Cardiometabolic health in people with HIV: expert consensus review.

OBJECTIVES: To develop consensus data statements and clinical recommendations to provide guidance for improving cardiometabolic health outcomes in people with HIV based on the knowledge and experience of an international panel of experts. METHODS: A targeted literature review including 281 conference presentations, peer-reviewed articles, and background references on cardiometabolic health in adults with HIV published between January 2016 and April 2022 was conducted and used to develop draft consensus data statements. Using a modified Delphi method, an international panel of 16 experts convened in workshops and completed surveys to refine consensus data statements and generate clinical recommendations. RESULTS: Overall, 10 data statements, five data gaps and 14 clinical recommendations achieved consensus. In the data statements, the panel describes increased risk of cardiometabolic health concerns in people with HIV compared with the general population, known risk factors, and the potential impact of antiretroviral therapy. The panel also identified data gaps to inform future research in people with HIV. Finally, in the clinical recommendations, the panel emphasizes the need for a holistic approach to comprehensive care that includes regular assessment of cardiometabolic health, access to cardiometabolic health services, counselling on potential changes in weight after initiating or switching antiretroviral therapy and encouraging a healthy lifestyle to lower cardiometabolic health risk. CONCLUSIONS: On the basis of available data and expert consensus, an international panel developed clinical recommendations to address the increased risk of cardiometabolic disorders in people with HIV to ensure appropriate cardiometabolic health management for this population.

Evaluation of Self-Collected Versus Health Care Professional (HCP)-Performed Sampling and the Potential Impact on the Diagnostic Results of Asymptomatic Sexually Transmitted Infections (STIs) in High-Risk Individuals.

Sexually transmitted infections (STIs) are increasing among men who have sex with men (MSM). Screening can improve the detection and outcome of asymptomatic STIs in high-risk populations. Self-sampling may be a resource-optimized strategy; however, its diagnostic reliability compared to testing by healthcare professionals (HCPs) requires further investigation. In this prospective, multicenter cohort study in a high-income country, asymptomatic MSM with a sexual risk profile for STIs were included. Sequential swabs for STI nucleic acid-based diagnosis of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) were performed after randomization, either through self-sampling or HCP-performed sampling. Baseline demographic information, sexual risk behavior, and acceptance and feedback on self-sampling were recorded using an electronic questionnaire. Out of 236 asymptomatic MSM, 47 individuals (19.9%) tested positive for CT and/or NG through self- or HCP-performed sampling. For CT, the sensitivity was 93.3% for both sampling methods, while for NG, it was 90.0% for self-sampling and 95.0% for HCP-performed sampling. Our study demonstrates that self-sampling for asymptomatic STIs has a comparable diagnostic outcome to HCP-performed sampling, with high acceptance in high-risk MSM.

Long-range fiber-optic earthquake sensing by active phase noise cancellation.

We present a long-range fiber-optic environmental deformation sensor based on active phase noise cancellation (PNC) in metrological frequency dissemination. PNC sensing exploits recordings of a compensation frequency that is commonly discarded. Without the need for dedicated measurement devices, it operates synchronously with metrological services, suggesting that existing phase-stabilized metrological networks can be co-used effortlessly as environmental sensors. The compatibility of PNC sensing with inline amplification enables the interrogation of cables with lengths beyond 1000 km, making it a potential contributor to earthquake detection and early warning in the oceans. Using spectral-element wavefield simulations that accurately account for complex cable geometry, we compare observed and computed recordings of the compensation frequency for a magnitude 3.9 earthquake in south-eastern France and a 123 km fiber link between Bern and Basel, Switzerland. The match in both phase and amplitude indicates that PNC sensing can be used quantitatively, for example, in earthquake detection and characterization.

Seroconversion rate of SARS-CoV-2 IgG antibodies and dating behaviour in HIV-PrEP users in a German metropolis during the COVID-19 pandemic.

