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Background: Ethnic minority groups experience a disproportionately high burden of infections, hospitalizations and mortality due to COVID-19, and therefore should be especially encouraged to receive SARS-CoV-2 vaccination. This study aimed to investigate the intent to vaccinate against SARS-CoV-2, along with its determinants, in six ethnic groups residing in Amsterdam, the Netherlands. Methods: We analyzed data of participants enrolled in the population-based multi-ethnic HELIUS cohort, aged 24 to 79 years, who were tested for SARS-CoV-2 antibodies and answered questions on vaccination intent from November 23, 2020 to March 31, 2021. During the study period, SARS-CoV-2 vaccination in the Netherlands became available to individuals working in healthcare or > 75 years old. Vaccination intent was measured by two statements on a 7-point Likert scale and categorized into low, medium, and high. Using ordinal logistic regression, we examined the association between ethnicity and lower vaccination intent. We also assessed determinants of lower vaccination intent per ethnic group. Results: A total of 2,068 participants were included (median age 56 years, interquartile range 46–63). High intent to vaccinate was most common in the Dutch ethnic origin group (369/466, 79.2%), followed by the Ghanaian (111/213, 52.1%), South-Asian Surinamese (186/391, 47.6%), Turkish (153/325, 47.1%), African Surinamese (156/362, 43.1%), and Moroccan ethnic groups (92/311, 29.6%). Lower intent to vaccinate was more common in all groups other than the Dutch group (P < 0.001). Being female, believing that COVID-19 is exaggerated in the media, and being < 45 years of age were common determinants of lower SARS-CoV-2 vaccination intent across most ethnic groups. Other identified determinants were specific to certain ethnic groups. Conclusions: Lower intent to vaccinate against SARS-CoV-2 in the largest ethnic minority groups of Amsterdam is a major public health concern. The ethnic-specific and general determinants of lower vaccination intent observed in this study could help shape vaccination interventions and campaigns.

In August 2021, a man who has sex with men was diagnosed with HIV-1 infection despite using event-driven pre-exposure prophylaxis for over 2 years with self-reported excellent adherence. Sequencing identified resistance-associated mutations (RAM) M184V and K65R, conferring resistance to emtricitabine and tenofovir, and RAM V108I and E138A. Background RAM prevalence was two of 164 (1.2%) new HIV diagnoses in Amsterdam (2017–19). We reiterate the need for frequent HIV testing among PrEP users and additional testing in case of symptoms.

The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose sparing strategies. Here, we evaluate the SARS-CoV-2 specific antibody responses following BNT162b2 vaccination in 150 previously SARS-CoV-2-infected individuals from a population-based cohort. One week after first vaccine dose, spike protein antibody levels are 27-fold higher and neutralizing antibody titers 12-fold higher, exceeding titers of fully vaccinated SARS-CoV-2-naive controls, with minimal additional boosting after the second dose. Neutralizing antibody titers against four variants of concern increase after vaccination, however overall neutralization breadth does not improve. Pre-vaccination neutralizing antibody titers and time since infection have the largest positive effect on titers following vaccination. COVID-19 severity and the presence of comorbidities have no discernible impact on vaccine response. In conclusion, a single dose of BNT162b2 vaccine up to 15 months after SARS-CoV-2 infection offers higher neutralizing antibody titers than two vaccine doses in SARS-CoV-2-naive individuals., Graphical Abstract, In a prospective cohort study, van Gils et al find that a single dose of BNT162b2 mRNA vaccine up to 15 months after SARS-CoV-2 infection provides neutralizing titers exceeding two vaccine doses in SARS-CoV-2-naive individuals. This supports wide implementation of a single-dose mRNA vaccine strategy after prior SARS-CoV-2 infection.

Importance: It is unclear when, where, and by whom health care workers (HCWs) working in hospitals are infected with SARS-CoV-2. Objective: To determine how often and in what manner nosocomial SARS-CoV-2 infection occurs in HCW groups with varying exposure to patients with COVID-19. Design, Setting, and Participants: This cohort study comprised 4 weekly measurements of SARS-CoV-2-specific antibodies and collection of questionnaires from March 23 to June 25, 2020, combined with phylogenetic and epidemiologic transmission analyses at 2 university hospitals in the Netherlands. Included individuals were HCWs working in patient care for those with COVID-19, HCWs working in patient care for those without COVID-19, and HCWs not working in patient care. Data were analyzed from August through December 2020. Exposures: Varying work-related exposure to patients infected with SARS-CoV-2. Main Outcomes and Measures: The cumulative incidence of and time to SARS-CoV-2 infection, defined as the presence of SARS-CoV-2-specific antibodies in blood samples, were measured. Results: Among 801 HCWs, there were 439 HCWs working in patient care for those with COVID-19, 164 HCWs working in patient care for those without COVID-19, and 198 HCWs not working in patient care. There were 580 (72.4%) women, and the median (interquartile range) age was 36 (29-50) years. The incidence of SARS-CoV-2 was increased among HCWs working in patient care for those with COVID-19 (54 HCWs [13.2%; 95% CI, 9.9%-16.4%]) compared with HCWs working in patient care for those without COVID-19 (11 HCWs [6.7%; 95% CI, 2.8%-10.5%]; hazard ratio [HR], 2.25; 95% CI, 1.17-4.30) and HCWs not working in patient care (7 HCWs [3.6%; 95% CI, 0.9%-6.1%]; HR, 3.92; 95% CI, 1.79-8.62). Among HCWs caring for patients with COVID-19, SARS-CoV-2 cumulative incidence was increased among HCWs working on COVID-19 wards (32 of 134 HCWs [25.7%; 95% CI, 17.6%-33.1%]) compared with HCWs working on intensive care units (13 of 186 HCWs [7.1%; 95% CI, 3.3%-10.7%]; HR, 3.64; 95% CI, 1.91-6.94), and HCWs working in emergency departments (7 of 102 HCWs [8.0%; 95% CI, 2.5%-13.1%]; HR, 3.29; 95% CI, 1.52-7.14). Epidemiologic data combined with phylogenetic analyses on COVID-19 wards identified 3 potential HCW-to-HCW transmission clusters. No patient-to-HCW transmission clusters could be identified in transmission analyses. Conclusions and Relevance: This study found that HCWs working on COVID-19 wards were at increased risk for nosocomial SARS-CoV-2 infection with an important role for HCW-to-HCW transmission. These findings suggest that infection among HCWs deserves more consideration in infection prevention practice..

