Intention and preference to use long-acting injectable PrEP among MSM in the Netherlands: a diffusion of innovation approach.

Long-acting injectable pre-exposure prophylaxis (LAI-PrEP) is efficacious in preventing HIV among men-who-have-sex-with-men (MSM) and will be soon available in Europe. This study investigated the intention and preference to use LAI-PrEP among MSM in the Netherlands by employing a diffusion of innovation approach. This study had a cross-sectional design nested within a cohort study established in 2017 to understand oral PrEP use among MSM. 309 MSM completed the survey on their awareness, interest, intention, and preference for LAI-PrEP in June 2022. Among them, 83% showed high/very-high interest in, and 63% showed high/very-high intention to use LAI-PrEP. A repeated innovator effect from the early adopters to LAI-PrEP was not observed. Early adopters did not show increased intention to use LAI-PrEP compared to other MSM subgroups, but neither did PrEP-naïve nor PrEP-discontinued MSM. However, among the 218 current oral PrEP users, suboptimal adherence was associated with preference for LAI-PrEP but not with intention to use it. In conclusion, our findings indicated that an effective, available, and affordable LAI-PrEP would be welcomed in the Netherlands, but that its introduction may not significantly expand PrEP coverage. However, the introduction of LAI-PrEP in the Netherlands could prove beneficial to MSM with suboptimal adherence to oral PrEP.

Scenarios of future mpox outbreaks among men who have sex with men: a modelling study based on cross-sectional seroprevalence data from the Netherlands, 2022.

BackgroundFollowing the 2022-2023 mpox outbreak, crucial knowledge gaps exist regarding orthopoxvirus-specific immunity in risk groups and its impact on future outbreaks.AimWe combined cross-sectional seroprevalence studies in two cities in the Netherlands with mathematical modelling to evaluate scenarios of future mpox outbreaks among men who have sex with men (MSM).MethodsSerum samples were obtained from 1,065 MSM attending Centres for Sexual Health (CSH) in Rotterdam or Amsterdam following the peak of the Dutch mpox outbreak and the introduction of vaccination. For MSM visiting the Rotterdam CSH, sera were linked to epidemiological and vaccination data. An in-house developed ELISA was used to detect vaccinia virus (VACV)-specific IgG. These observations were combined with published data on serial interval and vaccine effectiveness to inform a stochastic transmission model that estimates the risk of future mpox outbreaks.ResultsThe seroprevalence of VACV-specific antibodies was 45.4% and 47.1% in Rotterdam and Amsterdam, respectively. Transmission modelling showed that the impact of risk group vaccination on the original outbreak was likely small. However, assuming different scenarios, the number of mpox cases in a future outbreak would be markedly reduced because of vaccination. Simultaneously, the current level of immunity alone may not prevent future outbreaks. Maintaining a short time-to-diagnosis is a key component of any strategy to prevent new outbreaks.ConclusionOur findings indicate a reduced likelihood of large future mpox outbreaks among MSM in the Netherlands under current conditions, but emphasise the importance of maintaining population immunity, diagnostic capacities and disease awareness.

Spatio-temporal changes in pre-exposure prophylaxis uptake among MSM in mainland France between 2016 and 2021: a Bayesian small area approach with MSM population estimation.

