BackgroundPeople living with HIV (PLWH), even when viral replication is controlled through antiretroviral therapy (ART), experience persistent inflammation. This inflammation is partly attributed... Show moreBackgroundPeople living with HIV (PLWH), even when viral replication is controlled through antiretroviral therapy (ART), experience persistent inflammation. This inflammation is partly attributed to intestinal microbial dysbiosis and translocation, which may lead to non-AIDS-related aging-associated comorbidities. The extent to which living with HIV - influenced by the infection itself, ART usage, sexual orientation, or other associated factors - affects the biological age of the intestines is unclear. Furthermore, the role of microbial dysbiosis and translocation in the biological aging of PLWH remains to be elucidated. To investigate these uncertainties, we used a systems biology approach, analyzing colon and ileal biopsies, blood samples, and stool specimens from PLWH on ART and people living without HIV (PLWoH) as controls.ResultsPLWH exhibit accelerated biological aging in the colon, ileum, and blood, as measured by various epigenetic aging clocks, compared to PLWoH. Investigating the relationship between microbial translocation and biological aging, PLWH had decreased levels of tight junction proteins in the intestines, along with increased microbial translocation. This intestinal permeability correlated with faster biological aging and increased inflammation. When investigating the relationship between microbial dysbiosis and biological aging, the intestines of PLWH had higher abundance of specific pro-inflammatory bacteria, such as Catenibacterium and Prevotella. These bacteria correlated with accelerated biological aging. Conversely, the intestines of PLWH had lower abundance of bacteria known for producing the anti-inflammatory short-chain fatty acids, such as Subdoligranulum and Erysipelotrichaceae, and these bacteria were associated with slower biological aging. Correlation networks revealed significant links between specific microbial genera in the colon and ileum (but not in feces), increased aging, a rise in pro-inflammatory microbe-related metabolites (e.g., those in the tryptophan metabolism pathway), and a decrease in anti-inflammatory metabolites like hippuric acid.ConclusionsWe identified specific microbial compositions and microbiota-related metabolic pathways that are intertwined with intestinal and systemic biological aging. This microbial signature of biological aging is likely reflecting various factors including the HIV infection itself, ART usage, sexual orientation, and other aspects associated with living with HIV. A deeper understanding of the mechanisms underlying these connections could offer potential strategies to mitigate accelerated aging and its associated health complications.1fCw832AZENtKENNTh8vkGVideo AbstractConclusionsWe identified specific microbial compositions and microbiota-related metabolic pathways that are intertwined with intestinal and systemic biological aging. This microbial signature of biological aging is likely reflecting various factors including the HIV infection itself, ART usage, sexual orientation, and other aspects associated with living with HIV. A deeper understanding of the mechanisms underlying these connections could offer potential strategies to mitigate accelerated aging and its associated health complications.1fCw832AZENtKENNTh8vkGVideo Abstract Show less
Background: Digital triage tools for sexually transmitted infection (STI) testing can potentially be used as a substitute for the triage that general practitioners (GPs) perform to lower their work... Show moreBackground: Digital triage tools for sexually transmitted infection (STI) testing can potentially be used as a substitute for the triage that general practitioners (GPs) perform to lower their work pressure. The studied tool is based on medical guidelines. The same guidelines support GPs' decision-making process. However, research has shown that GPs make decisions from a holistic perspective and, therefore, do not always adhere to those guidelines. To have a high-quality digital triage tool that results in an efficient care process, it is important to learn more about GPs' decision-making process. Objective: The first objective was to identify whether the advice of the studied digital triage tool aligned with GPs' daily medical practice. The second objective was to learn which factors influence GPs' decisions regarding referral for diagnostic testing. In addition, this study provides insights into GPs' decision-making process. Methods: A qualitative vignette-based study using semistructured interviews was conducted. In total, 6 vignettes representing patient cases were discussed with the participants (GPs). The participants needed to think aloud whether they would