Angela Cristina Vasconcelos de Andrade

Factors associated with increased prevalence of human papillomavirus infection in a cohort of HIV-infected Brazilian women

OBJECTIVES Human papillomavirus (HPV) infection is a major risk factor for cervical disease. Using baseline data from the HIV-infected cohort of Evandro Chagas Clinical Research Institute at Fiocruz, Rio de Janeiro, Brazil, factors associated with an increased prevalence of HPV were assessed. METHODS Samples from 634 HIV-infected women were tested for the presence of HPV infection using hybrid capture II and polymerase chain reaction. Prevalence ratios (PR) were estimated using Poisson regression analysis with robust variance. RESULTS The overall prevalence of HPV infection was 48%, of which 94% were infected with a high-risk HPV. In multivariate analysis, factors independently associated with infection with high-risk HPV type were: younger age (<30 years of age; PR 1.5, 95% confidence interval (CI) 1.1-2.1), current or prior drug use (PR 1.3, 95% CI 1.0-1.6), self-reported history of HPV infection (PR 1.2, 95% CI 0.96-1.6), condom use in the last sexual intercourse (PR 1.3, 95% CI 1.1-1.7), and nadir CD4+ T-cell count <100cells/mm(3) (PR 1.6, 95% CI 1.2-2.1). CONCLUSIONS The estimated prevalence of high-risk HPV-infection among HIV-infected women from Rio de Janeiro, Brazil, was high. Close monitoring of HPV-related effects is warranted in all HIV-infected women, in particular those of younger age and advanced immunosuppression.

Assessing sexually transmitted infections in a cohort of women living with HIV/AIDS, in Rio de Janeiro, Brazil

A cohort of 458 HIV-positive women under antiretroviral therapy has been followed at a reference hospital in Rio de Janeiro, Brazil. Most of them belong to impoverished social strata. Patients were screened for sexually transmitted infections (STIs) and gynaecologic conditions. Some STIs were found to be uncommon (e.g. chlamydial and gonococcal infections), while some conditions (bacterial vaginosis) and STIs, e.g. hepatitis B and human papilloma virus (HPV) infection, were found to be quite prevalent. The latter is of special concern, due to the high prevalence of HIV/HPV co-infection (∼51%) and its association with severe immunodeficiency, in a context of unacceptable high levels of uterine cancer and uneven gynaecological care. HIV-positive women are in need of comprehensive health services, including high-quality, regular, gynaecologic care in order to diagnose and treat lower genital tract infections and prevent the evolution of HPV-related lesions. Reproductive counselling should be a part of this approach.

Factors associated with colposcopy-histopathology confirmed cervical intraepithelial neoplasia among HIV-infected women from Rio De Janeiro Brazil.

Introduction Despite the availability of preventive strategies (screening tests and vaccines), cervical cancer continues to impose a significant health burden in low- and medium-resourced countries. HIV-infected women are at increased risk for infection with human papillomavirus (HPV) and thus development of cervical squamous intraepithelial neoplasia (CIN). Methods Study participants included HIV-infected women enrolling the prospective open cohort of Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation (IPEC/FIOCRUZ). At cohort entry, women were subjected to conventional Papanicolaou test, HPV-DNA test and colposcopy; lesions suspicious for CIN were biopsied. Histopathology report was based on directed biopsy or on specimens obtained by excision of the transformation zone or cervical conization. Poisson regression modeling was used to assess factors associated with CIN2+ diagnosis. Results The median age of the 366 HIV-infected women included in the study was 34 years (interquartile range: 28–41 years). The prevalence of CIN1, CIN2 and CIN3 were 20.0%, 3.5%, and 2.2%, respectively. One woman was found to have cervical cancer. The prevalence of CIN2+ was 6.0%. Factors associated with CIN2+ diagnosis in the multivariate model were age < years compared to ≥35 years (aPR  =  3.22 95%CI 1.23–8.39), current tobacco use (aPR  =  3.69 95%CI 1.54–8.78), nadir CD4 T-cell count <350 cells/mm3 when compared to ≥ 350 cells/mm3 (aPR  =  6.03 95%CI 1.50–24.3) and concomitant diagnosis of vulvar and/or vaginal intraepithelial lesion (aPR  =  2.68 95%CI 0.99–7.24). Discussion Increased survival through wide-spread use of highly active antiretroviral therapy might allow for the development of cervical cancer. In Brazil, limited cytology screening and gynecological care adds further complexity to the HIV-HPV co-infection problem. Integrated HIV care and cervical cancer prevention programs are needed for the prevention of cervical cancer mortality in this group of women.

Predictors of early menopause in HIV-infected women: a prospective cohort study.

