Dataset Information

The Role of Late Presenters in HIV-1 Transmission Clusters in Europe.

ABSTRACT:

Background

Investigating the role of late presenters (LPs) in HIV-1 transmission is important, as they can contribute to the onward spread of HIV-1 virus before diagnosis, when they are not aware of their HIV status.

Objective

To characterize individuals living with HIV-1 followed up in Europe infected with subtypes A, B, and G and to compare transmission clusters (TC) in LP vs. non-late presenter (NLP) populations.

Methods

Information from a convenience sample of 2679 individuals living with HIV-1 was collected from the EuResist Integrated Database between 2008 and 2019. Maximum likelihood (ML) phylogenies were constructed using FastTree. Transmission clusters were identified using Cluster Picker. Statistical analyses were performed using R.

Results

2437 (91.0%) sequences were from subtype B, 168 (6.3%) from subtype A, and 74 (2.8%) from subtype G. The median age was 39 y/o (IQR: 31.0-47.0) and 85.2% of individuals were males. The main transmission route was via homosexual (MSM) contact (60.1%) and 85.0% originated from Western Europe. In total, 54.7% of individuals were classified as LPs and 41.7% of individuals were inside TCs. In subtype A, individuals in TCs were more frequently males and natives with a recent infection. For subtype B, individuals in TCs were more frequently individuals with MSM transmission route and with a recent infection. For subtype G, individuals in TCs were those with a recent infection. When analyzing cluster size, we found that LPs more frequently belonged to small clusters (<8 individuals), particularly dual clusters (2 individuals).

Conclusion

LP individuals are more present either outside or in small clusters, indicating a limited role of late presentation to HIV-1 transmission.

SUBMITTER: Miranda MNS

PROVIDER: S-EPMC10746990 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

The Role of Late Presenters in HIV-1 Transmission Clusters in Europe.

Miranda Mafalda N S MNS Pimentel Victor V Gomes Perpétua P Martins Maria do Rosário O MDRO Seabra Sofia G SG Kaiser Rolf R Böhm Michael M Seguin-Devaux Carole C Paredes Roger R Bobkova Marina M Zazzi Maurizio M Incardona Francesca F Pingarilho Marta M Abecasis Ana B AB

Viruses 20231213 12

<h4>Background</h4>Investigating the role of late presenters (LPs) in HIV-1 transmission is important, as they can contribute to the onward spread of HIV-1 virus before diagnosis, when they are not aware of their HIV status.<h4>Objective</h4>To characterize individuals living with HIV-1 followed up in Europe infected with subtypes A, B, and G and to compare transmission clusters (TC) in LP vs. non-late presenter (NLP) populations.<h4>Methods</h4>Information from a convenience sample of 2679 indi ...[more]

PMID: 38140659

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Project description:BackgroundThe increased use of antiretroviral therapy (ART) has decreased mortality and morbidity of HIV-1 infected people but increasing levels of HIV drug resistance threatens the success of ART regimens. Conversely, late presentation can impact treatment outcomes, health costs, and potential transmission of HIV.ObjectiveTo describe the patterns of transmitted drug resistance (TDR) and acquired drug resistance (ADR) in HIV-1 infected patients followed in Europe, to compare its patterns in late presenters (LP) vs non-late presenters (NLP), and to analyze the most prevalent drug resistance mutations among HIV-1 subtypes.MethodsOur study included clinical, socio-demographic, and genotypic information from 26,973 HIV-1 infected patients from the EuResist Integrated Database (EIDB) between 1981 and 2019.ResultsAmong the 26,973 HIV-1 infected patients in the analysis, 11,581 (42.9%) were ART-naïve patients and 15,392 (57.1%) were ART-experienced. The median age was 37 (IQR: 27.0-45.0) years old and 72.6% were males. The main transmission route was through heterosexual contact (34.9%) and 81.7% of patients originated from Western Europe. 71.9% of patients were infected by subtype B and 54.8% of patients were classified as LP. The overall prevalence of TDR was 12.8% and presented an overall decreasing trend (p for trend < 0.001), the ADR prevalence was 68.5% also with a decreasing trend (p for trend < 0.001). For LP and NLP, the TDR prevalence was 12.3 and 12.6%, respectively, while for ADR, 69.9 and 68.2%, respectively. The most prevalent TDR drug resistance mutations, in both LP and NLP, were K103N/S, T215rev, T215FY, M184I/V, M41I/L, M46I/L, and L90M.ConclusionOur study showed that the overall TDR (12.8%) and ADR (68.5%) presented decreasing trends during the study time period. For LP, the overall TDR was slightly lower than for NLP (12.3 vs 12.6%, respectively); while this pattern was opposite for ADR (LP slightly higher than NLP). We suggest that these differences, in the case of TDR, can be related to the dynamics of fixation of drug resistance mutations; and in the case of ADR with the more frequent therapeutic failure in LPs.

