Staging of immuno-virological dynamics during acute HIV infection in a Belgian prospective cohort study.

Background: The events during acute HIV infection (AHI) set the stage for the subsequent course of the disease. Early initiation of antiretroviral therapy (ART) has been associated with favorable immunovirological outcomes, yet the precise impact of ART timing during AHI remains unclear, particularly on lymphoid tissues. Materials and methods: The ACS cohort is a prospective cohort study in Belgium, collecting longitudinal clinical data and human bodily material (HBM) from people diagnosed and treated during AHI. The aim of the cohort is to study the impact of ART initiation during AHI on HIV reservoir and immune dysfunction in peripheral blood and anatomical sanctuary sites, as well as its effect on the gut microbiome. The cohort consists of two HBM sampling trajectories: one limited (blood, stool and leukapheresis) and a more extensive one (blood, stool, leukapheresis, colonoscopy, inguinal lymph node excision and lumbar puncture). Here we describe the baseline characteristics, immunovirological outcomes, safety and tolerability of HBM sampling. Results: Between March 2016 and April 2024, 47 participants were enrolled, predominantly men who have sex with men (MSM), with a median age of 36 years [IQR 30-43.5]. Almost 90 % of participants initiated ART within 72 h after study inclusion, irrespective of HBM sampling trajectory. The timing of ART initiation according to the Fiebig stage did not significantly impact immune recovery (CD4/CD8 ratio ≥1) or the time to viral suppression. Approximately 40 % of participants opted for the extensive HBM sampling trajectory during AHI. However, the participation rate for the extensive trajectory decreased by nearly half at the longitudinal follow-up timepoint. In general, study-related procedures were safe and well-tolerated, with limited procedure-related adverse events (AEs). Inguinal lymph node excision was associated with the highest AE rate, in line with previous reports. Conclusions: Our findings reaffirm the beneficial effect of ART initiation during AHI on long term immunovirological outcomes, regardless of Fiebig stage at treatment initiation. Additionally, we demonstrate that the collection of HBM during and longitudinally after AHI is safe and feasible, without compromising time to ART initiation. Cohorts that integrate comprehensive clinical data with high-quality HBM samples are essential to longitudinally study the impact of early ART on reservoir dynamics and immune responses across various anatomical sites after AHI.

Clinical performance evaluation of an HIV Duo assay: From HIV screening to acute and non-acute HIV infection detection.

BACKGROUND: Evaluating the clinical performance of Elecsys HIV Duo assay for primary human immunodeficiency virus (HIV) screening and acute HIV infection detection. METHODS: This study was conducted from April 2022 to April 2023 and involved two distinct populations. For the HIV screening population, three HIV Duo results [HIV Duo, HIV antigen (Ag), and HIV antibody (Ab)] in primary screening were obtained (January 2021 to June 2021). In the diagnosed HIV population, retrospective samples from November 2016 to March 2023 were measured. RESULTS: The HIV screening population included 111,383 samples from a real-world screening program. The assay demonstrated a specificity of 99.91 % (95 % CI: 99.89 %, 99.93 %) and a PPV of 0.8516 (95 % CI: 0.8225, 0.8776). Regarding the diagnosed HIV population, 836 HIV patients were enrolled, including 14 acute HIV infectious patients with only HIV Ag + and a Western Blot (WB) confirmation rate of 0 %. The median (IQR) of the numeric cut-off index (COI) ratios of HIV Duo Ab and Ag significantly differed among the Ag + Ab-, Ag-Ab+, and Ag + Ab + subgroups. CONCLUSION: The Elecsys HIV Duo assay is suitable for primary HIV screening and can be integrated into a novel laboratory HIV testing algorithm to improve acute HIV detection in Chinese clinical practice. ABBREVIATIONS: HIV, Human immunodeficiency virus; AIDS, acquired immunodeficiency syndrome; Ag, antigen; Ab, antibody; WB, Western Blot; COI, numeric cut-off index; CI, confidence interval; NAT, nucleic acid tests; EDC, electronic data capture systems; CDC, Chinese Centers for Disease Control and Prevention; IQR, interquartile range; PPV, positive predictive value; HCV, hepatitis C virus; HBV, hepatitis B virus; CI, confidence interval; ND, not able to define; F, female; M, male.

