DeSheng Su

Fertility desires and intentions of HIV-positive women of reproductive age in Ontario, Canada: a cross-sectional study.

Background Improvements in life expectancy and quality of life for HIV-positive women coupled with reduced vertical transmission will likely lead numerous HIV-positive women to consider becoming pregnant. In order to clarify the demand, and aid with appropriate health services planning for this population, our study aims to assess the fertility desires and intentions of HIV-positive women of reproductive age living in Ontario, Canada. Methodology/Principal Findings A cross-sectional study with recruitment stratified to match the geographic distribution of HIV-positive women of reproductive age (18–52) living in Ontario was carried out. Women were recruited from 38 sites between October 2007 and April 2009 and invited to complete a 189-item self-administered survey entitled “The HIV Pregnancy Planning Questionnaire” designed to assess fertility desires, intentions and actions. Logistic regression models were fit to calculate unadjusted and adjusted odds ratios of significant predictors of fertility intentions. The median age of the 490 participating HIV-positive women was 38 (IQR, 32–43) and 61%, 52%, 47% and 74% were born outside of Canada, living in Toronto, of African ethnicity and currently on antiretroviral therapy, respectively. Of total respondents, 69% (95% CI, 64%–73%) desired to give birth and 57% (95% CI, 53%–62%) intended to give birth in the future. In the multivariable model, the significant predictors of fertility intentions were: younger age (age<40) (p<0.0001), African ethnicity (p<0.0001), living in Toronto (p = 0.002), and a lower number of lifetime births (p = 0.02). Conclusions/Significance The proportions of HIV-positive women of reproductive age living in Ontario desiring and intending pregnancy were higher than reported in earlier North American studies. Proportions were more similar to those reported from African populations. Healthcare providers and policy makers need to consider increasing services and support for pregnancy planning for HIV-positive women. This may be particularly significant in jurisdictions with high levels of African immigration.

Magnitude of Virologic Blips Is Associated With a Higher Risk for Virologic Rebound in HIV-Infected Individuals: A Recurrent Events Analysis

BACKGROUND The importance of human immunodeficiency virus (HIV) blip magnitude on virologic rebound has been raised in clinical guidelines relating to viral load assays. METHODS Antiretroviral-naive individuals initiating combination antiretroviral therapy (cART) after 1 January 2000 and achieving virologic suppression were studied. Negative binomial models were used to identify blip correlates. Recurrent event models were used to determine the association between blips and rebound by incorporating multiple periods of virologic suppression per individual. RESULTS 3550 participants (82% male; median age, 40 years) were included. In a multivariable negative binomial regression model, the Amplicor assay was associated with a lower blip rate than branched DNA (rate ratio, 0.69; P < .01), controlling for age, sex, region, baseline HIV-1 RNA and CD4 count, AIDS-defining illnesses, year of cART initiation, cART type, and HIV-1 RNA testing frequency. In a multivariable recurrent event model controlling for age, sex, intravenous drug use, cART start year, cART type, assay type, and HIV-1 RNA testing frequency, blips of 500-999 copies/mL were associated with virologic rebound (hazard ratio, 2.70; P = .002), whereas blips of 50-499 were not. CONCLUSIONS HIV-1 RNA assay was an important determinant of blip rates and should be considered in clinical guidelines. Blips ≥500 copies/mL were associated with increased rebound risk.

Screening for HIV-Associated Anal Cancer: Correlation of HPV Genotypes, p16, and E6 Transcripts with Anal Pathology