BackgroundSurveillance data in high-income countries have reported more frequent SARS-CoV-2 diagnoses in ethnic minority groups. We examined the cumulative incidence of SARS-CoV-2 and its determinants in six ethnic groups in Amsterdam, the Netherlands.MethodsWe analyzed participants enrolled in the population-based HELIUS cohort, who were tested for SARS-CoV-2-specific antibodies and answered COVID-19-related questions between June 24-October 9, 2020 (after the first wave) and November 23, 2020-March 31, 2021 (during the second wave). We modeled SARS-CoV-2 incidence from January 1, 2020-March 31, 2021 using Markov models adjusted for age and sex. We compared incidence between ethnic groups over time and identified determinants of incident infection within ethnic groups.Findings2,497 participants were tested after the first wave; 2,083 (83·4%) were tested during the second wave. Median age at first visit was 54 years (interquartile range=44-61); 56·6% were female. Compared to Dutch-origin participants (15·9%), cumulative SARS-CoV-2 incidence was higher in participants of South-Asian Surinamese (25·0%; adjusted hazard ratio [aHR]=1·66;95%CI=1·16-2·40), African Surinamese (28·9%;aHR=1·97;95%CI=1·37-2·83), Turkish (37·0%;aHR=2·67;95%CI=1·89-3·78), Moroccan (41·9%;aHR=3·13;95%CI=2·22-4·42), and Ghanaian (64·6%;aHR=6·00;95%CI=4·33-8·30) origin. Compared to those of Dutch origin, differences in incidence became wider during the second versus first wave for all ethnic minority groups (all p for interactionInterpretationSARS-CoV-2 incidence was higher in the largest ethnic minority groups of Amsterdam, particularly during the second wave. Prevention measures, including vaccination, should be encouraged in these groups.FundingZonMw, Public Health Service of Amsterdam, Dutch Heart Foundation, European Union, European Fund for the Integration of non-EU immigrants.

Key summary points Aim To assess whether in the nursing home (NH) setting a single-swab sampling method, in which one swab can be used to perform both the Ag-RDT and RT-PCR, can be used for rapid COVID-19 detection during an outbreak. Findings In the NH setting, the single-swab method had a sensitivity of 51% and a specificity of 89% compared to RT-PCR, which was lower than in the laboratory setting (69% and 100%, respectively). During focus groups, both advantages and disadvantages of the single-swab method emerged. Message For the vulnerable NH residents, it is important to find the right balance between effective testing policy and the burden this imposes. Supplementary Information The online version contains supplementary material available at 10.1007/s41999-021-00584-3., Purpose To assess whether one swab can be used to perform both the antigen-detection rapid diagnostic test (Ag-RDT) and reverse transcriptase polymerase chain reaction (RT-PCR) for COVID-19 detection during an outbreak in the nursing home (NH) setting. Methods The single-swab method (SSM), where the Ag-RDT is performed with the transport medium used for RT-PCR, was evaluated in three Dutch NHs and compared to the laboratory setting. We collected Ag-RDT and RT-PCR results, NH resident characteristics and symptomatology. In addition, two focus groups were held with the involved care professionals to gain insight into the feasibility of the SMM in the NH setting. Results In the NH setting, the SSM had a sensitivity of 51% and a specificity of 89% compared to RT-PCR. These were lower than in the laboratory setting (69% and 100% respectively). Yet, when stratified for cycle threshold values, the sensitivity became comparable between the settings. Symptoms occurred more frequent in the Ag-RDT+ group than Ag-RDT− group. Resident characteristics did not differ between these groups. Based on the focus groups, the SSM was feasible to perform if certain requirements, such as availability of staff, equipment and proper training, were met. However, the rapid availability of the test results were perceived as a dilemma. Conclusion The advantages and disadvantages need to be considered before implementation of the SSM can be recommended in the NH setting. For the vulnerable NH residents, it is important to find the right balance between effective testing policy and the burden this imposes. Supplementary Information The online version contains supplementary material available at 10.1007/s41999-021-00584-3.

BackgroundEthnic minorities have higher rates of SARS-CoV-2 diagnoses, but little is known about ethnic differences in past exposure. We aimed to determine whether prevalence and determinants of SARS-CoV-2 exposure varied between six ethnic groups in Amsterdam, the Netherlands.MethodsParticipants aged 25-79 years enrolled in a population-based prospective cohort were randomly selected within ethnic groups and invited to test for SARS-CoV-2-specific antibodies and answer COVID-19 related questions. We estimated prevalence and determinants of SARS-CoV-2 exposure within ethnic groups using survey-weighted logistic regression adjusting for age, sex and calendar time.ResultsBetween June 24-October 9, 2020, we included 2497 participants. Adjusted SARS-CoV-2 seroprevalence was comparable between ethnic-Dutch (25/498; 5.5%, 95%CI=3.2-7.9), South-Asian Surinamese (22/451; 4.8%, 95%CI=2.1-7.5), African Surinamese (22/400; 8.2%, 95%CI=3.0-13.4), Turkish (30/408; 7.8%, 95%CI=4.3-11.2) and Moroccan (32/391; 7.0%, 95%CI=4.0-9.9) participants, but higher among Ghanaians (95/327; 26.5%, 95%CI=18.7-34.4). 57.1% of SARS-CoV-2-positive participants did not suspect or were unsure of being infected, which was lowest in African Surinamese (18.2%) and highest in Ghanaians (90.5%). Determinants of SARS-CoV-2 exposure varied across ethnic groups, while the most common determinant was having a household member suspected of infection. In Ghanaians, seropositivity was associated with older age, larger household sizes, living with small children, leaving home to work and attending religious services.ConclusionsNo remarkable differences in SARS-CoV-2 seroprevalence were observed between the largest ethnic groups in Amsterdam after the first wave of infections. The higher infection seroprevalence observed among Ghanaians, which passed mostly unnoticed, warrants wider prevention efforts and opportunities for non-symptom-based testing.

