In the Netherlands, general practitioners (GPs) play a key role in HIV testing. However, the proportion of people diagnosed with late-stage HIV remains high, and opportunities for earlier diagnosis ...are being missed. We implemented an educational intervention to improve HIV and STI testing in primary care in Amsterdam, the Netherlands.
GPs were invited to participate in an educational program between 2015 and 2020, which included repeat sessions using audit and feedback and quality improvement plans. Data on HIV, chlamydia and gonorrhoea testing by GPs were collected from 2011 through 2020. The primary outcome was HIV testing frequency, which was compared between GPs before and after participation using Poisson regression. Secondary outcomes were chlamydia and gonorrhoea testing frequencies, and positive test proportions. Additional analyses stratified by patient sex and age were done.
GPs after participation performed 7% more HIV tests compared to GPs before participation (adjusted relative ratio aRR 1.07, 95%CI 1.04-1.09); there was no change in the proportion HIV positive tests (aRR 0.87, 95%CI 0.63-1.19). HIV testing increased most among patients who were female and ≤19 or 50-64 years old. After participation, HIV testing continued to increase (aRR 1.02 per quarter, 95%CI 1.01-1.02). Chlamydia testing by GPs after participation increased by 6% (aRR 1.06, 95%CI 1.05-1.08), while gonorrhoea testing decreased by 2% (aRR 0.98, 95%CI 0.97-0.99). We observed increases specifically in extragenital chlamydia and gonorrhoea testing.
The intervention was associated with a modest increase in HIV testing among GPs after participation, while the proportion positive HIV tests remained stable. Our results suggest that the intervention yielded a sustained effect.
Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by human sera is a strong correlate of protection against symptomatic and severe Coronavirus Disease 2019 (COVID-19). ...The emergence of antigenically distinct SARS-CoV-2 variants of concern (VOCs) and the relatively rapid waning of serum antibody titers, however, raises questions about the sustainability of serum protection. In addition to serum neutralization, other antibody functionalities and the memory B cell (MBC) response are suggested to help maintaining this protection. In this study, we investigate the breadth of spike (S) protein-specific serum antibodies that mediate effector functions by interacting with Fc-gamma receptor IIa (FcgammaRIIa) and FcgammaRIIIa, and of the receptor binding domain (RBD)-specific MBCs, following a primary SARS-CoV-2 infection with the D614G, Alpha, Beta, Gamma, Delta, Omicron BA.1 or BA.2 variant. Irrespectively of the variant causing the infection, the breadth of S protein-specific serum antibodies that interact with FcgammaRIIa and FcgammaRIIIa and the RBD-specific MBC responses exceeded the breadth of serum neutralization, although the Alpha-induced B cell response seemed more strain-specific. Between VOC groups, both quantitative and qualitative differences in the immune responses were observed, suggesting differences in immunogenicity. Overall, this study contributes to the understanding of protective humoral and B cell responses in the light of emerging antigenically distinct VOCs, and highlights the need to study the immune system beyond serum neutralization to gain a better understanding of the protection against emerging variants.
Migrants are not routinely screened for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) in the Netherlands. We estimated the prevalence and determined factors ...associated with HBV, HCV and/or HIV infections among undocumented migrants and uninsured legal residents.
In this cross-sectional study, undocumented migrants and uninsured legal residents were recruited at a non governmental organization (NGO), healthcare facility in the Netherlands and were invited to be tested for hepatitis B surface antigen (HBsAg), anti-hepatitis B core antibodies (anti-HBcAb), HCV-RNA, and anti-HIV antibodies or HIV antigen at a local laboratory.
Of the 1376 patients invited, 784 (57%) participated. Participants originated from Africa (35%), Asia (30%) and North/South America (30%). 451/784 (58%) participants went to the laboratory for testing. Of participants 30% were HBV exposed (anti-HBcAb-positive), with 27% (n = 119/438, 95% CI 23.1% to 31.6%) having resolved HBV infection (HBsAg-negative) and 2.5% (n = 11/438, 95%CI 1.3% to 4.5%, 64% new infection) having chronic HBV infection (HBsAg-positive). Compared to HBV non-exposed, HBV exposed individuals were older (p = 0.034) and more often originated from Africa (p<0.001). Prevalence of chronic HCV infection (HCV-RNA-positive) was 0.7% (n = 3/435, 95%CI 0.1% to 2.0%, all new infections) and HIV infection 1.1% (n = 5/439, 95%CI 0.04% to 2.6%, 40% new infection).