advise an STI test for the patient and why. A thematic analysis was conducted on the transcripts of the interviews. The vignette patient cases were also passed through the digital triage tool, resulting in advice to test or not for an STI. A comparison was made between the advice of the tool and that of the participants. Results: In total, 10 interviews were conducted. Participants (GPs) had a mean age of 48.30 (SD 11.88) years. For 3 vignettes, the advice of the digital triage tool and of all participants was the same. In those vignettes, the patients' risk factors were sufficiently clear for the participants to advise the same as the digital tool. For 3 vignettes, the advice of the digital tool differed from that of the participants. Patient-related factors that influenced the participants' decision-making process were the patient's anxiety, young age, and willingness to be tested. Participants would test at a lower threshold than the triage tool because of those factors. Sometimes, participants wanted more information than was provided in the vignette or would like to conduct a physical examination. These elements were not part of the digital triage tool. Conclusions: The advice to conduct a diagnostic STI test differed between a digital triage tool and GPs. The digital triage tool considered only medical guidelines, whereas GPs were open to discussion reasoning from a holistic perspective. The GPs' decision-making process was influenced by patients' anxiety, willingness to be tested, and age. On the basis of these results, we believe that the digital triage tool for STI testing could support GPs and even replace consultations in the future. Further research must substantiate how this can be done safely. Show less
Purpose: Immediate initiation of antiretroviral treatment following HIV infection is a cornerstone of the current HIV ‘universal test and treat’ approach. Delayed progress along the HIV care... Show morePurpose: Immediate initiation of antiretroviral treatment following HIV infection is a cornerstone of the current HIV ‘universal test and treat’ approach. Delayed progress along the HIV care continuum is thus framed as a major stumbling block in effective HIV epidemic control. Through examining the HIV care trajectories of people diagnosed with HIV in Shinyanga Region, Tanzania, we offer a critical interrogation of the HIV care continuum. Methods: Data are drawn from a social science study on the uptake of a ‘treat all’ model of HIV prevention and care conducted from 2018 to 2019. Methods included interviews with participants who tested positive (n = 30) and interviews (n = 25) with health staff involved in the testing campaigns.Findings: Exploring individuals’ care trajectories, we found that most participants followed pathways to care that do not easily align with the current emphasis on rapid, linear progress from testing to treatment initiation. Instead, participants’ trajectories from diagnosis to treatment happened on a different, non-linear time scale mediated through social relations and diverse communities of care. We thus conceptualize five pathways of linkage to care - virtuous/immediate, delayed testing, repeat testing, negotiated, and ‘failed’.Conclusion: Based on our findings we propose a community-centered HIV care continuum that exposes moments of potential connection with or rupture from the health system and centers the importance of social support structures and forms of relational labor involving broader communities of care. Show less
Nziza, N.; Jung, W.Y.; Mendu, M.; Chen, T.A.; McNamara, R.P.; Fortune, S.M.; ... ; Alter, G. 2023
Introduction: Placental transfer of maternal antibodies is essential for neonatal immunity over the first months of life. In the setting of maternal HIV infection, HIV-exposed uninfected (HEU)... Show moreIntroduction: Placental transfer of maternal antibodies is essential for neonatal immunity over the first months of life. In the setting of maternal HIV infection, HIV-exposed uninfected (HEU) infants are at higher risk of developing severe infections, including active tuberculosis (TB). Given our emerging appreciation for the potential role of antibodies in the control of Mycobacterium tuberculosis (Mtb), the bacteria that causes TB, here we aimed to determine whether maternal HIV status altered the quality of Mtb-specific placental antibody transfer. Methods: Antigen-specific antibody systems serology was performed to comprehensively characterize the Mtb-specific humoral immune response in maternal and umbilical cord blood from HIV infected and uninfected pregnant people in Uganda. Results: Significant differences were noted in overall antibody profiles in HIV positive and negative maternal plasma, resulting in heterogeneous transfer of Mtb-specific antibodies. Altered antibody transfer in HIV infected dyads was associated with impaired binding to IgG Fc-receptors, which was directly linked to HIV viral loads and CD4 counts. Conclusions: These results highlight the importance of maternal HIV status on antibody transfer, providing clues related to alterations in transferred maternal immunity that may render HEU infants more vulnerable to TB than their HIV-unexposed peers. Show less