INTRODUCTION: In France, oral pre-exposure prophylaxis (PrEP) for HIV prevention has been publicly available since 2016, mainly targeting at men who have sex with men (MSM). Reliable and robust estimations of the actual PrEP uptake among MSM on a localized level can provide additional insights to identify and better reach marginalized MSM within current HIV prevention service provision. This study used national pharmaco-epidemiology surveillance data and regional MSM population estimations to model the spatio-temporal distribution of PrEP uptake among MSM in France 2016-2021 to identify marginalized MSM at risk for HIV and increase their PrEP uptake. METHODS: We first applied Bayesian spatial analyses with survey-surveillance-based HIV incidence data as a spatial proxy to estimate the size of (1) regional HIV-negative MSM populations and (2) MSM who could be eligible for PrEP use according to French PrEP guidelines. We then applied Bayesian spatio-temporal ecological regression modelling to estimate the regional prevalence and relative probability of the overall- and new-PrEP uptake from 2016 to 2021 across France. RESULTS: HIV-negative and PrEP-eligible MSM populations vary regionally across France. Île-de-France was estimated to have the highest MSM density compared to other French regions. According to the final spatio-temporal model, the relative probability of overall PrEP uptake was heterogeneous across France but remained stable over time. Urban areas have higher-than-average probabilities of PrEP uptake. The prevalence of PrEP use increased steadily (ranging from 8.8% [95% credible interval 8.5%;9.0%] in Nouvelle-Aquitaine to 38.2% [36.5%;39.9%] in Centre-Val-de-Loire in 2021). CONCLUSIONS: Our results show that using Bayesian spatial analysis as a novel methodology to estimate the localized HIV-negative MSM population is feasible and applicable. Spatio-temporal models showed that despite the increasing prevalence of PrEP use in all regions, geographical disparities and inequalities of PrEP uptake continued to exist over time. We identified regions that would benefit from greater tailoring and delivery efforts. Based on our findings, public health policies and HIV prevention strategies could be adjusted to better combat HIV infections and to accelerate ending the HIV epidemic.

The BAF complex inhibitor pyrimethamine reverses HIV-1 latency in people with HIV-1 on antiretroviral therapy.

Reactivation of the latent HIV-1 reservoir is a first step toward triggering reservoir decay. Here, we investigated the impact of the BAF complex inhibitor pyrimethamine on the reservoir of people living with HIV-1 (PLWH). Twenty-eight PLWH on suppressive antiretroviral therapy were randomized (1:1:1:1 ratio) to receive pyrimethamine, valproic acid, both, or no intervention for 14 days. The primary end point was change in cell-associated unspliced (CA US) HIV-1 RNA at days 0 and 14. We observed a rapid, modest, and significant increase in (CA US) HIV-1 RNA in response to pyrimethamine exposure, which persisted throughout treatment and follow-up. Valproic acid treatment alone did not increase (CA US) HIV-1 RNA or augment the effect of pyrimethamine. Pyrimethamine treatment did not result in a reduction in the size of the inducible reservoir. These data demonstrate that the licensed drug pyrimethamine can be repurposed as a BAF complex inhibitor to reverse HIV-1 latency in vivo in PLWH, substantiating its potential advancement in clinical studies.

Characteristics and short- and long-term direct medical costs among adults with timely and delayed presentation for HIV care in the Netherlands.

INTRODUCTION: In Europe, half of people living with HIV (PLWH) present late to care, with associated higher morbidity and mortality. This study aims to assess short- and long-term costs of HIV-care based on time of presentation and identify other factors contributing to higher costs in the first and fifth year after antiretroviral therapy (ART) initiation. MATERIAL AND METHODS: We included ATHENA cohort data which prospectively includes 98% of PLWH in the Netherlands. PLWH who initiated ART in 2013 were included and followed over five years. PLWH were divided in three categories based on CD4 cell-count at time of ART initiation: timely presentation (CD4>350cells/µL), late presentation (CD4 200-350cells/µL or >350cells/µL with AIDS-defining illness) and very late presentation (CD4<200cells/µL). The total HIV-care cost was calculated distinguishing ART medication and non-ART medication costs (hospitalization, outpatient clinic visits, co-medications, and HIV-laboratory tests). RESULTS: From 1,296 PLWH, 273 (21%) presented late and 179 (14%) very late. Nearly half of those who entered HIV-care in a very late stage were of non-Dutch origin, with 21% originating from sub-Saharan Africa. The mean cost per patient in the first year was €12,902 (SD€11,098), of which about two-thirds due to ART (€8,250 (SD€3,142)). ART costs in the first and fifth year were comparable regardless of time of presentation. During the first year on treatment, non-ART medication costs were substantially higher among those with late presentation (€4,749 (SD€8,009)) and very late presentation (€15,886 (SD€ 21,834)), compared with timely presentation (€2,407(SD€4,511)). Higher non-ART costs were attributable to hospitalization and co-medication. The total non-ART costs incurred across five years on treatment were 56% and 246% higher for late and very late presentation respectively as compared to timely presentation. CONCLUSION: Very late presentation is associated with substantial costs, with non-ART costs nearly seven times higher than for those presenting timely. Hospitalization and co-medication costs are likely to continue to drive higher costs for individuals with late presentation into the future. Programs that identify individuals earlier will therefore likely provide significant short- and long-term health cost savings.

