Kristina Thorsteinsson

Impact of gender on the risk of AIDS-defining illnesses and mortality in Danish HIV-1-infected patients: A nationwide cohort study

Abstract Background: Gender differences in the risk of AIDS-defining illness (ADI) and mortality have been reported in the HIV-1-infected (HIV-positive) population, with conflicting findings. We aimed to assess the impact of gender on the risk of ADI and death in HIV-positive patients infected sexually. Methods: This was a population-based, nationwide cohort study of incident Danish HIV-positive individuals infected by sexual contact. Outcomes were progression to AIDS and death. We used Cox proportional hazards models and Poisson regression analyses to calculate the risk of progression to AIDS and mortality rate ratios (MRR) between risk groups and compared these with the general Danish population. Results: We identified 587 heterosexually infected women, 583 men who have sex with women (MSW), and 1089 men who have sex with men (MSM). The total follow-up time was 13,708 person-y. At the time of HIV diagnosis MSM had a lower prevalence of AIDS compared to MSW. Women and MSW presented more often with tuberculosis and less often with AIDS-defining cancers compared to MSM. In the adjusted analyses we observed no differences in progression to AIDS. In the adjusted analyses of risk of death, there were no differences between the 3 risk groups, although we saw a trend towards a higher risk of death in older MSW. MSM had a lower risk of death compared to the background population than women and MSW. Conclusions: In the Danish HIV population, gender has no major impact on progression to AIDS or mortality. Differences in these factors between women, MSW, and MSM are mainly due to confounding from race and CD4 + cell count at diagnosis.

Adherence to national guidelines for initiation of antiretroviral regimens in HIV patients: a Danish nationwide study

AIM To determine the adherence to the national guidelines for start of highly active antiretroviral treatment (HAART) in HIV infected patients. METHODS We used a Danish nationwide cohort of HIV infected patients to calculate the fraction of patients who in the period 1997-2006 started HAART according to the guidelines from The Danish Society of Infectious Diseases. We used Kaplan-Meier tables to estimate time from fulfilling the criteria for start of HAART to initiation of the treatment. Cox regression and logistic regression was used to identify risk factors for delayed initiation of treatment and chance of being included in clinical trials. RESULTS The study included 3223 patients, 74% of whom initiated HAART in the study period. Ninety-four% fulfilled the criteria for start of HAART, with minor differences over calendar periods. Ninety-four% initiated a recommended regimen or were included in a clinical trial. Intravenous drug use predicted initiation of a non-recommended regimen and delay in start of HAART, while non-Caucasians were less likely to be included in clinical trials. CONCLUSIONS In a Western world setting, the adherence to national guidelines for start of HAART can be high. We suggest that simplicity of the guidelines, centralization of treatment and involvement of local clinicians in the development of guidelines are of major importance for high adherence to treatment guidelines.

Impact of gender on response to highly active antiretroviral therapy in HIV-1 infected patients: a nationwide population-based cohort study

BackgroundImpact of gender on time to initiation, response to and risk of modification of highly active antiretroviral therapy (HAART) in HIV-1 infected individuals is still controversial.MethodsFrom a nationwide cohort of Danish HIV infected individuals we identified all heterosexually infected women (N=587) and heterosexually infected men (N=583) with no record of Hepatitis C infection diagnosed with HIV after 1 January 1997. Among these subjects, 473 women (81%) and 435 men (75%) initiated HAART from 1 January 1997 to 31 December 2009. We used Cox regression to calculate hazard ratio (HR) for time to initiation of HAART, Poisson regression to assess incidence rate ratios (IRR) of risk of treatment modification the first year, logistic regression to estimate differences in the proportion with an undetectable viral load, and linear regression to detect differences in CD4 count at year 1, 3 and 6 after start of HAART.ResultsAt initiation of HAART, women were younger, predominantly of Black ethnicity and had a higher CD4 count (adjusted p=0.026) and lower viral load (adjusted p=0.0003). When repeating the analysis excluding pregnant women no difference was seen in CD4 counts (adjusted p=0.21). We observed no delay in time to initiation of HAART in women compared to men (HR 0.91, 95% CI 0.79-1.06). There were no gender differences in risk of treatment modification of the original HAART regimen during the first year of therapy for either toxicity (IRR 0.97 95% CI 0.66-1.44) or other/unknown reasons (IRR 1.18 95% CI 0.76-1.82). Finally, CD4 counts and the risk of having a detectable viral load at 1, 3 and 6 years did not differ between genders.ConclusionsIn a setting with free access to healthcare and HAART, gender does neither affect time from eligibility to HAART, modification of therapy nor virological and immunological response to HAART. Differences observed between genders are mainly attributable to initiation of HAART in pregnant women.

Reduced IL-7R T cell expression and increased plasma sCD127 in late presenting HIV-infected individuals.

Background: Late presentation of HIV infection is associated with reduced chance of optimal immune recovery after initiating combination antiretroviral therapy (cART). Interleukin-7 (IL-7) and the corresponding receptor, IL-7 receptor (IL-7R) made up of CD127 and CD132, are crucial for T cell homeostasis. This study aimed to describe IL-7R and IL-7 before and after initiation of cART in late presenting HIV-infected individuals, and the impact on immune recovery and T cell subset distribution after initiation of cART. Methods: A total of 100 HIV-infected individuals initiating cART were included in a prospective study. Samples were collected at baseline and after 6, 12, and 24 months of cART. Proportion and expression {[median fluorescence intensity (MFI)]} of IL-7R on T cells, and plasma concentrations of soluble CD127 (sCD127) and IL-7 were determined. Results: The IL-7R expression was reduced in late presenters with CD4 cell count <200 cells per microliter compared with nonlate presenters and healthy controls as demonstrated by lower proportion of CD127 + CD132 + T cells and lower CD127 MFI. In contrast, plasma sCD127 was higher. These differences were partly reversed after suppressive cART. Interestingly, the CD127 MFI on CD4+ T cells was found to be a predictor of increased thymic output after 24 months of suppressive cART. Conclusions: Severely altered IL-7R expression was found in late presenters, and associations between IL-7R expression and thymic output after 24 months of suppressive cART indicate an impact of a IL-7 response for the long term de novo production from thymus.

