HIV clinics in Ontario, Canada, from 2015 to 2017. The population was HIV-positive adult males. The intervention was standing orders for syphilis serological testing with viral loads, and control was usual practice. We obtained test results via linkage with the centralized provincial laboratory and defined cases using a standardized clinical worksheet and medical record review. We employed a generalized linear mixed model with a logit link to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of the intervention. RESULTS: A total of 3895 men were followed over 7471 person-years. The mean number of syphilis tests increased from 0.53 to 2.02 tests per person per year. There were 217 new diagnoses of syphilis (control, 81; intervention, 136), for which 147 (68%) were cases of early syphilis (control, 61 [75%]; intervention, 86 [63%]). The annualized proportion with newly detected early syphilis increased from 0.009 to 0.032 with implementation of the intervention; the corresponding time-adjusted OR was 1.25 (95% CI, .71-2.20). CONCLUSIONS: The implementation of standing orders for syphilis testing with HIV viral loads was feasible and increased testing, yet produced less-than-expected increases in case detection compared to past uncontrolled pre-post trials. CLINICAL TRIALS REGISTRATION: NCT02019043.

Influence of previous experience with and beliefs regarding anal cancer screening on willingness to be screened among men living with HIV.

BACKGROUND: Implementation of anal cancer screening requires the procedure to be acceptable to the target population. Our objective was to assess the beliefs of men living with HIV regarding anal cancer screening and identify factors associated with their willingness to participate in screening. METHODS: We developed a cross-sectional questionnaire using the Theory of Planned Behavior to examine beliefs regarding prevention of human papillomavirus (HPV)-related diseases, administered to men living with HIV in 2016-2017 in a multi-site HIV clinical cohort. Correspondence analysis was used to examine the interrelationships between men's beliefs and willingness to undergo anal cancer screening. We used multivariable proportional odds models to identify factors associated with increasing willingness. Results were reported as adjusted odds ratios (aOR) with 95% confidence intervals (CI). RESULTS: Among 1677 male participants, the vast majority (90%) would be willing to undergo screening by "anal Pap test"; willingness clustered with positive beliefs (e.g. confident they can get screened; disagree that they will feel pain) in the correspondence analysis. Higher self-perceived risk for anal cancer and positive beliefs regarding screening were associated with higher willingness to be screened. Gay, bisexual and other men who have sex with men had higher willingness (aOR = 1.62; 95% CI: 1.15, 2.29) than heterosexual men. Racialized men reported lower willingness (aOR = 0.68; 95% CI: 0.54, 0.89) than white men. CONCLUSIONS: Men generally had positive beliefs and were willing to undergo screening, though there were differences by sexual orientation and racial identity. Tailored community-led initiatives could focus on men's understanding of their risk and expectations of anal cancer screening to facilitate participation.

Low human papillomavirus (HPV) vaccine uptake among men living with human immunodeficiency virus (HIV): Cross-sectional findings from a clinical cohort.

Men living with human immunodeficiency virus (HIV) are internationally recognized as a priority population for human papillomavirus (HPV) vaccination. Our objective was to explore HPV vaccine uptake among men living with HIV in Ontario, Canada, and investigate differences between vaccinated and unvaccinated men. We used data from a cross-sectional questionnaire administered between 2016 and 2017 among men living with HIV and participating in the Ontario HIV Treatment Network Cohort Study. We calculated the proportion vaccinated against HPV, described vaccination experiences, and HPV vaccine knowledge, and calculated differences in characteristics between vaccinated and unvaccinated men. Among 1651 men (mean age = 51 years, 72% identified as gay), 7% were vaccinated (95% confidence interval[CI] 5.5-7.9%); 85% received their first dose at a primary care or HIV clinic. Among unvaccinated men, 40% were unaware of the HPV vaccine, 65% reported low perceived risk for HPV, and 8% discussed HPV vaccination with a physician. Compared to unvaccinated men, vaccinated men were younger, most identified as gay, had a higher education/income, reported a higher number of recent sex partners, and had a history of bacterial sexually transmitted infections (STIs), HPV, anogenital warts, and/or anal cancer. Our findings reveal that few men living with HIV were vaccinated against HPV. This may be influenced by low HPV awareness, prohibitive cost, and lack of physician recommendation. Several men reporting lower socio-economic status, older men, and heterosexual, bisexual, and other men who have sex with men were missed for vaccination. Primary care and HIV clinics may be ideal locations to increase uptake.