Predicted effects of the introduction of long-acting injectable cabotegravir pre-exposure prophylaxis in sub-Saharan Africa: a modelling study.

BACKGROUND: Long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) is recommended by WHO as an additional option for HIV prevention in sub-Saharan Africa, but there is concern that its introduction could lead to an increase in integrase-inhibitor resistance undermining treatment programmes that rely on dolutegravir. We aimed to project the health benefits and risks of cabotegravir-PrEP introduction in settings in sub-Saharan Africa. METHODS: With HIV Synthesis, an individual-based HIV model, we simulated 1000 setting-scenarios reflecting both variability and uncertainty about HIV epidemics in sub-Saharan Africa and compared outcomes for each with and without cabotegravir-PrEP introduction. PrEP use is assumed to be risk-informed and to be used only in 3-month periods (the time step for the model) when having condomless sex. We consider three groups at risk of integrase-inhibitor resistance emergence: people who start cabotegravir-PrEP after (unknowingly) being infected with HIV, those who seroconvert while on PrEP, and those with HIV who have residual cabotegravir drugs concentrations during the early tail period after recently stopping PrEP. We projected the outcomes of policies of cabotegravir-PrEP introduction and of no introduction in 2022 across 50 years. In 50% of setting-scenarios we considered that more sensitive nucleic-acid-based HIV diagnostic testing (NAT), rather than regular antibody-based HIV rapid testing, might be used to reduce resistance risk. For cost-effectiveness analysis we assumed in our base case a cost of cabotegravir-PrEP drug to be similar to oral PrEP, resulting in a total annual cost of USD$144 per year ($114 per year and $264 per year considered in sensitivity analyses), a cost-effectiveness threshold of $500 per disability-adjusted life years averted, and a discount rate of 3% per year. FINDINGS: Reflecting our assumptions on the appeal of cabotegravir-PrEP, its introduction is predicted to lead to a substantial increase in PrEP use with approximately 2·6% of the adult population (and 46% of those with a current indication for PrEP) receiving PrEP compared with 1·5% (28%) without cabotegravir-PrEP introduction across 20 years. As a result, HIV incidence is expected to be lower by 29% (90% range across setting-scenarios 6-52%) across the same period compared with no introduction of cabotegravir-PrEP. In people initiating antiretroviral therapy, the proportion with integrase-inhibitor resistance after 20 years is projected to be 1·7% (0-6·4%) without cabotegravir-PrEP introduction but 13·1% (4·1-30·9%) with. Cabotegravir-PrEP introduction is predicted to lower the proportion of all people on antiretroviral therapy with viral loads less than 1000 copies per mL by 0·9% (-2·5% to 0·3%) at 20 years. For an adult population of 10 million an overall decrease in number of AIDS deaths of about 4540 per year (-13 000 to -300) across 50 years is predicted, with little discernible benefit with NAT when compared with standard antibody-based rapid testing. AIDS deaths are predicted to be averted with cabotegravir-PrEP introduction in 99% of setting-scenarios. Across the 50-year time horizon, overall HIV programme costs are predicted to be similar regardless of whether cabotegravir-PrEP is introduced (total mean discounted annual HIV programme costs per year across 50 years is $151·3 million vs $150·7 million), assuming the use of standard antibody testing. With antibody-based rapid HIV testing, the introduction of cabotegravir-PrEP is predicted to be cost-effective under an assumed threshold of $500 per disability-adjusted life year averted in 82% of setting-scenarios at the cost of $144 per year, in 52% at $264, and in 87% at $114. INTERPRETATION: Despite leading to increases in integrase-inhibitor drug resistance, cabotegravir-PrEP introduction is likely to reduce AIDS deaths in addition to HIV incidence. Long-acting cabotegravir-PrEP is predicted to be cost-effective if delivered at similar cost to oral PrEP with antibody-based rapid HIV testing. FUNDING: Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

HIV transmission among acutely infected participants of a Dutch cohort study 2015-2021 is not associated with large, clustered outbreaks.