Hemophilia is a rare X-linked hereditary bleeding disorder, caused by a mutation in the F8 or F9 gene. In the last 50 years, hemophilia treatment has changed tremendously and the impact of these... Show moreHemophilia is a rare X-linked hereditary bleeding disorder, caused by a mutation in the F8 or F9 gene. In the last 50 years, hemophilia treatment has changed tremendously and the impact of these changes on current clinical outcomes is unknown.Therefore, we comprehensively assessed the changes in health status over time of patients with hemophilia using observational study data. Our results show that clinical outcomes of these patients have improved tremendously over the past decades. The annual bleeding rate and the proportion of patients with joint impairment have decreased strongly. In addition, HCV has almost been eradicated among patients with hemophilia in the Netherlands. As a result, life expectancy has increased to where it is almost equal to that of the general population.Although clinical outcomes have improved in many ways, inhibitor development continues to be a significant problem in patients treated with clotting factor products. Therefore, using three different study approaches, we also evaluated several methods to better predict the risk of inhibitor development (which is still a significant complication of treatment with FVIII). The results of these studies are promising and could be used to improve current inhibitor prediction strategies and inform future research on this topic. Show less
Background: Viral load (VL) determination in patients with human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV) and hepatitis C virus (HCV) is essential for proper patient... Show moreBackground: Viral load (VL) determination in patients with human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV) and hepatitis C virus (HCV) is essential for proper patient management and follow-up. New molecular platforms have been developed to fully automate these diagnostic assays.Objective: Evaluation of the clinical performance of HIV-1, HBV and HCV VL assays on the Alinity m (Abbott) and NeuMoDx (Qiagen) molecular platforms.Method: Test panels of the three viruses have been compiled of 100 plasma and/or serum samples per target containing non-detectable, non-quantifiable and quantifiable VLs. All samples were retrospectively tested on the Alinity m and NeuMoDx platforms according to manufacturers' instructions. Results: A total of 74, 86 and 66 samples with valid results for both platforms were included in the HIV-1, HBV and HCV analysis respectively. Overall qualitative agreement of the assays on both platforms was 78% for HIV-1, 93% for HBV and 100% for HCV. Quantitative agreement (less than 0.5 log difference) was shown to be 68% for HIV-1, 68% for HBV and 94% for HCV.Conclusion: The Alinity m and NeuMoDx HCV assay have a comparable performance. Quantification differences in the HIV-1 assay were mostly apparent in the lower VLs and under-quantification of the NeuMoDx HBV assay was observed. Show less
BackgroundObservational studies in humans have reported a link between schistosome infection and lower adiposity, but this may be explained by socioeconomic and demographic factors, intensity of... Show moreBackgroundObservational studies in humans have reported a link between schistosome infection and lower adiposity, but this may be explained by socioeconomic and demographic factors, intensity of infection, or common co-infections such as HIV. MethodsThis was a cross-sectional study that investigated the relationship between schistosome infection and adiposity in a large, well-described cohort of Tanzanian adults living with and without HIV. Cross-sectional data were collected among adults living in Mwanza, Tanzania who were enrolled in the Chronic Infections, Co-morbidities and Diabetes in Africa (CICADA) cohort study. Schistosome circulating anodic antigen, secreted by both Schistosoma mansoni and haematobium which are endemic to Tanzania, was quantified from stored samples. Schistosome infection diagnosed by serum circulating anodic antigen levels. The primary outcome was fat mass measured by bioimpedance analysis. Secondary outcomes included fat-free mass, waist circumference, mid-upper arm circumference, and body mass index. ResultsThe study enrolled 1,947 adults, of whom 1,923 (98.8%) had serum available for schistosome testing. Of these, 873 (45.4%) had a serum circulating anodic antigen >= 30 pg/mL, indicating schistosome infection. Compared