The study investigated markers of inflammation and endothelial activation in HIV infected patients after 12 years of successful combination antiretroviral treatment (cART).
Inflammation and ...endothelial activation were assessed by measuring levels of immunoglobulins, β2-microglobulin, interleukin (IL) 8, tumor necrosis factor α (TNFα), vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), sE-Selectin, and sP-Selectin.
HIV infected patients had higher levels of β2-microglobulin, IL-8, TNFα, and sICAM-1 than uninfected controls, and HIV infected patients lacked correlation between platelet counts and sP-Selectin levels found in uninfected controls.
Discrete signs of systemic and vascular inflammation persist even after very long term cART.
Background. Elevated interleukin 6 (IL-6) levels have been linked to cardiovascular disease, cancer and death. Persons with human immunodeficiency virus (HIV) infection receiving treatment have ...higher IL-6 levels, but few data are available on factors associated with circulating IL-6. Methods. Participants in 3 trials with IL-6 measured at baseline were included (N = 9864). Factors associated with IL-6 were identified by linear regression. Demographic and HIV variables (nadir/entry CD4⁺ cell count, HIV RNA level, antiretroviral therapy regimen) were investigated in all 3 trials. In the SMART (Strategies for Management of Anti-Retroviral Therapy) trial, CD4/CD8 ratio, smoking, comorbid conditions, serum lipids, renal function (estimated glomerular filtration rate eGFR), and educational level were assessed. Results. Demographics associated with higher IL-6 levels were older age and lower education, whereas black race was associated with lower IL-6. Higher HIV RNA levels were associated with higher IL-6 levels, and higher nadir CD4⁺ cell counts with lower IL-6 levels. Compared with efavirenz, protease inhibitors were associated with higher and nevirapine with lower IL-6 levels. Smoking and all comorbid conditions were related to higher IL-6. IL-6 levels increased with decreasing eGFR and decreasing serum lipids. Conclusions. Higher levels of IL-6 were associated with older age, nonblack race, higher body mass index, lower serum lipid levels, HIV replication, low nadir CD4⁺ cell count, protease inhibitor use, comorbid conditions, and decreased eGFR. Multiple factors affect inflammation in HIV and should be considered in studies of IL-6 as a biomarker of clinical outcomes.
We report a case series of four patients with cystic fibrosis (CF) and previous solid organ transplantation (SOT) receiving elexacaftor/tezacaftor/ivacaftor therapy for 6 months or more. Data was ...collected retrospectively. The treatment was well tolerated and all patients reported subjective improvements.
Background: Long-term follow-up studies of COVID-19 olfactory and gustatory disorders (OGDs) are scarce. OGD, parosmia, and dysgeusia affect health-related quality of life (HRQoL) and the ability to ...detect potential hazards. Methods: In this study, 29 patients reporting OGD 1 month after severe-to-critical COVID-19 were tested at 3–6 months and retested at 12 months in case of hyposmia/anosmia. We used Sniffin Sticks Threshold, Discrimination, and Identification (TDI) test, Sniffin Sticks Identification Test (SIT16), Brief Smell Identification Test (BSIT), taste strips, and HRQoL. The patients were part of the prospective SECURe cohort. Results: Overall, 28% OD (TDI), 12% GD, 24% parosmia, and 24% dysgeusia (questionnaire) at 3–6 months (n = 29) and 28% OD (TDI), 38% parosmia, and 25% dysgeusia (questionnaire) at 12 months (n = 8) were observed. OGD decreased HRQoL: For 13%, it had a negative effect on daily life and, for 17%, it affected nutrition, 17% reported decreased mood, and 87–90% felt unable to navigate everyday life using their sense of smell and taste. A comparison of SIT16 and BSIT to TDI found sensitivity/specificity values of 75%/100% and 88%/86%. Conclusions: This is the first study to examine TDI, SIT16, BSIT, taste strips, and HRQoL up to 1 year after severe-to-critical COVID-19. The patients suffering from prolonged OGD, parosmia, and dysgeusia experienced severely decreasing HRQoL. We recommend including ear–nose–throat specialists in multidisciplinary post-COVID clinics.