Prevalence of chronic HBV, chronic HCV and HIV infections in our study population is higher compared to the Dutch population, thus emphasizing the importance of case finding for these infections through primary care and public health in this specific group of migrants. Screening uptake could be improved by on-site testing.
Antiretroviral therapy (ART) has dramatically lengthened lifespan among people with HIV (PWH), but this population experiences heightened rates of inflammation-related comorbidities. HIV-associated ...inflammation is linked with an altered microbiome; whether such alterations precede inflammation-related comorbidities or occur as their consequence remains unknown. We find that ART-treated PWH exhibit depletion of gut-resident bacteria that produce short-chain fatty acids (SCFAs)—crucial microbial metabolites with anti-inflammatory properties. Prior reports establish that fecal SCFA concentrations are not depleted in PWH. We find that gut-microbiota-mediated SCFA production capacity is better reflected in serum than in feces and that PWH exhibit reduced serum SCFA, which associates with inflammatory markers. Leveraging stool and serum samples collected prior to comorbidity onset, we find that HIV-specific microbiome alterations precede morbidity and mortality in ART-treated PWH. Among these microbiome alterations, reduced microbiome-mediated conversion of lactate to propionate precedes mortality in PWH. Thus, gut microbial fiber/lactate conversion to SCFAs may modulate HIV-associated comorbidity risk.
Display omitted
•Gut microbiota propionate production is better represented in serum than feces•People with HIV exhibit loss of microbiota-encoded SCFA production•Systemic SCFAs associate inversely with inflammation in people with HIV•Failure to convert lactate to propionate precedes death and comorbid events in PWH
Sereti et al. examine microbiota composition and short-chain fatty acid (SCFA) dynamics in serum and stool of people with HIV (PWH) sampled prior to onset of comorbidities or death. Systemic SCFAs are significantly depleted in PWH and are associated with prognostic inflammatory markers, and decreases in gut microbial SCFA production pathways precede comorbidities and death in PWH.
Increasing numbers of pyelonephritis-associated uropathogenic Escherichia coli (UPEC) are exhibiting high resistance to antibiotic therapy. They include a particular clonal group, the ...CTX-M-15-producing O25b:H4-ST131 clone, which has been shown to have a high dissemination potential. Here we show that a representative isolate of this E. coli clone, referred to as TN03, has enhanced metabolic capacities, acts as a potent intestine- colonizing strain, and displays the typical features of UPEC strains. In a modified streptomycin-treated mouse model of intestinal colonization where streptomycin was stopped 5 days before inoculation, we show that TN03 outcompetes the commensal E. coli strains K-12 MG1655, IAI1, and ED1a at days 1 and 7. Using an experimental model of ascending UTI in C3H/HeN mice, we then show that TN03 colonized the urinary tract. One week after the transurethral inoculation of the TN03 isolates, the bacterial loads in the bladder and kidneys were significantly greater than those of two other UPEC strains (CFT073 and HT7) belonging to the same B2 phylogenetic group. The differences in bacterial loads did not seem to be directly linked to differences in the inflammatory response, since the intrarenal expression of chemokines and cytokines and the number of polymorphonuclear neutrophils attracted to the site of inflammation was the same in kidneys colonized by TN03, CFT073, or HT7. Lastly, we show that in vitro TN03 has a high maximum growth rate in both complex (Luria-Bertani and human urine) and minimum media. In conclusion, our findings indicate that TN03 is a potent UPEC strain that colonizes the intestinal tract and may persist in the kidneys of infected hosts.