to uninfected individuals, those with schistosome infections had -1.1 kg [95% CI -1.9 to -0.3] lower fat mass after adjusting for age, sex, physical activity, tobacco use, education level, and socioeconomic status. Infected participants also had lower waist circumference, mid-upper arm circumference, and body mass index. Fat-free mass was not different between the two groups. Neither being HIV-infected, nor receiving antiretroviral therapy, modified associations between schistosome infection and adiposity. These associations were also not affected by Schistosoma worm burden. ConclusionsSchistosome infection was associated with lower fat mass and less central adiposity without a difference in muscle mass, irrespective of confounders, HIV status, or the intensity of schistosome infection. Future studies should adjust for socioeconomic and demographic factors that are associated with schistosome infection and adiposity. Identifying mechanistic pathways by which schistosome infection reduces adiposity while preserving muscle mass could yield new strategies for obesity control and cardiovascular disease prevention. Show less
Background. The COVIH study is a prospective coronavirus disease 2019 (COVID-19) vaccination study in 1154 people with HIV (PWH), of whom 14% showed reduced antibody levels after primary... Show moreBackground. The COVIH study is a prospective coronavirus disease 2019 (COVID-19) vaccination study in 1154 people with HIV (PWH), of whom 14% showed reduced antibody levels after primary vaccination. We evaluated whether an additional vaccination boosts immune responses in these hyporesponders.Methods. The primary end point was the increase in antibodies 28 days after additional mRNA-1273 vaccination. Secondary end points included neutralizing antibodies, S-specific T-cell and B-cell responses, and reactogenicity.Results. Of the 66 participants, 40 previously received 2 doses ChAdOx1-S, 22 received 2 doses BNT162b2, and 4 received a single dose Ad26.COV2.S. The median age was 63 years (interquartile range [IQR], 60-66), 86% were male, and median CD4(+) T-cell count was 650/mu L (IQR, 423-941). The mean S1-specific antibody level increased from 35 binding antibody units (BAU)/mL (95% confidence interval [CI], 24-46) to 4317 BAU/mL (95% CI, 3275-5360) (P<.0001). Of all participants, 97% showed an adequate response and the 45 antibody-negative participants all seroconverted. A significant increase in the proportion of PWH with ancestral S-specific CD4(+) T cells (P=.04) and S-specific B cells (P=.02) was observed.Conclusions. An additional mRNA-1273 vaccination induced a robust serological response in 97% of PWH with a hyporesponse after primary vaccination. Show less
Olislagers, Q.; Leth, F. van; Shabalala, F.; Dlamini, N.; Simelane, N.; Masilela, N.; ... ; Molemans, M. 2022
Eswatini has a high HIV prevalence but has made progress towards improving HIV-status awareness, ART uptake and viral suppression. However, there is still a delay in ART initiation, which could... Show moreEswatini has a high HIV prevalence but has made progress towards improving HIV-status awareness, ART uptake and viral suppression. However, there is still a delay in ART initiation, which could partly be attributed to positive HIV-retesting. This study examines reasons for, and factors associated with, positive HIV-retesting among MaxART participants in Eswatini. Data from 601 participants is included in this cross-sectional study. Descriptive statistics and logistic regressions were used. Of the participants, 32.8% has ever retested after a previous positive result. Most participants who retested did this because they could not accept their results (61.9% of all retesters). Other main reasons are related to external influences, gender or the progression of their HIV infection (respectively 18.3%, 10.2%, and 6.1% of all retesters). Participants without a current partner and participants with less time since their first positive test have lower odds of retesting. To decrease retesting and reduce the delay in ART initiation resulting from it, efforts could be made on increasing the acceptance of positive HIV results. Providing more information on the process of testing and importance of early ART initiation, could be part of the solution. Show less
Luenen, S. van; Garnefski, N.; Spinhoven, P.; Kraaij, V. 2022
