Questioning risk compensation: pre-exposure prophylaxis (PrEP) and sexually transmitted infections among men who have sex with men, capital region of Denmark, 2019 to 2022.

BackgroundPre-exposure prophylaxis (PrEP) effectively prevents HIV, but its association with sexually transmitted infections (STIs) has raised concerns about risk compensation, potentially impacting the expansion of PrEP programmes.AimWe examined the relationship between PrEP and the incidence of chlamydia, gonorrhoea and syphilis.MethodsIn this prospective cohort study, we compared STI rates before and after PrEP initiation among users in the capital region of Denmark (2019-2022), calculating incidence rate ratios adjusted for age and testing frequency (aIRR). To pinpoint when increases began, we plotted weekly STI rates, adjusting the timeline to correspond with PrEP initiation.ResultsThe study included 1,326 PrEP users with a median age of 35 years. The STI incidence rate per 100,000 person-years rose from 35.3 before to 81.2 after PrEP start, with an aIRR of 1.35 (95% CI: 1.18-1.56). Notably, this increase preceded PrEP initiation by 10-20 weeks. Specific aIRR for chlamydia, gonorrhoea and syphilis were 1.23 (95% CI: 1.03-1.48), 1.24 (95% CI: 1.04-1.47) and 1.15 (95% CI: 0.76-1.72), respectively. In subanalyses for anatomical sites aIRR was 1.26 (95% CI: 1.01-1.56) for rectal chlamydia and 0.66 (95% CI: 0.45-0.96) for genital gonorrhoea.ConclusionWe found a 35% increase in STI incidence associated with PrEP use. It started before PrEP initiation, challenging the assumption that PrEP leads to risk compensation. Instead, the data suggest that individuals seek PrEP during periods of heightened sexual risk-taking. Consequently, PrEP programmes should include sexual health consultations, STI testing, treatment and prevention strategies to prevent HIV and improve sexual health.

Stratum Corneum Lipids in Non-Lesional Atopic and Healthy Skin following Moisturizer Application: A Randomized Clinical Experiment.

INTRODUCTION: It is an international standard to recommend patients with atopic dermatitis (AD) to use moisturizers; however, little is known about their effect on lipids in the stratum corneum (SC). METHODS: In this randomized clinical experiment of 30 Caucasian participants (15 with AD and 15 healthy controls), the superficial SC lipid profile was assessed through tape stripping non-lesional skin following treatment thrice daily for seven days with a moisturizer, and subsequently compared with untreated skin. RESULTS: No discernible disparity in superficial SC lipid quantity was evident between the AD group and the control group. However, the SC lipid composition diverged significantly, with the AD group exhibiting diminished levels of long-chain EO CERs (p = 0.024) and elevated levels of short-chain C34 CERs (p = 0.025) compared to healthy skin. Moisturizer application significantly reduced the total SC lipids and all lipid subgroups in both groups. Within the AD group, a non-significant inclination towards an augmentation in EO CERs (p = 0.053) and reduction in C34 CERs (p = 0.073) was observed. CONCLUSION: The recent identification of distinctions in SC lipid composition between AD and healthy skin was substantiated by our findings. Topical moisturizer application, despite reducing overall total lipids, indicated a potential tendency towards a healthier lipid constitution in AD skin.

Carriage of methicillin-resistant Staphylococcus aureus in children <6 years old: a retrospective follow-up study of the natural course and effectiveness of decolonization treatment.

BACKGROUND: Decolonization treatment of MRSA carriers is recommended in Denmark, except in households with MRSA-positive children <2 years old (wait-and-see approach). OBJECTIVES: To investigate a wait-and-see approach in children 2-5 years old, and the effect of decolonization treatment of MRSA carriage in all children <6 years old. PATIENTS AND METHODS: In this retrospective follow-up study, we included MRSA carriers <6 years old in the Capital Region of Denmark from 2007 to 2021. Data were collected from laboratory information systems and electronic patient records. We divided children into age groups of <2 years or 2-5 years and decolonization treatment versus no treatment. Treatment was chlorhexidine body washes and nasal mupirocin, sometimes supplemented with systemic antibiotics. Children were followed until becoming MRSA free, or censoring. The probability of becoming MRSA free was investigated with Cox regression (higher HRs indicate faster decolonization). RESULTS: Of 348 included children, 226 were <2 years old [56/226 (25%) received treatment] and 122 were 2-5 years old [90/122 (74%) received treatment]. Multivariable analyses did not show a larger effect of decolonization treatment versus no treatment in <2-year-olds (HR 0.92, 95% CI 0.52-1.65) or 2-5-year-olds (HR 0.54, 95% CI 0.26-1.12). Without treatment, 2-5-year-olds tended to clear MRSA faster than <2-year-olds (HR 1.81, 95% CI 0.98-3.37). CONCLUSIONS: We did not find a larger effect of decolonization treatment versus no treatment in children <6 years old, and 2-5-year-olds tended to become MRSA free faster than <2-year-olds. These results support a wait-and-see approach for all children <6 years old, but further studies are needed.

