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The human immunodeficiency virus type 1 (HIV-1) epidemic has been a major public health threat on a global scale since the early 1980s. Despite the introduction of combination antiretroviral therapy (cART), the incidence of new HIV-1 infections continues to rise in some regions around the world. Thus, with the continuous transmission of HIV-1 and the lack of a cure, it is imperative for molecular epidemiological studies to be performed, to monitor the infection and ultimately be able to control the spread of this virus. This work provides a comprehensive molecular epidemiological analysis of the HIV-1 infection in Cyprus, through examining 305 HIV-1 sequences collected between 9 March 2017 and 14 October 2021. Employing advanced statistical and bioinformatic techniques, the research delved deeply into understanding the transmission dynamics of the HIV-1 epidemic in Cyprus, as well as the monitoring of HIV-1’s genetic diversity and the surveillance of transmitted drug resistance. The characterization of Cyprus’s HIV-1 epidemic revealed a diverse landscape, comprising 21 HIV-1 group M pure subtypes and circulating recombinant forms (CRFs), alongside numerous uncharacterized recombinant strains. Subtypes A1 and B emerged as the most prevalent strains, followed by CRF02_AG. The findings of this study also revealed high levels of transmitted drug resistance (TDR) patterns, raising concerns for the efficacy of cART. The demographic profiles of individuals involved in HIV-1 transmission underscored the disproportionate burden borne by young to middle-aged Cypriot males, particularly those in the MSM community, who reported contracting the virus in Cyprus. An assessment of the spatiotemporal evolutionary dynamics illustrated the global interconnectedness of HIV-1 transmission networks, implicating five continents in the dissemination of strains within Cyprus: Europe, Africa, Asia, North America, and Oceania. Overall, this study advances the comprehension of the HIV-1 epidemic in Cyprus and highlights the importance of understanding HIV-1’s transmission dynamics through continuous surveillance efforts. Furthermore, this work emphasizes the critical role of state-of-the-art bioinformatics analyses in addressing the challenges posed by HIV-1 transmission globally, laying the groundwork for public health interventions aimed at curbing its spread and improving patient outcomes.

Abstract Introduction Long‐acting injectable cabotegravir (CAB‐LA) demonstrated superiority to daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV pre‐exposure prophylaxis (PrEP) in the HPTN 083/084 trials. We compared the potential impact of expanding PrEP coverage by offering CAB‐LA to men who have sex with men (MSM) in Atlanta (US), Montreal (Canada) and the Netherlands, settings with different HIV epidemics. Methods Three risk‐stratified HIV transmission models were independently parameterized and calibrated to local data. In Atlanta, Montreal and the Netherlands, the models, respectively, estimated mean TDF/FTC coverage starting at 29%, 7% and 4% in 2022, and projected HIV incidence per 100 person‐years (PY), respectively, decreasing from 2.06 to 1.62, 0.08 to 0.03 and 0.07 to 0.001 by 2042. Expansion of PrEP coverage was simulated by recruiting new CAB‐LA users and by switching different proportions of TDF/FTC users to CAB‐LA. Population effectiveness and efficiency of PrEP expansions were evaluated over 20 years in comparison to baseline scenarios with TDF/FTC only. Results Increasing PrEP coverage by 11 percentage points (pp) from 29% to 40% by 2032 was expected to avert a median 36% of new HIV acquisitions in Atlanta. Substantially larger increases (by 33 or 26 pp) in PrEP coverage (to 40% or 30%) were needed to achieve comparable reductions in Montreal and the Netherlands, respectively. A median 17 additional PYs on PrEP were needed to prevent one acquisition in Atlanta with 40% PrEP coverage, compared to 1000+ in Montreal and 4000+ in the Netherlands. Reaching 50% PrEP coverage by 2032 by recruiting CAB‐LA users among PrEP‐eligible MSM could avert >45% of new HIV acquisitions in all settings. Achieving targeted coverage 5 years earlier increased the impact by 5–10 pp. In the Atlanta model, PrEP expansions achieving 40% and 50% coverage reduced differences in PrEP access between PrEP‐indicated White and Black MSM from 23 to 9 pp and 4 pp, respectively. Conclusions Achieving high PrEP coverage by offering CAB‐LA can impact the HIV epidemic substantially if rolled out without delays. These PrEP expansions may be efficient in settings with high HIV incidence (like Atlanta) but not in settings with low HIV incidence (like Montreal and the Netherlands).