The aim of this study was to investigate the long-term effectiveness (3-4 years later) of an online intervention that was previously found to effectively reduce depressive symptoms in people with... Show moreThe aim of this study was to investigate the long-term effectiveness (3-4 years later) of an online intervention that was previously found to effectively reduce depressive symptoms in people with HIV on the short term. Participants were people with HIV who had participated in the large RCT on the short-term effectiveness of the guided online intervention. The primary outcome measure was depressive symptoms [Patient Health Questionnaire-9 (PHQ-9)] and the secondary outcome measure was anxiety symptoms [Generalized Anxiety Disorder-2 (GAD-2) scale]. Forty-seven participants completed the long-term follow-up. PHQ-9 scores, previously found to have been significantly reduced on the short term, remained low on the long term. GAD-2 scores did not decrease significantly on the short term, however, on the long term, a significant decrease was found. The intervention may not only be effective in lowering depressive symptoms on the short term but also retain the results on the long term. Show less
Tuberculosis (TB) is among the leading causes of death worldwide from a single infectious agent, second only to COVID-19 in 2020. TB is caused by infection with Mycobacterium tuberculosis (Mtb),... Show moreTuberculosis (TB) is among the leading causes of death worldwide from a single infectious agent, second only to COVID-19 in 2020. TB is caused by infection with Mycobacterium tuberculosis (Mtb), that results either in a latent or active form of disease, the latter associated with Mtb spread. In the absence of an effective vaccine, epidemiologic modeling suggests that aggressive treatment of individuals with active TB (ATB) may curb spread. Yet, clinical discrimination between latent (LTB) and ATB remains a challenge. While antibodies are widely used to diagnose many infections, the utility of antibody-based tests to diagnose ATB has only regained significant traction recently. Specifically, recent interest in the humoral immune response to TB has pointed to potential differences in both targeted antigens and antibody features that can discriminate latent and active TB. Here we aimed to integrate these observations and broadly profile the humoral immune response across individuals with LTB or ATB, with and without HIV co-infection, to define the most discriminatory humoral properties and diagnose TB disease more easily. Using 209 Mtb antigens, striking differences in antigen-recognition were observed across latently and actively infected individuals that was modulated by HIV serostatus. However, ATB and LTB could be discriminated, irrespective of HIV-status, based on a combination of both antibody levels and Fc receptor-binding characteristics targeting both well characterized (like lipoarabinomannan, 38 kDa or antigen 85) but also novel Mtb antigens (including Rv1792, Rv1528, Rv2435C or Rv1508). These data reveal new Mtb-specific immunologic markers that can improve the classification of ATB versus LTB. Show less
Okere, N.E.; Meta, J.; Maokola, W.; Martelli, G.; Praag, E. van; Naniche, D.; ... ; Hermans, S. 2022
Background: Differentiated service delivery (DSD) offers benefits to people living with HIV (improved access, peer support), and the health system (clinic decongestion, efficient service delivery).... Show moreBackground: Differentiated service delivery (DSD) offers benefits to people living with HIV (improved access, peer support), and the health system (clinic decongestion, efficient service delivery). ART clubs, 15–30 clients who usually meet within the community, are one of the most common DSD options. However, evidence about the quality of care (QoC) delivered in ART clubs is still limited.Materials and methods: We conducted a concurrent triangulation mixed-methods study as part of the Test & Treat project in northwest Tanzania. We surveyed QoC among stable clients and health care workers (HCW) comparing between clinics and clubs. Using a Donabedian framework we structured the analysis into three levels of assessment: structure (staff, equipment, supplies, venue), processes (time-spent, screenings, information, HCW-attitude), and outcomes (viral load, CD4 count, retention, self-worth).Results: We surveyed 629 clients (40% in club) and conducted eight focus group discussions, while 24 HCW (25% in club) were surveyed and 22 individual interviews were conducted. Quantitative results revealed that in terms of structure, clubs fared better than clinics except for perceived adequacy of service delivery venue (94.4% vs 50.0%, p = 0.013). For processes, time spent receiving care was significantly more in clinics than clubs (119.9 vs 49.9 minutes). Regarding outcomes, retention was higher in the clubs (97.6% vs 100%), while the proportion of clients with recent viral load <50 copies/ml was higher in clinics (100% vs 94.4%). Qualitative results indicated that quality care was perceived similarly among clients in clinics and clubs but for different reasons. Clinics were generally perceived as places with expertise and clubs as efficient places with peer support and empathy. In describing QoC, HCW emphasized structure-related attributes while clients focused on processes. Outcomes-related themes such as improved client health status, self-worth, and confidentiality were similarly perceived across clients and HCW.Conclusion: We found better structure and process of care in clubs than clinics with comparable outcomes. While QoC was perceived similarly in clinics and clubs, its meaning was understood differently between clients. DSD catered to the individual needs of clients, either technical care in the clinic or proximate and social care in the club. Our findings highlight that both clinic and DSD care are required as many elements of QoC were individually perceived. Show less