BACKGROUND: At the beginning of the COVID-19 pandemic, when mortality was high, social distance was the only option to prevent transmission of SARS-CoV-2 and prohibit uncontrolled spreading. As the impact of social distancing on sexual behavior was unclear, we aimed to assess the influence of sexual risk behavior on SARS-CoV-2 seroconversion in HIV pre-exposition prophylaxis (PrEP) users after declaration of the pandemic. METHODS: Prospective study on SARS-CoV-2 IgG-antibody seroconversion rate over time in men having sex with men (MSM) using PrEP at a single tertiary university hospital in Munich, Germany, during quarterly (Q) routine HIV-PrEP visits over 1 year per participant (May 2020 - September 2021). Seroconversion was defined as at least one positive anti-nucleocapsid (anti-N) SARS-CoV-2 IgG antibody test as surrogate for past infection. In addition, sexually transmitted infections (STIs), personal estimated risk behavior and sexual contacts were assessed. RESULTS: Seroconversion rate during the full observation period was 7.3% (9/124 subjects) by September 2021. Percentage of subjects with symptomatic STIs (T. pallidum, N. gonorrhoeae, C. trachomatis and M. genitalium) was 18.7% in Q3-20, 8.1% in Q4-20, 11.1% in Q1-21, 11.6% in Q2-21 and 9.5% in Q3-21. Perception of subjective threat of SARS-CoV-2 infection and adequacy of preventive measures decreased during the observation period. However, self-reported sex behavior remained stable during the observation period. CONCLUSIONS: Our cohort showed low proportion of PrEP-users with anti-N IgG by September 2021, comparable to the local incidence. Sexual behavior in this cohort did not change, despite local recommendations for social distancing.

Long-Acting Cabotegravir and Rilpivirine Dosed Every 2 Months in Adults With Human Immunodeficiency Virus 1 Type 1 Infection: 152-Week Results From ATLAS-2M, a Randomized, Open-Label, Phase 3b, Noninferiority Study.

BACKGROUND: Cabotegravir (CAB) + rilpivirine (RPV) dosed intramuscularly monthly or every 2 months is a complete, long-acting (LA) regimen for the maintenance of HIV-1 virologic suppression. Here, we report the antiretroviral therapy as long acting suppression (ATLAS)-2M study week 152 results. METHODS: ATLAS-2M is a phase 3b, randomized, multicenter study assessing the efficacy and safety of CAB+RPV LA every 8 weeks (Q8W) versus every 4 weeks (Q4W). Virologically suppressed (HIV-1 RNA <50 copies/mL) individuals were randomized to receive CAB+RPV LA Q8W or Q4W. Endpoints included the proportion of participants with plasma HIV-1 RNA ≥50 copies/mL and <50 copies/mL, incidence of confirmed virologic failure (CVF; 2 consecutive measurements ≥200 copies/mL), safety, and tolerability. RESULTS: A total of 1045 participants received CAB+RPV LA (Q8W, n = 522; Q4W, n = 523). CAB+RPV LA Q8W demonstrated noninferior efficacy versus Q4W dosing, with 2.7% (n = 14) and 1.0% (n = 5) of participants having HIV-1 RNA ≥50 copies/mL, respectively, with adjusted treatment difference being 1.7% (95% CI: 0.1-3.3%), meeting the 4% noninferiority threshold. At week 152, 87% of participants maintained HIV-1 RNA <50 copies/mL (Q8W, 87% [n = 456]; Q4W, 86% [n = 449]). Overall, 12 (2.3%) participants in the Q8W arm and 2 (0.4%) in the Q4W arm had CVF. Eight and 10 participants with CVF had treatment-emergent, resistance-associated mutations to RPV and integrase inhibitors, respectively. Safety profiles were comparable, with no new safety signals observed since week 48. CONCLUSIONS: These data demonstrate virologic suppression durability with CAB+RPV LA Q8W or Q4W for ∼3 years and confirm long-term efficacy, safety, and tolerability of CAB+RPV LA as a complete regimen to maintain HIV-1 virologic suppression.

Clinical and virological features of first human monkeypox cases in Germany.