Low human papillomavirus (HPV) knowledge related to low risk perception among men living with HIV: Implications for HPV-associated disease prevention.

Human papillomavirus (HPV)-associated anal cancer is orders of magnitude higher among men living with HIV than the general male population. Our objective was to examine factors associated with HPV awareness and self-perceived risk for HPV-associated anal cancer among men living with HIV, which may influence uptake of cancer prevention strategies. A cross-sectional questionnaire on HPV was administered from 2016 to 2017 to 1677 men in a multisite, HIV clinical cohort in Ontario, Canada. We used logistic regression and proportional odds models to identify factors associated with being familiar with HPV and increasing self-perceived risk for anal cancer, respectively. We used correspondence analysis to examine associations of specific HPV-related knowledge with self-perceived risk. Only 52% were familiar with HPV, and 72% felt they had no or low risk for anal cancer. Familiarity with HPV was more common among men who have sex with men than heterosexual men (58% vs. 21%). Older men were less likely to be familiar with HPV (adjusted odds ratio [aOR] per 10 years = 0.77; 95% confidence interval [CI]: 0.69, 0.85). Familiarity with HPV was associated with increasing self-perceived risk (aOR = 2.39; 95% CI: 1.87, 3.04). After accounting for differences in HPV awareness and sexual orientation, racialized men had lower self-perceived risk (aOR = 0.68; 95% CI: 0.52, 0.88). In the correspondence analysis, risk-focused HPV-related knowledge (e.g., knowing smoking increases risk) was associated with highest risk perception. Efforts are needed to improve HPV-related health literacy in this population. Our findings suggest specific HPV-related knowledge may differentially influence self-perceived risk for anal cancer.

Economic barriers, evidentiary gaps, and ethical conundrums: a qualitative study of physicians' challenges recommending HPV vaccination to older gay, bisexual, and other men who have sex with men.

BACKGROUND: The human papillomavirus (HPV) is the most common sexually transmitted infection (STI) worldwide. Gay, bisexual, and other men who have sex with men (GBM), and GBM living with HIV in particular, are disproportionately impacted by HPV-associated cancers. The HPV vaccine, given early enough in life, may markedly reduce the likelihood of such cancers. In Canada, most provincial insurance programs only cover HPV vaccination for GBM up to the age of 26. Our objective was to understand physicians' everyday experiences and challenges in recommending HPV vaccination to older GBM patients. METHODS: As part of the HPV Screening and Vaccine Evaluation (HPV-SAVE) Study, we conducted semi-structured interviews with 25 HIV-positive GBM patients who had received anal cancer screening and 15 service providers, including 13 physicians, who had arranged for anal cancer screening in the Canadian provinces of Ontario and British Columbia. In this analysis, we draw upon the 13 physician interviews, which were coded following Grounded Theory. RESULTS: Physicians strongly supported the HPV vaccine for all GBM and considered it to be important for the management of HIV-related care. However, the overall support for HPV vaccination among physicians did not translate into consistent recommendation practices. There were two overarching factors that limited the strength/frequency of physicians' vaccine recommendation practices. First, cost/insurance coverage for some older patients impacted if and how the HPV vaccine was discussed. Second, physicians had diverse perspectives on both the prevention and therapeutic benefits of vaccinating older GBM and the reality that national guidelines are incongruent with publicly funded vaccine programs for vaccinating patients over 26 years old. These two interrelated factors have co-produced an apparent economic-evidentiary conundrum for many physicians regarding how and for whom to offer HPV vaccination. CONCLUSION: Economic barriers coupled with evidentiary and guideline gaps have created clinical practice challenges for physicians and has resulted in different messages being communicated to some older GBM patients about how important HPV vaccination is for their health.