Heemelaar, S.; Hangula, A.L.; Chipeio, M.L.; Josef, M.; Stekelenburg, J.; Akker, T.H. van den; ... ; Mackenzie, S.B.P. 2021
Background & Aims Namibia has been suffering from an outbreak of hepatitis E genotype 2 since 2017. As nearly half of hepatitis E-related deaths were among pregnant and postpartum women, we... Show moreBackground & Aims Namibia has been suffering from an outbreak of hepatitis E genotype 2 since 2017. As nearly half of hepatitis E-related deaths were among pregnant and postpartum women, we analysed maternal and fetal outcomes of pregnancies complicated by acute hepatitis E and assessed whether HIV-status impacted on outcome. Methods A retrospective cross-sectional study was performed at Windhoek Hospital Complex. Pregnant and postpartum women, admitted between 13 October 2017 and 31 May 2019 with reactive IgM for Hepatitis E, were included. Outcomes were acute liver failure (ALF), maternal death, miscarriage, intra-uterine fetal death and neonatal death. Odds ratios (OR) and 95% confidence interval (CI) were calculated. Results Seventy women were included. ALF occurred in 28 (40.0%) of whom 13 died amounting to a case fatality rate of 18.6%. Sixteen women (22.9%) were HIV infected, compared to 16.8% among the general pregnant population (OR 1.47, 95% CI 0.84-2.57, P = .17). ALF occurred in 4/5 (80%) HIV infected women not adherent to antiretroviral therapy compared to 1/8 (12.5%) women adherent to antiretroviral therapy (OR 28.0, 95% CI 1.4-580.6). There were 10 miscarriages (14.3%), five intra-uterine fetal deaths (7.1%) and four neonatal deaths (5.7%). Conclusions One in five pregnant women with Hepatitis E genotype 2 died, which is comparable to genotype 1 outbreaks. Despite small numbers, HIV infected women receiving antiretroviral therapy appear to be less likely to develop ALF in contrast with HIV infected women not on treatment. As there is currently no curative treatment, this phenomenon needs to be assessed in larger cohorts. Show less
Schistosome infection is recognized as a potentially modifiable risk factor for HIV in women by the World Health Organization. Alterations in cervicovaginal bacteria have been associated with HIV... Show moreSchistosome infection is recognized as a potentially modifiable risk factor for HIV in women by the World Health Organization. Alterations in cervicovaginal bacteria have been associated with HIV acquisition and have not been studied in schistosome infection. We collected cervical swabs from Tanzanian women with and without S. mansoni and S. haematobium to determine effects on cervicovaginal microbiota. Infected women were treated, and follow-up swabs were collected after 3 months. 16S rRNA sequencing was performed on DNA extracted from swabs. We compared 39 women with S. mansoni with 52 uninfected controls, and 16 with S. haematobium with 27 controls. S. mansoni-infected women had increased abundance of Peptostreptococcus (p = 0.026) and presence of Prevotella timonesis (p = 0.048) compared to controls. High-intensity S. haematobium infection was associated with more diverse cervicovaginal bacterial communities than uninfected controls (p = 0.0159). High-intensity S. mansoni infection showed a similar trend (p = 0.154). At follow-up, we observed increased alpha diversity in S. mansoni (2.53 vs. 1.72, p = 0.022) and S. haematobium (2.05 vs. 1.12, p = 0.066) infection groups compared to controls. Modifications in cervicovaginal microbiota, particularly increased diversity and abundance of taxa associated with bacterial vaginosis and HIV (Peptostreptococcus, Prevotella), were associated with schistosome infection. Show less
