Variations in CD4 counts during pregnancy in women living with HIV.

OBJECTIVE: Our objective was to determine the frequency at which CD4 counts drop below 200 cells/mm3 during pregnancy in women living with HIV and to identify factors associated with this. METHODS: Data from 2005 to 2020 from two prospective Canadian cohorts of pregnant women living with HIV were extracted. As per national guidelines, women received antiretroviral therapy and CD4 counts were monitored once per trimester and at delivery. RESULTS: Among 775 included cases, 72 (9.3%) had CD4 counts <200 cells/mm3 at the first pregnancy visit. Of the 703 remaining pregnancies with CD4 counts ≥200 cells/mm3 at the initial visit, 20 (2.8%) were associated with a drop to <200 cells/mm3 . In univariate analysis, factors associated with this drop were coinfection with hepatitis B virus or hepatitis C virus (odds ratio [OR] 4.0, 95% confidence interval [CI] 1.52-10.50), lower first visit CD4 counts (OR 0.165, 95% CI 0.08-0.34), and baseline haemoglobin levels <11 g/dL (OR 2.89, 95% CI 1.04-8.00). In multivariable analysis, only CD4 count at first visit remained independently associated with this drop. A cut-off CD4 count ≤450 cells/mm3 at the first pregnancy visit had a sensitivity of 100% to detect cases of CD4 drop to <200 cells/mm3 . CONCLUSION: A drop of CD4 count to <200 cells/mm3 is uncommon during pregnancy in women living with HIV. Our results suggest that CD4 monitoring only once in pregnancy would be safe in women whose CD4 count is >450 cells/mm3 at the first pregnancy visit.

Elevated Blood Mitochondrial DNA in Early Life Among Uninfected Children Exposed to Human Immunodeficiency Virus and Combination Antiretroviral Therapy in utero.

BACKGROUND: Combination antiretroviral therapy (cART) during pregnancy prevents vertical transmission, but many antiretrovirals cross the placenta and several can affect mitochondria. Exposure to maternal human immunodeficiency virus (HIV) and/or cART could have long-term effects on children who are HIV exposed and uninfected (CHEU). Our objective was to compare blood mitochondrial DNA (mtDNA) content in CHEU and children who are HIV unexposed and uninfected (CHUU), at birth and in early life. METHODS: Whole-blood mtDNA content at birth and in early life (age 0-3 years) was compared cross-sectionally between CHEU and CHUU. Longitudinal changes in mtDNA content among CHEU was also evaluated. RESULTS: At birth, CHEU status and younger gestational age were associated with higher mtDNA content. These remained independently associated with mtDNA content in multivariable analyses, whether considering all infants, or only those born at term. Longitudinally, CHEU mtDNA levels remained unchanged during the first 6 months of life, and gradually declined thereafter. A separate age- and sex-matched cross-sectional analysis (in 214 CHEU and 214 CHUU) illustrates that the difference in mtDNA between the groups remains detectable throughout the first 3 years of life. CONCLUSION: The persistently elevated blood mtDNA content observed among CHEU represents a long-term effect, possibly resulting from in utero stresses related to maternal HIV and/or cART. The clinical impact of altered mtDNA levels is unclear.

Urinary symptoms and quality of life in women living with HIV: a cross-sectional study.