OBJECTIVE: Timely identification of acute or early HIV infection (AEHI) is important to help prevent onward transmission, and understanding the number of secondary infections resulting from individuals with AEHI is key to planning HIV prevention services and case finding. DESIGN: We performed a phylogenetic investigation of a dense sample of individuals with AEHI who took part in the Netherlands Cohort Study on Acute HIV infection (NOVA) in the Netherlands during 2015-2021. METHODS: Transmission clusters were identified using phylogenetic analyses based on HIV pol sequences. The Tamura-Nei model was used to estimate genetic distance. A number of 1000 bootstraps was used to check the reliability of clustering using maximum likelihood. A cluster was defined as having a bootstrap value of at least 95% and a genetic distance of at most 1.5%. Sensitivity analyses using different values for the bootstrap and genetic distance were performed to study the reproducibility of the clustering. RESULTS: Of the 156 participants included in NOVA between July 2015 and April 2021, 134 individuals for whom baseline characteristics and genotypic resistance data at baseline were available could be included. We identified 10 clusters, but the majority of persons (111/134) were not part of a cluster, suggesting mainly independent transmission events. CONCLUSION: Mainly independent transmission events among a study population consisting predominantly of MSM in a low-incidence high-resource setting is likely the result of active AEHI case finding and direct start of treatment, and the roll-out over recent years of preventive measures such as preexposure prophylaxis.

HIV-1 resistance against dolutegravir fluctuates rapidly alongside erratic treatment adherence: a case report.

OBJECTIVES: We report a case of incomplete HIV-1 suppression on a dolutegravir, lamivudine, and abacavir single-tablet regimen with the emergence of the H51Y and G118R integrase resistance mutations. METHODS: Integrase sequencing was performed retrospectively by Sanger and next-generation sequencing. Rates of emergence and decline of resistance mutations were calculated using next-generation sequencing data. Dolutegravir plasma concentrations were measured by ultra-performance liquid chromatography-tandem mass spectrometry. The effects of H51Y and G118R on infectivity, fitness, and susceptibility to dolutegravir were quantified using cell-based assays. RESULTS: During periods of non-adherence to treatment, mutations were retrospectively documented only by next-generation sequencing. Misdiagnosis by Sanger sequencing was caused by the rapid decline of mutant strains within the retroviral population. This observation was also true for a M184V lamivudine-resistant reverse transcriptase mutation found in association with integrase mutations on single HIV genomes. Resistance rebound upon treatment re-initiation was swift (>8000 copies per day). Next-generation sequencing indicated cumulative adherence to treatment. Compared to WT HIV-1, relative infectivity was 73%, 38%, and 43%; relative fitness was 100%, 35%, and 10% for H51Y, G118R, and H51Y+G118R viruses, respectively. H51Y did not change the susceptibility to dolutegravir, but G188R and H51Y+G118R conferred 7- and 28-fold resistance, respectively. CONCLUSION: This case illustrates how poorly-fit drug-resistant viruses wax and wane alongside erratic treatment adherence and are easily misdiagnosed by Sanger sequencing. We recommend next-generation sequencing to improve the clinical management of incomplete virological suppression with dolutegravir.

Persistent Transmission of HCV among Men Who Have Sex with Men despite Widespread Screening and Treatment with Direct-Acting Antivirals.

