Alexandra de Pokomandy

Prevalence, Clearance, and Incidence of Anal Human Papillomavirus Infection in HIV-Infected Men: The HIPVIRG Cohort Study

BACKGROUND Human immunodeficiency virus (HIV)-seropositive men who have sex with men (MSM) are at higher risk of human papillomavirus (HPV) infection. This study was conducted to better understand the natural history of type-specific HPV infection in the anus. METHODS A cohort study was conducted among HIV-seropositive MSM in Montreal to investigate acquisition and loss of anal HPV infection. Participants were followed up every 6 months for 3 years for risk behaviors, HIV-related parameters, and HPV testing. RESULTS HPV DNA was detected in 97.9% of the 247 participants at baseline (median, 5 HPV types). The most common types were HPV-16 (38.2%) and HPV-6 (35.3%). Prevalent HPV-16 infections had the lowest clearance rate (12.2 cleared episodes per 1000 person-months [95% confidence interval {CI}, 8.5-17.7]) and a mean retention time of 36 months (95% CI, 32.7-38.8). The highest incidence rates were found for HPV-16 (10.8 new cases per 1000 person-months [95% CI, 8.0-14.7]), HPV-52 (10.8 new cases per 1000 person-months [95% CI, 8.2-14.1]), and HPV-53 (9.8 new cases per 1000 person-months [95% CI, 7.4-13.0]), with cumulative incidences at 36 months of approximately 30%. CONCLUSIONS Multiple HPV types were common in the anal canals of HIV-seropositive MSM. Incidence and clearance rates were not similar among HPV types. Ongoing surveillance of this cohort will help our understanding of the determinants of HPV persistence and progression to lesions.

HAART and Progression to High-Grade Anal Intraepithelial Neoplasia in Men Who Have Sex with Men and Are Infected with HIV

BACKGROUND Human immunodeficiency virus (HIV)-seropositive men who have sex with men (MSM) are at risk for anal intraepithelial neoplasia (AIN) and cancer. The goal of this study was to identify risk factors associated with high-grade AIN (AIN-2,3) in HIV-positive MSM, including the receipt of highly active antiretroviral therapy (HAART). METHODS A cohort study involving 247 HIV-seropositive MSM receiving HAART or initiating HAART was followed up every 6 months for 3 years with human papillomavirus (HPV) testing and high-resolution anoscopy to identify predictors of AIN-2,3 by Cox regression analysis and period prevalence logistic regression. RESULTS AIN-2,3 was observed during the study in 132 (53%) of 247 participants. The progression rate to AIN-2,3 from a lesser abnormality at baseline was 12.8 cases per 1000 person-months (95% confidence interval [CI], 9.8-16.5 cases per 1000 person-months). The risk of AIN-2,3 increased with age (odds ratio [OR], 3.09 [95% CI, 1.12-8.52] for men 40-49 years of age and 4.78 [95% CI, 1.29-17.73] for men >50 years of age, compared with men <40 years of age) and for men whose CD4+ cell counts were <50 cells/mm(3) before starting HAART (OR, 14.40 [95% CI, 1.45-143.58]). Men who had been receiving their current HAART regimen for >4 years had a marginally significant lower risk of AIN-2,3 after adjustment for HPV (OR, 0.28 [95% CI, 0.07-1.06]) compared with those treated for <4 years. Anal HPV type 16 (HPV16) or type 18 (HPV18) infections (OR, 14.18; [95% CI, 3.51-57.32]) and HPV16 and HPV18 co-infection (OR, 31.03 [ 95% CI, 5.68-169.60]) were strongly associated with progression to AIN-2,3. CONCLUSION HPV16 and HPV18 infections and a low nadir CD4+ cell count increase the risk of AIN-2,3. Receiving the same HAART regimen for >4 years may contribute some benefit against AIN-2,3.

Virologic Failure Following Persistent Low-level Viremia in a Cohort of HIV-Positive Patients: Results From 12 Years of Observation