INTRODUCTION AND HYPOTHESIS: To determine prevalence and quality of life impact of lower urinary tract symptoms (LUTS) in women living with HIV (WLWH). METHODS: Cross-sectional urinary questionnaires were included in a multicenter national prospective study of the HPV vaccine in WLWH. Demographic and clinical information was abstracted from the parent study. The Urinary Distress Inventory (UDI-6) and Urinary Impact Questionnaire (UIQ-7) were administered. Wilcoxon rank sum, two-sample chi-square or Fisher's exact tests were used as appropriate to compare women with UDI-6 score ≥ 25 to those with lower UDI-6 scores on demographic and HIV-related factors. Significant categorical variables were followed up with logistic regression to estimate odds ratios (OR). RESULTS: One hundred seventy-seven women completed urinary questionnaires (85.5% of cohort). Median age was 44.1 (37.2-50.6). Mean CD4 count was 621 (410-785), and 132 women (74.6%) were virologically suppressed. Median UDI-6 score was 4.2 (0-25). Fifty-one women (28.8%) had a UIQ-7 score > 0. Among those with a UDI-6 score of at least 25, median UIQ-7 was 9.5 (0-47.6). UDI-6 ≥ 25 was significantly associated with increasing age, higher BMI, Canada as country of origin, peri-/postmenopausal status (OR 3.37, 95% CI = 1.71 to 6.75) and being parous (OR 2.92, 95% CI = 1.27 to 7.59) (all p < 0.05). HIV-related factors were not associated with UDI-6 ≥ 25. CONCLUSIONS: LUTS were common, but we did not demonstrate a negative impact on quality of life in this sample of WLWH. Large comparative studies are needed to determine whether HIV is a risk factor for bothersome LUTS in women.

Quasispecies Diversity Is a Major Risk Factor for Vertical Hepatitis C Virus Transmission.

BACKGROUND: Vertical transmission is the major cause of pediatric hepatitis C virus (HCV) infection. The objective of this study was to better understand HCV pathogenesis in pregnant women and provide insights into risk factors and mechanisms involved in vertical transmission. METHODS: Evolutionary dynamics of HCV variant spectra and HCV-specific neutralizing antibody responses were examined using high-throughput sequencing and pseudoparticle-based assays in pregnant women monoinfected with HCV (n = 17) or coinfected with HCV and human immunodeficiency virus (HIV)-1 (n = 15). RESULTS: Overall, statistically significant associations were found between HCV quasispecies diversity, selective pressure exerted on the HCV E2 envelope protein, and neutralizing activity of maternal immunoglobulins. Women with low quasispecies diversity displayed significantly higher mean aspartate aminotransferase and alanine aminotransferase levels throughout pregnancy, but this difference was restricted to monoinfected participants. Low quasispecies diversity and inefficient neutralizing activity were also significantly associated with vertical transmission, but only in the monoinfected group. CONCLUSIONS: These results indicate that maternal neutralizing antibody responses play a role in the prevention of vertical HCV transmission, but not in presence of HIV-1 coinfection, and suggest that the mechanism of vertical transmission may be different between monoinfected and coinfected women. These findings could inform management strategies for the prevention of vertical HCV transmission.

Leukocyte Telomere Length at Birth and During the Early Life of Children Exposed to but Uninfected With HIV After In Utero Exposure to Antiretrovirals.

Background: Maternal combination antiretroviral therapy (cART) during pregnancy could impact the health of human immunodeficiency virus (HIV)-exposed, HIV-uninfected (HEU) children, because some antiretrovirals cross the placenta and can inhibit telomerase. Our objective was to compare leukocyte telomere length (LTL) in HEU children and HIV-unexposed, HIV-uninfected (HUU) children at birth and in early life and to investigate any relationship with cART exposure. Methods: HEU and HUU children's blood LTL was compared cross-sectionally at birth, and during the first three years of life. Longitudinal HEU LTL dynamics was evaluated over that same period. Results: At birth, the LTL in HEU children (n = 114) was not shorter than that in HUU children (n = 86), but female infants had longer LTL than male infants. Maternal cART (duration or type) showed no association with shorter infant LTL. Among 214 HEU children age- and sex-matched at a 1:1 ratio to HUU children, LTL declined similarly in both groups. In a longitudinal analysis, LTL attrition in HEU children was rapid from birth to 1 year of age and gradual thereafter. Zidovudine prophylaxis did not significantly alter LTL. Conclusions: Our results indicate that from birth to 3 years of age, the LTL in HEU children is not negatively affected by exposure to maternal HIV infection and cART, at least not to the regimens used within this Canadian cohort, a reassuring finding.