BACKGROUND: In the Netherlands, unrestricted access to direct-acting antivirals (DAAs) halved the incidence of acute hepatitis C virus (HCV) infections among HIV-infected men who have sex with men (MSM). To develop strategies that can further reduce the spread of HCV, it is important to understand the transmission dynamics of HCV. We used phylogenetic analysis of a dense sample of MSM to provide insight into the impact of unrestricted access to DAAs on HCV transmission in the Netherlands and in Belgium. METHODS: We included 89 MSM that were recently infected with HCV genotype 1a in ten Dutch and one Belgian HIV treatment centers. Sequences were generated using next gene sequencing and Sanger sequencing. Maximum likelihood phylogenetic analysis (general time reversible model) was performed on concatenated NS5A and NS5B sequences and a reference set of 389 highly similar control sequences selected from GenBank. A cluster was based on a minimum bootstrap support of 90% and a 3% genetic distance threshold. RESULTS: We found that 78 (88%) of individuals were part of seven major clusters. All clusters included individuals from across the study region, however, different cities were part of different clusters. In three clusters, HIV-negative MSM clustered with sequences from HIV-positive MSM. All clusters that were observed before the introduction of DAAs persisted after unrestricted access to DAAs became available. CONCLUSION: Recently acquired HCV infections among MSM in the Netherlands and Belgium are strongly clustered and therefore highly suitable for targeted prevention strategies, such as contact tracing and partner notification. Importantly, despite an HCV incidence reduction after high DAA uptake and continuously monitoring, HCV transmission persisted in the same clusters.

Serum Markers Associated with Disease Severity in a Bosnian Hemorrhagic Fever with Renal Syndrome Cohort.

Puumala orthohantavirus (PUUV) is endemic in Europe and can cause hemorrhagic fever with renal syndrome (nephropathia epidemica). Disease features include fever, thrombocytopenia, and acute kidney injury (AKI). This retrospective cohort study of forty PUUV patients aims to characterize associations of serum immunological, hemostatic or kidney injury markers to disease severity. While interleukin-18 (IL-18) was significantly increased in severely thrombocytopenic patients (<100 × 109 platelets/L) compared to patients with higher platelet counts, RANTES was significantly decreased in these patients. These data suggest that patients with significant thrombocytopenia might have experienced pronounced Th1 immune responses. When kidney dysfunction was used as the primary disease outcome, recently identified AKI biomarkers (Cystatin C, insulin-like growth factor-binding protein 7, Nephrin, and trefoil factor 3) were significantly upregulated in patients with severe PUUV infection, defined as the estimated glomerular filtration rate (eGFR) below 30 m/min/1.73 m2. The increased expression of these markers specifically indicates pathology in glomeruli and proximal tubuli. Furthermore, E-selectin was significantly higher while interferon gamma-induced protein 10 (IP-10) was significantly lower in PUUV patients with more severe kidney dysfunction compared to patients with higher eGFR-values. Increased E-selectin illustrates the central role of endothelial cell activation, whereas decreased IP-10 could indicate a less important role of this cytokine in the pathogenesis of kidney dysfunction.

Catchet-MS identifies IKZF1-targeting thalidomide analogues as novel HIV-1 latency reversal agents.

A major pharmacological strategy toward HIV cure aims to reverse latency in infected cells as a first step leading to their elimination. While the unbiased identification of molecular targets physically associated with the latent HIV-1 provirus would be highly valuable to unravel the molecular determinants of HIV-1 transcriptional repression and latency reversal, due to technical limitations, this has been challenging. Here we use a dCas9 targeted chromatin and histone enrichment strategy coupled to mass spectrometry (Catchet-MS) to probe the differential protein composition of the latent and activated HIV-1 5'LTR. Catchet-MS identified known and novel latent 5'LTR-associated host factors. Among these, IKZF1 is a novel HIV-1 transcriptional repressor, required for Polycomb Repressive Complex 2 recruitment to the LTR. We find the clinically advanced thalidomide analogue iberdomide, and the FDA approved analogues lenalidomide and pomalidomide, to be novel LRAs. We demonstrate that, by targeting IKZF1 for degradation, these compounds reverse HIV-1 latency in CD4+ T-cells isolated from virally suppressed people living with HIV-1 and that they are able to synergize with other known LRAs.

From more testing to smart testing: data-guided SARS-CoV-2 testing choices, the Netherlands, May to September 2020.