Evaluation of a point-of-care rapid HIV antibody test with insights into acute HIV symptomatology in a population with low prevalence.

Many emergency departments (ED) use rapid human immunodeficiency virus (HIV) antibody tests as screening tools, despite limited sensitivity for detecting acute HIV infections. In a 4-year retrospective analysis of 1,192 patients, we evaluated the performance of a third-generation rapid HIV antibody assay tested at point-of-care (POC, Chembio Sure Check HIV 1/2) against in-lab fourth-generation screening (Abbott Architect Ag/Ab Combo). Compared to complete algorithmic testing, the POC test demonstrated a 92.5% sensitivity (95% CI = 84.6-96.5), 98.1% specificity (95% CI = 97.1-98.8), 99.5% negative predictive value (NPV; 95% CI = 98.8-99.8), and a 77.9% positive predictive value (PPV; 95% CI = 68.6-85.1). Notably, the POC test failed to detect 100% (3/3) of acute HIV infections (defined as Fiebig stage 2) and 3.8% (2/52) established HIV infections, where viral loads were 5.9, 6.7, and >7 log10 copies/mL. Symptoms such as fever, nausea/vomiting, malaise, headache, and photophobia were significantly associated with acute HIV infections diagnosed in the ED. The rapid HIV antibody test demonstrated high sensitivity, specificity, and NPV in our study population, reaffirming its effectiveness as a valuable screening tool. However, the low PPV and 100% failure to detect acute HIV infections underscore the importance of prioritizing in-lab fourth-generation HIV antigen/antibody combination immunoassays in cases of suspected acute HIV infection to ensure a timely and accurate diagnosis.

Rhabdomyolysis in Acute HIV Infection.

Rhabdomyolysis is a rare but potentially life-threatening complication of acute HIV infection. We present a case report of a young adult male who presented with fever, myalgia, and elevated creatine phosphokinase levels, ultimately diagnosed with acute HIV infection-associated rhabdomyolysis. This case highlights the importance of considering HIV infection in the differential diagnosis of rhabdomyolysis, particularly in at-risk populations, even in the absence of typical HIV-related symptoms.

Cytokine Storm Syndrome as a Manifestation of Primary HIV Infection.

HIV infection triggers an inflammatory response that manifests as acute retroviral syndrome (ARS) in most individuals infected by HIV. While this syndrome is usually self-limited, primary HIV infection sometimes triggers a fulminant inflammatory process consistent with cytokine storm syndrome (CSS). Many of the key findings of CSS including fever, splenomegaly, and cytopenias are routinely observed in ARS, suggesting CSS may be under recognized in the setting of acute HIV infection. Unlike other CSS scenarios, ARS-associated CSS generally responds well to HIV-targeted therapies. Advanced HIV infection is also associated with CSS, although typically this involves additional infectious insults. Occasionally, HIV therapy results in rapid recovery of the immune response that evolves into CSS.

Central Nervous System Effects of Early HIV Infection and Consequences of Antiretroviral Therapy Initiation during Acute HIV.

HIV infection is a multi-organ disease that involves the central nervous system (CNS). While devastating CNS complications such as HIV-associated dementia and CNS opportunistic infection typically manifest years after HIV acquisition, HIV RNA is readily detected in the cerebrospinal fluid in untreated neuroasymptomatic people with HIV, highlighting that HIV neuroinvasion predates overt clinical manifestations. Over the past two decades, increased awareness of HIV infection within the at-risk population, coupled with the accessibility of nucleic acid testing and modern HIV immunoassays, has made the detection of acute and early HIV infection readily achievable. This review aims to summarize research findings on CNS involvement during acute and early HIV infection, as well as the outcomes following the immediate initiation of antiretroviral therapy during this early stage of infection. The knowledge gap in long-term neuroprotection through early ART within the first year of infection will be discussed.

Identification of a circulating long non-coding RNA signature panel in plasma as a novel biomarker for the detection of acute/early-stage HIV-1 infection.