Background There is increasing data that show a persistently impaired pulmonary function upon recovery after severe infection. Little is known however about the extent, recovery and determinants of ...pulmonary impairment across the full spectrum of COVID-19 severity over time. Methods In a well characterized, prospective cohort of both hospitalised and non-hospitalised individuals with SARS-CoV-2 infection, the RECoVERED study, pulmonary function (diffusing capacity for carbon monoxide (DLCO)) and spirometry) was measured until one year after disease onset. Additionally, data on sociodemographics, clinical characteristics, symptoms, and health-related quality of life (HRQL) were collected. Pulmonary function and these determinants were modelled over time using mixed-effect linear regression. Determinants of pulmonary function impairment at 12 months after disease onset were identified using logistic regression. Findings Between May 2020 and December 2021, 301 of 349 participants underwent at least one pulmonary function test. After one year of follow-up, 25% of the participants had an impaired pulmonary function which translates in 11%, 22%, and 48% of the participants with mild, moderate and severe/critical COVID-19. Improvement in DLCO among the participants continued over the period across one, six and twelve months. Being older, having more than three comorbidities (p<0·001) and initial severe/critical disease (p<0·001) were associated with slower improvement of pulmonary function over time, adjusted for age and sex. HRQL improved over time and at 12 months was comparable to individuals without impaired pulmonary function. Interpretation The prevalence of impaired pulmonary function after twelve months of follow-up, was still significant among those with initially moderate or severe/critical COVID-19. Pulmonary function increased over time in most of the severity groups. These data imply that guidelines regarding revalidation after COVID-19 should target individuals with moderate and severe/critical disease severities.
As individual sexual behavior is variable over time, the timing of interventions might be vital to reducing HIV transmission. We aimed to investigate transitions between HIV risk levels among men who ...have sex with men (MSM), and identify determinants associated with behavior change. Participants in a longitudinal cohort study among HIV-negative MSM (Amsterdam Cohort Studies) completed questionnaires about their sexual behavior during biannual visits (2008-2017). Visits were assigned to different HIV risk levels, based on latent classes of behavior. We modelled transitions between risk levels, and identified determinants associated with these transitions at the visit preceding the transition using multi-state Markov models. Based on 7,865 visits of 767 participants, we classified three risk levels: low (73% of visits), medium (22%), and high risk (5%). For MSM at low risk, the six-month probability of increasing risk was 0.11. For MSM at medium risk, the probability of increasing to high risk was 0.08, while the probability of decreasing to low risk was 0.33. For MSM at high risk, the probability of decreasing risk was 0.43. Chemsex, erection stimulants and poppers, high HIV risk perception, and recent STI diagnosis were associated with increased risk at the next visit. High HIV risk perception and young age were associated with decreasing risk. Although the majority of MSM showed no behavior change, a considerable proportion increased HIV risk. Determinants associated with behavior change may help to identify MSM who are likely to increase risk in the near future and target interventions at these individuals, thereby reducing HIV transmission.
An increasing number of countries are currently implementing or scaling-up HIV pre-exposure prophylaxis (PrEP) care. With the introduction of PrEP, there was apprehension that condom use would ...decline and sexually transmitted infections (STIs) would increase. To inform sexual health counselling and STI screening programmes, we aimed to study sexual behaviour and STI incidence among men who have sex with men (MSM) and transgender women who use long-term daily or event-driven PrEP.
The Amsterdam PrEP demonstration project (AMPrEP) was a prospective, closed cohort study, providing oral daily PrEP and event-driven PrEP to MSM and transgender women from 2015 to 2020. Participants could choose their PrEP regimen and could switch at each three-monthly visit. STI testing occurred at and, upon request, in-between 3-monthly study visits. We assessed changes in numbers of sex partners and condomless anal sex (CAS) acts with casual partners over time using negative binomial regression, adjusted for age. We assessed HIV incidence and changes in incidence rates (IRs) of any STI (i.e., chlamydia, gonorrhoea, or infectious syphilis) and individual STIs over time using Poisson regression, adjusted for age and testing frequency. A total of 367 participants (365 MSM) commenced PrEP and were followed for a median 3.9 years (interquartile range IQR = 3.4-4.0). Median age was 40 years (IQR = 32-48), 315 participants (85.8%) self-declared ethnicity as white and 280 (76.3%) had a university or university of applied sciences degree. Overall median number of sex partners (past 3 months) was 13 (IQR = 6-26) and decreased per additional year on PrEP (adjusted rate ratio aRR = 0.86/year, 95% confidence interval CI = 0.83-0.88). Overall median number of CAS acts with casual partners (past 3 months) was 10 (IQR = 3-20.5) and also decreased (aRR = 0.92/year, 95% CI = 0.88-0.97). We diagnosed any STI in 1,092 consultations during 1,258 person years, resulting in an IR of 87/100 person years (95% CI = 82-92). IRs of any STI did not increase over time for daily PrEP or event-driven PrEP users. Two daily PrEP users, and no event-driven PrEP users, were diagnosed with HIV during their first year on PrEP. Study limitations include censoring follow-up due to COVID-19 measures and an underrepresentation of younger, non-white, practically educated, and transgender individuals.