Project description:BackgroundLate HIV diagnosis (i.e CD4≤350 cells/µL) is associated with poorer outcomes. However, determinants of long-term mortality and factors influencing immune recovery within the first years after antiretroviral treatment (ART) initiation are poorly defined.MethodsFrom PISCIS cohort, we included all HIV-positive adults, two-year survivors after initiating ART between 2005-2019. The primary outcome was all-cause mortality according to the two-year CD4 count. We used Poisson regression. The secondary outcome was incomplete immune recovery (i.e., two-year CD4<500 cells/µL). We used logistic regression and propensity score matching.FindingsWe included 2,719 participants (16593·1 person-years): 1441 (53%) late presenters (LP) and 1278 non-LP (1145 non-LP with two-year CD4 count >500 cells/µL, reference population). Overall, 113 patients (4·2%) died. Mortality was higher among LP with two-year CD4 count 200-500 cells/µL (aMRR 1·95[95%CI:1·06-3·61]) or <200 cells/µL (aMRR 4·59[2·25-9·37]).Conversely, no differences were observed in participants with two-year CD4 counts >500 cells/µL, regardless of being initially LP or non-LP (aMRR 1·05[0·50-2·21]). Mortality rates within each two-year CD4 strata were not affected by the initial CD4 count at ART initiation (test-interaction, p = 0·48). The stronger factor influencing immune recovery was the CD4 count at ART initiation. First-line integrase-inhibitor-(INSTI)-based regimens were associated with reduced mortality compared to other regimens (aMRR 0·54[0·31-0·93]) and reduced risk of incomplete immune recovery in LP (aOR 0·70[0·52-0·95]).InterpretationTwo-year immune recovery is a good early predictor of long-term mortality in LP after surviving the first high-risk 2 years. Nearly half experienced a favorable immune recovery with a life expectancy similar to non-LP. INSTI-based regimens were associated with higher rates of successful immune recovery and better survival compared to non-INSTI regimens.FundingSouthern-Denmark University, Danish AIDS-foundation, and Region of Southern Denmark.

Project description:BackgroundIntegrase inhibitors (INI) induce a rapid decline of HIV-RNA in plasma and CD4+ T-cell recovery in blood. Both characteristics are also associated with immune reconstitution inflammatory syndrome (IRIS). Whether the use of INI-containing combination antiretroviral therapy (cART) increases the risk of IRIS is being questioned.MethodsStudy within the Dutch ATHENA HIV observational cohort. HIV-1 infected late presenters initiating cART after March 2009 were included if they had <200 CD4+ T-cells per μL and were diagnosed with an opportunistic infection. IRIS was defined either according to the criteria by French et al. (IRISFRENCH) or by a clinical IRIS diagnosis of the physician (IRISCLINICAL). The primary outcomes were the association between INI and the occurrence of IRISFRENCH and IRISFRENCH+CLINICAL in multivariable logistic regression.Findings672 patients with a median CD4+ T-cell count of 35 cells per μL were included. Treatment with INI was independently associated with IRISFRENCH as well as IRISFRENCH+CLINICAL (OR 2·43, 95%CI:1·45-4·07, and OR 2·17, 95%CI:1·45-3·25). When investigating INI separately, raltegravir (RAL) remained significantly associated with IRISFRENCH (OR 4·04 (95%CI:1·99-8·19) as well as IRISFRENCH+CLINICAL (OR 3·07, 95%CI:1·66-5·69), while dolutegravir (DTG) became associated with IRISFRENCH+CLINICAL after it replaced RAL as preferred INI in the cohort after 2015 (OR 4·08, 95%CI:0·99-16·82, p=0·052). Too few patients used elvitegravir to draw meaningful conclusions. Steroid initiation for IRIS was more likely in those who initiated INI versus in those who did not, but no increased hospital (re)admission or mortality rates were observed.InterpretationIn HIV late presenters from a resource rich setting, INI based treatment initiation increased the risk of IRIS. This was observed for RAL and DTG when being initiated as preferential INI in the presence of specific AIDS-conditions, indicative of channeling bias. Although we controlled for all relevant measured confounders, we cannot exclude that the observed association is partially explained by residual confounding. INI use was not associated with mortality nor hospitalization. Therefore, our observation is no reason to avoid INI in late presenters.FundingThe ATHENA database is maintained by Stichting HIV Monitoring and supported by a grant from the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment.

Project description:IntroductionHIV late presenters were defined as individuals presenting with a CD4 count below 350 cells/μL or with an AIDS-defining event, according to the European Late Presenter Consensus working group. Early diagnosis and treatment of HIV have proven beneficial for people living with HIV (PLHIV), reducing the burden on healthcare systems, and contributing to ending the HIV/AIDS epidemic. However, in Malaysia, over 50% of newly diagnosed HIV patients present late, leading to increased morbidity and premature mortality. This study aims to determine the prevalence of late HIV presenters and its association with HIV-related stigma and HIV knowledge among PLHIV attending public primary care clinics in Selangor.MethodsA cross-sectional study was conducted at selected public health clinics in Selangor, involving PLHIV aged 18 years and older, who were diagnosed since 2019. HIV-related stigma was measured using the Malay version of Berger's HIV Stigma Scale, and HIV knowledge was assessed using the Malay version of Brief HIV-KQ-18. Univariate and multivariate logistic regression analyses were performed to identify factors associated with late HIV presentation.ResultsA total of 400 participants were included in the study, with 60.0% (n = 240, 95% CI: 55.0-65.0) classified as late presenters. The participants had a mean age of 30.29 (±7.77) years. The risk factors for late presenters were high levels of HIV-related stigma (aOR = 1.049, 95% CI: 1.034-1.063, p-value <0.001), low levels of HIV knowledge (aOR = 0.709, 95% CI: 0.646-0.778, p-value <0.001), tertiary education background (aOR = 15.962, 95% CI: 1.898-134.235, p-value = 0.011), and being single (aOR = 3.582, 95% CI: 1.393-9.208, p-value = 0.008).ConclusionThis study highlights the association between high levels of HIV-related stigma, low levels of HIV knowledge, and late HIV presentation. Interventions targeting stigma reduction and HIV education can promote early testing and prompt access to care, improving health outcomes for PLHIV.

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Dataset Information

The Role of Late Presenters in HIV-1 Transmission Clusters in Europe.

Background

Objective

Methods

Results

Conclusion

Publications

The Role of Late Presenters in HIV-1 Transmission Clusters in Europe.

Similar Datasets

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