OBJECTIVE This study sought to investigate the age at natural menopause and its predictors in a cohort of human immunodeficiency virus (HIV)-infected women in Rio de Janeiro, Brazil. STUDY DESIGN HIV-infected women ≥30 years of age were included. Menopause was defined as having ≥1 year since the last menstrual period. Early age at natural menopause was defined as the onset of menopause at ≤45 years of age. Multivariate Cox proportional hazards analysis was applied. RESULTS A total of 667 women were included, and the median age at baseline was 34.9 years (interquartile range, 30.9-40.5 years). In all, 507 (76%) women were premenopausal, and 160 (24%) reached menopause during the observational period; of these, 36 of 160 (27%) had early menopause. The median age at natural menopause was 48 years (interquartile range, 45-50 years). Menarche at <11 years of age (hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.23-3.37), cigarette smoking during the observational period (HR, 1.59; 95% CI, 1.08-2.33), chronic hepatitis C virus (HCV) infection (HR, 2.53; 95% CI, 1.27-5.07), and CD4 count <50 cells/mm(3) (HR, 3.07; 95% CI, 1.07-8.80) were significantly associated with an earlier age at natural menopause. The magnitudes of the effects of menarche at <11 years of age (HR, 2.7; 95% CI, 1.23-5.94), cigarette smoking during the observational period (HR, 3.00; 95% CI, 1.39-6.45), chronic HCV infection (HR, 6.26; 95% CI, 2.12-18.52), and CD4 count <50 cells/mm(3) (HR, 6.64; 95% CI, 1.91-23.20) were much higher and significantly associated with early natural menopause. CONCLUSION Early natural menopause was frequent among the HIV-infected women. In addition to menarche and cigarette smoking, which are menopausal factors among women in general, HIV-related immunodeficiency and chronic HCV were additional predictors for an earlier age at natural menopause. Adequate management of HIV in women is critical, as early onset of menopause has been associated with increased morbidity and mortality.

Cervical cytological abnormalities and factors associated with high-grade squamous intraepithelial lesions among HIV-infected women from Rio de Janeiro, Brazil:

Although cervical cancer remains a major public health problem in Brazil, knowledge of cervical cytological abnormalities among HIV-infected women remains scarce. At baseline evaluation of a cohort followed in Rio de Janeiro, Brazil, 703 HIV-infected women underwent cytology-based cervical cancer screening and human papillomavirus (HPV) DNA testing. Poisson regression analysis was used to evaluate the association of factors with the presence of high-grade squamous intraepithelial lesions (HSIL). Cervical cytology was abnormal in 24.3% of the women; 4.1% had HSIL. Beyond HPV infection, factors independently associated with the presence of HSIL was age (≥25 and ≤40 years, prevalence ratio [PR] 2.60, 95% confidence interval [CI] 1.11–6.10), and more than three pregnancies was protective (PR 0.33, 95% CI 0.11–0.94). High coverage of cervical cancer screening is warranted to prevent morbidity and mortality from cervical cancer in this population.

Breast cancer in a cohort of human immunodeficiency virus (HIV)-infected women from Rio de Janeiro, Brazil: a cases series report and an incidence rate estimate

Highly active antiretroviral therapy (HAART) has changed the morbidity pattern affecting HIV-infected individuals to include non-AIDS-defining cancers. We describe the breast cancer cases occurring in a cohort of 860 HIV-infected women followed in Rio de Janeiro, Brazil, and estimate the incidence rate of breast cancer for this population. Nine cases were identified; median age at diagnosis was 46 years. Median survival after breast cancer diagnosis was 12 months. Breast cancer diagnosis was made within 2 to 15 years of HIV-infection diagnosis. At breast cancer diagnosis, CD4 counts ranged from 135 to 782 cells/mm3; six women were receiving HAART. Histological analysis indicated infiltrating ductal carcinoma in all cases. The incidence rate of breast cancer was 133 cases per 100,000 persons-year. Patients from our case series were late diagnosed with breast cancer and thus suffered from worse prognosis. Strategies targeting earlier diagnosis and prompt initiation of treatment are needed.