In this prospective cohort with a comparatively long follow-up period of 4 years, we observed very low HIV incidence and decreases in the numbers of casual sex partners and CAS acts over time. Although the STI incidence was high, it did not increase over time.
The study was registered at the Netherlands Trial Register (NL5413) https://www.onderzoekmetmensen.nl/en/trial/22706.
Recent studies have reported disproportionate weight gain associated with integrase strand transfer inhibitor (INSTI) initiation in antiretroviral therapy(ART)-naive people with HIV (PWH), ...particularly among black women. We investigated if HIV-positive AGEhIV participants with suppressed viremia switching to INSTI-containing ART experienced more weight gain compared to HIV-positive virally-suppressed non-switching and HIV-negative controls.
In the AGEhIV cohort, standardized weight measurements were performed biennially. Participants switching to INSTI-containing ART were 1:2:2 propensity score-matched with controls by age, gender, ethnicity and body mass index. Mean weight changes and proportions experiencing >5% or >10% weight gain were compared between study-groups using linear mixed-effects models and logistic regression, respectively.
121 INSTI-switching participants and 242 participants from each of the control groups were selected. Across groups, median age was 53-55 years, 83-91% were male and 88-93% white. Mean weight change after switch among INSTI-switching participants was +0.14 kg/year (95%CI -0.25, +0.54) and similar among HIV-positive +0.13 kg/year (95%CI +0.07, +0.33; P = .9) and HIV-negative +0.18 kg/year (95%CI 0.00, +0.37; P = .9) controls. Weight gain >5% occurred in 28 (23.1%) INSTI-switching, 38 HIV-positive (15.7%, P = .085) and 32 HIV-negative controls (13.2%, P = .018). Weight gain >10% was rare.
Switching to INSTI-containing ART in our cohort of predominantly white men on long-term ART was not associated with greater mean weight gain, but >5% weight gain was more common than in controls. These results suggest that not all, but only certain, PWH may be particularly prone to gain a clinically significant amount of weight as a result of switching to INSTI.
ObjectivesDetailed simulation models are needed to assess strategies for prevention and treatment of hepatitis B virus (HBV) infection, the world’s leading cause of liver disease. We sought to ...develop and validate a simulation model of chronic HBV that incorporates virological, serological and clinical outcomes.MethodsWe developed a novel Monte Carlo simulation model (the HEPA-B Model) detailing the natural history of chronic HBV. We parameterised the model with epidemiological data from the Western Pacific and sub-Saharan Africa. We simulated the evolution of HBV DNA, ‘e’ antigen (HBeAg) and surface antigen (HBsAg). We projected incidence of HBeAg loss, HBsAg loss, cirrhosis, hepatocellular carcinoma (HCC) and death over 10-year and lifetime horizons. We stratified outcomes by five HBV DNA categories at the time of HBeAg loss, ranging from HBV DNA<300 copies/mL to >106 copies/mL. We tested goodness of fit using intraclass coefficients (ICC).ResultsModel-projected incidence of HBeAg loss was 5.18% per year over lifetime (ICC, 0.969 (95% CI: 0.728 to 0.990)). For people in HBeAg-negative phases of infection, model-projected HBsAg loss ranged from 0.78% to 3.34% per year depending on HBV DNA level (ICC, 0.889 (95% CI: 0.542 to 0.959)). Model-projected incidence of cirrhosis was 0.29–2.09% per year (ICC, 0.965 (95% CI: 0.942 to 0.979)) and HCC incidence was 0.06–1.65% per year (ICC, 0.977 (95% CI: 0.962 to 0.986)). Over a lifetime simulation of HBV disease, mortality rates were higher for people with older age, higher HBV DNA level and liver-related complications, consistent with observational studies.ConclusionsWe simulated HBV DNA-stratified clinical outcomes with the novel HEPA-B Model and validated them to observational data. This model can be used to examine strategies of HBV prevention and management.
PDF