BACKGROUNDIt is unclear how, when and where health care workers (HCW) working in hospitals are infected with SARS-CoV-2.METHODSProspective cohort study comprising 4-weekly measurement of SARS-CoV-2 specific antibodies and questionnaires from March to June 2020. We compared SARS-CoV-2 incidence between HCW working in Covid-19 patient care, HCW working in non-Covid-19 patient care and HCW not in patient care. Phylogenetic analyses of SARS-CoV-2 samples from patients and HCW were performed to identify potential transmission clusters.RESULTSWe included 801 HCW: 439 in the Covid-19 patient care group, 164 in the non-Covid-19 patient care group and 198 in the no patient care group. SARS-CoV-2 incidence was highest in HCW working in Covid-19 patient care (13.2%), as compared with HCW in non-Covid-19 patient care (6.7%, hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.2 to 4.3) and in HCW not working in patient care (3.6%, HR 3.9, 95% CI 1.8 to 8.6). Within the group of HCW caring for Covid-19 patients, SARS-CoV-2 cumulative incidence was highest in HCW working on Covid-19 wards (25.7%), as compared with HCW working on intensive care units (7.1%, HR 3.6, 95% CI 1.9 to 6.9), and HCW working in the emergency room (8.0%, HR 3.3, 95% CI 1.5 to 7.1). Phylogenetic analyses on Covid-19 wards identified multiple potential HCW-to-HCW transmission clusters while no patient-to-HCW transmission clusters were identified.CONCLUSIONSHCW working on Covid-19 wards are at increased risk for nosocomial SARS-CoV-2 infection, with an important role for HCW-to-HCW transmission.(Funded by the Netherlands Organization for Health Research and Development ZonMw & the Corona Research Fund Amsterdam UMC; Netherlands Trial Register number NL8645)

Chloroquine (CQ) and Hydroxychloroquine (HCQ) have been proposed to be effective at treating COVID-19 patients. We, and others, have previously reported on the capacity of CQ to reduce HIV-1 replication in vitro. We tested CQ administration in post-partum mothers on influencing HIV-1 viral loads in human milk as a means of lowering mother to child transmission. A Phase I/II, randomized, placebo-controlled study to evaluate chloroquine administration to reduce HIV-1 RNA levels in human milk: the CHARGE study. Thirty HIV-1 positive pregnant Rwandese women (CQ n = 20; placebo n = 10) were enrolled in a 16-week study, with the treatment group receiving a 200 mg oral dose of CQ daily. Base-line plasma viral load (pVL) measurements and CD4 counts were determined prior to delivery, and pVL, breast milk VL (bmVL) and CQ levels measured during treatment. For women receiving treatment, CQ concentration was higher in breast milk compared to plasma (over 2.5-fold), with a positive correlation between the levels in the two compartments (P < 0.003). A link between high CQ concentrations in plasma and high CD4 counts (P < 0.001) was observed. Surprisingly, we found a significant increase in pVL after CQ treatment in over half of the mothers (n=11; P < 0.001) and with no alteration to bmVL measurements. No specific amino acid alterations in the gp120 envelope sequences could be associated with CQ administration. CQ usage is associated with a significant increase to pVL in early breastfeeding mothers from Rwanda which cautions against the use of CQ in such individuals. Our results highlight a discrepancy between CQ effects on modulating HIV-1 replication in vitro versus in vivo and indicate caution when prescribing CQ to postpartum HIV-1 untreated mothers. This discrepancy should be taken into consideration when testing CQ or HCQ treatment in COVID-19 clinical trials, especially relating to the post-partum setting.

Plasma viral load (VL) and CD4(+) T cell count are widely used as biomarkers of HIV type 1 (HIV-1) replication, pathogenesis, and response to antiretroviral therapy (ART). However, the clinical potential of cell-associated (CA) HIV-1 molecular markers is much less understood. Here, we measured CA HIV-1 RNA and DNA in HIV-infected individuals treated with temporary ART initiated during primary HIV-1 infection. We demonstrate substantial predictive value of CA RNA for (a) the virological and immunological response to early ART, (b) the magnitude and time to viral rebound after discontinuation of early ART, and (c) disease progression in the absence of treatment. Remarkably, when adjusted for CA RNA, plasma VL no longer appeared as an independent predictor of any clinical endpoint in this cohort. The potential of CA RNA as an HIV-1 clinical marker, in particular as a predictive biomarker of virological control after stopping ART, should be explored in the context of HIV-1 curative interventions.