BackgroundSARS-CoV-2 RT-PCR assays are more sensitive than rapid antigen detection assays (RDT) and can detect viral RNA even after an individual is no longer infectious. RDT can reduce the time to test and the results might better correlate with infectiousness.AimWe assessed the ability of five RDT to identify infectious COVID-19 cases and systematically recorded the turnaround time of RT-PCR testing.MethodsSensitivity of RDT was determined using a serially diluted SARS-CoV-2 stock with known viral RNA concentration. The probability of detecting infectious virus at a given viral load was calculated using logistic regression of viral RNA concentration and matched culture results of 78 specimens from randomly selected non-hospitalised cases. The probability of each RDT to detect infectious cases was calculated as the sum of the projected probabilities for viral isolation success for every viral RNA load found at the time of diagnosis in 1,739 confirmed non-hospitalised COVID-19 cases.ResultsThe distribution of quantification cycle values and estimated RNA loads for patients reporting to drive-through testing was skewed to high RNA loads. With the most sensitive RDT (Abbott and SD Biosensor), 97.30% (range: 88.65-99.77) of infectious individuals would be detected. This decreased to 92.73% (range: 60.30-99.77) for Coris BioConcept and GenBody, and 75.53% (range: 17.55-99.77) for RapiGEN. Only 32.9% of RT-PCR results were available on the same day as specimen collection.ConclusionThe most sensitive RDT detected infectious COVID-19 cases with high sensitivity and may considerably improve containment through more rapid isolation and contact tracing.

The epidemiological impact and cost-effectiveness of key population-led PrEP delivery to prevent HIV among men who have sex with men in Thailand: A modelling study.

Background: Although key populations (KPs), such as men-who-have-sex-with-men (MSM) are disproportionately affected by HIV, many prevention and treatment services are not easily accessible for KP members. To address the needs of KPs, Thailand established pre-exposure prophylaxis (PrEP) service delivery together with and led by KP members. This study determines the epidemiological impact and cost-effectiveness of key population-led (KP-led) PrEP. Methods: We calibrated a compartmental deterministic HIV transmission model to the HIV epidemic among Thai MSM. Besides KP-led PrEP, we included other Thai service delivery models of PrEP (fee-based PrEP, the government PrEP program).Data on consistent PrEP use (5 years daily use, 95% effectiveness for preventing HIV) came from Thai PrEP delivery models. For the period 2015-2032, we ranged the number of PrEP starters (40,000-120,000), effectiveness of PrEP (45%-95%), and proportion of consistent users (10%-50%). The analysis started in 2015 when PrEP was introduced. A cost-effectiveness ratio of <160,000 Baht per quality-adjusted life year (QALY) over 40 years was cost-effective. Findings: Without PrEP, 53,800 (interquartile range 48,700-59,700) new HIV infections are expected in 2015-2032. KP-led PrEP was found to have the strongest epidemiological impact of all delivery models averting 58% of infections compared to without PrEP. The epidemiological impact depends on the number of PrEP starters and proportion of consistent use. Although all PrEP service delivery models are cost-effective, KP-led PrEP is most cost-effective with incremental cost-effectiveness ratios of 28,000-37,300 Thai Baht per QALY. Interpretation: Our model projects KP-led PrEP having the greatest epidemiological impact and being the most cost-effective service delivery model of PrEP in Thailand. Funding: This study was supported by the US Agency for International Development and U.S. President's Emergency Plan for AIDS Relief through the Linkages Across the Continuum of HIV Services for Key Populations cooperative agreement (AID-OAA-A-14- 0045) managed by FHI 360.

Clinical outcomes among adolescents living with HIV in Kenya following initiation on antiretroviral treatment.

