Modern Antiretroviral Therapy Research Articles

Reducing Cardiovascular Risk in HIV: The Unseen Impact of Visceral Fat

While modern antiretroviral therapy (ART) for people with HIV (PWH) increases life expectancy, there is still an increased risk of developing cardiovascular disease (CVD) in this population. As one factor associated with this increased risk is excess visceral abdominal fat (EVAF), the Visceral Adiposity Measurement and Observations Study (VAMOS) aimed to assess the impact of EVAF on CVD risk in PWH taking modern ART. Participants were grouped according to visceral adipose tissue (VAT) surface area <130 cm2 (non-EVAF group) or ≥130 cm2 (EVAF group), quantified by CT scan. Findings presented at IDWeek 2024 revealed significant differences between EVAF and non-EVAF groups in 10-year atherosclerotic CVD (ASCVD) risk score, as well as many of their individual components. VAMOS also showed correlations between increasing VAT surface area and increasing 10-year ASCVD risk score and insulin resistance measures. Accordingly, VAT may represent a targetable factor to reduce ASCVD risk. Also shown was an inverse relationship between growth hormone (GH) levels and VAT surface area. As GH reductions related to obesity are associated with elevated CVD risk, increasing GH levels may consequently reduce ASCVD risk score. Analysis of two Phase III trials of the GH-releasing hormone (GHRH) analogue tesamorelin, which can significantly reduce VAT in PWH, was also presented at IDWeek 2024. A significant overall trend in 10-year ASCVD risk score reduction was shown in tesamorelin-treated participants, around half of which were already taking lipid lowering therapies. This suggests a benefit of targeting and reducing EVAF to further impact ASCVD risk.

Causes and Consequences of Persistent Anemia after 6 Months of Antiretroviral Therapy in Tanzania: An Observational Comparative Cohort Study.

Anemia is common among people living with HIV (PLWH), particularly in Africa. Outcomes for PLWH on modern antiretroviral therapy (ART) regimens are not well documented. We conducted an observational study to determine the outcomes and predictors of anemia after ART initiation in Tanzania. We enrolled and followed ART-naïve PLWH and HIV-uninfected individuals at three clinics in Tanzania. We grouped participants into four longitudinal categories based on hemoglobin concentration measured at baseline and 6 months after ART initiation (normal, resolved anemia, incident anemia, and persistent anemia) and followed them for 24 months. There were 991 study participants (494 PLWH, 497 HIV uninfected). After 6 months of ART, 33.9% of PLWH had persistent anemia and 9.9% had incident anemia compared with 12.6% and 9.6% for HIV-uninfected controls. Female sex (adjusted odds ratio [aOR]: 2.62; 95% CI: 1.91-6.75) and low income (aOR: 3.10; 95% CI: 1.36-7.20) were strong predictors of persistent anemia for both PLWH and HIV-uninfected individuals. For PLWH, having a CD4+ T cell count of less than 350 cells/mm3 (aOR: 0.34; 95% Cl: 0.15-0.73) was significantly associated with anemia resolution. Mortality was higher for PLWH who had persistent anemia or incident anemia than for PLWH who had normal hemoglobin or improved anemia (hazard ratio: 4.0, 95% Cl 1.3-12.2). One-third of adults in Tanzania had persistent anemia after 6 months on ART, and persistent anemia was associated with increased mortality. PLWH with persistent or incident anemia after 6 months on modern ART deserve close follow-up, particularly women and low-income adults.

Expert Consensus Statement on an Updated Definition of Unintended Weight Loss Among Persons With Human Immunodeficiency Virus in the Modern Treatment Era.

The era of modern antiretroviral therapy (ART) has markedly improved health and survival among persons with human immunodeficiency virus (HIV) (PWH). In the pre-ART era, wasting was associated with HIV disease progression to acquired immunodeficiency syndrome and death. Effective ART has reduced the prevalence and incidence of this pre-ART form of HIV-associated wasting. However, a subgroup of ART-treated virally suppressed PWH continue to lose weight, often accompanied by aging-related comorbidities and/or functional deficits. For this subgroup of patients, the older definition of HIV-associated wasting (HIVAW) cannot and should not be applied. An expert panel comprising the authors of this white paper convened to review the existing definition of HIVAW and to create an updated definition that they termed HIV-associated weight loss, based on clinically defined parameters among contemporary PWH receiving ART. Here, clinical features and laboratory biomarkers associated with HIV-associated weight loss are reviewed and approaches to screening and treatment are considered. Available management approaches, including the use of current US Food and Drug Administration-approved medications for HIVAW and other available therapies are discussed. The expert panel also identified knowledge gaps and provided recommendations for clinicians, payers, and researchers.