Background: HIV-positive men with a history of anal-receptive intercourse are at risk for anal cancer. We determined whether human papilloma virus (HPV) biomarkers were correlated with anal pathology in these men. Methods: HPV genotype was determined by PCR/line blot assay. Real-time PCR assays were done for viral load, E6 transcripts for HPV genotypes 16, 18, and 31, and p16 transcripts. Results: The most common oncogenic HPV types were HPV 16 (38%), 18 (19%), 45 (22%), and 52 (19%). HPV types 16, 18, 31, 52, 59, and 68 were associated with high-grade histology. The number of HPV genotypes per anal swab was higher for anal intraepithelial neoplasia (AIN) 2/3 than for normal or AIN 1 histology [median, 5 types (interquartile range) (IQR), 3-7 versus 3.5 (IQR), 2-6; P = 0.0005]. HPV 16 viral load was also associated with AIN 2/3 histology. There was no difference in p16 or E6 transcripts between histologic grades. In the multivariable logistic regression model, HPV genotypes 16 [odds ratio, 2.58; 95% confidence interval (95% CI), 1.31-5.08; P = 0.006] and 31 (odds ratio, 4.74; 95% CI, 2.00-11.22; P = 0.0004), baseline CD4 count < 400 cells/mm3 (odds ratio, 2.96; 95% CI, 1.46-5.99; P = 0.0025), and Acquired Immunodeficiency Syndrome (AIDS)-defining illness (odds ratio, 2.42; 95% CI, 1.22-4.82; P = 0.01) were associated with high-grade histology after adjusting for age. Conclusions: The presence of high-grade anal pathology (AIN 2/3) in HIV-positive men was associated with multiple HPV genotypes, HPV genotypes 16 and 31, and HPV 16 viral load. (Cancer Epidemiol Biomarkers Prev 2009;18(7):1986–92)

Effect of raltegravir intensification on HIV proviral DNA in the blood and gut mucosa of men on long-term therapy: a randomized controlled trial.

Background:Highly active antiretroviral therapy (HAART) dramatically reduces plasma HIV-1 viremia. However, despite completely suppressive HAART, it has been suggested that low-levels of viral replication may persist in the gut mucosa and elsewhere in individuals on long-term HAART. Objective:We conducted a double-blind randomized, placebo-controlled trial evaluating whether intensification of HAART in long-term virologically suppressed individuals with raltegravir is associated with a reduction in the level of proviral HIV-1 DNA in CD4+ T cells in blood and the sigmoid colon (gut). Methods:Long-term (>4 years) virologically suppressed HIV-infected individuals on standard HAART were randomized 1 : 1 in a double-blind fashion to receive raltegravir (400 mg twice/day) or placebo for 48 weeks. After week 48, all participants were treated with raltegravir to week 96. Blood and sigmoid biopsies were sampled and the frequency of CD4+ T cells carrying HIV-1 proviral DNA was determined. Results:Twenty-four study patients were recruited. At 48 weeks, no difference was apparent between participants receiving raltegravir or placebo in blood HIV-1 proviral levels (P = 0.62), CD4+ T-cell counts (P = 0.25) and gut proviral loads (P = 0.74). Similarly, prolonged raltegravir intensification up to week 96 had no further effect on both blood and gut HIV-1 proviral loads and blood CD4+ T-cell counts. Conclusion:In long-term virologically suppressed patients on standard HAART, intensification with raltegravir did not result in further decay of CD4+ T cells carrying HIV-1 proviral DNA in either the blood or gut after 48 or 96 weeks of therapy, or in any increase in CD4+ T-cell counts.

Regional differences in rates of HIV-1 viral load monitoring in Canada: Insights and implications for antiretroviral care in high income countries

BackgroundViral load (VL) monitoring is an essential component of the care of HIV positive individuals. Rates of VL monitoring have been shown to vary by HIV risk factor and clinical characteristics. The objective of this study was to determine whether there are differences among regions in Canada in the rates of VL testing of HIV-positive individuals on combination antiretroviral therapy (cART), where the testing is available without financial barriers under the coverage of provincial health insurance programs.MethodsThe Canadian Observational Cohort (CANOC) is a collaboration of nine Canadian cohorts of HIV-positive individuals who initiated cART after January 1, 2000. The study included participants with at least one year of follow-up. Generalized Estimating Equation (GEE) regression models were used to determine the effect of geographic region on (1) the occurrence of an interval of 9 months or more between two consecutive recorded VL tests and (2) the number of days between VL tests, after adjusting for demographic and clinical covariates. Overall and regional annual rates of VL testing were also reported.Results3,648 individuals were included in the analysis with a median follow-up of 42.9 months and a median of 15 VL tests. In multivariable GEE logistic regression models, gaps in VL testing >9 months were more likely in Quebec (Odds Ratio (OR) = 1.72, p < 0.0001) and Ontario (OR = 1.78, p < 0.0001) than in British Columbia and among injection drug users (OR = 1.68, p < 0.0001) and were less likely among older individuals (OR = 0.77 per 10 years, p < 0.0001), among men having sex with men (OR = 0.62, p < 0.0001), within the first year of cART (OR = 0.15, p < 0.0001), among individuals on cART at the time of the blood draw (OR = 0.34, p < 0.0001) and among individuals with VL < 50 copies/ml at the previous visit (OR = 0.56, p < .0001).ConclusionsSignificant variation in rates of VL testing and the probability of a significant gap in testing were related to geographic region, HIV risk factor, age, year of cART initiation, type of cART regimen, being in the first year of cART, AIDS-defining illness and whether or not the previous VL was below the limit of detection.