Summary: 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

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

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.

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.

Severe COVID-19 can be considered a systemic disease as many extrarespiratory complications occur. However, the systemic pathogenesis is poorly understood.

Introduction: The World Health Organization declared the goal of hepatitis C virus (HCV) elimination by 2030. Micro-elimination, which is the reduction of incidence to zero in targeted populations, is less complex and costly and may be the first step to prove whether elimination is feasible. A suitable target group are HIV-positive men who have sex with men (MSM) because of their high-risk behaviour and high incidence rates. Moreover, HCV monitoring is integrated in HIV care. The current HCV monitoring approach is suboptimal and complex and may miss new HCV infections. Alternative monitoring strategies, based on alanine aminotransferase, HCV-PCR and HCV-core antigen (HCV-cAg), combined with immediate direct-acting antiviral (DAA) treatment, may be more effective in reducing new HCV infections. Methods: A deterministic mathematical transmission model was constructed representing the Dutch HCV epidemic among HIV-positive MSM to compare different HCV monitoring strategies from 2018 onwards. We evaluated the epidemiological impact of alternative and intensified monitoring in MSM with HCV. In addition, the cost-effectiveness was calculated over a lifetime horizon. Results: Current HCV monitoring and treatment is projected to result in an incidence of 1.1/1000 person-years, 0.24% prevalence, at a cost of €61.8 million (interquartile range 52.2–73.9). Compared with current monitoring, intensified monitoring will result in a maximum 27% reduction of incidence and 33% in prevalence at an increased cost. Conversely, compared with current monitoring, targeted HCV-cAg monitoring will result in a comparable incidence (1.1/1000 person-years) and prevalence (0.23%) but will be €1 million cheaper with increased quality-adjusted life year. Conclusion: Targeted monitoring reduces the HCV epidemic in a cost-saving manner; however, micro-elimination may not be obtained by 2030, highlighting the need for harm-reduction programmes.

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 (9 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.

BackgroundIn Europe, a continuous programme (SPREAD) has been in place for ten years to study transmission of drug resistant HIV. We analysed time trends of transmitted drug resistance mutations (TDRM) in relation to the risk behaviour reported.MethodsHIV-1 patients newly diagnosed in 27 countries from 2002 through 2007 were included. Inclusion was representative for risk group and geographical distribution in the participating countries in Europe. Trends over time were calculated by logistic regression.ResultsFrom the 4317 patients included, the majority was men-having-sex-with-men -MSM (2084, 48%), followed by heterosexuals (1501, 35%) and injection drug users (IDU) (355, 8%). MSM were more often from Western Europe origin, infected with subtype B virus, and recently infected (ConclusionsMSM showed to have significantly higher TDRM prevalence compared to heterosexuals and IDU. The increasing NNRTI resistance in MSM is likely to negatively influence the therapy response of first-line therapy, as most include NNRTI drugs.

Programs that monitor local, national, and regional levels of transmitted HIV-1 drug resistance inform treatment guidelines and provide feedback on the success of HIV-1 treatment and prevention programs. To accurately compare transmitted drug resistance rates across geographic regions and times, the World Health Organization has recommended the adoption of a consensus genotypic definition of transmitted HIV-1 drug resistance. In January 2007, we outlined criteria for developing a list of mutations for drug-resistance surveillance and compiled a list of 80 RT and protease mutations meeting these criteria (surveillance drug resistance mutations; SDRMs). Since January 2007, several new drugs have been approved and several new drug-resistance mutations have been identified. In this paper, we follow the same procedures described previously to develop an updated list of SDRMs that are likely to be useful for ongoing and future studies of transmitted drug resistance. The updated SDRM list has 93 mutations including 34 NRTI-resistance mutations at 15 RT positions, 19 NNRTI-resistance mutations at 10 RT positions, and 40 PI-resistance mutations at 18 protease positions.