Residual immune activation and skewed T cell maturation may contribute to excess comorbidity and mortality in successfully treated HIV-infected patients, and long-term effects of combination ...antiretroviral therapy (cART) on immune reconstitution remain a debated issue. Quantitative T cell reconstitution and activation and its association with residual viremia in patients with 12 years of viremic suppression were investigated.
Blood samples collected cross-sectionally from 71 HIV-infected patients with cART-induced viremic suppression through 12 years were compared with samples from 16 healthy controls.
Several different subsets of naive, memory, and activated T cells were analyzed in fresh whole blood by 6-color flowcytometry, and ultrasensitive quantification of HIV RNA was performed.
HIV-infected patients had lower absolute and relative CD4 T cell counts and higher absolute and relative CD8 T cell counts than controls. HIV-infected patients had lower concentrations of naive CD4 cells than controls, but proportions were similar. HIV-infected patients had higher concentrations of CD8 T cells than controls in all the examined subsets but only a higher proportion of CD8 cells in the intermediately differentiated and activated subsets. Residual viremia did not correlate to proportions of naive CD4, CD4 recent thymic emigrants, or activated CD8 T cells.
This study demonstrated some degree of T cell imbalance even after 12 years of successful cART. Large longitudinal studies are needed to establish whether these discrete changes have clinical relevance.
Bacterial vaginosis (BV) has been found to be associated with HIV acquisition and transmission. This is suggested to be due to higher HIV RNA levels in cervicovaginal fluids in women living with HIV ...(WLWH) with BV, as bacteria associated with BV may induce viral replication and shedding in the genital tract despite undetectable HIV RNA plasma viral load. We examined the prevalence and diagnostic predictors of BV and HIV-1 RNA vaginal shedding in women living with HIV (WLWH) in Denmark, taking into account the presence of human papillomavirus (HPV) and herpes viridae.
WLWH between 18-51 years were recruited from six Departments of Infectious Diseases in Denmark during enrolment in the SHADE cohort; a prospective cohort study of WLWH attending regular outpatient care. BV was diagnosed by microscopy of vaginal swabs and PCR was used for detection of BV-associated bacteria, HPV, herpes viridae, and vaginal HIV viral load.
Median age of the 150 included women was 41 years; ethnicity was predominantly White (35%) or Black (47%). The majority (96%) was on ART and had undetectable (85%) plasma HIV RNA (<40 copies/mL). BV was diagnosed in 32%. Overall, 11% had detectable vaginal HIV RNA. Both before and after adjustment for BV, age, ethnicity, plasma HIV RNA, CD4 cell count, herpes viridae and HPV, we found no significant predictors of HIV RNA vaginal shedding.
In well-treated WLWH, BV, herpes viridae or HPV do not predict vaginal HIV RNA shedding. This implies that HIV shedding does not seem to be increased by BV.
•Cervical and anal HPV infection is highly prevalent in women living with HIV.•Anal HPV infection is associated with cervical HPV infection.•Non-16/18 hrHPV genotypes were predominant at all ...anatomical sites.•Half of hrHPV infections could have been prevented by the 9-valent HPV vaccine.
Women living with HIV (WLWH) have elevated risk of human papillomavirus (HPV) related cancers.
To assess prevalence, distribution and concordance of cervical, oral, and anal HPV infection, and predictors of oral and anal HPV in WLWH in Denmark.
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.
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)).
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.
Background:
Several studies have shown an association between abacavir (ABC) and increased risk of myocardial infarction (MI), but the causative mechanism has not been established. Both vascular ...endothelial inflammation and platelet activation have been proposed as contributing factors.