Antiretroviral Therapy and Cardiovascular Risk in People With HIV in the United States-An Updated Analysis.

Several antiretroviral therapy (ART) medications have been associated with increased cardiovascular risk, but less is known about the safety of modern ART. We sought to compare the risk of major adverse cardiac events (MACEs) among different ART regimens. Using insurance claims databases from 2008 to 2020, we identified adults aged <65 years who newly initiated ART. We compared non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens to protease inhibitors (PI)- and integrase inhibitors (INSTI)-based regimens. We used propensity score-weighted Kaplan-Meier functions to estimate the 6, 12, 18, 24, 36, and 48 months' risk and risk differences (RD) of MACE. Among 37 935 ART initiators (median age, 40 years; 23% female; 26% Medicaid-insured), 45% started INSTI-, 16% PI-, and 39% NNRTI-based regimens. MACE occurred in 418 individuals (1.1%) within 48 months after ART initiation. Compared to NNRTI initiators, the risk of MACE was higher at 12 months (RD, 0.50; 95% CI, 0.14-0.99), 18 months (RD, 0.53; 95% CI, 0.11-1.06), and 24 months (RD, 0.62; 95% CI, 0.04-1.29) for PI initiators, and at 12 (RD, 0.20; 95% CI, 0.03-0.37) and 18 months (RD, 0.31; 95% CI, 0.06-0.54) for INSTI initiators; the precision of estimates was limited for longer duration of follow-up. Among ART initiators, PI-based and INSTI-based regimens were associated with higher short-term risk of MACE compared to NNRTI-based regimens. The pattern of association between INSTIs and PIs with excess risk of MACE was similar.

Mechanisms underlying the development of type 1 diabetes in ART-treated people living with HIV: an enigmatic puzzle.

The immunopathogenesis of HIV infection remains poorly understood. Despite the widespread use of effective modern antiretroviral therapy (ART), people living with HIV (PLWH) are known to develop several comorbidities, including type 1 diabetes (T1DM). However, the etiology and critical mechanisms accounting for the onset of T1DM in the preceding context remain unknown. This article proposes to address this topic in order to provide further understanding and future research directions.

Low-level HIV-1 viremia affects T-cell activation and senescence in long-term treated adults in the INSTI era

BackgroundAround 10% of people with HIV (PWH) exhibit a low-level viremia (LLV) under antiretroviral therapy (ART). However, its origin and clinical significance are largely unknown, particularly at viremias between 50 and 200 copies/mL and under modern ART based on integrase strand transfer inhibitors (INSTIs). Our aim was to characterize their poor immune response against HIV in comparison to individuals with suppressed viremia (SV) and non-HIV controls (NHC).MethodsTransversal observational study in 81 matched participants: 27 PWH with LLV, 27 PWH with SV, and 27 NHC. Activation (CD25, HLA-DR, and CD38) and senescence [CD57, PD1, and HAVCR2 (TIM3)] were characterized in peripheral T-cell subsets by spectral flow cytometry. 45 soluble biomarkers of systemic inflammation were evaluated by immunoassays. Differences in cell frequencies and plasma biomarkers among groups were evaluated by a generalized additive model for location, scale, and shape (GAMLSS) and generalized linear model (GLM) respectively, adjusted by age, sex at birth, and ART regimen.ResultsThe median age was 53 years and 77.8% were male. Compared to NHC, PWH showed a lower CD4+/CD8+ ratio and increased activation, senescence, and inflammation, highlighting IL-13 in LLV. In addition, LLV showed a downtrend in the frequency of CD8+ naive and effector memory (EM) type 1 compared to SV, along with higher activation and senescence in CD4+ and CD8+ EM and terminally differentiated effector memory RA+ (TEMRA) subpopulations. No significant differences in systemic inflammation were observed between PWH groups.ConclusionLLV between 50 and 200 copies/mL leads to reduced cytotoxic activity and T-cell dysfunction that could affect cytokine production, being unable to control and eliminate infected cells. The increase in senescence markers suggests a progressive loss of immunological memory and a reduction in the proliferative capacity of immune cells. This accelerated immune aging could lead to an increased risk of developing future comorbidities. These findings strongly advocate for heightened surveillance of these PWH to promptly identify potential future complications.