Background Treatment of patients with hemophilia has advanced over the past decades, but it is unknown whether this has resulted in a normal life expectancy in the Netherlands.Objective This... Show moreBackground Treatment of patients with hemophilia has advanced over the past decades, but it is unknown whether this has resulted in a normal life expectancy in the Netherlands.Objective This observational cohort study aimed to assess all-cause and cause-specific mortality in patients with hemophilia in the Netherlands between 2001 and 2018 and to compare mortality and life expectancy with previous survival assessments from 1973 onward.Patients/methods All 1066 patients with hemophilia who participated in a nationwide survey in 2001 were followed until July 2018.Results Information on 1031 individuals (97%) was available, of whom 142 (14%) deceased during follow-up. Compared with the general Dutch male population, mortality of patients with hemophilia was still increased (standardized mortality ratio: 1.4, 95% confidence interval: 1.2-1.7). Intracranial bleeding and malignancies were the most common causes of death. Estimated median life expectancy of patients with hemophilia was 77 years, 6 years lower than the median life expectancy of the general Dutch male population (83 years). Over the past 45 years, death rates of patients with hemophilia have consistently decreased, approaching the survival experience of the general population. Over the past decades, mortality due to human immunodeficiency virus and hepatitis C virus infections has decreased, death due to intracranial hemorrhages has increased, and death due to ischemic heart disease has remained consistently low over time.Conclusions Survival in patients with hemophilia in the Netherlands has improved over time but is still lower than that of the general population. Show less
Objectives To quantify the burden of HIV, syphilis and schistosome infection and associated risk factors among adults living in seven fishing communities of Lake Victoria in northwest Tanzania... Show moreObjectives To quantify the burden of HIV, syphilis and schistosome infection and associated risk factors among adults living in seven fishing communities of Lake Victoria in northwest Tanzania.Methods Cross-sectional study conducted between 2015 and 2016 in the selected communities. In each community, we randomly selected a sample of adults from the general population and from three putative risk groups including the following: (i) fishermen, (ii) fish processors and traders, and (iii) women working in the recreational facilities. Participants were interviewed to obtain information about potential risk factors, and venous blood was collected for detection of HIV, syphilis and schistosome infections. We used logistic regression models to quantify the associations between potential risk factors and HIV, and also between schistosome infection and HIV.Results We enrolled 1128 people from selected fishing communities. The overall prevalence of HIV, syphilis and schistosome infection was 14.2%, 15.6% and 83.1%, respectively. Female recreational facility workers had the highest prevalence of HIV (30.4%) and syphilis (24%). The odds of being HIV infected were generally higher in all age categories. Transactional sex was commonly reported and especially receiving gifts for sex was found to be strongly associated with HIV (adjusted OR = 2.50; 95% CI: 1.44-4.34, P = 0.008). Confirmed serological syphilis was associated with increased odds of having HIV infection. HIV was not associated with schistosome infection in a combined dataset and when we examined this separately for men and women alone.Conclusions We observed a high burden of HIV, syphilis and schistosome infections in the fishing communities. Targeted efforts to treat and control infections have the potential to improve health among their residents. Show less
Reitsema, M.; Heijne, J.; Visser, M.; Sighem, A. van; Loeff, M.S. van der; Coul, E.L.M. op de; ... ; Xiridou, M. 2020
Objectives To investigate the impact and efficiency of combined testing for HIV and other STIs on HIV and STI transmission among men who have sex with men (MSM) and to assess what subgroups of MSM... Show moreObjectives To investigate the impact and efficiency of combined testing for HIV and other STIs on HIV and STI transmission among men who have sex with men (MSM) and to assess what subgroups of MSM should be targeted for frequent testing. Methods We developed an agent-based transmission model that simulates infection with HIV orNeisseria gonorrhoeae(NG) among MSM. We examined scenarios with increased percentages of MSM getting tested six monthly, among all MSM or only specific subgroups of MSM (defined according to recent gonorrhoea, number of partners and engagement in condomless anal intercourse (CAI)) and scenarios with reduced intervals between HIV/STI tests. Results The most efficient strategies were those with increased percentage of MSM getting tested every 6 months among MSM with a recent gonorrhoea diagnosis; or among MSM who had CAI and >= 10 partners; or MSM who had >= 10 partners. Over 10 years, these strategies resulted in 387-718 averted HIV infections and required 29-164 additional HIV tests per averted HIV infection or one to seven additional gonorrhoea tests per averted NG infection. The most effective strategy in reducing HIV transmission was the one where the intervals between tests were reduced by half, followed by the strategy with increased percentage of MSM getting tested every 6 months among all MSM. Over 10 years, these strategies resulted in 1362 and 1319 averted HIV infections, but required 663 and 584 additional HIV tests per averted HIV infection, respectively. Conclusions Targeting MSM with recent gonorrhoea diagnosis or MSM with many partners is efficient in terms of HIV/STI tests needed to prevent new HIV or NG infections. Major reductions in HIV incidence can be achieved with consistent HIV/STI testing every 6 months among larger groups, including low-risk MSM. To impede HIV transmission, frequent testing should be combined with other prevention measures. Show less