ObjectivesIt has been suggested that ethnic minorities have been disproportionally affected by the COVID-19. We aimed to determine whether prevalence and correlates of past SARS-CoV-2 exposure varied between six ethnic groups in Amsterdam, the Netherlands.Design, setting, participantsParticipants aged 25–79 years enrolled in the Healthy Life in an Urban Setting population-based prospective cohort (n=16 889) were randomly selected within ethnic groups and invited to participate in a cross-sectional COVID-19 seroprevalence substudy.Outcome measuresWe tested participants for SARS-CoV-2-specific antibodies and collected information on SARS-CoV-2 exposures. We estimated prevalence and correlates of SARS-CoV-2 exposure within ethnic groups using survey-weighted logistic regression adjusting for age, sex and calendar time.ResultsBetween 24 June and 9 October 2020, we included 2497 participants. Adjusted SARS-CoV-2 seroprevalence was comparable between ethnic Dutch (24/498; 5.1%, 95% CI 2.8% to 7.4%), South-Asian Surinamese (22/451; 4.9%, 95% CI 2.2% to 7.7%), African Surinamese (22/400; 8.3%, 95% CI 3.1% to 13.6%), Turkish (30/408; 7.9%, 95% CI 4.4% to 11.4%) and Moroccan (32/391; 7.2%, 95% CI 4.2% to 10.1%) participants, but higher among Ghanaians (95/327; 26.3%, 95% CI 18.5% to 34.0%). 57.1% of SARS-CoV-2-positive participants did not suspect or were unsure of being infected, which was lowest in African Surinamese (18.2%) and highest in Ghanaians (90.5%). Correlates of SARS-CoV-2 exposure varied across ethnic groups, while the most common correlate was having a household member suspected of infection. In Ghanaians, seropositivity was associated with older age, larger household sizes, living with small children, leaving home to work and attending religious services.ConclusionsNo remarkable differences in SARS-CoV-2 seroprevalence were observed between the largest ethnic groups in Amsterdam after the first wave of infections. The higher infection seroprevalence observed among Ghanaians, which passed mostly unnoticed, warrants wider prevention efforts and opportunities for non-symptom-based testing.

Summary Background Pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate is highly effective against acquisition of HIV infection, and only two cases of infection with a multidrug-resistant virus have been reported under adequate long-term adherence, as evidenced by tenofovir diphosphate concentrations in dried blood spots. We report a case of wild-type HIV-1 infection despite consistent use of emtricitabine and tenofovir disoproxil fumarate. Methods The patient participated in the Amsterdam PrEP project, a demonstration project of daily and event-driven PrEP. We did extensive testing for HIV, including plasma HIV RNA and nested PCR on bulk peripheral blood mononuclear cells (PBMCs) and sigmoid biopsies after seroconversion. Findings A 50-year-old man who has sex with men and had been on daily emtricitabine and tenofovir disoproxil fumarate for 8 months presented with fever, urinary tract infection caused by Escherichia coli , anal lymphogranuloma venereum infection, and a positive fourth-generation HIV test. We found an atypical seroconversion pattern, with initially only gp160 antibodies detected in the western blot. HIV RNA could not be detected in plasma, and nested PCR for HIV RNA and DNA on bulk PBMCs and sigmoid biopsies were negative. PrEP was discontinued; 3 weeks later HIV RNA was detected in plasma. No drug-resistant mutations were detected. Tenofovir diphosphate concentrations in dried blood spots were stable and high. Interpretation To our knowledge, this is the first detailed case report suggesting wild-type HIV-1 infection despite good adherence, evidenced by repeatedly high concentrations of tenofovir diphosphate in dried blood spots. PrEP providers need to be aware that infection can occur despite good adherence. Regular HIV testing and awareness of atypical patterns of seroconversion is highly recommended. Funding ZonMw, National Institute for Public Health and the Environment, Internal GGD research funds, Aidsfonds, Stichting AmsterdamDiner Foundation, Gilead Sciences, Janssen Pharmaceutica, M A C AIDS Fund, and ViiV Healthcare.

Background: To examine the suggested resurgence of the HIV epidemic among men who have sex with men (MSM), we studied trends in HIV-1 incidence rates, sexual risk behaviour, risk factors for HIV-1 seroconversion, and source of HIV-1 infection among MSM in the Amsterdam Cohort Studies from 1984 to 2009. Methods: Trends in HIV-1 incidence and risk factors for HIV-1 infection were studied using Poisson regression. Trends in sexual risk behaviour were evaluated using logistic regression, correcting for intra-individual correlation via generalized estimating equations. Trends in the source of HIV-1 infection were modelled via logistic regression. Results: Of 1642 HIV-1-negative individuals, 217 seroconverted during follow-up. HIV-1 incidence rates strongly decreased from 8.6/100 person-years in 1985 to 1.3/100 person-years in 1992; remained relatively stable around 1.0/100 person-years between 1992 and 1996, and slowly increased to 2.0/100 person-years in 2009 (P = 0.14; linear trend 1996-2009). Reports of unprotected anal intercourse (UAI) increased significantly from 1996 onwards. HIV-1 seroconversion was associated with receptive UAI with casual partners, more than five sexual partners, a history of gonorrhoea (all in the preceding 6 months), and a lower educational level. Currently, MSM are more likely to have contracted HIV-1 from casual partners than from steady partners, but trends of recent years suggest that steady partners became a growing source with increasing age. Conclusions: Following increases in sexual risk behaviour from 1996 onwards, HIV-1 continues to spread among MSM. Targeted prevention messages should continue to focus on sexual behaviour with casual partners, but also on sexual behaviour within steady relationships. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

SUMMARY The HIV latent reservoir forms the major hurdle to an HIV cure. The discovery of CD32 as marker of this reservoir has aroused much interest, but subsequent reports have challenged this finding. Here, we observe a positive correlation between the percentages of CD32+ cells among CD4+ T cells of aviremic cART-treated, HIV-infected individuals and their HIV DNA loads in peripheral blood. Moreover, optimization of the CD32+CD4+ T cell purification protocol reveals prominent enrichment for HIV DNA (mean, 292-fold) in these cells. However, no enrichment for HIV RNA is observed in CD32+CD4+ cells, yielding significantly reduced HIV RNA/DNA ratios. Furthermore, HIV proviruses in CD32+CD4+ cells can be reactivated ex vivo to produce virus, strongly suggesting that these cells support HIV transcriptional latency. Our results underscore the importance of isolating pure, bona fide CD32+CD4+ T cells for future studies and indicate that CD32 remains a promising candidate marker of the HIV reservoir., Graphical Abstract, In Brief CD32a was recently proposed to mark the HIV reservoir, but this finding was subsequently challenged. By using a sequential cell-sorting protocol to purify bona fide CD32+CD4+ cells, Darcis et al. demonstrate HIV DNA enrichment and ex vivo reactivation-mediated virus production in these cells, reinforcing CD32 as an HIV reservoir marker.