Vaginal health and hygiene practices and product use in Canada: a national cross-sectional survey.

BACKGROUND: The vaginal microbiome influences quality of life and health. The composition of vaginal microbiota can be affected by various health behaviors, such as vaginal douching. The purpose of this study was to examine the types and prevalence of diverse vaginal/genital health and hygiene behaviors among participants living in Canada and to examine associations between behavioral practices and adverse gynecological health conditions. METHOD: An anonymous online survey, available in English and French, was distributed across Canada. The sample consisted of 1435 respondents, 18 years or older, living in Canada. RESULTS: Respondents reported engaging in diverse vaginal/genital health and hygiene behavioral practices, including the use of commercially manufactured products and homemade and naturopathic products and practices. Over 95% of respondents reported using at least one product in or around the vaginal area. Common products and practices included vaginal/genital moisturizers, anti-itch creams, feminine wipes, washes, suppositories, sprays, powders, and waxing and shaving pubic hair. The majority of the sample (80%) reported experiencing one or more adverse vaginal/genital symptom in their lifetime. Participants who had used any vaginal/genital product(s) had approximately three times higher odds of reporting an adverse health condition. Several notable associations between specific vaginal/genital health and hygiene products and adverse health conditions were identified. CONCLUSIONS: This study is the first of its kind to identify the range and prevalence of vaginal/genital health and hygiene behaviors in Canada. Despite a lack of credible information about the impact of these behaviors on women's health, the use of commercially manufactured and homemade products for vaginal/genital health and hygiene is common. Future research can extend the current exploratory study by identifying causal relationships between vaginal/genital health and hygiene behaviors and changes to the vaginal microbiome.

No. 354-Canadian HIV Pregnancy Planning Guidelines.

OBJECTIVE: The objective of the Canadian HIV Pregnancy Planning Guidelines is to provide clinical information and recommendations for health care providers to assist Canadians affected by HIV with their fertility, preconception, and pregnancy planning decisions. These guidelines are evidence- and community-based and flexible and take into account diverse and intersecting local/population needs based on the social determinants of health. INTENDED OUTCOMES: EVIDENCE: Literature searches were conducted by a librarian using the Medline, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase databases for published articles in English and French related to HIV and pregnancy and HIV and pregnancy planning for each section of the guidelines. The full search strategy is available upon request. VALUES: The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the SOGC under the leadership of the principal authors, and recommendations were made according to the guidelines developed by the Canadian Task Force on Preventive Health Care and through use of the Appraisal of Guidelines Research and Evaluation instrument for the development of clinical guidelines. BENEFITS, HARMS, AND COSTS: Guideline implementation should assist the practitioner in developing an evidence-based approach for the prevention of unplanned pregnancy, preconception, fertility, and pregnancy planning counselling in the context of HIV infection. VALIDATION: These guidelines have been reviewed and approved by the Infectious Disease Committee and the Executive and Council of the SOGC. SPONSOR: Canadian Institutes of Health Research Grant Planning and Dissemination grant (Funding Reference # 137186), which funded a Development Team meeting in 2016.

Self-collection based HPV testing for cervical cancer screening among women living with HIV in Uganda: a descriptive analysis of knowledge, intentions to screen and factors associated with HPV positivity.