BACKGROUND: Individuals with acute / early HIV-1 infection are often unaware that they are infected with HIV-1 and may be involved in high-risk behavior leading to transmission of HIV-1. Identifying individuals with acute / early HIV-1 infection is critical to prevent further HIV-1 transmission, as diagnosis can lead to several effective HIV-1 prevention strategies. Identification of disease-stage specific non-viral host biomarkers would be useful as surrogate markers to accurately identify new HIV-1 infections. The goal of this study was to identify a panel of host derived plasma long non-coding RNAs (lncRNAs) that could serve as prognostic and predictive biomarkers to detect early/acute HIV-1 infection. METHODS: A total of 84 lncRNAs were analyzed in sixteen plasma samples from HIV-1 infected individuals and four healthy controls using the lncRNA PCR-array. Twenty-one lncRNAs were selected and validated in 80 plasma samples from HIV-1 infected individuals [HIV-1 infected patients in the eclipse stage (n = 20), acute stage (n = 20), post-seroconversion p31 negative stage (n = 20), and post-seroconversion p31 positive stage (n = 20) of infection] and 20 healthy controls. The validation study results were used to develop a plasma lncRNA panel that was evaluated in the panel test phase to detect early/acute HIV-1 infection in 52 independent samples. RESULTS: We identified a lncRNA panel (Pmodel-I) containing eight lncRNAs (DISC2, H19, IPW, KRASP1, NEAT1, PRINS, WT1-AS and ZFAS1) that could distinguish HIV-1 infection from healthy controls with high AUC 0·990 (95% CI 0.972-1.000), sensitivity (98.75%), and specificity (95%). We also found that Pmodel-II and Pmodel-III demonstrates 100% sensitivity and specificity (AUC 1·00; 95%CI:1·00-1·00) and could distinguish eclipse stage and acute stage of HIV-1 infection from healthy controls respectively. Antiretroviral treatment (ART) cumulatively restored the levels of lncRNAs to healthy controls levels. CONCLUSION: lncRNA expression changes significantly in response to HIV-1 infection. Our findings also highlight the potential of using circulating lncRNAs to detect both the eclipse and acute stages of HIV-1 infection, which may help to shorten the window period and facilitate early detection and treatment initiation. Initiating ART treatment at this stage would significantly reduce HIV-1 transmission. The differentially expressed lncRNAs identified in this study could serve as potential prognostic and diagnostic biomarkers of HIV-1 infection, as well as new therapeutic targets.

Real-world performance of HIV low viral load values in diagnosing acute HIV infection in a tertiary care hospital in Beijing, China.

BACKGROUND: Early diagnosis of HIV infection decreases the time from HIV diagnosis to viral suppression and reduces further HIV transmission. The Chinese Guidelines for the Diagnosis and Treatment of HIV/AIDS (2021 edition) state that an HIV RNA level > 5,000 copies/mL is the threshold for diagnosing HIV infection. The impact of low viral load values on HIV diagnosis needs to be investigated. METHODS: There were 3455 human immunodeficiency virus (HIV1 + 2) antibody results (immunoblotting method) and 65,129 HIV viral load values at Beijing Youan Hospital from 2019 to 2022. A total of 2434 patients had both antibody confirmatory results and viral load results. The confirmatory antibody results and HIV viral load results of 2434 patients were analyzed to investigate the impact of low viral load values on HIV diagnosis. RESULTS: Of the 2434 patients who had both confirmatory antibody results and viral load results, the viral load values of 140 patients (5.8%) had viral loads ranging from 40 copies/mL to 5,000 copies/mL before positive confirmatory antibody result, and of these 140 patients, the sample receipt time for the viral load tests of 96 (66.7%) individuals was 1 to 6 days earlier than the corresponding sample receipt time for the confirmatory antibody test. In addition, 34 patients (1.4%) had low viral loads ranging from 40 copies/mL to 1,000 copies/mL before positive confirmatory antibody result. CONCLUSION: This study revealed that there is a risk of missed diagnosis if a threshold of 5000 copies/mL is used for the diagnosis of HIV infection. These data provide valuable information for the early diagnosis of HIV infection, and our findings have potential benefits for decreasing HIV transmission.

Plasma, intracellular and lymph node antiretroviral concentrations and HIV DNA change during primary HIV infection: Results from the INACTION P25 study.