Background The latent HIV-1 reservoir in treated patients primarily consists of resting memory CD4+ T cells. Stimulating the T-cell receptor (TCR), which facilitates transition of resting into effector T cells, is the most effective strategy to purge these latently infected cells. Here we supply evidence that TCR-stimulated effector T cells still frequently harbor latent HIV-1. Methods Primary HIV-1 infected cells were used in a latency assay with or without dendritic cells (DCs) and reversion of HIV-1 latency was determined, in the presence or absence of specific pathway inhibitors. Findings Renewed TCR-stimulation or subsequent activation with latency reversing agents (LRAs) did not overcome latency. However, interaction of infected effector cells with DCs triggered further activation of latent HIV-1. When compared to TCR-stimulation only, CD4+ T cells from aviremic patients receiving TCR + DC-stimulation reversed latency more frequently. Such a “one-two punch” strategy seems ideal for purging the reservoir. We determined that DC contact activates the PI3K-Akt-mTOR pathway in CD4+ T cells. Interpretation This insight could facilitate the development of a novel class of potent LRAs that purge latent HIV beyond levels reached by T-cell activation.

Background: Detecting SARS-CoV-2 antibodies may help to diagnose COVID-19. Head-to-head validation of different types of immunoassays in well-characterized cohorts of hospitalized patients remains needed. Methods: We validated three chemiluminescence immunoassays (CLIAs) (Liaison, Elecsys, and Abbott) and one single molecule array assay (SIMOA) (Quanterix) for automated analyzers, one rapid immunoassay RIA (AllTest), and one ELISA (Wantai) in parallel in first samples from 126 PCR confirmed COVID-19 hospitalized patients and 158 pre-COVID-19 patients. Specificity of the AllTest was also tested in 106 patients with confirmed parasitic and dengue virus infections. Specificity of the Wantai assay was not tested due to limitations in sample volumes. Results: Overall sensitivity in first samples was 70.6 % for the Liaison, 71.4 % for the Elecsys, 75.4 % for the Abbott, 70.6 % for the Quanterix, 77.8 % for the AllTest, and 88.9 % for the Wantai assay, respectively. Sensitivity was between 77.4 % (Liaison) and 94.0 % (Wantai) after 10 dpso. No false positive results were observed for the Elecsys and Abbott assays. Specificity was 91.1 % for the Quanterix, 96.2 % for the Liaison, and 98.1 % for the AllTest assay, respectively. Conclusion: We conclude that low sensitivity of all immunoassays limits their use early after onset of illness in diagnosing COVID-19 in hospitalized patients. After 10 dpso, the Wantai ELISA has a relatively high sensitivity, followed by the point-of-care AllTest RIA that compares favorably with automated analyzer immunoassays.

The HIV latent reservoir forms the major hurdle to an HIV cure. The discovery of CD32 as marker of this reservoir has aroused much interest, but subsequent reports have challenged this finding. Here, we observe a positive correlation between the percentages of CD32+ cells among CD4+ T cells of aviremic cART-treated, HIV-infected individuals and their HIV DNA loads in peripheral blood. Moreover, optimization of the CD32+CD4+ T cell purification protocol reveals prominent enrichment for HIV DNA (mean, 292-fold) in these cells. However, no enrichment for HIV RNA is observed in CD32+CD4+ cells, yielding significantly reduced HIV RNA/DNA ratios. Furthermore, HIV proviruses in CD32+CD4+ cells can be reactivated ex vivo to produce virus, strongly suggesting that these cells support HIV transcriptional latency. Our results underscore the importance of isolating pure, bona fide CD32+CD4+ T cells for future studies and indicate that CD32 remains a promising candidate marker of the HIV reservoir., info:eu-repo/semantics/published

The latent HIV-1 reservoir in treated patients primarily consists of resting memory CD4+ T cells. Stimulating the T-cell receptor (TCR), which facilitates transition of resting into effector T cells, is the most effective strategy to purge these latently infected cells. Here we demonstrate that TCR-stimulated effector T cells still frequently harbor latent HIV-1. Renewed TCR-stimulation or subsequent activation with latency reversing agents (LRAs) did not overcome latency. However, interaction of infected effector cells with dendritic cells (DCs) triggered further activation of latent HIV-1. When compared to TCR-stimulation only, CD4+ T cells from aviremic patients receiving TCR+DC-stimulation reversed latency more frequently. Such a “one-two punch” strategy seems ideal for purging the reservoir. We determined that DC contact activates the PI3K-Akt-mTOR pathway in CD4+ T cells. This insight could facilitate the development of a novel class of potent LRAs that purge latent HIV beyond levels reached by T-cell activation.

Cervicovaginal microbiota not dominated by lactobacilli may facilitate transmission of HIV and other sexually transmitted infections (STIs), as well as miscarriages, preterm births and sepsis in pregnant women. However, little is known about the exact nature of the microbiological changes that cause these adverse outcomes. In this study, cervical samples of 174 Rwandan female sex workers were analyzed cross-sectionally using a phylogenetic microarray. Furthermore, HIV-1 RNA concentrations were measured in cervicovaginal lavages of 58 HIV-positive women among them. We identified six microbiome clusters, representing a gradient from low semi-quantitative abundance and diversity dominated by Lactobacillus crispatus (cluster R-I, with R denoting 'Rwanda') and L. iners (R-II) to intermediate (R-V) and high abundance and diversity (R-III, R-IV and R-VI) dominated by a mixture of anaerobes, including Gardnerella, Atopobium and Prevotella species. Women in cluster R-I were less likely to have HIV (P=0.03), herpes simplex virus type 2 (HSV-2; P

The human immunodeficiency virus type 1 (HIV-1) envelope protein provides the primary contact between the virus and host, and is the main target of the adaptive humoral immune response. The length of gp120 variable loops and the number of N-linked glycosylation events are key determinants for virus infectivity and immune escape, while the V3 loop overall positive charge is known to affect co-receptor tropism. We selected two families in which both parents and two children had been infected with HIV-1 for nearly 10 years, but who demonstrated variable parameters of disease progression. We analysed the gp120 envelope sequence and compared individuals that progressed to those that did not in order to decipher evolutionary alterations that are associated with disease progression when individuals are infected with genetically related virus strains. The analysis of the V3-positive charge demonstrated an association between higher V3-positive charges with disease progression. The ratio between the amino acid length and the number of potential N-linked glycosylation sites was also shown to be associated with disease progression with the healthier family members having a lower ratio. In conclusion in individuals initially infected with genetically linked virus strains the V3-positive charges and N-linked glycosylation are associated with HIV-1 disease progression and follow varied evolutionary paths for individuals with varied disease progression.