The psychological impact of being screened for anal cancer in HIV-infected men who have sex with men.

BACKGROUND: Anal cancer screening may be considered in HIV-infected men who have sex with men because they are at increased risk. Cancer screening can provoke anxiety, which may lead to poorer screening compliance. OBJECTIVE: This study aimed to measure the psychological consequences of anal cancer screening in HIV-infected men who have sex with men. DESIGN: This investigation is a prospective cohort study. SETTING: This study was conducted in primary and tertiary care HIV clinics in Toronto, Canada. PATIENTS: One hundred four HIV-infected men who have sex with men were studied. MAIN OUTCOME MEASURES: Psychological impact was measured at 4 time points (before screening, after screening, after receiving results, and before follow-up) using the Impact of Events Scale, the Illness Intrusiveness Ratings Scale, and the Psychological Consequences Questionnaire. RESULTS: Median age was 44, 77% were receiving antiretroviral therapy, and 11% had high-grade anal dysplasia (anal intraepithelial neoplasia 2/3). Fifteen to 32% of the patients reported high levels of negative psychological consequences across the 4 time points; the highest levels occurred at time 2. Higher HIV symptom count and baseline level of negative impact were significantly associated with higher Impact of Events scores, whereas younger age and a higher baseline level of negative impact were significantly associated with higher scores with use of the Illness Intrusiveness Ratings Scale. CONCLUSIONS: Anal cancer screening is not associated with greater adverse psychological impact in most HIV-infected men who have sex with men. Younger patients, those with more HIV-related symptoms and greater baseline psychological distress, are at risk for increased psychological distress during screening.

The importance of motherhood in HIV-positive women of reproductive age in Ontario, Canada

Motherhood is personally, culturally, and historically rooted. Recent publications have focused on medical issues related to pregnancy and HIV, with attention on fetal well-being. There is limited literature on the importance of motherhood for HIV-positive women. Our studys purpose was to investigate the importance of motherhood among HIV-positive women of reproductive age in Ontario, Canada and to analyze the correlates thereof. We present our findings using a secondary analysis of cross-sectionally collected data from a study assessing fertility desires and intentions of HIV-positive women. The sub-analysiss outcome of interest was based on the question: “Being a mother is important to me” with a 5-point Likert scale that was dichotomized into strongly agree/agree vs. neutral/disagree/strongly disagree. Logistic regression models were fit to calculate unadjusted and adjusted odds ratios (ORs) for significant correlates. Of the 497 respondents, median age was 38 (interquartile range [IQR] 32–43), 46% were African, 74% had given birth, and 57% intended to give birth. A total of 452 (91%) agreed (N = 75) or strongly agreed (N = 377) that being a mother was important to them. Age less than 40 years (OR 3.0; 95% confidence interval [CI] 1.6–5.7, African ethnicity (OR 9.2; 95% CI 3.2–26.3), immigration within 10 years (OR 19.6, 95% CI 4.6–83.1), and partner or family desire for a pregnancy (OR 3.3; 95% CI 1.5–7.3) were significant correlates of the importance of motherhood in a univariate analysis. Importance of motherhood was associated with desire (OR 6.2, 95% CI 3.1–12.3) and intention to give birth (OR 6.9, 95% CI 3.1–15.2), and previous birth (OR 8.5, 95% CI 4.2–16.8). In the multivariable model, the significant correlates were of age less than 40 years (OR 3.9; 95% CI 1.8–8.4), immigration within 10 years (OR 14.1; 95% CI 3.2–61.5), and having previously given birth (OR 11.2; 95% CI 5.1–24.4). The majority of women felt strongly that motherhood was important to them particularly among younger women, recent immigrants, and women who were mothers.