Despite its effectiveness, combination antiretroviral treatment (cART) has a limited effect on HIV DNA reservoir, which establishes early during primary HIV infection (PHI) and is maintained by latency, homeostatic T-cells proliferation, and residual replication. This limited effect can be associated with low drug exposure in lymphoid tissues and/or suboptimal adherence to antiretroviral drugs (ARVs). The aim of this study was to assess ARV concentrations in plasma, peripheral blood mononuclear cells (PBMCs) and lymph nodes (LNs), and their association to HIV RNA and HIV DNA decay during PHI. Participants were randomised to receive standard doses of darunavir/cobicistat (Arm I), dolutegravir (Arm II) or both (Arm III), with a backbone of tenofovir alafenamide and emtricitabine. Total HIV DNA was measured using digital-droplet PCR in PBMCs at baseline, 12 and 48 weeks. Drug concentrations in plasma and PBMCs were determined at 2, 12 and 48 weeks (LNs at 12 weeks) by UHPLC-MS/MS. Seventy-two participants were enrolled, mostly male (n=68), with a median age of 34 years and variable Fiebig stages (V-VI 57.7%, I-II 23.9%, and III-IV 18.3%). Twenty-six patients were assigned to Arm I, 27 to Arm II and 19 to Arm III. After 48 weeks, most patients had undetectable viremia, with minor differences in HIV RNA decay between arms. Patients with Fiebig I-II showed faster HIV RNA and HIV DNA decay. Intracellular tissue penetration was high for nucleoside analogues and low-moderate for darunavir and dolutegravir. Only tenofovir diphosphate concentrations in PBMCs showed correlation with HIV DNA decay. Overall, these results indicate that the timing of treatment initiation and intracellular tenofovir penetration are primary and secondary factors, respectively, affecting HIV reservoir.

Stakeholder-engaged development of a rapid test for detection of acute HIV infection.

Background/Objective: The utilization of rapid HIV tests has been effective at reducing transmission rates in high-risk populations by allowing individuals to receive diagnosis in as little as one minute and begin treatment. However, no current rapid tests can detect HIV immediately after infection in the acute HIV infection (AHI) phase, when the virus is at its most infectious, and instead require a waiting period of up to 90 days after exposure. Rapid HIV tests to detect AHI are currently under development. Investigation of stakeholder perspectives and context-specific needs are critical to ensure successful translation of novel AHI tests. The objectives of this study were to 1) understand context-specific factors such as barriers to HIV testing in Indiana, a state with one of 48 prioritized counties for HIV elimination; 2) assess the acceptability of a novel rapid AHI test, and 3) identify key implementation considerations for such a device, including ideal end-users. Methods: Semi-structured in-depth interviews were conducted with staff (n = 14) and clients (n = 5) of Indiana-based organizations that conduct HIV testing, including syringe service programs. Utilizing human-centered design frameworks, interview guides were developed and tailored to each participant group to understand their experiences with HIV testing, perspectives on a novel rapid AHI test in development, and preferences for self-testing versus testing by a community health worker (CHW) or a peer recovery coach. Thematic analysis was conducted to identify major themes, including barriers to HIV testing and perceived benefits and concerns of the proposed AHI test. Results: Overall acceptability for a novel AHI rapid test was high with a greater preference for CHW/Peerled testing. While self-testing was not a preferred modality, it was still seen as a potential tool to reach and address key barriers among high-risk individuals. Key considerations for implementation emphasized accuracy, cost-effectiveness, ease of use, ensuring access to counseling, education, and navigation to care while maintaining a human element to self-testing. Conclusion: Stakeholder engagement is meaningfully informing the design, development, and implementation of rapid AHI testing in order to facilitate adoption among populations at high-risk for HIV.

Rapid Biphasic Decay of Intact and Defective HIV DNA Reservoir During Acute Treated HIV Disease.

Despite antiretroviral therapy (ART), HIV persists in latently-infected cells ("the reservoir") which decay slowly over time. Here, leveraging >500 longitudinal samples from 67 people with HIV (PWH) treated during acute infection, we developed a novel mathematical model to predict reservoir decay from peripheral CD4+ T cells. Nonlinear generalized additive models demonstrated rapid biphasic decay of intact DNA (week 0-5: t1/2~2.83 weeks; week 5-24: t1/2~15.4 weeks) that extended out to 1 year. These estimates were ~5-fold faster than prior decay estimates among chronic treated PWH. Defective DNA had a similar biphasic pattern, but data were more variable. Predicted intact and defective decay rates were faster for PWH with earlier timing of ART initiation, higher initial CD4+ T cell count, and lower pre-ART viral load. These data add to our limited understanding of HIV reservoir decay at the time of ART initiation, informing future curative strategies targeting this critical time.