BACKGROUND: Monkeypox is a zoonotic orthopoxvirus infection endemic in central and western Africa. In May 2022, human monkeypox infections including human-to-human transmission were reported in a multi-country outbreak in Europe and North America. CASE PRESENTATIONS: Here we present the first two cases of monkeypox infection in humans diagnosed in Germany. We present clinical and virological findings, including the detection of monkeypox virus DNA in blood and semen. The clinical presentation and medical history of our patients suggest close physical contact during sexual interactions as the route of infection. CONCLUSION: Monkeypox requires rapid diagnosis and prompt public health response. The disease should be considered in the current situation especially the differential diagnosis of vesicular or pustular rash, particularly in patients with frequent sexual contacts. Most importantly, it is essential to raise awareness among all health professionals for the rapid and correct recognition and diagnosis of this disease, which is probably still underreported in Europe (Adler et al. in Lancet Infect Dis https://doi.org/10.1016/s1473-3099(22)00228-6 , 2022).

Clinical characteristics of monkeypox virus infections among men with and without HIV: A large outbreak cohort in Germany.

BACKGROUND: Since May 2022, increasing numbers of monkeypox virus (MPXV) infections have been reported from across Europe and North America. Studies, mainly from Africa, have suggested a higher risk for severe MPXV cases in people living with HIV. METHODS: This was a retrospective study of all confirmed MPXV infections observed in the participating centres since 19 May 2022. We conducted a chart review to evaluate clinical characteristics, comorbidities, and coinfections, including HIV, viral hepatitis, and sexually transmitted infections (STIs). RESULTS: By 30 June 2022, a total of 546 MPXV infections were reported from 42 German centres. All patients were men who have sex with men (MSM), of whom 256 (46.9%) were living with HIV, mostly with a preserved immune system and with viral suppression. In total, 232 (42.5%) MSM were also taking HIV pre-exposure prophylaxis (PrEP) and 58 (10.6%) MSM had no known HIV infection or PrEP use. The median age was 39 years (range 20-67), and comorbidities were rare. However, 52.4% and 29.4% of all patients had been diagnosed with at least one STI within the last 6 months or within the last 4 weeks, respectively. The most frequent localizations of MPXV infection were genital (49.9%) and anal (47.9%), whereas fever (53.2%) and lymphadenopathy (42.6%) were the most frequent general symptoms. The hospitalization rate was low (4.0%), and no fatal course was observed. The clinical picture showed no apparent differences between MSM with or without HIV. CONCLUSIONS: In this preliminary cohort analysis from a current large outbreak among MSM in Germany, the clinical picture of MPXV infection did not differ between MSM with and without HIV infection. Severe courses were rare and hospitalization rates were low. However, most patients were relatively healthy, and only a few people living with HIV were viremic or severely immunosuppressed.

The renal-bone axis in older people living with HIV on stable antiretroviral therapy: A sub-analysis of the GS-US-104-0423 study.

BACKGROUND: Data on low bone mineral density (BMD) in people living with HIV (PLWH) are mainly derived from younger adults; little is known about how antiretroviral therapy (ART) and alterations in the renal-bone axis relate to BMD in older PLWH. METHODS: Cross-sectional study of men > 50 years and post-menopausal women with HIV. Antiretroviral therapy exposure was stratified into four groups based on use of tenofovir disoproxil fumarate (TDF) and protease inhibitors (PI): non-TDF/non-PI, non-TDF/PI, TDF/non-PI, and TDF/PI. Bone mineral density was measured by dual X-ray absorptiometry (DXA). Bone turnover/regulatory markers and renal tubular function were analysed in stored plasma and urine samples. The association of ART exposure and bone/renal biomarkers on BMD was explored using logistic regression models. RESULTS: 247 individuals (median [IQR] age 57 [53, 65] years; 47% female; 13% of Black ethnicity; CD4 count 643 [473, 811] cells/mm3; and 98% with HIV RNA < 200 copies/mL) were included. Bone turnover and renal tubular function differed significantly by ART exposure. In analyses adjusted for demographic and traditional renal/bone risk factors, exposure to TDF and PI was associated with a fourfold greater risk of low BMD at the femoral neck and exposure to TDF and/or PI with a threefold greater risk of low BMD at the lumbar spine. The relationship between ART and low BMD was not altered by further adjustment for bone turnover or renal tubular function markers. CONCLUSIONS: The associations between low BMD and ART exposure (TDF vs. non-TDF and boosted vs. unboosted third agents) were minimally affected by adjustments for bone and kidney biomarkers.