In Kenya, HIV/AIDS remains a leading cause of morbidity and mortality among adolescents living with HIV (ALHIV). Our study evaluated associations between demographic and healthcare factors and HIV treatment outcomes among ALHIV in care in Kenya. This retrospective cohort study evaluated the clinical outcomes of newly diagnosed ALHIV enrolled in HIV care during January 2017-June 2018 at 32 healthcare facilities in Homabay and Kakamega Counties. Demographic and clinical data were abstracted from patient clinical records and registers during the follow up study period January 2017-through May 2019. ALHIV were stratified by age (10-14 versus 15-19 years). Categorical variables were summarized using descriptive statistics; continuous variables were analyzed using mean values. The latest available treatment and virological outcomes for ALHIV were assessed. 330 ALHIV were included in the study (mean age 15.9 years; 81.8% female, 63.0% receiving HIV care at lower-level healthcare facilities). Most (93.2%) were initiated on ART within 14 days of diagnosis; 91.4% initiated EFV-based regimens. Of those on ART, only 44.6% were active on care at the end of the study period. Of those eligible for viral load testing, 83.9% were tested with 84.4% viral suppression rate. Retention in care was higher at higher-level facilities (67.5%) compared to lower-level facilities (28.6%). Factors associated with higher retention in care were school attendance (aRR = 1.453), receipt of disclosure support (aRR = 13.315), and receiving care at a high-level health facility (aRR = 0.751). Factors associated with viral suppression included older age (15-19 years) (aRR = 1.249) and pre-ART clinical WHO stage I/II (RR = .668). Viral suppression was higher among older ALHIV. Studies are needed to evaluate effective interventions to improve outcomes among ALHIV in Kenya.

Significant Impact of Coronavirus Disease 2019 (COVID-19) on Human Immunodeficiency Virus (HIV) Care in Hospitals Affecting the First Pillar of the HIV Care Continuum.

During COVID-19 lockdown, the in-hospital number of HIV indicator conditions decreased disproportionally compared with other non-COVID-19 diseases, which was accompanied by reduced HIV testing rates, number and proportion of positive HIV tests, and new HIV referrals, with more late presentation after lockdown cessation, indicating a significantly impacted HIV care continuum.

Quality of life among people living with HIV in England and the Netherlands: a population-based study.

BACKGROUND: HIV is now considered a chronic condition, and people living with HIV, when treated, have a similar life expectancy as compared to the general population. Consequently, improving and ensuring a good health-related quality of life (HrQoL) among people living with HIV (people living with HIV) is increasingly important and has risen on the global agenda in recent years. A 'fourth 90' as 90% of people with viral load suppression have a good HrQoL should therefore be adopted alongside the other 90-90-90 targets. This study aims to report the progress on HrQoL as the 'fourth 90' and compare against the general population in the Netherlands and England. METHODS: In the Netherlands, individuals attending the HIV outpatient clinic of a tertiary hospital were asked to complete the EQ-5D-5L from June 2016 until December 2018. In England, individuals attending one of 73 HIV outpatient clinics were randomly sampled to complete the Positive Voices survey, which included the EQ-5D-5L, from January to September 2017. HrQoL scores were combined with demographic data and compared to general population data. FINDINGS: The EQ-5D-5L was filled-out by 895 people living with HIV in the NL and 4,137 in England. HrQoLutility was 0·85 among Dutch and 0·83 among English people living with HIV. This equated to 98% and 94% of the general population HrQoLutility in the Netherlands and England, respectively. Of the EQ-5D domains, anxiety/depression was mostly affected, with one-third in Dutch (35%) and almost half (47%) of English people living with HIV reporting symptoms. This was higher compared to their respective general populations (21% NL and 31% England). INTERPRETATION: Overall, HrQoLutility for people living with HIV was high in both countries and highly comparable to the general populations Nevertheless, there should be an increased focus on anxiety and depression in the people living with HIV population The EQ-5D-5L proved an easy HrQoL measurement tool and identified areas for improvement by social and behavioural interventions. FUNDING: The study received funding (unrestricted grants) from: Gilead sciences, ViiV Healthcare, MSD, and Jansen pharmaceuticals.

Expanding reimbursement of immediate treatment using direct acting antivirals to reduce hepatitis C incidence among HIV positive men who have sex with men in Bangkok, Thailand: A cost effectiveness modelling study.