Chao, A.; Spiegelman, D.; Khan, S.; Walsh, F.; Mazibuko, S.; Pasipamire, M.; ... ; Okello, V. 2020
Objectives Current WHO guidelines recommend the treatment of all HIV-infected individuals with antiretroviral therapy (ART) to improve survival and quality of life, and decrease infection of others... Show moreObjectives Current WHO guidelines recommend the treatment of all HIV-infected individuals with antiretroviral therapy (ART) to improve survival and quality of life, and decrease infection of others. MaxART is the first implementation trial of this strategy embedded within a government-managed health system, and assesses mortality as a secondary outcome. Because primary findings strongly supported scale-up of the 'treat all' strategy (hereafter Treat All), this analysis examines mortality as an additional indicator of its impact.Methods MaxART was conducted in 14 Eswatinian health clinics through a clinic-based stepped-wedge design, by transitioning clinics from then-national standard of care (SoC) to the Treat All intervention. All-cause, disease-related, and HIV-related mortality were analysed using the Cox proportional hazards model, censoring SoC participants at clinic transition. Median follow-up time among study participants was 292 days. There were 36/2034 deaths in SoC (1.77%) and 49/1371 deaths in Treat All (3.57%).Results Between September 2014 and August 2017, 3405 participants were enrolled. In SoC and Treat All interventions, respectively, the multivariable-adjusted 12-month all-cause mortality rates were 1.42% [95% confidence interval (CI): 0.66-2.17] and 1.60% (95% CI: 0.78-2.40), disease-related mortality rates were 1.02% (95% CI: 0.40-1.64) and 1.10% (95% CI: 0.46-1.73), and HIV-related mortality rates were 1.03% (95% CI: 0.40-1.65) and 0.99% (95% CI: 0.40-1.58). Treat All had no impact on all-cause [hazard ratio (HR) = 1.12, 95% CI: 0.58-2.18, P = 0.73], disease-related (HR = 1.04, 95% CI: 0.52-2.11, P = 0.90), or HIV-related mortality (HR = 0.93, 95% CI: 0.46-1.87, P = 0.83).Conclusion There was no immediate benefit of the Treat All strategy on mortality, nor evidence of harm. Longer follow-up of participants is needed to establish long-term consequences. Show less
Reitsema, M.; Hoek, A.J. van; Loeff, M.S. van der; Hoornenborg, E.; Sighem, A. van; Wallinga, J.; ... ; Xiridou, M. 2020
Objectives: To assess the impact of a preexposure prophylaxis (PrEP) programme for high-risk men who have sex with men (MSM), which includes gonorrhoea testing and treatment, on the transmission of... Show moreObjectives: To assess the impact of a preexposure prophylaxis (PrEP) programme for high-risk men who have sex with men (MSM), which includes gonorrhoea testing and treatment, on the transmission of HIV and Neisseria among MSM in the Netherlands and the cost-effectiveness of such programme with and without risk compensation (in the form of reduced condom use). Methods: We developed a stochastic agent-based transmission model of HIV and gonorrhoea. We simulated a capped (max 2.5% of MSM) and uncapped (5.5% of MSM in 2018 declining to 3% in 2027) daily PrEP programme for high-risk MSM, with 3-monthly HIV and gonorrhoea testing, with and without risk compensation. Epidemiological outcomes were calculated from the transmission model and used in an economic model to calculate costs, quality-adjusted life-years (QALY), and incremental cost-effectiveness ratios (ICER), over 2018-2027, taking a healthcare payer perspective. Results: Without risk compensation, PrEP can lead to a reduction of 61 or 49% in the total number of new HIV infections in 2018-2027, if the programme is uncapped or capped to 2.5% of MSM, respectively. With risk compensation, this reduction can be 63 or 46% in the uncapped and capped programmes, respectively. In all scenarios, gonorrhoea prevalence decreased after introducing PrEP. Without risk compensation, 92% of simulations were cost-effective (of which 52% cost-saving). With risk compensation, 73% of simulations were cost-effective (of which 23% was cost-saving). Conclusion: A nationwide PrEP programme for high-risk MSM can result in substantial reductions in HIV and gonorrhoea transmission and be cost-effective, even with risk compensation. Show less