BACKGROUND: Women living with HIV (WHIV) are disproportionately impacted by cervical dysplasia and cancer. The burden is greatest in low-income countries where limited or no access to screening exists. The goal of this study was to describe knowledge and intentions of WHIV towards HPV self-collection for cervical cancer screening, and to report on factors related to HPV positivity among women who participated in testing. METHODS: A validated survey was administered to 87 HIV positive women attending the Kisenyi Health Unit aged 30-69 years old, and data was abstracted from chart review. At a later date, self-collection based HPV testing was offered to all women. Specimens were tested for high risk HPV genotypes, and women were contacted with results and referred for care. Descriptive statistics, Chi Square and Fischer-exact statistical tests were performed. RESULTS: The vast majority of WHIV (98.9%) women did not think it necessary to be screened for cervical cancer and the majority of women had never heard of HPV (96.4%). However, almost all WHIV found self-collection for cervical cancer screening to be acceptable. Of the 87 WHIV offered self-collection, 40 women agreed to provide a sample at the HIV clinic. Among women tested, 45% were oncogenic HPV positive, where HPV 16 or 18 positivity was 15% overall. CONCLUSIONS: In this group of WHIV engaged in HIV care, there was a high prevalence of oncogenic HPV, a large proportion of which were HPV genotypes 16 or 18, in addition to low knowledge of HPV and cervical cancer screening. Improved education and cervical cancer screening for WHIV are sorely needed; self-collection based screening has the potential to be integrated with routine HIV care in this setting.

No 211-Dépistage et prise en charge de la vaginose bactérienne pendant la grossesse.

OBJECTIF: Analyser les résultats et fournir des recommandations au sujet du dépistage et de la prise en charge de la vaginose bactérienne pendant la grossesse. OPTIONS: Les options de pratique clinique prises en considération au moment de formuler la présente directive clinique. ISSUES: Parmi les issues évaluées, on trouve les taux d'efficacité et de guérison de l'antibiothérapie, et l'influence de la prise en charge de la vaginose bactérienne sur les taux d'issues de grossesse indésirables (tels que le travail et l'accouchement prétermes, et la rupture prématurée des membranes préterme). RéSULTATS: Des recherches ont été menées dans les bases de données Medline, EMBASE, CINAHL et Cochrane afin d'en tirer les articles, publiés en anglais avant le fin de juin 2007, traitant de la vaginose bactérienne pendant la grossesse. VALEURS: Les données obtenues ont été évaluées au moyen des critères élaborés par le Groupe d'étude canadien sur les soins de santé préventifs. Avantages, désavantages et coûts : La mise en œuvre de la présente directive clinique aidera le praticien à élaborer une approche quant au diagnostic et à la prise en charge de la vaginose bactérienne chez les femmes enceintes. Les patientes bénéficieront d'une prise en charge appropriée de cette pathologie. VALIDATION: La présente directive clinique a été rédigée par le comité sur les maladies infectieuses et approuvée par le comité exécutif et le Conseil de la Société des obstétriciens et gynécologues du Canada. COMMANDITAIRE: La Société des obstétriciens et gynécologues du Canada. RECOMMANDATIONS: Il n'existe présentement aucun consensus quant à la question de savoir s'il faut procéder au dépistage ou à la prise en charge de la vaginose bactérienne, au sein de la population générale de femmes enceintes, afin de prévenir la survenue d'issues indésirables (telles que l'accouchement préterme).

No. 211-Screening and Management of Bacterial Vaginosis in Pregnancy.

OBJECTIVE: To review the evidence and provide recommendations on screening for and management of bacterial vaginosis in pregnancy. OPTIONS: The clinical practice options considered in formulating the guideline. OUTCOMES: Outcomes evaluated include antibiotic treatment efficacy and cure rates, and the influence of the treatment of bacterial vaginosis on the rates of adverse pregnancy outcomes such as preterm labour and delivery and preterm premature rupture of membranes. EVIDENCE: Medline, EMBASE, CINAHL, and Cochrane databases were searched for articles, published in English before the end of June 2007 on the topic of bacterial vaginosis in pregnancy. VALUES: The evidence obtained was rated using the criteria developed by the Canadian Task Force on Preventive Health Care. BENEFITS, HARMS, AND COSTS: Guideline implementation will assist the practitioner in developing an approach to the diagnosis and treatment of bacterial vaginosis in pregnant women. Patients will benefit from appropriate management of this condition. VALIDATION: These guidelines have been prepared by the Infectious Diseases Committee of the SOGC, and approved by the Executive and Council of the SOGC. SPONSORS: The Society of Obstetricians and Gynaecologists of Canada. RECOMMENDATIONS: There is currently no consensus as to whether to screen for or treat bacterial vaginosis in the general pregnant population in order to prevent adverse outcomes, such as preterm birth.