BACKGROUND The current goal of antiretroviral therapy (ART) is to maintain a suppressed human immunodeficiency virus (HIV) viral load below limits of assay detection. When viral loads remain in low-level viremia (LLV), especially between 50 and 200 copies/mL, the best management and clinical consequences remain unknown. Our objective was to study the long-term impact of persistent LLV on the subsequent risk of virologic failure in a cohort of people living with HIV in Montreal, Canada. METHODS We compared the cumulative incidence of subsequent virologic failure (defined as an HIV RNA viral load of >1000 copies/mL) in patients receiving ART for at least 12 months by following 4 persistence categories (<50, 50-199, 200-499, and 500-999 copies/mL) for 6, 9, or 12 months, using Kaplan-Meier analysis. The association between subsequent virologic failure and persistence status were estimated using a Cox proportional hazards model. RESULTS The cumulative incidence of virologic failure 1 year after having maintained a LLV for 6 months was 22.7% (95% confidence interval [CI], 14.9-33.6) for 50-199 copies/mL, 24.2% (95% CI, 14.5-38.6) for 200-499 copies/mL, and 58.9% (95% CI, 43.1-75.2) for 500-999 copies/mL, compared with 6.6% (95% CI, 5.3-8.2) for an undetectable HIV RNA viral load. Even after adjustment for potential confounders, a persistent LLV of 50-199 copies/mL for 6 months doubled the risk of virologic failure (hazard ratio, 2.22; 95% CI, 1.60-3.09), compared with undetectable viral loads for the same duration. Similar results have been found for persistent LLV of 9 or 12 months. CONCLUSIONS In this cohort, all categories of persistent LLV between 50 and 999 copies/mL were associated with an increased risk of virologic failure. The results shed new light for the management of patients with LLV, especially with regard to LLV of 50-199 copies/mL.

Confirmatory Real-Time PCR Assay for Human Papillomavirus (HPV) Type 52 Infection in Anogenital Specimens Screened for HPV Infection with the Linear Array HPV Genotyping Test

ABSTRACT A novel real-time PCR assay for detection of human papillomavirus type 52 (HPV-52) DNA (RT-52) was evaluated on 265 anogenital samples. RT-52 had a sensitivity of 98.4% and a specificity of 100% compared to conventional HPV-52 typing assays, including hybridization of PGMY products with an HPV-52-specific probe and PCR sequencing of HPV-52 E6.

Genotyping of human papillomavirus DNA in anal biopsies and anal swabs collected from HIV-seropositive men with anal dysplasia.

Background:Human papillomavirus (HPV) causes anal intraepithelial neoplasia (AIN) in HIV-seropositive men. The detection of HPV genotypes in anal biopsies and swabs was compared. Methods:HPV DNA was detected in anal swabs and biopsies obtained concurrently from 154 HIV-seropositive men [31 without AIN, 60 low-grade AIN (AIN-1), 62 high-grade AIN (AIN-2,3), and 1 indeterminate AIN] under or eligible to highly active antiretroviral therapy. Results:HPV DNA was detected in 24.2% of normal biopsies compared with 93.5% with AIN-2,3 (P < 0.001) and 88.3% with AIN-1 (P < 0.001). The proportion of biopsies containing multiple genotypes was greater in AIN-1 (n = 21, 35.0%; P = 0.002) and AIN-2,3 (n = 38, 58%; P < 0.001) than in normal biopsies (n = 2, 6.5%). The most frequent genotypes in order of frequency were in AIN-2,3 biopsies HPV-16, 18, 58, and 45 and were in AIN-1 biopsies HPV-6, 11, 16, and 39. Controlling for age, CD4 count, and smoking, the presence of high-risk HPV DNA in biopsies [odds ratio (OR) = 50.8, 95% confidence interval (CI): 13.0 to 199.5] but not in swabs (OR = 2.0, 95% CI: 0.6 to 7.0) was associated with AIN-2,3. Conclusions:AIN-2,3 was associated with high-risk HPV infection detected in biopsies but not in swabs in men under or starting highly active antiretroviral therapy, possibly due to the presence of HPV foci outside of the neoplastic lesion.

Women-specific HIV/AIDS services: identifying and defining the components of holistic service delivery for women living with HIV/AIDS.

The increasing proportion of women living with HIV has evoked calls for tailored services that respond to womens specific needs. The objective of this investigation was to explore the concept of women‐specific HIV/AIDS services to identify and define what key elements underlie this approach to care.

Environmental scan of anal cancer screening practices: worldwide survey results

Anal squamous cell carcinoma is rare in the general population but certain populations, such as persons with HIV, are at increased risk. High‐risk populations can be screened for anal cancer using strategies similar to those used for cervical cancer. However, little is known about the use of such screening practices across jurisdictions. Data were collected using an online survey. Health care professionals currently providing anal cancer screening services were invited to complete the survey via email and/or fax. Information was collected on populations screened, services and treatments offered, and personnel. Over 300 invitations were sent; 82 providers from 80 clinics around the world completed the survey. Fourteen clinics have each examined more than 1000 patients. Over a third of clinics do not restrict access to screening; in the rest, eligibility is most commonly based on HIV status and abnormal anal cytology results. Fifty‐three percent of clinics require abnormal anal cytology prior to performing high‐resolution anoscopy (HRA) in asymptomatic patients. Almost all clinics offer both anal cytology and HRA. Internal high‐grade anal intraepithelial neoplasia (AIN) is most often treated with infrared coagulation (61%), whereas external high‐grade AIN is most commonly treated with imiquimod (49%). Most procedures are performed by physicians, followed by nurse practitioners. Our study is the first description of global anal cancer screening practices. Our findings may be used to inform practice and health policy in jurisdictions considering anal cancer screening.