BackgroundThe concept of demand characteristics, which involves research participants being aware of what the researcher is investigating, is well known and widely used within psychology, particularly in laboratory-based studies. Studies of this phenomenon may make a useful contribution to broader consideration of the effects of taking part in research on participant behaviour. This systematic review seeks to summarise data from studies of the effects of demand characteristics on participant behaviours in non-laboratory settings.Methodology/Principal FindingsElectronic databases were searched to identify eligible studies. These had to be purposely designed to evaluate possible effects of demand characteristics on at least one behavioural outcome under the autonomous control of the participants and use longitudinal study designs. Only 7 studies were included, 6 providing observational data and 1 experimental study, with 5 studies involving examination of possible effects on health behaviours. Although studies provided some evidence of effects of demand characteristics on participant behaviour, heterogeneous operationalisation of the construct, the limited number of studies and poor quality of study designs made synthesis and interpretation of study findings challenging.Conclusions/SignificanceAlthough widely accepted as important in psychology, there have been few dedicated studies of the effects of demand characteristics on research participant behaviours outside laboratory settings. This body of literature does not currently contribute to the wider study of research participation effects. A systematic review of data from laboratory-based studies is needed, as are high-quality primary studies in non-laboratory settings. We suggest that unqualified use of the term demand characteristics should be abandoned.

BACKGROUND In vitro, animal, and mathematical models suggest that human immunodeficiency virus (HIV) co- or superinfection would result in increased fitness of the pathogen and, possibly, increased virulence. However, in patients, the impact of dual HIV type 1 (HIV-1) infection on disease progression is unclear, because parameters relevant for disease progression have not been strictly analyzed. The objective of the present study is to analyze the effect of dual HIV-1 infections on disease progression in a well-defined cohort of men who have sex with men. METHODS Between 2000 and 2009, 37 men who had primary infection with HIV-1 subtype B, no indication for immediate need of combination antiretroviral therapy (cART), and sufficient follow-up were characterized with regard to dual infection or single infection and to coreceptor use. Patients were followed to estimate the effect of these parameters on clinical disease progression, as defined by the rate of CD4(+) T-cell decline and the time to initiation of cART. RESULTS Four patients presented with HIV-1 coinfection; 6 patients acquired HIV-1 superinfection, on average 8.5 months from their primary infection; and 27 patients remained infected with a single strain. Slopes of longitudinal CD4(+) T-cell counts and time-weighted changes from baseline were significantly steeper for patients with dual infection compared with patients with single infection. Multivariate analysis showed that the most important parameter associated with CD4(+) T-cell decline over time was dual infection (P = .001). Additionally, patients with HIV-1 coinfection had a significantly earlier start of cART (P

In 2007, 14 Dutch men having sex with men (MSM) filed a criminal case against three other men, accusing them of administering sedative drugs, sexual abuse, and deliberate subcutaneous injections with HIV-1-infected blood. Medical files showed that 9 of 17 men presented with an acute HIV-1 infection syndrome during 2006–2007. Two men were not infected with HIV. Analysis of viral strains in the 12 MSM and the three alleged donors showed that one donor and six recipients were double infected with two distinct HIV-1 subtype B strains, while another five recipients and one donor were single infected with either strain. Two men were infected with unrelated strains. The finding of multiple double infections with very similar HIV-1 strains is without precedent.

Background Transient episodes of HIV type-1 viraemia are frequently observed in patients on suppressive combination antiretroviral therapy (cART). We studied the effect of such episodes and of treatment interruptions on clinical outcome and immunological response. Methods A total of 3,321 patients from the ATHENA cohort had virological suppression (HIV type-1 RNA400 copies/ml) viraemia and the outcomes death, AIDS or immunological response (CD4+ T-cell count increase ≥50% from 24 weeks) was studied with Poisson regression models, including either time-updated cumulative follow-up, time spent per type of episode or modelling episodes as binary status indicators. Results During 11,165 person-years of follow-up, 88 patients died, 111 developed AIDS and 2,019 had an immunological response. Longer follow-up time in treatment interruptions increased the risk of AIDS (relative risk [RR] 8.07, 95% confidence interval [CI] 3.98–16.4 per year longer) and impaired immunological response (RR 0.22, 95% CI 0.12–0.41). High-level viraemia was only associated with immunological response (RR 0.55, 95% CI 0.40–0.74), whereas low-level viraemia was not associated with any of the three outcomes. Status indicator models gave similar results. When also including time-updated CD4+ T-cell counts, the observed associations diminished. Conclusions Treatment interruptions and high-level, but not low-level, viraemia are strongly associated with clinical outcome, mainly via their effect on CD4+ T-cell counts.

Objective: To investigate the association between an unexpected increase in the blood plasma HIV-1 viral load in chronically untreated HIV-infected patients and the occurrence of an HIV superinfection, we analyzed the HIV-1 quasispecies in plasma samples before and at peak level in 14 patients. Results: Phylogenetic analysis of HIV-1 env-V3 fragments showed that in 2 patients a superinfection had occurred: their dominant V3 population at the peak level clustered separately from the V3 sequences in a sample predating the peak level. The rapid rise in viral load could be attributed to upper respiratory tract infections or a vaccination in 4 patients, suggesting that even minor health problems can result in significantly increased HIV-1 replication. In most other patients, no minor or major medical condition accompanied the rise in HIV-1 viral load, implying that in these patients the viral load increase was probably associated with disease progression. Conclusion: This study suggests that an unexpected rapid rise in the plasma HIV-1 viral load of untreated patients can infrequently be ascribed to an HIV-1 superinfection.