Use of antidepressants in women after prophylactic bilateral oophorectomy: A Danish national cohort study.

OBJECTIVE: To investigate the association between prophylactic bilateral oophorectomy and use of antidepressants in women with a family history of cancer. METHODS: Nationwide population-based cohort study using Danish National Registries including women oophorectomized due to a family history of cancer (n = 2,002) and an age matched reference group (n = 18,018). Analyses were stratified by age at time of bilateral oophorectomy and use of hormone replacement therapy (HRT). RESULTS: Women oophorectomized at age ≤ 45 years were more likely to use antidepressants from the first year after bilateral oophorectomy (OR = 1.34; 95 % CI: 1.08-1.65) compared to the reference group. Women oophorectomized at age 46-55 years and at age >55 years had no significantly increased use of antidepressants (OR = 0.90; 95 % CI: 0.68-1.18 and OR = 1.14; 95 % CI: 0.81-1.61). The increased use of antidepressants in women oophorectomized at age ≤ 45 years was limited to women treated with HRT (OR = 1.51; 95 % CI: 1.18-1.94) whereas women oophorectomized at age ≤ 45 years not treated with HRT had no increased use of antidepressants (OR = 1.03; 95 % CI: 0.70-1.51). CONCLUSIONS: Women oophorectomized due to a family history of cancer at age ≤ 45 years were more likely to use antidepressants after bilateral oophorectomy. The increased use of antidepressants was limited to women treated with HRT. The study calls for further large-scale studies to understand how bilateral oophorectomy and concomitant HRT affects risk of depression in women with a family history of cancer.

Anti-müllerian hormone levels are reduced in women living with human immunodeficiency virus compared to control women: a case-control study from Copenhagen, Denmark.

OBJECTIVES: Anti-müllerian hormone (AMH) is a marker of ovarian reserve. The purpose of this study was to compare AMH in women living with HIV with an age-matched control group of HIV-uninfected women, and to identify possible variables associated with decreasing AMH levels in women living with HIV. METHODS: AMH was measured in frozen EDTA samples from 84 white women living with HIV, aged 20 -40 years, with fully suppressed HIV RNA viral loads for at least 6 months and no hepatitis B or C virus co-infection. All women living with HIV were age-matched with HIV-uninfected control women. RESULTS: Eighty-four women living with HIV and 252 control women were included. Median age for the women living with HIV was 33.5 years (interquartile range [IQR] 30.6-35.3), and 33.2 years (IQR 30.6-35.5) for the control women. A significant difference (P=0.03) was found in the mean AMH levels for all age groups combined, which was 17.23 pmol/L (95% confidence interval [CI] 14.56-19.89) in the women living with HIV versus 21.65 pmol/L (95% CI 19.50-23.81) in the control women, although levels were within reference limits in both groups.Only increasing age was significantly associated with decreasing AMH levels and not CD4 cell count, AIDS prior to inclusion, antiretroviral treatment/lack of treatment or antiretroviral treatment regimen. CONCLUSIONS: Well-treated, white women living with HIV in Denmark, have reduced AMH levels compared with age-matched control HIV-uninfected women. The only variable associated with decreasing AMH levels in women living with HIV was increasing age.

Mortality and Risk of Cancer After Prophylactic Bilateral Oophorectomy in Women With a Family History of Cancer.