Sexual inactivity and sexual satisfaction among women living with HIV in Canada in the context of growing social, legal and public health surveillance

Women represent nearly one‐quarter of the 71,300 people living with HIV in Canada. Within a context of widespread HIV‐related stigma and discrimination and on‐going risks to HIV disclosure, little is known about the influence of growing social, legal and public health surveillance of HIV on sexual activity and satisfaction of women living with HIV (WLWH).

Episomal and integrated human papillomavirus type 16 loads and anal intraepithelial neoplasia in HIV-seropositive men

Objectives:To assess levels of episomal and integrated human papillomavirus type 16 (HPV-16) loads in HIV-seropositive men who have sex with men (MSM) in anal infection and to study the association between episomal and integrated HPV-16 loads and anal intraepithelial neoplasia (AIN). Study design:A cohort study of 247 HIV-positive MSM followed each 6 months for 3 years. Overall, 135 (54.7%) men provided 665 HPV-16-positive anal samples. Methods:Episomal and integrated HPV-16 loads were measured with quantitative real-time PCR assays. HPV-16 integration was confirmed in samples with a HPV-16 E6/E2 of 1.5 or more with PCR sequencing to demonstrate the presence of viral–cellular junctions. Results:The HPV-16 DNA forms in anal samples were characterized as episomal only in 627 samples (94.3%), mixed in 22 samples (3.3%) and integrated only in nine samples (1.4%). HPV-16 episomal load [odds ratio (OR) = 1.5, 95% confidence interval (CI) 1.1–2.1], number of HPV types (OR = 1.4, 95% CI 1.1–1.8) and current smoking (OR = 4.8, 95% CI 1.3–18.6) were associated with high-grade AIN (AIN-2,3) after adjusting for age and CD4 cell counts. Integrated HPV-16 load was not associated with AIN-2,3 (OR = 0.7, 95% CI 0.4–1.1). Considering men with AIN-1 at baseline, four (16.7%) of the 24 men who progressed to AIN-2,3 had at least one sample with integrated HPV-16 DNA compared with three (23.1%) of 13 men who did not progress (OR = 0.7, 95% CI 0.2–3.8; P = 0.64). Integration was detected in similar proportions in samples from men without AIN, with AIN-1 or AIN-2,3. Conclusion:High episomal HPV-16 load but not HPV-16 integration load measured by real-time PCR was associated with AIN-2,3.

Establishing the Canadian HIV Women’s Sexual and Reproductive Health Cohort Study (CHIWOS): Operationalizing Community-based Research in a Large National Quantitative Study

BackgroundCommunity-based research has gained increasing recognition in health research over the last two decades. Such participatory research approaches are lauded for their ability to anchor research in lived experiences, ensuring cultural appropriateness, accessing local knowledge, reaching marginalized communities, building capacity, and facilitating research-to-action. While having these positive attributes, the community-based health research literature is predominantly composed of small projects, using qualitative methods, and set within geographically limited communities. Its use in larger health studies, including clinical trials and cohorts, is limited. We present the Canadian HIV Women’s Sexual and Reproductive Health Cohort Study (CHIWOS), a large-scale, multi-site, national, longitudinal quantitative study that has operationalized community-based research in all steps of the research process. Successes, challenges and further considerations are offered.DiscussionThrough the integration of community-based research principles, we have been successful in: facilitating a two-year long formative phase for this study; developing a novel survey instrument with national involvement; training 39 Peer Research Associates (PRAs); offering ongoing comprehensive support to PRAs; and engaging in an ongoing iterative community-based research process. Our community-based research approach within CHIWOS demanded that we be cognizant of challenges managing a large national team, inherent power imbalances and challenges with communication, compensation and volunteering considerations, and extensive delays in institutional processes. It is important to consider the iterative nature of community-based research and to work through tensions that emerge given the diverse perspectives of numerous team members.ConclusionsCommunity-based research, as an approach to large-scale quantitative health research projects, is an increasingly viable methodological option. Community-based research has several advantages that go hand-in-hand with its obstacles. We offer guidance on implementing this approach, such that the process can be better planned and result in success.