Objective: An important pending question is whether temporary highly active antiretroviral therapy during primary HIV infection can influence viral rebound dynamics and the subsequently established viral setpoint, through preservation and enhancement of HIV-1-specific immune responses, or through other mechanisms. Methods: We included all patients from two prospective studies who underwent a single treatment interruption while being well suppressed on highly active antiretroviral therapy. One group started highly active antiretroviral therapy during primary HIV infection, and the other group started it during chronic HIV infection with CD4 cell counts above 350 cells/ml. Data were collected up to 48 weeks from treatment interruption.Themediantimetoviralreboundwasanalysedforthreelevelsofviraemia: 50, 500 and 5000 copies HIV-RNA/ml plasma. Results: The median time to viral rebound was significantly longer in primary HIV infection patients (n ¼24) than in chronic HIV infection patients (n ¼46): 8 versus 4 weeks (P

The effectiveness of highly active antiretroviral therapy (HAART), the standard of care for the treatment of human immunodeficiency virus type 1 (HIV-1) infection, is assessed by measuring the viral RNA load in plasma. A patient is considered to be successfully treated when the HIV-1 load in plasma stays below the detection limit of commercial assays. However, virus replication and evolution do continue in patients under HAART, which may eventually result in the development of drug-resistant HIV-1 strains and therapy failure. To monitor this low-level virus replication in peripheral blood mononuclear cells (PBMC), sensitive methods are required to measure HIV-1 molecular markers. We report the development of highly sensitive methods for the quantitation of unspliced and multiply spliced HIV-1 RNA and proviral DNA in PBMC. The methods are based on innovative seminested real-time reverse transcription-PCR (RT-PCR) that combines the accuracy and precision of real-time PCR and the sensitivity of nested PCR. We show that the newly developed methods are superior to the conventional single-step real-time RT-PCR in their sensitivity, accuracy, dynamic range, and the power of quantitative detection of HIV-1 RNA and DNA in clinical samples. These easy-to-perform methods can be widely used in research, including clinical studies, to monitor intracellular processes of virus replication.

Objectives: The incidence of HIV-1 dual infections is generally thought to be low, but as dual infections have been associated with accelerated disease progression, its recognition is clinically important. Methods to identify HIV-1 dual infections are time consuming and are not routinely performed. Design: Genotyping of the HIV-1 protease and reverse transcriptase (prot/RT) genes is commonly performed in the western world to detect drug-resistance mutations in clinical isolates. In our hospital, prot/RT baseline sequencing is part of the patient care for all newly infected patients in the Amsterdam region since 2003. We reasoned that degenerate base codes in this sequence could indicate either extensive viral evolution or infection with multiple HIV-1 strains. Methods: We amplified, cloned and sequenced multiple HIV-1 envelope (env)-V3 and gag sequences from patients with 34 or more (range 34‐99) degenerate base codes in the ViroSeq genotyping RT sequence (37 out of 1661 available records) to estimate the number of HIV-1 dual infections in this group. Results: Of the 37 patients included in this study, 16 (43.2%, equal to 1% of the 1661 total records) had an HIV-1 dual infection based on phylogenetic analysis of env-V3/gag sequences. If only sequences with 45 or more degenerate base codes were taken into account, 73.3% of patients showed evidence of a dual infection. Conclusion: We describe an additional use of routinely performed HIV-1 genotyping. In patients with a high number of degenerate bases ( 34) in RT it is important to consider the possibility of a dual HIV-1 infection. 2007 Lippincott Williams & Wilkins AIDS 2007, 21:807‐811

OBJECTIVE. To improve adherence and virologic suppression, we assessed the feasibility and effectiveness of a once-daily regimen of efavirenz with 3 nucleoside reverse transcriptase inhibitors as first-line or second-line highly active antiretroviral therapy in a cohort of HIV-1–infected children.METHODS. HIV-1–infected children naive to efavirenz were treated with a combination of efavirenz, abacavir, didanosine, and lamivudine in an observational, prospective, single-center study. Virologic failure-free survival was assessed with Kaplan-Meier analysis. The CD4+ T-cell increase was estimated by using a generalized linear model incorporating repeated measurements.RESULTS. Thirty-six children received the study medication for a median of 69 weeks. Virologic failure-free survival rates were 76% and 67% after 48 weeks and 96 weeks, respectively. No significant difference was found in efficacy between first-line and second-line highly active antiretroviral therapy. All children receiving highly active antiretroviral therapy showed a sustained CD4+ T-cell increase, irrespective of virologic suppression. Growth rates improved with highly active antiretroviral therapy. Study medication administration was stopped for 14 children, mostly because of nonadherence (4 cases) or virologic rebound (5 cases) and because of adverse events (unrelated death and grade 2 liver toxicity) in 2 cases. Lipid abnormalities and abacavir-related hypersensitivity were not observed.CONCLUSIONS. For the first time, once-daily highly active antiretroviral therapy is demonstrated to be a safe, convenient, and potent antiretroviral regimen for HIV-1–infected children.