BACKGROUND: Increasing number of hepatitis C virus (HCV) infections among HIV positive men whohave sex with men (MSM) as in an acute HIV infection cohort study in Bangkok, reached an incidence of 45/1000 person-years in 2018. Direct-acting antivirals (DAAs), that cure HCV infection and thereby can prevent transmission, are expensive, their reimbursement being presently delayed to the chronic stages of liver fibrosis. The aim of this study was to determine the cost-effectiveness of immediate DAA treatment to reduce HCV transmission among HIV positive MSM in Bangkok. METHODS: A deterministic transmission model was calibrated to the HCV epidemic among HIV positive MSM in Bangkok. We compared the current practice of starting DAAs at METAVIR stage F2 rather than at stage F1, or immediately after diagnosis, at stage F0. Cost-effectiveness was examined from a payer's perspective, using a 3% annual discounting rate. RESULTS: Compared to the incidence in 2018, delaying DAA treatment to METAVIR stage F2 or F1, increases HCV incidence in 2030 to 63/1000 person-years and 56/1000 person-years, respectively. Conversely, immediate DAA treatment reduces the incidence to 26/1000 person-years. Compared to initiating treatment at stage F2, immediate treatment is cost saving within seven years and saves $17 million over 40 years. One-way sensitivity analysis showed that lower cost savings were achieved at a higher price of DAA treatment and at less frequent HCV screening. CONCLUSION: Immediate DAA treatment is cost saving and increases health benefits by reducing HCV incidence among HIV-infected MSM.

Temporal Kinetics of RNAemia and Associated Systemic Cytokines in Hospitalized COVID-19 Patients.

COVID-19 is associated with a wide range of extrarespiratory complications, of which the pathogenesis is currently not fully understood. However, both systemic spread and systemic inflammatory responses are thought to contribute to the systemic pathogenesis. In this study, we determined the temporal kinetics of viral RNA in serum (RNAemia) and the associated inflammatory cytokines and chemokines during the course of COVID-19 in hospitalized patients. We show that RNAemia can be detected in 90% of the patients who develop critical disease, compared to 50% of the patients who develop moderate or severe disease. Furthermore, RNAemia lasts longer in patients who develop critical disease. Elevated levels of interleukin-10 (IL-10) and MCP-1-but not IL-6-are associated with viral load in serum, whereas higher levels of IL-6 in serum were associated with the development of critical disease. In conclusion, RNAemia is common in hospitalized patients, with the highest frequency and duration in patients who develop critical disease. The fact that several cytokines or chemokines are directly associated with the presence of viral RNA in the circulation suggests that the development of RNAemia is an important factor in the systemic pathogenesis of COVID-19. IMPORTANCE Severe COVID-19 can be considered a systemic disease as many extrarespiratory complications occur. However, the systemic pathogenesis is poorly understood. Here, we show that the presence of viral RNA in the blood (RNAemia) occurs more frequently in patients who develop critical disease, compared to patients with moderate or severe disease. In addition, RNAemia is associated with increased levels of inflammatory cytokines and chemokines, like MCP-1 and IL-10, in serum during the course of disease. This suggests that extrarespiratory spread of SARS-CoV-2 contributes to systemic inflammatory responses, which are an important factor in the systemic pathogenesis of COVID-19.

Clinical Evaluation of Roche SD Biosensor Rapid Antigen Test for SARS-CoV-2 in Municipal Health Service Testing Site, the Netherlands.

Rapid detection of infection is essential for stopping the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The Roche SD Biosensor rapid antigen test for SARS-CoV-2 was evaluated in a nonhospitalized symptomatic population. We rapid-tested a sample onsite and compared results with those from reverse transcription PCR and virus culture. We analyzed date of onset and symptoms using data from a clinical questionnaire. Overall test sensitivity was 84.9% (95% CI 79.1-89.4) and specificity was 99.5% (95% CI 98.7-99.8). Sensitivity increased to 95.8% (95% CI 90.5-98.2) for persons who sought care within 7 days of symptom onset. Test band intensity and time to result correlated strongly with viral load; thus, strong positive results could be read before the recommended time. Approximately 98% of all viable specimens with cycle threshold <30 were detected. Rapid antigen tests can detect symptomatic SARS-CoV-2 infections in the early phase of disease, thereby identifying the most infectious persons.