Progression From Perianal High-Grade Anal Intraepithelial Neoplasia to Anal Cancer in HIV-Positive Men Who Have Sex With Men.

BACKGROUND: High-grade intraepithelial neoplasia is known to progress to invasive squamous-cell carcinoma of the anus. There are limited reports on the rate of progression from high-grade intraepithelial neoplasia to anal cancer in HIV-positive men who have sex with men. OBJECTIVES: The purpose of this study was to describe in HIV-positive men who have sex with men with perianal high-grade intraepithelial neoplasia the rate of progression to anal cancer and the factors associated with that progression. DESIGN: This was a prospective cohort study. SETTINGS: The study was conducted at an outpatient clinic at a tertiary care center in Toronto. PATIENTS: Thirty-eight patients with perianal high-grade anal intraepithelial neoplasia were identified among 550 HIV-positive men who have sex with men. INTERVENTION: All of the patients had high-resolution anoscopy for symptoms, screening, or surveillance with follow-up monitoring/treatment. MAIN OUTCOME MEASURES: We measured the incidence of anal cancer per 100 person-years of follow-up. RESULTS: Seven (of 38) patients (18.4%) with perianal high-grade intraepithelial neoplasia developed anal cancer. The rate of progression was 6.9 (95% CI, 2.8-14.2) cases of anal cancer per 100 person-years of follow-up. A diagnosis of AIDS, previously treated anal cancer, and loss of integrity of the lesion were associated with progression. Anal bleeding was more than twice as common in patients who progressed to anal cancer. LIMITATIONS: There was the potential for selection bias and patients were offered treatment, which may have affected incidence estimates. CONCLUSIONS: HIV-positive men who have sex with men should be monitored for perianal high-grade intraepithelial neoplasia. Those with high-risk features for the development of anal cancer may need more aggressive therapy.

Raoultella planticola bacteremia following consumption of seafood.

Raoultella planticola is a Gram-negative bacillus commonly found in water, soil and aquatic environments. There have only been 16 cases of R planticola infection documented in the literature to date. R planticola possesses the ability to convert histidine to histamine and can produce symptoms of scombroid poisoning when poorly prepared seafood is consumed in large amounts. The present report describes a case involving a 56-year-old woman who presented with R planticola bacteremia and symptoms consistent with cholangitis four days after consuming a seafood salad containing squid and octopus. She was successfully treated with intravenous ceftriaxone followed by oral ciprofloxacin. Recent chemotherapy, proton pump inhibitor use and altered biliary flow secondary to hepatic metastases may have been contributing factors to the pathogenesis of disease.

La Raoultella planticola est un bacille à Gram négatif qu'on trouve souvent dans l'eau, la terre et les milieux aquatiques. Seulement 16 cas d'infection à R planticola ont été répertoriés dans les publications jusqu'à présent. Le R planticola peut convertir l'histidine en histamine et produire des symptômes de scombroïdose après la consommation de grandes quantités de fruits de mer mal préparés. Le présent rapport décrit le cas d'une femme de 56 ans qui a consulté à cause d'une bactériémie à R planticola et de symptômes évocateurs d'une cholangite quatre jours après avoir consommé une salade de fruits de mer contenant du calmar et de la pieuvre. Elle a été traitée avec succès au moyen de ceftriaxone par voie intraveineuse suivie de ciprofloxacine par voie orale. Une récente chimiothérapie, la prise d'inhibiteurs de la pompe à protons et une perturbation de l'écoulement biliaire secondaire à des métastases hépatiques peuvent avoir contribué à la pathogenèse de la maladie.

Ano-genital human papillomavirus type 97 infection is detected in Canadian men but not women at risk or infected with the human immunodeficiency virus.