Objective:
The study aims to investigate the effects of ABC relative to tenofovir disoproxil (TDF) on functional assays of primary and secondary hemostasis and a comprehensible range of relevant biomarkers.
Methods:
In an investigator-initiated, open-labeled, crossover trial, we included HIV-infected males receiving either ABC or TDF and switched treatment to the alternate drug. At inclusion and after three months on the new regimen, we performed Multiplate
®
and thromboelastography (TEG
®
) and measured biomarkers of coagulation, inflammation, platelet reactivity, endothelial disruption and activation, and fibrinolysis, lipids, HIV RNA, CD4, CD8, and creatinine. Treatment effects were assessed by comparing intraindividual differences between the two treatment orders by the Wilcoxon Rank Sum test.
Results:
In total, 43 individuals completed the study. No intraindividual differences were observed for Multiplate
®
or TEG
®
when switching between regimens. We observed a significant treatment effect on coagulation factors II-VII-X (p<0.0001), sCD40L (a biomarker of platelet reactivity, p=0.04), thrombomodulin (biomarker of endothelial damage, p=0.04), lipids, and CD8 cell counts (p=0.04), with higher values during ABC treatment compared to TDF.
Conclusion:
Compared to TDF, ABC treatment affected several outcome measures in a pro-coagulant direction. Suggesting that the risk of MI associated with ABC may be caused by the sum of multiple, discrete disturbances in the hemostatic system and endothelium.
Study Registration:
The trial was registered at clinicaltrials.gov (NCT02093585).
Mycoplasma genitalium (M. genitalium) is a sexually transmitted pathogen associated with urethritis, cervicitis, and pelvic inflammatory disease. Previous studies have shown a strong association ...between M. genitalium and HIV infection, therefore screening and treatment for M. genitalium has been suggested as part of HIV prevention strategies. The objective of this study was to determine the prevalence of M. genitalium in women living with HIV (WLWH) in Denmark, and to compare the result with data on symptoms from the lower abdomen, sexual habits and immune status. 234 women, recruited from Danish HIV centres as part of a larger observational study on aspects of living with HIV as a woman (the SHADE study), were included.
We tested cervical samples for M. genitalium by specific PCR. We found three samples positive (1.3%). The women were between 30 and 50 years old, all were of Asian origin, sexually active, and on antiretroviral treatment with supressed HIV RNA and CD4 count >350 cells/µL. None reported symptoms from the lower abdomen. The prevalence of M. genitalium infection in WLWH in Denmark is low, thus systematic screening for M. genitalium in this group does not seem relevant.
To identify disclosure, stigma and predictors of non-disclosure among women living with HIV in Denmark.
A questionnaire study of women living with HIV in Denmark was performed. The enrolment period ...was from February 2013 to March 2014. Logistic regression was used to estimate predictors of non-disclosure.
A total of 234 participants were included. The majority (94%) had disclosed their HIV status to at least one person outside their healthcare environment, although 29% had disclosed to fewer than three people. Confidantes were mostly partners (96%), siblings (63%), friends (63%) and children (41%). The primary reason for non-disclosure was a feeling that it did not concern others (55%), although reactions upon disclosure were mainly positive in 53%. Predictors of non-disclosure were being of black or Asian ethnicity. Following their HIV diagnosis, 40% no longer dared to have sex, 40% felt isolated and 23% felt that others were afraid and kept a physical distance. In contrast, after disclosure 75% felt better at taking decisions about life and 50% were in closer contact with family and friends.
Almost one-third of participants disclosed their HIV diagnosis to fewer than three people and black or Asian ethnicity predicted non-disclosure. HIV-related stigma regarding sex and contact with others is still highly prevalent; however, reactions to disclosure were mainly positive and associated with secondary positive gains. We strongly urge healthcare professionals to initiate a dialogue regarding stigma and disclosure with women living with HIV with a view to increasing disclosure and minimising stigmatisation in this vulnerable population.
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