No. 208-Guidelines for the Management of Herpes Simplex Virus in Pregnancy.

OBJECTIVE: To provide recommendations for the management of genital herpes infection in women who want to get pregnant or are pregnant and for the management of genital herpes in pregnancy and strategies to prevent transmission to the infant. OUTCOMES: More effective management of complications of genital herpes in pregnancy and prevention of transmission of genital herpes from mother to infant. EVIDENCE: Medline was searched for articles published in French or English related to genital herpes and pregnancy. Additional articles were identified through the references of these articles. All study types and recommendation reports were reviewed. VALUES: Recommendations were made according to the guidelines developed by the Canadian Task Force on Preventive Health Care. RECOMMENDATIONS: VALIDATION: These guidelines have been reviewed and approved by the Infectious Diseases Committee of the SOGC. SPONSOR: The Society of Obstetricians and Gynaecologists of Canada.

An Evaluation of Introduction of Rapid HIV Testing in a Perinatal Program.

OBJECTIVE: This study was conducted to evaluate the roll-out of rapid HIV testing as part of an emergency Prevention of Perinatal HIV Transmission Program. Specifically, HIV prevalence in this population, the reason(s) for performing the rapid HIV test, and compliance with recommendations for antiretroviral prophylaxis were assessed. METHODS: Since November 2011, all women presenting to a tertiary labour and delivery unit with unknown HIV status or with ongoing risk of HIV infection since their last HIV test were offered rapid HIV testing. Through retrospective chart review, demographic data, HIV risk and prior testing history, and antiretroviral prophylaxis, data were collected and descriptive statistics were performed. RESULTS: One hundred fourteen rapid HIV tests were conducted and there were two preliminary reactive rapid results (one true positive, one false positive). None of the infants was HIV infected. Sixty-three percent of women had multiple risk factors for HIV acquisition, most commonly intravenous drug use (54%). Forty-four percent of women were within the 4-week seroconversion window at the time of delivery; 25% of these women and 52% of their infants received prophylactic drug therapy. CONCLUSION: Rapid HIV testing identified a high-risk cohort and enabled aggressive management of a newly diagnosed HIV-positive pregnancy, successfully preventing perinatal HIV transmission. Risk factors for HIV acquisition were ongoing within the seroconversion window for over half of the women, impacting the utility of the test in eliminating unnecessary antiretroviral prophylaxis in this population because prophylaxis is recommended despite a negative rapid HIV test in these cases.

Mobile Text Messaging to Improve Medication Adherence and Viral Load in a Vulnerable Canadian Population Living With Human Immunodeficiency Virus: A Repeated Measures Study.