Human and Viral microRNA Expression in Acute and Chronic HIV Infections.

Human and viral microRNAs (miRNAs) are involved in the regulation of gene transcription, and the establishment of their profiles in acute (AHI) and chronic (CHI) HIV infections may shed light on the pathogenetic events related to different phases of HIV disease. Next-generation sequencing (NGS) of miRNA libraries was performed, and the reads were used to analyze miRNA differential expression in the plasma with AHI and CHI. Functional analysis was then undertaken to investigate the biological processes characterizing the two phases of HIV infection. Except for hsa-miR-122-5p, which was found in 3.39% AHI vs. 0.18% CHI, the most represented human miRNAs were similarly represented in AHI and CHI. However, when considering the overall detected miRNAs in AHI and CHI, 15 displayed differential expression (FDR p < 0.05). Functional analysis identified 163 target mRNAs involved in promoting angiogenesis activation in AHI versus CHI through the action of hsa-miR10b-5p, hsa-miR1290, hsa-miR1-3p, and hsa-miR296-5p. The viral miRNAs detected, all belonging to herpesviruses, accounted for only 0.014% of total reads. The present data suggest that AHI patients exhibit strong innate immune activation through the upregulation of hsa-miR-122-5p and early activation of angiogenesis. More specific investigations are needed to study the role of viral miRNAs in HIV pathogenesis.

Acute Hepatitis due to Primary Human Immunodeficiency Virus Infection.

The acute retroviral syndrome may present with diverse systemic manifestations and laboratory abnormalities. Here we present a rare case of primary human immunodeficiency virus (HIV) infection causing severe acute hepatitis. Liver histopathology demonstrated a pattern of lymphocytic inflammation consistent with acute hepatitis, high levels of HIV proviral DNA were detected within liver tissue, and immunofluorescence showed HIV p24 antigen within immune and parenchymal cells including hepatocytes. We review the literature pertaining to HIV infection of cell compartments within the liver and discuss the implications for HIV-associated acute liver disease.

HLA-A*23 Is Associated With Lower Odds of Acute Retroviral Syndrome in Human Immunodeficiency Virus Type 1 Infection: A Multicenter Sub-Saharan African Study.

The role of human leukocyte antigen (HLA) class I and killer immunoglobulin-like receptor molecules in mediating acute retroviral syndrome (ARS) during human immunodeficiency virus type 1 (HIV-1) infection is unclear. Among 72 sub-Saharan African adults, HLA-A*23 was associated with lower odds of ARS (adjusted odds ratio, 0.10 [95% confidence interval, .01-.48]; P = .009), which warrants further studies to explore its role on HIV-1-specific immunopathogenesis.

Cohort Profile: The Zurich Primary HIV Infection Study.

The Zurich Primary HIV Infection (ZPHI) study is a longitudinal cohort study established in 2002, aiming to study the clinical, epidemiological, and biological characteristics of primary HIV infection. The ZPHI enrolls individuals with documented primary HIV-1 infection. At the baseline and thereafter, the socio-demographic, clinical, and laboratory data are systematically collected, and regular blood sampling is performed for biobanking. By the end of December 2022, 486 people were enrolled, of which 353 were still undergoing active follow-up. Of the 486 participants, 86% had an acute infection, and 14% a recent HIV-1 infection. Men who have sex with men accounted for 74% of the study population. The median time from the estimated date of infection to diagnosis was 32 days. The median time from diagnosis to the initiation of antiretroviral therapy was 11 days, and this has consistently decreased over the last two decades. During the seroconversion phase, 447 (92%) patients reported having symptoms, of which only 73% of the patients were classified as having typical acute retroviral syndrome. The ZPHI study is a well-characterized cohort belonging to the most extensively studied primary HIV infection cohort. Its findings contribute to advancing our understanding of the early stages of HIV infection and pathogenesis, and it is paving the way to further improve HIV translational research and HIV medicine.