Monkeypox Virus Infection in Humans across 16 Countries - April-June 2022.

BACKGROUND: Before April 2022, monkeypox virus infection in humans was seldom reported outside African regions where it is endemic. Currently, cases are occurring worldwide. Transmission, risk factors, clinical presentation, and outcomes of infection are poorly defined. METHODS: We formed an international collaborative group of clinicians who contributed to an international case series to describe the presentation, clinical course, and outcomes of polymerase-chain-reaction-confirmed monkeypox virus infections. RESULTS: We report 528 infections diagnosed between April 27 and June 24, 2022, at 43 sites in 16 countries. Overall, 98% of the persons with infection were gay or bisexual men, 75% were White, and 41% had human immunodeficiency virus infection; the median age was 38 years. Transmission was suspected to have occurred through sexual activity in 95% of the persons with infection. In this case series, 95% of the persons presented with a rash (with 64% having ≤10 lesions), 73% had anogenital lesions, and 41% had mucosal lesions (with 54 having a single genital lesion). Common systemic features preceding the rash included fever (62%), lethargy (41%), myalgia (31%), and headache (27%); lymphadenopathy was also common (reported in 56%). Concomitant sexually transmitted infections were reported in 109 of 377 persons (29%) who were tested. Among the 23 persons with a clear exposure history, the median incubation period was 7 days (range, 3 to 20). Monkeypox virus DNA was detected in 29 of the 32 persons in whom seminal fluid was analyzed. Antiviral treatment was given to 5% of the persons overall, and 70 (13%) were hospitalized; the reasons for hospitalization were pain management, mostly for severe anorectal pain (21 persons); soft-tissue superinfection (18); pharyngitis limiting oral intake (5); eye lesions (2); acute kidney injury (2); myocarditis (2); and infection-control purposes (13). No deaths were reported. CONCLUSIONS: In this case series, monkeypox manifested with a variety of dermatologic and systemic clinical findings. The simultaneous identification of cases outside areas where monkeypox has traditionally been endemic highlights the need for rapid identification and diagnosis of cases to contain further community spread.

Inadequate PTH Response to Hypocalcemia in People Living with HIV.

BACKGROUND: Small experimental studies suggest that PTH-secretion following hypocalcemia might be blunted in people living with HIV. OBJECTIVE: The aim of the study was to estimate the frequency of inadequately low concentrations of parathyroid hormone in the presence of hypocalcemia in people living with HIV. METHODS: This was a retrospective study that was conducted among PLWH enrolled in the ongoing ArcHIV study between 2016 and 2017. PLWH with routine measurements for both calcium and parathyroid hormone levels were included in this analysis. The proportion of patients with a combination of low levels of both calcium and parathyroid hormone was the primary endpoint of this analysis. RESULT: 496 PLWH were included (mean age 47.1 (± 10.2) years, 393 (79.2 %) men). In 14 (2.8 %) PLWH, low calcium levels with low levels of PTH were observed in the assessment conducted in both years. Undergoing a tenofovir disoproxil-containing treatment in both years was the only explanatory variable significantly associated with inadequately low levels of PTH in the presence of hypocalcemia in both years (OR 4.3 [CI95: 1.4; 16.0]). CONCLUSION: The combination of low levels of both calcium and PTH was found more frequent in our study sample when compared to what is expected from the general population. Interestingly, undergoing a tenofovir disoproxil-containing therapy was associated with this combination throughout both the years.

Humoral response to SARS-CoV-2 vaccines in people living with HIV.