BACKGROUND: Human papillomavirus type 97 (HPV97) DNA was detected in nearly 5% of anal samples collected from HIV-seropositive men living in Montreal, Canada. The rate of detection of HPV97 in the genital tract of Canadian women is unknown. Whether HPV97 is a local epidemic in HIV-seropositive men living in Montreal is also unknown. The prevalence of human papillomavirus type 97 (HPV97) was assessed in cervicovaginal cells from women living in Canada and in anal samples from HIV-seropositive men living in Toronto. FINDINGS: Cervicovaginal lavages collected from 904 women (678 HIV-seropositive, 226 HIV-seronegative) women living in Canada and anal cells collected from 123 HIV-seropositive men living in Toronto were tested for the presence of HPV97 with PCR. HPV97-positive samples were further tested by PCR-sequencing for molecular variant analysis to assess if all HPV97-positive men were infected with the same strain. All cervicovaginal samples were negative for HPV97. HPV97 was detected in anal samples from 6 HIV-seropositive men (4.9%, 95% confidence interval 2.0-10.5%), of whom five had high-grade and one had low-grade anal intraepithelial neoplasia, in addition to 2 to 8 HPV genital genotypes per sample. Four HPV97 variants were defined by four variation sites in the viral control region. CONCLUSION: These findings indicate that HPV97 infects in the anal canal of HIV-seropositive men but is not detected in the genital tract of women.

Hepatitis C virus testing in a clinical HIV cohort in Ontario, Canada, 2000 to 2015.

BACKGROUND: HIV-positive individuals may acquire HCV via injection drug use (IDU) and condomless anal sex. HIV care provides opportunities for HCV testing and cure with direct-acting antiviral agents (DAAs). METHODS: We analyzed data from the Ontario HIV Treatment Network Cohort Study. Among those not HCV-positive or diagnosed previously (n = 4586), we used Cox regression to test the rates of ever HCV testing (serological or RNA) in HIV care by DAA era (pre-DAA: 2000-2010; after DAA: 2011-2015) and compared the proportion diagnosed with HCV. We identified correlates of annual proportions of serological testing using Poisson generalized estimating equations. RESULTS: After DAA vs pre-DAA, the hazard rate ratio (95% CI) of ever HCV testing was 1.70 (1.59, 1.81). The proportion (95% CI) tested annually increased from 9.2% (8.0%, 10.7%) in 2000 to 39.1% (37.1%, 41.1%) in 2015 (P < 0.0001). The proportion diagnosed with HCV declined by 74% pre-DAA to 11% after DAAs. Annual testing increased per calendar year (16% steeper slope after DAA vs pre-DAA) and was more common among men who have sex with men; those more educated (post-secondary vs ≤ high school); and those positive for syphilis or reporting any IDU. Annual testing decreased per decade of age and time since HIV diagnosis. DISCUSSION: Annual HCV testing increased over time with higher testing among those reporting sexual or IDU risk factors, but fell short of clinical guidelines. Targeted interventions to boost testing may be needed to close these gaps and reach WHO 2030 HCV elimination targets.

Cytology-based screening for anal intraepithelial neoplasia in women with a history of cervical intraepithelial neoplasia or cancer.