A Case of Acute HIV-1 and Monkeypox Coinfection After Condomless Insertive Anal Sex in the Previous 69 Days - Beijing Municipality, China, August-October, 2023.

What is already known about this topic?: The prevalence of monkeypox (mpox) infections is primarily observed among young men who engage in sexual activities with other men, and there is a possibility of sexual transmission. Co-occurring sexually transmitted infections have also been documented. What is added by this report?: In this report, we present a case of a patient in China who was simultaneously diagnosed with mpox, and acute human immunodeficiency virus (HIV) infection. The patient exhibited symptoms of fever and widespread papules on the trunk, face, and genital area. What are the implications for public health practice?: It is crucial for health agencies to prioritize HIV testing when mpox is suspected or diagnosed in individuals with recent engagement in high-risk sexual behavior.

Early antiretroviral therapy and its impact on natural killer cell dynamics in HIV-1 infected men who have sex with men: a cross-sectional pilot study evaluating the impact of early ART initiation on NK cell perturbation in HIV infection.

Phenotypic changes and functional impairment of natural killer (NK) cells occur early in HIV-1 infection. Antiretroviral therapy (ART) effectively restores CD4+ T cell counts and suppresses HIV-1 to undetectable levels. The role and efficacy of immediate ART initiation in mitigating NK cell aberrations remain to be elucidated comprehensively. This study hypothesized that HIV-1 infection negatively influences NK cell evolution and that early ART initiation restores these perturbations. Blood samples were collected longitudinally from five acutely HIV-1 infected men who have sex with men in Nairobi, Kenya. Participants were immediately initiated on ART after HIV-1 diagnosis. Blood samples were drawn pre-infection and at sequential bi-weekly post-infection time points. Peripheral blood mononuclear cells were stained with panel NK cells surface markers to assess HIV-induced phenotypic changes by flow cytometry. Some cells were also stimulated overnight with K562 cell line, IL-2, and IL-15 and stained for flow cytometry functionality. HIV-1 infection was associated with significant reductions in the production of IFN-γ (P = 0.0264), expression of CD69 (P = 0.0110), and expression of NK cell inhibitory receptor Siglec7 (P = 0.0418). We observed an increased NK cell degranulation (P = 0.0100) and an upregulated expression of cell exhaustion marker PD-1 (P = 0.0513) at post-infection time points. These changes mainly were restored upon immediate initiation of ART, except for Siglec7 expression, whose reduced expression persisted despite ART. Some HIV-associated changes in NK cells may persist despite the immediate initiation of ART in acute HIV-1 infections. Our findings suggest that understanding NK cell dynamics and their restoration after ART can offer insights into optimizing HIV-1 treatment and potentially slowing disease progression.IMPORTANCENatural killer (NK) cells play a crucial role in controlling of HIV-1 replication and progression to disease. Perturbations of their functionality may therefore result in deleterious disease outcomes. Previous studies have demonstrated reduced NK cell functionality in chronic HIV-1 infection that positively correlated to HIV-1 viral load. This may suggest that control of HIV-1 viremia in acute HIV-1 infection may aid in enhancing NK cell response boosting the inate immunity hence effective control of viral spread and establishment of viral reservoir. Antiretroviral therapy (ART) effectively supresses HIV-1 viremia to undectable levels and restores CD4+ T cell counts. Our study highlights the significant role of early ART initiation in mitigating NK cell disruptions caused by acute HIV-1 infection. Our results suggest that early initiation of ART could have benefits beyond suppressing viral load and restoring CD4+ T cell counts. In addition, it could boost the innate immunity necessary to control disease progression.

Framingham risk score based vascular outcomes in acute versus chronic HIV cohorts after 6 years of ART.