PURPOSE: To describe the humoral immune response to COVID-19 vaccines in people living with HIV and identify factors associated with the magnitude of anti-SARS-CoV-2 antibody concentrations. METHODS: Retrospective analysis of electronic patient files in a big single HIV center in Munich, Germany. Non-parametric methods were used for descriptive and comparative statistics. Generalized linear models were used to analyze associations of general and HIV-specific variables with anti-SARS-CoV-2 antibody concentrations after standard vaccination. RESULT: Overall, 665 people living with HIV were included into the analysis (median age: 53 [IQR: 43; 59]), 560 [84.2%] males). Median concentration of anti-SARS-CoV-2-antibodies was 1400 (IQR 664; 2130) BAU/mL. In 18 (2.7%) subjects, antibody concentrations below the threshold of 34 BAU/mL were found. Among PLWH with CD4 cell count < 200 cells/µL, median anti-SARS-CoV-2-Abs were 197 (IQR 44.6; 537.2) as compared to 1420 (IQR 687; 2216) for the group ≥ 200 cells/µL (p < 0.001). In a cumulative logit model, a vaccination scheme including an mRNA vaccine [OR: 4.64 (3.58; 6.02)], being female [OR: 2.14 (1.76; 2.61)], and having higher CD4 cells [OR per 100 cells/µL: 1.06 (1.04; 1.08)] were significantly associated with anti-SARS-CoV-2 antibody concentrations in higher quartiles, when adjusted for the time after vaccination. CONCLUSION: We found a robust antibody response in people living with HIV undergoing standard vaccination against SARS-CoV-2. mRNA-containing vaccination schemes, being female, and having a higher CD4 cell count was associated with a higher concentration of antibodies in people living with HIV in our study sample. Particularly in the subgroup with CD4 cell counts < 200 cells/µL, antibody response was poor.

Functional Hypogonadism and Testosterone Deficiency in Aging Males With and Without HIV-infection.

INTRODUCTION: HIV infection has become a chronic, well-treatable disease and the focus of caretakers has shifted to diagnosis and treatment of comorbidities. Hypogonadism in elderly men with HIV might be of particular relevance, however, little is known about its epidemiology in contrast to non-infected peers and men with other chronic medical conditions, such as type 2 diabetes. This study aimed at comparing the prevalence of testosterone deficiency and functional hypogonadism in men ≥ 50 years in these three groups. PATIENTS AND METHODS: Multi-center, cross-sectional substudy of the German-wide 50/2010 study, including men aged 50 years or older with HIV-infection, type 2 diabetes, and controls. RESULTS: Altogether, 322 men were included (mean age: 62 years (SD±7.9)). The prevalence of testosterone deficiency in men living with HIV, type 2 diabetes, and controls was 34.5, 44.9, and 35.0%, respectively; the prevalence of functional hypogonadism was 7.7, 14.3 and 3.5%, respectively. Single-factor ANOVA demonstrated significant differences between the groups for total testosterone (p<0.001), SHBG (p<0.001), as well as for free testosterone concentrations (p=0.006). Comorbidities were, however, most important single factor in multi-factor analysis. DISCUSSION: Despite a comparable prevalence of testosterone deficiency, functional hypogonadism was more frequent in men living with HIV when compared to non-infected controls. This was the result of a higher burden of symptoms that might, however, also be secondary to other conditions. Number of comorbidities was a more important factor than belonging to one of the groups.

Risk factors for bleeding from gastrointestinal angiodysplasia: a case-control study in patients with bleeding and non-bleeding angiodysplasia.

OBJECTIVES: Angiodysplasia (AD) is a common source of gastrointestinal bleeding. Yet, little is known about factors forwarding bleeding in these vascular malformations. The presented study aims to determine risk factors for bleeding that occurs only in patients with symptomatic, but not with asymptomatic, AD. METHODS: Case-control study in patients with AD and either a positive or a negative history of gastrointestinal bleeding in Munich, Germany. Groups were compared by clinical, laboratory, and endoscopic features. RESULTS: 80 patients with (58, f 31, med. age 72) or without bleeding AD (22, f 12, med. age 61) were included. Bleeding from AD was significantly associated with the total number of AD (OR 1.4 (95 % CI 1.1-1.7) p = 0.01) and closure time in PFA/collagen-epinephrine test (OR 1.0 (95 % CI 1.0-1.0) p < 0.01). The total number of AD correlated significantly with age (r = 0.36; p = 0.01). AD were mainly detected in the upper small intestine (> 30 %). Although patients with aortic stenosis suffered not significantly more frequently from bleeding from AD, they demonstrated a loss of high molecular multimers of VWF. CONCLUSIONS: The amount of AD is clearly correlated to the age of the patient. A higher number of ADs and inhibition of primary hemostasis increase the risk of bleeding.