Absence of effect of menopause status at initiation of first-line antiretroviral therapy on immunologic or virologic responses: a cohort study from Rio de Janeiro, Brazil

Objective To compare the effectiveness of first-line combination antiretroviral therapy (cART) between premenopausal and postmenopausal women. Methods ART-naïve women initiating cART between January 2000/June 2010 at the Instituto de Pesquisa Clínica Evandro Chagas Cohort were studied. Women were defined as postmenopausal after 12 consecutive months of amenorrhea. CD4 cell counts and HIV-1 RNA viral load (VL) measurements were compared between pre- and postmenopausal at 6, 12 and 24 months after cART initiation. Women who modified/discontinued a drug class or died due to an AIDS defining illness were classified as ART-failures. Variables were compared using Wilcoxon test, χ2 or Fisher’s exact test. The odds of cART effectiveness (VL<400 copies/mL and/or no need to change cART) were compared using logistic regression. Linear model was used to access relationship between CD4 change and menopause. Results Among 383 women, 328 (85%) were premenopausal and 55 (15%) postmenopausal. Median pre cART CD4 counts were 231 and 208 cells/mm3 (p = 0.14) in pre- and postmenopausal women, respectively. No difference in the median pre cART VL was found (both 4.8 copies/mL). Median CD4 changes were similar at 6 and 12 months. At 24 months after cART initiation, CD4 changes among postmenopausal women were significantly lower among premenopausal women (p = 0.01). When the analysis was restricted to women with VL<400 copies/mL, no statistical difference was observed. Overall, 63.7% achieved cART effectiveness at 24 months without differences between groups at 6, 12 and 24 months. Conclusion Menopause status at the time of first-line cART initiation does not impact CD4 cell changes at 24 months among women with a virologic response. No relationship between menopause status and virologic response was observed.

Subclinical infection of the genital tract with Neisseria meningitidis

We report the isolation of Neisseria meningitidis, characterized as B:NT:P1.7, from a female patients genital tract in an outpatient clinic for HIV care. The gynecology clinic, as part of the follow up, collects specimens from all patients with HIV infection for routine exams and for early laboratory detection of sexually transmitted diseases . A Gram-negative diplococcus was isolated from the cervix of a heterosexual patient with AIDS. Based on this and other reported cases, urogenital infection with N. meningitidis can no longer be considered uncommon. The rising incidence of N. meningitidis isolated from this and similar sites has significant medical and diagnostic implications.

Desempenho do exame citológico e da captura híbrida II no rastreamento de lesões intraepiteliais escamosas de alto grau em mulheres HIV

HIV-infected women are at increased risk of developing high-grade squamous intraepithelial lesions (HSIL), the precursor lesions for cervical cancer. This study estimated and compared the performance of cytology and hybrid capture II in screening for precursor lesions of cervical cancer among HIV-infected women. The study population consisted of women from the open prospective cohort at the Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation (IPEC/Fiocruz). Colposcopy and histology were considered jointly in defining the gold standard. Cytology showed 31.8% sensitivity and 95.5% specificity, while hybrid capture II showed higher sensitivity (100%) and lower specificity (52%). The positive likelihood ratio was 7.1 for cytology and 2.1 for hybrid capture II, while the negative likelihood ratio was 0.7 for cytology and 0.0 for hybrid capture II.

Hybrid capture as a tool for cervical lesions screening in HIV-infected women: insights from a Brazilian cohort

INTRODUCTION Cervical cancer remains an important burden for HIV-infected women in the era of combination antiretroviral therapy. Recommendations for cervical screening in these women diverge and may include high-risk HPV (HRHPV) testing. We aimed to evaluate the clinical usefulness of a single HRHPV testing for cervical screening of HIV-infected women. METHODS 723 HIV-infected women from a Brazilian prospective cohort were included between 1996 and 2012. Inclusion criteria were: normal cervical cytology at baseline and having a HRHPV-test at baseline. We calculated incidence rates of any squamous intraepithelial lesion (SIL) and high grade SIL+ (HSIL+) and negative predictive values (NPV) within 12 and 36 months. Hazard Ratios were obtained using Cox proportional hazards regression models. RESULTS Incidence rate for both outcomes was low (9.9 cases per 100 PY [95% CI 8.8-11.0] for any SIL and 1.3 cases per 100 PY [95% IC 0.9-1.8] for HSIL+). Women with a HRHPV positive status at baseline had 1.7-fold (95% CI 1.3-2.2) and 3.2-fold (95% CI 1.5-7.1) increased risk of presenting any SIL and HSIL+, respectively, during follow-up. Negative-HRHPV test presented high NPV for both periods and outcomes (any SIL: 92.4% [95% CI 89.7-94.6] for 12 months and 80.9% [95% CI 77.2-84.3] for 36 months; and HSIL+: 99.8% [95% CI 98.9-100.0] for 12 months and 99.0 [95% CI 97.6-99.7] for 36 months). CONCLUSIONS Incidence of any and high grade cytological abnormality was significantly higher among HIV-infected women with positive-HRHPV test. A single negative-HRHPV test helped reassure follow-up free of cytological abnormalities through three years of follow-up in HIV-infected women with negative cytology.