BACKGROUND: Combination antiretroviral therapy (cART) as treatment for human immunodeficiency virus (HIV) infection is effective and available, but poor medication adherence limits benefits, particularly in vulnerable populations. In a Kenyan randomized controlled trial, a weekly text-messaging intervention (WelTel) improved cART adherence and HIV viral load (VL). Despite growing evidence for short message service (SMS) text-message interventions in HIV care, there is a paucity of data utilizing these interventions in marginalized or female cohorts. OBJECTIVE: This study was undertaken to assess whether the standardized WelTel SMS text-message intervention applied to a vulnerable, predominantly female, population improved cART adherence and VL. METHODS: We conducted a repeated measures study of the WelTel intervention in high-risk HIV-positive persons by measuring change in VL, CD4 count, and self-reported adherence 12 months before and 12 months after the WelTel intervention was introduced. Inclusion criteria included VL ≥200 copies/mL, indication for treatment, and meeting vulnerability criteria. Participants were given a mobile phone with unlimited texting (where required), and weekly check-in text messages were sent for one year from the WelTel computer platform. Clinical data were collected for control and intervention years. Participants were followed by a multidisciplinary team in a clinical setting. Outcomes were assessed using Wilcoxon signed ranks tests for change in CD4 and VL from control year to study end and mixed-effects logistic regressions for change in cART adherence and appointment attendance. A secondary analysis was conducted to assess the effect of response rate on the outcome by modeling final log10 VL by number of responses while controlling for mean log10 VL in the control year. RESULTS: Eighty-five participants enrolled in the study, but 5 withdrew (final N=80). Participants were predominantly female (90%, 72/80) with a variety of vulnerabilities. Mean VL decreased from 1098 copies/mL in the control year to 439 copies/mL at study end (P=.004). Adherence to cART significantly improved (OR 1.14, IQR 1.10-1.18; P<.001), whereas appointment attendance decreased slightly with the intervention (OR 0.81, IQR 0.67-0.99; P=.03). A response was received for 46.57% (1753/3764) of messages sent and 9.62% (362/3764) of text messages sent were replied to with a problem. An outcome analysis examining relationship between reply rate and VL did not meet statistical significance (P=.07), but may be worthy of investigating further in a larger study. CONCLUSIONS: WelTel may be an effective tool for improving cART adherence and reducing VLs among high-risk, vulnerable HIV-positive persons. TRIAL REGISTRATION: Clinicaltrials.gov NCT02603536; https://clinicaltrials.gov/ct2/show/NCT02603536 (Archived by WebCite at http://www.webcitation.org/6qK57zCwv).

Endocrine abnormalities in HIV-infected women are associated with peak viral load - the Children and Women: AntiRetrovirals and Markers of Aging (CARMA) Cohort.

OBJECTIVES: To investigate the prevalence of endocrine disturbances in a group of HIV-positive (HIV+) women and to identify factors affecting presence of these disorders. To examine specifically whether cellular ageing, as measured by leukocyte telomere length (LTL), is correlated with the presence of endocrine disturbance. DESIGN: A cross-sectional retrospective substudy of an ongoing prospective cohort study. PATIENTS: Adult HIV+ (≥19 years) women enrolled in the CARMA (Children and Women: AntiRetrovirals and Markers of Aging) cohort study (N = 192). Prevalences of T2DM, glucose intolerance, dyslipidaemia, thyroid disorders, adrenal insufficiency, hypogonadism, primary ovarian insufficiency (POI), demographics, HIV and hepatitis C virus (HCV) infection status, baseline LTL, combined antiRetroviral therapy (cART) and substance exposures were collected. Statistical analysis included univariable followed by multivariable Poisson regression and step-wise reduction to refine the multivariable model. RESULTS: Prevalence of any endocrine abnormality was 58% (dyslipidaemia 43%, glucose intolerance/T2DM 13%, thyroid disorders 15%). In multivariable analysis, age was associated with number and type (any, glucose, lipid) of abnormality, while increasing body mass index (BMI) was associated with number of diagnoses and with glucose metabolism disorders. Interestingly, peak HIV pVL ≥100 000 copies/ml was associated with any abnormality, total number of disorders and presence of a thyroid disorder, while any disorder, glucose abnormalities and dyslipidaemia were negatively associated with alcohol use. LTL was not associated with number or type of endocrine abnormalities in this study. CONCLUSION: Further studies examining the relationship between duration and extent of exposure to HIV viraemia in relation to developing abnormal endocrine function are warranted.

Reduction in cervical intraepithelial neoplasia in young women in British Columbia after introduction of the HPV vaccine: An ecological analysis.