Monthly or Weekly Supplementation with Cholecalciferol 20,000 IU in People Living with HIV: Results from a Nested Cohort Study.

BACKGROUND: There is still considerable uncertainty in handling vitamin D deficiency in people living with HIV (PLWH), due to a lack of comparative data and the wide range of recommended daily intake. Nondaily supplementation might be preferred in many PLWH, but recommendation on dosing has not been established. We aimed to compare the efficacy of weekly versus monthly supplementation with cholecalciferol 20,000 IU in a group of PLWH with vitamin D deficiency in Western Europe. STUDY DESIGN: Longitudinal, retrospective nested cohort study of PLWH from two large clinical care centers in Munich, Germany. RESULTS: Of 307 patients with vitamin D deficiency, 124 patients received vitamin D supplementation (weekly supplementation in 84 (67.7%)). 46.4% and 22.5% of patients achieved 25(OH)D levels ≥30 ng/mL after 12 months of weekly and monthly supplementation with cholecalciferol 20,000 IU, respectively (p=0.011). Dosing interval as well as 25(OH)D baseline levels >15 ng/mL were associated with the normalization of 25(OH)D. CONCLUSION: A higher rate of 25(OH)D level normalization can be achieved via weekly supplementation. For several PLWH, even a weekly dose of cholecalciferol 20,000 IU might not be adequate to maintain 25(OH)D levels >30 ng/mL without an initial "loading" dose. The response to supplementation is poorly predictable at an individual level.

Prevalence of asymptomatic sexually transmitted infections in HIV-positive men who have sex with men in Germany: results of a multicentre cross-sectional study.

PURPOSE: Sexually transmitted infections (STIs) occur frequently in risk populations. Hereby, the role of screening-programmes remains controversial. Our study aimed to determine the prevalence of STI infections in HIV-positive men-who-have-sex-with-men (MSM). METHODS: We enrolled asymptomatic, HIV-MSM in a prospective cross-sectional study from February to August 2016 at seven German HIV-centres. All subjects were screened for Treponema-pallidum (TP) and hepatitis-B/C-infection. HIV RNA and screening for oral, rectal and urethral colonisation by Chlamydia-trachomatis (CT) and/or Neisseria-gonorrhoeae (NG) was performed. All subjects were asked to complete a sexual-risk-behaviour-questionnaire. RESULTS: In total, 296 subjects with a median age of 43.2 (36.2-49.5) years were enrolled; 99.3% were on ART for 5.5 (2.3-11.2) years. HIV RNA was < 50 copies/mL in 93.6%. Active syphilis infection was found in 5.0% of all patients, whereas 55.4% had history of infection. HCV seropositivity was found in 33 patients (13.2%) and positive HCV RNA was available in 39.4%. 66/294 (22.5%) showed negative anti-HBs-antibodies, indicating lack of immunity. Overall, 40/296 (13.5%) had positive CT/NG swabs (CT in 8.8%; 7.3% anorectal, 1.7% oropharyngeal, 1.0% urethral and NG in 6.8%; 4.5% anal, 2.0% oropharyngeal, 1.4% urethral). Time since HIV infection < 7 years (OR 2.6 (1.2-5.5); p = 0.012), the use of inhalative nitrites ("poppers") (OR 2.8 (1.3-5.9; p = 0.008) and reporting unprotected intercourse with > 20 partners within the last 6 months [OR 3.0 (1.2-7.8); p = 0.003] were significantly associated in multivariate analysis. CONCLUSION: We found high numbers of asymptomatic syphilis, hepatitis-C and CT/NG infections in HIV-MSM, remarkably in patients with shorter duration of HIV-infection with more sexual partners within last 6 months.