BACKGROUND: High-risk human papillomavirus (HPV) has been identified in the pathogenesis of anal cancer. The purpose of this study was to assess the prevalence of abnormal anal cytology and HPV in women aged ≥40 years who have a history of high-grade cervical squamous intraepithelial lesion (SIL) or cancer and to estimate the prevalence of anal intraepithelial neoplasia (AIN) using cytology as the primary screening modality. METHODS: Women who had a history of high-grade cervical SIL or cancer and were ≥40 years of age were included in this prospective study. Anal cytology with HPV-DNA testing was performed. All patients with abnormal anal cytology were referred for high-resolution anoscopy (HRA), and abnormal lesions were biopsied and treated if pathologically confirmed. Abnormal anal cytology correlated with HPV status, HRA findings, and clinical and demographic characteristics. RESULTS: A total of 317 women completed the study. Of these, 96 (30.3%) had abnormal anal cytology (high-grade SIL, 12.5%; low-grade SIL, 19.8%; atypical squamous cells, cannot exclude high-grade SIL, 6.3%; atypical squamous cells of undetermined significance, 61.5%) and 101 (31.9%) were HPV-DNA-positive. There was a significant association between abnormal cytology results and the presence of high-risk HPV. Of the 96 patients with abnormal cytology, 30 (31.3%) had biopsy-proven AIN on HRA, representing 9.5% of the total patient cohort; of these, 10 (33.3%) had low-grade AIN and 20 (66.7%) had high-grade AIN. Older age and smoking were significant risk factors for abnormal anal cytology. CONCLUSION: Women aged ≥40 years with a history of high-grade cervical SIL or cancer have a high rate of AIN. Screening for anal cancer may therefore be considered in this patient population. The optimal screening approach should be addressed in future studies.

Racial Disparities in Anal Cancer Screening Among Men Living With HIV: Findings From a Clinical Cohort Study.

BACKGROUND: Our objective was to quantify the extent of anal cancer screening among men receiving HIV specialty care in Ontario, Canada, and evaluate factors associated with screening. SETTING: Cross-sectional questionnaire within a multisite clinical HIV cohort. METHODS: A questionnaire assessing knowledge and experience with human papillomavirus-associated diseases and their prevention was administered in 2016-2017 to 1677 men in the Ontario HIV Treatment Network Cohort Study. We used logistic regression to identify factors associated with having discussed screening with a health care provider and self-reported receipt of screening [digital anal rectal examinations (DARE); anal cytology or anoscopy]. Results reported as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: Forty percent of men reported ever having had anal cytology/anoscopy, and 70% had ever had DARE. After accounting for differences in age, sexual orientation, years since HIV diagnosis, previous diagnosis with AIDS, knowing someone with human papillomavirus-associated cancer, comfort discussing anal health, education, and income, the proportion screened differed by self-identified race. Compared with white men, Asian men were less likely to have discussed screening with a health care provider (aOR = 0.48; 95% CI: 0.29 to 0.80) or to have been screened by DARE (aOR = 0.27; 95% CI: 0.17 to 0.44) or anal cytology/anoscopy (aOR = 0.51; 95% CI: 0.31 to 0.83), and African, Caribbean, or black men (aOR = 0.47; 95% CI: 0.31 to 0.70) were less likely to have had DARE. Results were consistent when restricting the analyses to gay, bisexual, and other men who have sex with men. CONCLUSION: Our findings highlight the potential for disparities in anal cancer screening that need to be considered when developing guidelines and screening programs to reduce the burden of anal cancer among men living with HIV and ensure health equity.

A possible cluster of sexually transmitted Entamoeba histolytica: genetic analysis of a highly virulent strain.

BACKGROUND: Transmission of Entamoeba histolytica generally occurs by fecal excretion of cysts followed by oral ingestion of contaminated food or water. However, fecal-oral transmission may occur within households and long-term care institutions, and sexual transmission occurs among men who have sex with men. Epidemiologically linked clusters of E. histolytica infection are rare in industrialized countries. We report such a sexually linked cluster in Canada. METHODS: An index case involving a young female with an amebic liver abscess led to an epidemiological investigation of sexual contacts. Anti-amebic serological analysis, stool specimen examinations, and abdominal ultrasounds were done for the contacts. Enzyme-linked immunosorbent assay was done for stool antigen specific to E. histolytica. Genotyping and phylogenetic analysis was performed on 1 stool isolate. RESULTS: By tracing sexual contacts related to the index case, we uncovered a cluster of 7 cases of amebiasis (3 with liver abscesses). Oral-anal sex was common in the group; the 5 female individuals were bisexual (4) or homosexual (1). The outbreak strain was genotyped, and cluster analysis indicated that this virulent strain differed substantially from asymptomatic or diarrheal E. histolytica isolates. CONCLUSIONS: E. histolytica can be transmitted by heterosexual activity as well as male and female homosexual activity. Patients with amebiasis should be counselled about possible sexual transmission.