We report on the rates of cervical intraepithelial neoplasia (CIN) in young women aged 15-22 years of age in British Columbia before and after the introduction of an HPV vaccine program. Rates of cervical intraepithelial neoplasia (CIN) 2+ for each age stratum (15-22) in the calendar years 2004-2012 for the province of British Columbia were obtained from the BC Cancer Agency's population-based cervical cancer program. Incidence rate ratios (IRR) of CIN2+ were described and compared before and after HPV vaccine program introduction in cohorts born in vaccine eligible years, and in non-vaccine eligible years using piece-wise Poisson regression analysis, and adjusted for age. Between 2004 and 2012, rates of CIN2 and CIN2+ in young women aged 15-22 years in the province of British Columbia have decreased overall. After the introduction of the HPV vaccine program, the age adjusted IRR for CIN2+ for young women aged 15-17 years decreased significantly from 0.91 (95% CI: 0.86-0.98 p < 0.01) to 0.36 (95% CI: 0.18-0.73 p < 0.01). During the same time period, no similar reduction was found in young women 18-22 years. After introduction of HPV vaccine program, IRR for CIN2+ in young women 15-17 was significantly reduced for CIN2+ (0.14; 95% CI: 0.04- 0.47; p < 0.01) and CIN2 (0.1; 95% CI: 0.02-0.54; p < 0.01). This ecological analysis shows a significant reduction in CIN2+ lesions in young women aged 15-17 years in British Columbia after the introduction of the HPV vaccine in young women despite vaccine uptake levels below 70%.

Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-adjuvanted vaccine in women older than 25 years: 4-year interim follow-up of the phase 3, double-blind, randomised controlled VIVIANE study.

BACKGROUND: Although adolescent girls are the main population for prophylactic human papillomavirus (HPV) vaccines, adult women who remain at risk of cervical cancer can also be vaccinated. We report data from the interim analysis of the ongoing VIVIANE study, the aim of which is to assess the efficacy, safety, and immunogenicity of the HPV 16/18 AS04-adjuvanted vaccine in adult women. METHODS: In this phase 3, multinational, double-blind, randomised controlled trial, we randomly assigned healthy women older than 25 years to the HPV 16/18 vaccine or control (1:1), via an internet-based system with an algorithm process that accounted for region, age stratum, baseline HPV DNA status, HPV 16/18 serostatus, and cytology. Enrolment was age-stratified, with about 45% of participants in each of the 26-35 and 36-45 years age strata and 10% in the 46 years and older stratum. Up to 15% of women in each age stratum could have a history of HPV infection or disease. The primary endpoint was vaccine efficacy against 6-month persistent infection or cervical intraepithelial neoplasia grade 1 or higher (CIN1+) associated with HPV 16/18. The primary analysis was done in the according-to-protocol cohort for efficacy, which consists of women who received all three vaccine or control doses, had negative or low-grade cytology at baseline, and had no history of HPV disease. Secondary analyses included vaccine efficacy against non-vaccine oncogenic HPV types. Mean follow-up time was 40·3 months. This study is registered with ClinicalTrials.gov, number NCT00294047. FINDINGS: The first participant was enrolled on Feb 16, 2006, and the last study visit for the present analysis took place on Dec 10, 2010; 5752 women were included in the total vaccinated cohort (n=2881 vaccine, n=2871 control), and 4505 in the according-to-protocol cohort for efficacy (n=2264 vaccine, n=2241 control). Vaccine efficacy against HPV 16/18-related 6-month persistent infection or CIN1+ was significant in all age groups combined (81·1%, 97·7% CI 52·1-94·0), in the 26-35 years age group (83·5%, 45·0-96·8), and in the 36-45 years age group (77·2%, 2·8-96·9); no cases were seen in women aged 46 years and older. Vaccine efficacy against atypical squamous cells of undetermined significance or greater associated with HPV 16/18 was also significant. We also noted significant cross-protective vaccine efficacy against 6-month persistent infection with HPV 31 (79·1%, 97·7% CI 27·6-95·9) and HPV 45 (76·9%, 18·5-95·6]) Serious adverse events occurred in 285 (10%) of 2881 women in the vaccine group and 267 (9%) of 2871 in the control group; five (<1%) and eight (<1%) of these events, respectively, were believed to be related to vaccination. INTERPRETATION: In women older than 25 years, the HPV 16/18 vaccine is efficacious against infections and cervical abnormalities associated with the vaccine types, as well as infections with the non-vaccine HPV types 31 and 45. FUNDING: GlaxoSmithKline Biologicals SA.