Secondary Hyperparathyroidism in HIV-Infected Patients in Central Europe.

Secondary hyperparathyroidism (sHPT) might be a contributor to increased risk of osteoporosis in adult HIV patients but there is little data available on this issue in this particular population. The aim of the study was to investigate the prevalence of sHPT in an HIV-infected population with normal kidney function and to evaluate its risk factors in HIV patients. This cross-sectional study was carried out in a single HIV center in Germany using routine data from patients with normal kidney function attending the clinic between January 1st and December 31st, 2016. In total, 1263 patients were included [998 (79.0%) male, median age 48 (IQR 38-54) years]. In 214 patients (16.9%) elevated PTH levels with low or normal calcium levels were found. Multivariate logistic regression modeling showed significant associations with elevated PTH for African ethnicity [OR: 2.12 (95% CI: 1.42-3.16); p<0.001], low 25-hydroxyvitamin D levels [OR: 1.82 (95% CI: 1.32-2.51); p<0.001], low calcium levels [OR 1.69 (95% CI: 1.22-2.33); p=0.001], and use of tenofovir disoproxil fumarate [OR 2.33 (95% CI: 1.62-3.36); p<0.001]. Additional to common risk factors like vitamin D insufficiency and hypocalcemia, we found a significant association between the use of TDF and sHPT. Prospective data are needed to ascertain whether PTH-mediated bone loss is the underlying mechanism of TDF bone-toxicity. Additional screening of PTH even in HIV-infected patients with normal or low calcium levels may help to identify patients at increased risk of bone mineral density loss.

Tenofovir Disoproxil Fumarate Is Associated with a Set-Point Variation in the Calcium-Parathyroid Hormone-Vitamin D Axis: Results from a German Cohort.

BACKGROUND: Higher levels of parathyroid hormone have been associated with the use of tenofovir disoproxil fumarate (TDF) in people with and without HIV infection. Yet, alterations in calcium levels have never been elucidated in detail. OBJECTIVE: To compare the association of parathyroid hormone with serum calcium levels and other markers of calcium and bone metabolism in people living with HIV on TDF- and non-TDF-containing antiretroviral therapy. PATIENTS AND METHODS: A retrospective single center cohort study in Munich, Germany. Median and interquartile ranges and absolute and relative frequencies were used to describe continuous and categorical variables, respectively. The Mann-Whitney U test and chi2-test were used for comparisons. Multivariate median regression was performed in a stepwise backward approach. RESULTS: 1,002 patients were included (786 (78.4%) male; median age 48 (40-55) years). 564 patients (56.3%) had a TDF-containing ART regimen. PTH concentrations were 46.9 (33.0-64.7) pg/mL and 35.2 (26.4-55.4) pg/mL (P=0.001), 43.3 (30.8-59.8) pg/mL and 31.8 (22.3-49.6) pg/mL (P < 0.001), 46.1 (29.5-65.4) pg/mL and 33.4 (22.6-50.1) pg/mL (P < 0.001), and 37.8 (25.3-57.9) pg/mL and 33.8 (20.1-45.3) pg/mL (P=0.012) within the first, second, third, and fourth quartile of corrected calcium levels for patients with and without TDF-containing ART, respectively. In multivariate median regression, PTH concentration was significantly associated with Cacorr. (-32.2 (-49.8 to -14.8); P < 0.001), female sex (5.2 (1.2-9.2); P=0.010), 25(OH)D (-0.4 (-0.5 to -0.3); P < 0.001), and TDF-use (9.2 (6.0-12.5); P < 0.001). DISCUSSION: Higher levels of PTH seem to be needed to maintain normal calcium levels in PLWH on TDF-containing ART compared to non-TDF-containing ART. Optimal concentrations for 25-hydroxy vitamin D and calcium might therefore be different in people using TDF than expected from general populations but also people living with HIV with non-TDF-containing antiretroviral therapy. This might require different supplementation strategies but warrants further investigation.

Corrigendum to "Fatal Systemic Vasoconstriction in a Case of Metastatic Small-Intestinal NET".

[This corrects the article DOI: 10.1155/2017/9810194.].