HIV-positive gay men's knowledge and perceptions of Human Papillomavirus (HPV) and HPV vaccination: A qualitative study.

The human papillomavirus (HPV) is the most common sexually transmitted infection worldwide. Gay, bisexual, and other men who have sex with men (GBM) living with HIV are disproportionately impacted by HPV-associated anal cancer, with rates about 100-fold that of the general population. Fortunately, HPV vaccination has proven efficacy in preventing both anogenital warts (condyloma) in males and anal pre-cancers (anal intraepithelial neoplasia; AIN) in GBM up to the age of 26. We conducted in-depth, semi-structured interviews with 25 HIV-positive gay men in Toronto to gain an understanding of their knowledge and experiences related to HPV and the HPV vaccine. These participants were part of The HPV Screening and Vaccine Evaluation (HPV-SAVE) Study, and received invitations to have anal cancer screening from their primary care doctors. Interviews were analyzed following a Grounded Theory Approach. Most participants had not received the HPV vaccine. Men described a lack of prior knowledge of the health consequences of HPV for GBM living with HIV and financial barriers to vaccine access. Participants did not articulate concerns about vaccine safety. Men frequently reported initial beliefs that HPV was predominantly-or exclusively-a risk for females or young girls, and thus they had not considered the vaccine to be necessary. Some participants remained uncertain if the current availability of the vaccine, and their newly acquired knowledge of its importance, was "too little, too late" because of their age and/or HPV exposure. Improving access and uptake of HPV vaccination requires addressing both financial barriers to access as well as increasing HPV health literacy levels, particularly by reframing the long-standing gendered associations of HPV. Physicians should provide clear, tailored messages regarding HPV vaccination.

CD4+ cell count decline despite HIV suppression: a probable didanosine-valganciclovir interaction.

OBJECTIVE: To describe a case of significant CD4+ cell decline despite complete viral suppression in an HIV-positive patient receiving didanosine and valganciclovir. CASE SUMMARY: A 68-year-old woman diagnosed with HIV and cytomegalovirus (CMV) enteritis (CD4+ cell count 22 cells/mm(3), viral load 88,898 [4.95 log] copies/mL) was treated with valganciclovir and began lamivudine, didanosine, and lopinavir/ritonavir. Three months later, her viral load was less than 50 copies/mL and CD4+ cell count was 317 cells/mm(3). Over the next 9 months, her viral load remained suppressed, but the CD4+ cell count declined to 83 cells/mm(3) and she experienced ongoing symptoms of didanosine toxicity. Didanosine was replaced with abacavir, leading to a complete CD4+ cell recovery and resolution of symptoms. DISCUSSION: Paradoxical declines in CD4+ cell counts have been reported in HIV-infected patients virally suppressed on tenofovir/didanosine regimens, presumably via inhibition of purine nucleoside phosphorylase (PNP) by tenofovir and enhancement of didanosine toxicity. Ganciclovir and its prodrug valganciclovir also inhibit PNP and increase didanosine concentrations; thus, a similar immunological effect with this combination is possible. This hypothesis is consistent with observations from a historic multicenter CMV retinitis study, where a negative CD4+ cell response was observed in patients receiving ganciclovir, while those treated with foscarnet experienced a CD4+ cell increase and a mortality advantage. Of the subjects who received any type of nucleoside therapy during this study, didanosine use was proportionally higher in the ganciclovir arm versus the foscarnet arm. According to the Naranjo probability scale, our patient experienced a probable adverse reaction associated with the combination of didanosine and valganciclovir. CONCLUSIONS: Patients receiving didanosine-containing highly active antiretroviral therapy and ganciclovir or valganciclovir for treatment of CMV infection should be monitored for didanosine toxicity and unexpected CD4+ cell loss or failure of CD4+ cell recovery. Reduction of didanosine dosage or substitution with an alternative antiretroviral may be necessary.