BACKGROUND: Current international guidelines recommend systemic hormone therapy (HT) to oophorectomized women until the age of natural menopause. Despite an inherited predisposition to estrogen-dependent malignancies, the guidelines also apply to women oophorectomized because of a family history of cancer. The objective of this study was to investigate the impact of HT on mortality and risk of cancer in women oophorectomized because of a family history of cancer. METHODS: A nationwide, population-based cohort was used to study women oophorectomized because of a family history of cancer (n = 2002). Comparison cohorts included women from the background population individually matched on age (n = 18 018). Oophorectomized women were subdivided into three groups: oophorectomized at 1) age 45 years or younger not using HT, 2) age 45 years or younger using HT, 3) older than age 45 years, and their respective population comparison cohorts. RESULTS: Women oophorectomized at age 45 years or younger using HT had increased overall mortality (mortality rate ratio [MRR] = 3.45, 95% confidence interval [CI] = 1.53 to 7.79), mortality because of cancer (MRR = 5.67, 95% CI = 1.86 to 17.34), and risk of overall cancer (incidence rate ratio [IRR] = 3.68, 95% CI = 1.93 - 6.98), primarily reflected in an increased risk of breast cancer (IRR = 4.88, 95% CI = 2.19 - 10.68). Women oophorectomized at age 45 years or younger not using HT and women oophorectomized at older than age 45 years did not have increased mortality, mortality because of cancer, or risk of overall cancer, but they had increased risk of breast cancer (IRR = 2.64, 95% CI = 1.14 to 6.13, and IRR = 1.72, 95% CI = 1.14 to 2.59, respectively). CONCLUSIONS: Use of HT in women oophorectomized at age 45 years or younger with a family history of cancer is associated with increased mortality and risk of overall cancer and breast cancer. Our study warrants further investigation to establish the impact of HT on mortality and cancer risk in oophorectomized women with a family history of cancer.

Incidence, clinical presentation, and outcome of HIV-1-associated cryptococcal meningitis during the highly active antiretroviral therapy era: a nationwide cohort study.

BACKGROUND: Human immunodeficiency virus (HIV) infection with advanced immunosuppression predisposes to cryptococcal meningitis (CM). We describe the incidence, clinical presentation, and outcome of CM in HIV-infected individuals during the highly active antiretroviral therapy (HAART) era. METHODS: A nationwide, population-based cohort of HIV-infected individuals was used to estimate incidence and mortality of CM including risk factors. A description of neurological symptoms of CM at presentation and follow-up in the study period 1995-2014 was included in this study. RESULTS: Among 6,351 HIV-infected individuals, 40 were diagnosed with CM. The incidence rates were 3.7, 1.8, and 0.3 per 1000 person-years at risk in 1995-1996, 1997-1999, and 2000-2014, respectively. Initiation of HAART was associated with decreased risk of acquiring CM [incidence rate ratio (IRR), 0.1 (95% CI, 0.05-0.22)]. African origin was associated with increased risk of CM [IRR, 2.05 (95% CI, 1.00-4.20)]. The main signs and symptoms at presentation were headache, cognitive deficits, fever, neck stiffness, nausea, and vomiting. All individuals diagnosed with CM had a CD4+ cell count <200 cells/µl [median 26; interquartile range (IQR), 10-50)]. Overall, mortality following CM was high and mortality in the first 4 months has not changed substantially over time. However, individuals who survived generally had a favorable prognosis, with 86% (18/21) returning to the pre-CM level of activity. CONCLUSION: The incidence of HIV-associated CM has decreased substantially after the introduction of HAART. To further decrease CM incidence and associated mortality, early HIV diagnosis and HAART initiation seems crucial.

Incidence, presentation and outcome of toxoplasmosis in HIV infected in the combination antiretroviral therapy era.