Uptake of community-based, self-collected HPV testing vs. visual inspection with acetic acid for cervical cancer screening in Kampala, Uganda: preliminary results of a randomised controlled trial.

OBJECTIVES: To compare two cervical cancer screening methods: community-based self-collection of high-risk human papillomavirus (HR-HPV) testing and visual inspection with acetic acid (VIA). METHODS: Pilot randomised controlled trial of 500 women aged 30-65 in the community of Kisenyi, Uganda. Women randomised to self-collection-based HR-HPV testing provided a cervico-vaginal swab for HR-HPV, and results were provided by phone after laboratory testing. Women who tested HPV positive were referred for VIA at the local health unit. Women randomised to VIA underwent screening at the local health unit, where women who tested positive with VIA were provided cryotherapy at time of screening, as per local standard of care. Women were referred for colposcopy when indicated. Outcome measures were uptake of screening, HR-HPV prevalence, VIA result and treatment rates. RESULTS: In the HR-HPV arm, 248 of 250 (p < 0.01) women provided samples, while in the VIA arm, 121 of 250 (48.4%) women attended screening. Among the 73 of 248 HR-HPV-positive women, 45.2% (N = 33) attended VIA screening for follow-up, 21.2% (N = 7) of whom screened positive; five received treatment and two were missing clinical follow-up records. Of the 121 women in the VIA arm who attended screening, 13.2% (N = 16) screened positive; seven received cryotherapy, three refused treatment, five were referred to colposcopy; and one woman had suspected cervical cancer and received treatment after confirmatory testing. CONCLUSIONS: This pilot study demonstrated trial feasibility and willingness of the women to participate and be randomised successfully into the two arms. Self-collection-based cervical cancer screening had a higher uptake than VIA.

Association between short leukocyte telomere length and HIV infection in a cohort study: No evidence of a relationship with antiretroviral therapy.

BACKGROUND: Individuals infected with human immunodeficiency virus (HIV) appear to age faster than the general population, possibly related to HIV infection, antiretroviral therapy, and/or social/environmental factors. We evaluated leukocyte telomere length (LTL), a marker of cellular aging, in HIV-infected and uninfected adults. METHODS: Clinical data and blood were collected from Children and women: AntiRetrovirals and the Mechanism of Aging (CARMA) cohort study participants. Variables found to be important in univariate analysis were multivariate model candidates. RESULTS: Of the 229 HIV-infected and 166 HIV-uninfected participants, 76% were women, and 71% were current/previous smokers. In a multivariate model of all participants, older age (P < .001), HIV infection (P = .04), active hepatitis C virus (HCV) infection (P = .02), and smoking (P < .003) were associated with shorter LTL. An interaction was detected, whereby smoking was associated with shorter LTL in HIV-uninfected subjects only. Among those, age and smoking (P ≤ .01) were related to shorter LTL. In 2 models of HIV-infected individuals, age (P ≤ .002) and either active HCV infection (P = .05) or peak HIV RNA ≥100 000 copies/mL (P = .04) were associated with shorter LTL, whereas other HIV disease or treatment parameters were unrelated. CONCLUSIONS: Our results suggest that acquisition of HIV and viral load are primarily responsible for the association between HIV-positive status and shorter LTL. The lack of association between LTL and time since HIV diagnosis, antiretroviral treatment, or degree of immune suppression would implicate HIV infection-related factors rather than disease progression or treatment. Smoking effects on LTL appear masked by HIV, and HCV infection may accelerate LTL shortening, particularly in coinfected individuals. The effect of early therapeutic intervention on LTL in HIV and HCV infections should be evaluated.