INTRODUCTION: Immune dysregulation persists in people with HIV (PWH) on antiretroviral therapy (ART) and may lead to accelerated vascular ageing and cardiovascular disease (CVD). While delayed time to initiation of ART has been linked to worse cardiovascular outcomes, the effect of ART initiation during acute infection on these outcomes is not well understood. METHODS: Participants were enrolled from the SEARCH010/RV254 acute HIV (AHI) and HIV-NAT chronic HIV (CHI) cohorts in Thailand. Participants with 6-year follow-up and viral suppression (viral load < 50 copies/µL) at follow-up were included. Both unmatched cohorts and age and gender-matched cohorts were analysed. Demographics, HIV laboratories, and cardiovascular risk factors from enrolment and 6-year follow-up were obtained from electronic records. Framingham Risk Score (FRS), vascular age (VA), vascular age deviation (VAD), and 10-year atherosclerotic cardiovascular disease (ASCVD) risk were calculated from previously published equations. Vascular outcomes in AHI and CHI cohorts were compared, and univariable and multivariable linear regression analyses were used to investigate risk factors associated with worse vascular scores. RESULTS: In all, 373 AHI participants and 608 CHI participants were identified. AHI participants were of younger age, had a higher prevalence of syphilis and a lower prevalence of prior hepatitis B, tuberculosis, diabetes, and hypertension. Higher CD4 T-cell and lower CD8 T-cell counts were seen in the AHI cohort at enrolment and 6-year follow-up. In all participants, the AHI cohort had a lower median FRS (p < 0.001) and VA (p < 0.001), but higher VAD (p < 0.001). However, in matched cohorts, no differences were found in FRS-based outcomes. In all participants, higher VAD after 6 years of ART was associated with higher body mass index (p < 0.001) and higher CD4 count (p < 0.001), which persisted in multivariable analysis. When FRS components were analysed individually, CD4 count was associated only with male sex and cholesterol. CONCLUSIONS: We did not identify differences in FRS-based vascular outcomes at 6 years in matched cohorts of participants who started ART during AHI versus CHI. We identified a correlation between higher CD4 count and worse FRS-based vascular outcomes, which may be driven by underlying metabolic risk factors. Further study is needed to confirm these findings and evaluate underlying mechanisms.

Reflex Human Immunodeficiency Virus (HIV) Type 1 RNA Testing Enables Timely Differentiation of False-Positive Results From Acute HIV Infection.

Accurate, timely human immunodeficiency virus (HIV) diagnosis is critical. Routine HIV screening program data were examined before and after reflex HIV type 1 RNA testing. Reflex testing facilitated confirmation of reactive HIV screening assays (as true or false positives) (odds ratio, 23.7 [95% confidence interval, 6.7-83.4]; P < .0001), improving detection of acute HIV and reducing unconfirmed discordant results.

Demographics of Youth With Newly Diagnosed Acute/Recent HIV Infection in Adolescent Trials Network 147: Early Treatment of Acute HIV Infection.

PURPOSE: Gay, bisexual, and other cisgender men who have sex with men, and racial minority youth are at elevated risk of acquiring HIV infection. The Adolescent Trials Network 147 recruited youth with acute/recent HIV-infection for early antiretroviral treatment. The cohort make-up is described here. METHODS: Treatment-naïve, recently identified HIV + youth, aged 12-24 years, from Los Angeles and New Orleans were recruited from community centers, clinics, social media, and a high-risk seronegative cohort (n = 1,727, the Adolescent Trials Network 149) using point-of-care assays. Acute HIV infection was determined by Fiebig staging. HIV RNA viral load (VL) and CD4 cell counts, along with demographic and behavioral data were assessed at enrollment. RESULTS: Between July 2017 and July 2021, 103 newly diagnosed youth were enrolled, initiating antiretroviral treatment within a week. Mean age was 20.8 years (standard deviation: 2.4); 90.3% identified as cis male, 83.5% were single or in casual relationships, 71.8% were gay, bisexual, and other cisgender men who have sex with men; 60.2% were Black. One-fourth (24.3%) reported homelessness ever; 10.7% within last 4 months. At enrollment, median plasma VL was 37,313 HIV RNA copies/ml (interquartile range: 5,849-126,162) and median CD4 count 445.5 cells/mm3 (interquartile range: 357-613). 40% of youth reported acute retroviral symptoms before or at enrollment. Acutely infected, seroconverting youth had the highest VL. Sexually transmitted coinfections were present at enrollment in 56% of the cohort, with syphilis being most frequent (39%). DISCUSSION: Early identification and treatment of HIV can increase positive HIV outcomes. A high sexually transmitted infection burden was present in recently HIV-infected youth. Acute retroviral symptoms were not reported by most participants, demonstrating that broad universal HIV screening is needed for identification of recent infection in youth.