BACKGROUND: HIV-associated incidence and prognosis of cerebral toxoplasmosis (CTX) is not well established during later years. METHODS: From the Danish HIV Cohort Study, we identified 6325 HIV-infected individuals. We assessed incidence, mortality, predictive and prognostic factors of CTX during the pre-combination antiretroviral therapy (pre-cART; 1995-1996) and cART-era (1997-2014). Adjusted incidence rate ratios (aIRR), mortality rate ratios (aMRR) and 95% confidence intervals (CI) were assessed using Poisson regression analysis. RESULTS: CTX IR was 1.17/1000 PYR (95% CI 0.93-1.47). We observed no change in CTX-risk in the first year after HIV-diagnosis, but a substantial reduction in mortality in the first 3 months after CTX diagnosis when comparing the cART-era to the pre-cART-era; {(aIRR: 0.79; 95% CI: 0.37-1.72) (aMRR: 0.15; 95% CI: 0.06-0.38)}. For individuals surviving the first year after HIV-diagnosis or the first 3 months after CTX-diagnosis, IRR and MRR had declined to minimal levels {(aIRR: 0.06; 95% CI: 0.03-0.10); (aMRR: 0.02; 95% CI: 0.01-0.05)}. Three years after CTX-diagnosis 30% of the patients still had neurological deficits. CONCLUSION: Although, CTX remains an important cause of morbidity and mortality in the cART-era, with high prevalence of neurological sequelae, incidence and mortality has largely declined, especially among those surviving the first year after diagnosis.

Agreement between Estimated and Measured Renal Function in an Everyday Clinical Outpatient Setting of Human Immunodeficiency Virus-Infected Individuals.

INTRODUCTION: Estimated renal function (eRF) has been widely implemented as a screening tool in handling human immunodeficiency virus (HIV)-infected individuals. Our primary objective was to investigate the agreement between measured renal function (mRF) and eRF in HIV-infected individuals in an everyday clinical setting. METHODS: A single-center study at the HIV-outpatient clinic at Copenhagen University Hospital, Rigshospitalet. Study period from January 1, 2004-June 1, 2015. We included all HIV-infected individuals who had an mRF performed and compared this with eRF assessed with 9 different serum-creatinine-based equations and the eRF reported by the Department of Clinical Biochemistry. We evaluated performance characteristics of the different eRFs, with concordance correlation coefficient, total deviation index, coverage probability, relative accuracy, and Bland Altman plots. We also evaluated whether exposure to (1) rilpivirine, cobicistat, or dolutegravir (RLP/COB/DTG), (2) protease inhibitors (PIs), or (3) tenofovir disoproxil fumarate (TDF) had an impact on agreement. Furthermore, we compared inter- and intra-individual differences between mRF and eRF. RESULTS: Ninety-eight individuals had an mRF performed during the study period. We found that the agreement between mRF and eRF was poor irrespective of the eRF equation. Exposure to RLP/COB/DTG and PIs was not associated with different agreement. Exposure to TDF was associated with statistically significant better agreement for 3 of the evaluated equations. CONCLUSION: Irrespective of calculation methods, the agreement between mRF and eRF is poor. Surprisingly TDF exposure was associated with a better agreement compared with TDF-unexposed individuals.

Five-year risk of HIV diagnosis subsequent to 147 hospital-based indicator diseases: a Danish nationwide population-based cohort study.

BACKGROUND: It has been suggested that targeted human immunodeficiency virus (HIV) testing programs are cost-effective in populations with an HIV prevalence >0.1%. Several indicator diseases are known to be associated with increased risk of HIV infection, but estimates of HIV frequency in persons with relevant indicator diseases are nonexistent. METHODS: In a nationwide population-based cohort study encompassing all Danish residents aged 20-60 years during 1994-2013, we estimated the 5-year risk of an HIV diagnosis (FYRHD) after a first-time diagnosis of 147 prespecified potential indicator diseases. To estimate the risk of HIV diagnosis in the general population without any indicator diseases, we calculated the FYRHD starting at age 25, 35, 45, and 55 years. RESULTS: The risk in the male general population was substantially higher than the female general population, and the risk was lower in the older age categories. Individuals of African origin had a higher FYRHD than individuals of Danish origin. A number of diseases were identified with a FYRHD >0.1%, with infectious diseases, such as syphilis, hepatitis, and endocarditis, associated with a particularly high FYRHD. Other potential indicator diseases, such as most urologic, nephrologic, rheumatologic, and endocrine disorders were generally associated with a low FYRHD. CONCLUSION: Our study identified a large number of indicator diseases associated with a FYRHD >0.1%. These data can be used as a tool for planning targeted HIV screening programs.

Incidence of benign prostate hypertrophy in Danish men with and without HIV infection.