Representativeness of an HIV cohort of the sites from which it is recruiting: results from the Ontario HIV Treatment Network (OHTN) cohort study

BackgroundParticipation bias is a well-known phenomenon in epidemiologic research, where individuals consenting to research studies differ from individuals who are not able or willing to participate. These dissimilarities may limit the generalizability of results of research studies. Quantification of the participation bias is essential for the interpretation of research findings.MethodsThe Ontario HIV Treatment Network Cohort Study (OCS) is an ongoing open cohort study of HIV positive individuals receiving care at one of 11 sites in Ontario. OCS participants from 4 sites were compared to non-participants (those who declined or were not approached) at those sites with regard to gender, age, HIV risk factor, CD4 count and viral load (VL). Generalized logit regression models were used to identify predictors of declining to participate or not being approached to participate.ResultsCompared to participants (P) in the OCS, individuals who declined to participate (D) and those who were not approached (NA) were slightly younger (D:45, NA:44 vs P:46), less likely to be male (D: 71%, NA:75% vs P:88%), less likely to be Caucasian (D:41%, NA:57% vs P:72%) and less likely to be Canadian-born (D: 39%, NA: 52% vs P: 69%). Patients who were not approached to participate were less likely to have VL < 50 copies/mL than other patients (D: 75%, NA: 62%, P: 74%) and had lower CD4 counts than OCS participants (D: 450 cells/mm3, NA: 420 cells/mm3, P: 480 cells/mm3).ConclusionsSignificant demographic and clinical differences were found between OCS participants and non-participants. Extrapolation of research findings to other populations should be undertaken cautiously.

Gender Differences in Severity and Correlates of Depression Symptoms in People Living with HIV in Ontario, Canada.

This study investigates the differences in severity and correlates of depression symptoms among 1069 men and 267 women living with HIV in Ontario, Canada, who completed the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). Women had higher CES-D scores than that of men (median [interquartile range]: 13 [5-26] versus 9 [3-20], P = .0004). More women had total CES-D scores >15 (mild-moderate depression; 44% versus 33%, P = .002) and >21 (severe depression; 31% versus 23%, P = .003). Unlike men, at age 40, women’s scores increased yearly (0.4 per increased year, P = .005). The distribution of scores differed by gender: There was no difference in the 10th percentile of depression scores, 0 (95% confidence interval [CI]: 1.0-1.0) but the 75th percentile of depression scores for women was 6 (95% CI: 2.0-10.0) points higher than that of men. Important gender differences exist in depression symptoms and in correlates of symptoms in people living with HIV.

Infectious Complications of Bio-Alcamid Filler Used for HIV-Related Facial Lipoatrophy

BACKGROUND Human immunodeficiency virus (HIV)-related facial lipoatrophy is a devastating adverse effect of antiretroviral therapy. At this time, the most viable treatment option is cosmetic surgery with synthetic fillers. Bio-Alcamid has many advantages over other fillers, and has become widely used. The objective of this study was to determine the incidence rate of infectious complications associated with Bio-Alcamid facial filler in patients with HIV-related facial lipoatrophy (FLA). METHODS This retrospective study identified patients who had received treatment with Bio-Alcamid, and reviewed their long-term outcomes. RESULTS Two hundred sixty-seven patients with Bio-Alcamid were reviewed. Infectious complications were documented in 56 (19%) patients. The incidence rate of infection was 0.07 per patient-year of follow-up. Among patients with infections, the median time from first Bio-Alcamid treatment to infection was 32 months (interquartile range, 21-42). We did not find an association between the development of infection and the level of immune suppression by HIV. Surgical drainage in addition to antibiotics was required for the majority of patients. Potential risk factors for infection include severity of FLA and a preceding history of facial manipulation, including Bio-Alcamid touch-up treatments, cosmetic surgery, facial trauma, and dental work. CONCLUSIONS Bio-Alcamid treatment of HIV-related FLA was associated with a high rate of infectious complications, often presenting years after treatment. Antibiotic prophylaxis should be considered in patients with Bio-Alcamid prior to dental work or facial manipulation.