We retrospectively screened 1836 men who have sex with men (MSM) participating in the Amsterdam Cohort Studies (1984-2003) for hepatitis C virus (HCV) antibodies. HCV incidence was 0.18/100 person-years (PY) in human immunodeficiency virus (HIV)-positive MSM (8/4408 PY [95% confidence interval {CI}, 0.08-0.36]) but was 0/100 PY in MSM without HIV (0/7807 PY [95% CI, 0.00-0.05]). After 2000, HCV incidence among HIV-positive men increased 10-fold to 0.87/100 PY (5/572 PY [95% CI, 0.28-2.03]). Additional hospital cases (n = 34) showed that MSM in Amsterdam who acquired HCV infection after 2000 reported high rates of ulcerative sexually transmitted infections (59%) and rough sexual techniques (56%), denied injection drug use, and were infected mainly with the difficult-to-treat HCV genotypes 1 (56%) and 4 (36%). Phylogenetic analysis showed 3 monophyletic clusters of MSM-specific HCV strains. The emergence of an MSM-specific transmission network suggests that HIV-positive MSM with high-risk sexual behaviors are at risk for sexually acquired HCV. Targeted prevention and routine HCV screening among HIV-positive MSM is needed to deter the spread of HCV.

According to the World Health Organization (WHO) nutritional support is an integral part of a comprehensive response to HIV/AIDS. There is evidence that nutrient intake can improve antiretroviral absorption and tolerance. Receiving appropriate nutrition can help improve the health and quality of life of HIV-infected individuals. Individuals who receive antiretroviral therapy (ART) with appropriate nutrition are more likely to regain weight and more likely to adhere to their medications thus helping them rejoin the work force and improve food security for themselves and their families. This document presents a U.S. Government (USG)- wide approach for addressing food and nutrition needs of PLWHA receiving treatment and care. Recognizing that this is too large and complex a problem for any one agency to handle on its own the Office of the Global AIDS Coordinator (OGAC) is partnering with other U.S. government agencies including the U.S. Agency for International Development (USAID) the U.S. Department of Agriculture(USDA) the U.S. Department of Health and Human Services (HHS) and the Peace Corps as well as relevant UN agencies and the private sector to leverage resources to carry out supplementary feeding micronutrient supplementation and food security and livelihood support. Through partnerships PEPFAR addresses the needs of HIV-affected communities especially affected families and caregivers of PLWHA. Furthermore PEPFAR are strengthens coordination at the country level in order to facilitate the implementation of these programs and to improve monitoring and evaluation. (excerpt)

Injecting drug users (DU) are at high risk for hepatitis C virus (HCV) and HIV infections. To examine the prevalence and incidence of these infections over a 20-year period (1985-2005), the authors evaluated 1276 DU from the Amsterdam Cohort Studies who had been tested prospectively for HIV infection and retrospectively for HCV infection. To compare HCV and HIV incidences, a smooth trend was assumed for both curves over calendar time. Risk factors for HCV seroconversion were determined using Poisson regression. Among ever-injecting DU, the prevalence of HCV antibodies was 84.5% at study entry, and 30.9% were co-infected with HIV. Their yearly HCV incidence dropped from 27.5/100 person years (PY) in the 1980s to 2/100 PY in recent years. In multivariate analyses, ever-injecting DU who currently injected and borrowed needles were at increased risk of HCV seroconversion (incidence rate ratio 29.9, 95% CI 12.6, 70.9) compared to ever-injecting DU who did not currently inject. The risk of HCV seroconversion decreased over calendar time. The HCV incidence in ever-injecting DU was on average 4.4 times the HIV incidence, a pattern seen over the entire study period. The simultaneous decline of both HCV and HIV incidence probably results from reduced risk behavior at the population level.

BACKGROUND: In The Netherlands, the western part, including Rotterdam and Amsterdam harbors the majority of the known HIV-infected population, of whom men who have sex with men (MSM) comprise the largest transmission category. Given a general rise in sexually transmitted infections (STI) and risky sexual behavior, we examine the HIV incidence among MSM in the Netherlands with data from three different sources. METHODS: To describe the HIV epidemic among MSM we use: a prospective cohort study in Rotterdam (ROHOCO: 1998-2003, n = 265) and another in Amsterdam (ACS: 1984-2005, n = 1498]) plus an anonymous HIV surveillance study (Amsterdam STI clinic: 1991-2004, n = 3733) in which HIV-positive MSM were tested with a less-sensitive HIV assay. We evaluated calendar trends in HIV incidence, also focusing on age effects. RESULTS: Since the start of the HIV epidemic in the early 1980s, incidence has declined strongly in the ACS. In recent years, an increase was noted among older MSM attending the Amsterdam STI clinic (P = 0.0334). In both cohort studies, HIV incidence was lower and recent time-trends were not statistically significant. Among recently infected men at the STI clinic, only 40% accepted named HIV testing at their STI consultation. CONCLUSIONS: Data suggest that among MSM in the Netherlands, the HIV incidence is between one and four infections per 100 person-years. The epidemic expands among older STI clinic attendees. Prevention should be developed specifically for older men, along with a more efficient HIV testing approach such as routine HIV testing of MSM when they are screened for STI.

New HIV diagnoses among men having sex with men (MSM) have not decreased appreciably in most countries, even though care and prevention services have been scaled up substantially in the past 20 years. To maximize the impact of prevention strategies, it is crucial to quantify the sources of transmission at the population level. We used viral sequence and clinical patient data from one of Europe's nationwide cohort studies to estimate probable sources of transmission for 617 recently infected MSM. Seventy-one percent of transmissions were from undiagnosed men, 6% from men who had initiated antiretroviral therapy (ART), 1% from men with no contact to care for at least 18 months, and 43% from those in their first year of infection. The lack of substantial reductions in incidence among Dutch MSM is not a result of ineffective ART provision or inadequate retention in care. In counterfactual modeling scenarios, 19% of these past cases could have been averted with current annual testing coverage and immediate ART to those testing positive. Sixty-six percent of these cases could have been averted with available antiretrovirals (immediate ART provided to all MSM testing positive, and preexposure antiretroviral prophylaxis taken by half of all who test negative for HIV), but only if half of all men at risk of transmission had tested annually. With increasing sequence coverage, molecular epidemiological analyses can be a key tool to direct HIV prevention strategies to the predominant sources of infection, and help send HIV epidemics among MSM into a decisive decline.