Incidence of cervical dysplasia and cervical cancer in women living with HIV in Denmark

Women living with HIV (WLWH) are reportedly at increased risk of invasive cervical cancer (ICC). A recent publication found that WLWH in Denmark attend the national ICC screening programme less often than women in the general population. We aimed to estimate the incidence of cervical dysplasia and ICC in WLWH in Denmark compared with that in women in the general population.

Perception of sexuality and fertility in women living with HIV: a questionnaire study from two Nordic countries

As the human immunodeficiency virus (HIV)‐positive population ages, issues concerning sexuality and fertility, among others, are becoming relevant. HIV is still surrounded by stigma and taboos, and there have been few studies conducted in industrialized settings concerning these questions. We therefore wanted to investigate the perception of sexuality and fertility in women living with HIV (WLWH) in an industrialized setting, using a questionnaire.

Assessment of mode of delivery and predictors of emergency caesarean section among women living with HIV in a matched-pair setting with women from the general population in Denmark, 2002-2014

We aimed to assess mode of delivery and predictors of emergency caesarean section (EmCS) in women living with HIV (WLWH) in a matched‐pair setting with women from the general population (WGP) in Denmark. Further, we analysed birth plan in WLWH.

Incidence of cervical dysplasia and cervical cancer in women living with HIV in Denmark: comparison with the general population

Women living with HIV (WLWH) are reportedly at increased risk of invasive cervical cancer (ICC). WLWH in Denmark attend the National ICC screening program less often than women in the general population. We aimed to estimate the incidence of cervical dysplasia and ICC in WLWH in Denmark.

Cardiac Microvascular Dysfunction in Women Living With HIV Is Associated With Cytomegalovirus Immunoglobulin G

Abstract Background People living with HIV (PLWH) appear to be at increased risk of cardiovascular disease (CVD), and this is possibly more pronounced in women living with HIV (WLWH). In the general population, men are more likely to develop obstructive coronary artery disease (CAD), and women often present with a nonobstructive pattern with cardiac microvascular dysfunction. We investigated cardiac microvascular function in men and women living with HIV and tested for association with cytomegalovirus (CMV) immunoglobulin G (IgG), as this has been associated with CVD in PLWH. Methods In a cross-sectional study, 94 PLWH on antiretroviral therapy were scanned with 82Rb positron emission tomography/computed tomography at rest and during adenosine-induced stress, which enables the quantification of the myocardial flow reserve (MFR). CMV IgG was measured in plasma. Results WLWH had significantly lower MFR compared with men living with HIV (MLWH; P = .003), and >45% of the women had an MFR indicative of cardiac microvascular dysfunction, whereas this was only true for 24% of men (P = .03). CMV IgG concentrations were inversely associated with MFR among WLWH but not MLWH (P = .05 for interaction). Conclusions In this first study comparing MFR in women and men living with HIV, we found that WLWH had significantly lower MFR than MLWH and 45% of the women had cardiac microvascular dysfunction despite younger age and lower cardiovascular risk. Furthermore, CMV IgG was inversely associated with MFR among women but not men. This calls for attention to CVD among young WLWH even with low cardiovascular risk.

Prevalence of cervical, oral, and anal human papillomavirus infection in women living with HIV in Denmark - The SHADE cohort study

BACKGROUND Women living with HIV (WLWH) have elevated risk of human papillomavirus (HPV) related cancers. OBJECTIVES To assess prevalence, distribution and concordance of cervical, oral, and anal HPV infection, and predictors of oral and anal HPV in WLWH in Denmark. STUDY DESIGN WLWH followed in the Study on HIV, cervical Abnormalities and infections in women in Denmark (SHADE) were enrolled and examined for cervical, oral, and anal HPV infection. Logistic regression models were used to identify predictors of anal and oral HPV. RESULTS A total of 214 of 334 WLWH had sufficient DNA for analysis at all three anatomical sites and were included in analyses. Cervical, oral, and anal high-risk (hr) HPV prevalence were 28.0%, 3.7% and 39.3%. Most frequent i) cervical, ii) oral and iii) anal hrHPV genotypes were i) hrHPV58 (8.4%), 52 (5.1%), 16 (5.1%) and 51 (5.1%); ii) 52 (1.4%) and iii) 51 (9.3%), 58 (8.9%), 16 (7.0%) and 18 (7.0%). Among present cervical, oral, and anal hrHPV genotypes, 6.7%, 12.5% and 17.9% were targeted by the 2-or 4-valent HPV vaccines, whereas 50.0%, 50.0% and 42.9% of hrHPV genotypes were covered by the 9-valent HPV vaccine. Anal HPV infection was predicted by cervical HPV infection (adjusted OR 4.47 (95%CI 2.25-8.89)). CONCLUSION Cervical and anal HPV infection were highly prevalent in WLWH. Non-16/18 hrHPV genotypes were predominant at all anatomical sites. Almost half of all hrHPV infections at the three anatomical sites could have been prevented by childhood/adolescent vaccination with the 9-valent HPV vaccine.