BACKGROUND: Information on risk of benign prostate hypertrophy (BPH) in HIV-infected men is sparse. We aimed to estimate the incidence of being diagnosed with BPH among HIV-infected men compared with an age and sex-matched comparison cohort from the background population. To exclude that family-associated risk factors influence risk of BPH diagnoses in families of HIV-infected individuals, we estimated risk of BPH in fathers of HIV-infected men and fathers of the comparison cohort. METHODS: In a nationwide, population-based, matched cohort study, we calculated incidence rates and used Poisson regression models to calculate incidence rate ratios (IRRs) of being diagnosed with BPH, defined as the earliest of date of the second redeemed prescription of a drug used to treat BPH, the first registration of a BPH diagnosis in the Danish National Hospital Registry (DNHR) or the first registration of a surgical procedure for BPH in DNHR. RESULTS: We identified 4633 HIV-infected men, 46 330 comparison cohort individuals, 1585 fathers of HIV-infected men and 20 449 fathers of the comparison cohort. Incidence rate of being diagnosed with BPH was 37.0 [95% confidence interval (95% CI) 31.5-43.1] per 10 000 person-years of follow-up among HIV-infected men and was not increased compared with the comparison cohort (IRR 1.04, 95% CI 0.88-1.22). Risk was not increased for fathers of HIV-infected men vs. fathers of the comparison cohort (IRR 0.99, 95% CI 0.87-1.12). Stratified analyses did not change the above results markedly. CONCLUSION: HIV-infected individuals do not have an increased risk of being diagnosed with BPH.

Smoking and renal function in people living with human immunodeficiency virus: a Danish nationwide cohort study.

INTRODUCTION: Smoking is a main risk factor for morbidity and mortality in people living with human immunodeficiency virus (PLHIV), but its potential association with renal impairment remains to be established. METHODS: We did a nationwide population-based cohort study in Danish PLHIV to evaluate the association between smoking status and 1) overall renal function and risk of chronic kidney disease (CKD), 2) risk of any renal replacement therapy (aRRT), and 3) mortality following aRRT. We calculated estimated creatinine clearance using the Cockcroft-Gault equation (CG-CrCl), and evaluated renal function graphically. We calculated cumulative incidence of CKD (defined as two consecutive CG-CrCls of ≤60 mL/min, ≥3 months apart) and aRRT and used Cox regression models to calculate incidence rate ratios (IRRs) for risk of CKD, aRRT, and mortality rate ratios (MRRs) following aRRT. RESULTS: From the Danish HIV Cohort Study, we identified 1,475 never smokers, 768 previous smokers, and 2,272 current smokers. During study period, we observed no association of smoking status with overall renal function. Previous and current smoking was not associated with increased risk of CKD (adjusted IRR: 1.1, 95% confidence interval [CI]: 0.7-1.7; adjusted IRR: 1.3, 95% CI: 0.9-1.8) or aRRT (adjusted IRR: 0.8, 95% CI: 0.4-1.7; adjusted IRR: 0.9, 95% CI: 0.5-1.7). Mortality following aRRT was high in PLHIV and increased in smokers vs never smokers (adjusted MRR: 3.8, 95% CI: 1.3-11.2). CONCLUSION: In Danish PLHIV, we observed no strong association between smoking status and renal function, risk of CKD, or risk of aRRT, but mortality was increased in smokers following aRRT.

Cohort profile update: the Danish HIV Cohort Study (DHCS).

The DHCS is a cohort of all HIV-infected individuals seen in one of the eight Danish HIV centres after 31 December 1994. Here we update the 2009 cohort profile emphasizing the development of the cohort. Every 12-24 months, DHCS is linked with the Danish Civil Registration System (CRS) in order to extract an age- and sex-matched comparison cohort from the general population, as well as cohorts of family members of the HIV-infected patients and of the comparison cohort. The combined cohort is linked with CRS, the Danish Cancer Registry, the Danish National Hospital Registry, the Danish Registry of Causes of Death, the Danish National Prescription Registry, the Attainment Register and the Integrated Database for Labour Market Research to get information on vital status, migration, cancer, hospital contacts, causes of death, dispensed prescriptions, education and employment. Using this design, rates of a range of outcomes have been compared between HIV-infected patients and the comparison cohort, as well as between families of these two cohorts in order to disaggregate the effects of HIV infection and familial/environmental factors. Data can be shared with foreign institutions following approval from the Danish Data Protection Agency. Potential collaborators can contact the study director, Niels Obel (e-mail: niels.obel@regionh.dk).