Palliative care considerations for the older adults with HIV/AIDS: a clinical practice review.

Human immunodeficiency virus (HIV) has historically been viewed as a terminal condition affecting younger populations, however, with advancements in antiretroviral therapy (ART) and better healthcare provisions, people with HIV are now living longer than ever before. This shift has highlighted the need to readdress the end-of-life care needs of patients aging with HIV. People aging with HIV face a double burden. Aging itself comes with an array of health challenges, including cognitive decline, frailty, and increased susceptibility to chronic illnesses. Despite effective management with ART, HIV is associated with ongoing inflammation, and may accelerate aging processes, increasing the risk of certain cancers and comorbidities, as well as an increased risk of cardiovascular disease. The stigma surrounding HIV, though diminished over the years, still lingers. People living with HIV have experienced decades of intersecting stigmatized identities in the context of social isolation, leading to potential psychological challenges like depression, anxiety, and loneliness, all of which may be amplified by aging. Addressing these emotional and social needs is as crucial as managing their physical health. The integration of primary palliative care into geriatric practice is crucial, as it improves the quality of life for older patients with chronic illnesses, life-limiting conditions. This is particularly relevant for aging individuals with HIV, who often face complex medical needs and multiple comorbidities. Primary palliative care is the basic, integrated palliative care support provided by non-specialists as part of routine care, while specialist palliative care involves more complex and specialized support from a team with specific training in palliative care. Incorporating palliative care principles enables geriatric healthcare providers to address these comprehensive needs more effectively. This approach encompasses not only physical symptom management but also the emotional well-being of patients. It aids in advanced care planning and decision-making that resonate with the patients' values and goals. Ultimately, this integrated approach leads to improved patient outcomes and a higher quality of care. This review delves into the unique considerations and challenges of providing palliative care to people aging with HIV, recognizing the interplay of age and HIV in the era of modern ART.

Risk factors for progression from prediabetes to diabetes among older people with HIV.

Risk factors for progression from prediabetes mellitus (pre-DM) to diabetes mellitus (DM) among people with HIV (PWH) receiving modern antiretroviral therapy (ART) require better characterization. AIDS Clinical Trials Group (ACTG) A5322 (HAILO) was an observational cohort study of PWH ≥40 years old. Participants initiated ART through ACTG randomized clinical trials. We used Cox proportional hazards regression models to identify risk factors for development of DM among HAILO participants with pre-DM. Among 1035 HAILO participants, 74 (7%) had pre-DM at entry and another 679 (66%) developed pre-DM during follow-up. Of 753 PWH with pre-DM, 167 (22%) developed DM. In multivariable models, the risk of developing DM was greater with higher BMI, lower CD4 count (≤200 cells/mm 3 ), hypertriglyceridemia, or higher waist circumference at pre-DM diagnosis ( P < 0.01). Rates of pre-DM and progression to DM remain high among virally suppressed PWH receiving modern ART regimens. Traditional risks for DM, such as higher BMI or waist circumference, are associated with increased risk of incident DM among PWH with pre-DM. The association between lower CD4 + and progression to DM suggests a role for advanced immunodeficiency and inflammation. Further investigation of interventions aimed at preventing DM among PWH with pre-DM is needed. Optimizing prevention and treatment for DM may be an intervenable opportunity to improve long-term outcomes for PWH.

Gut microbiome and cardiometabolic comorbidities in people living with HIV

BackgroundDespite modern antiretroviral therapy (ART), people living with HIV (PLWH) have increased relative risk of inflammatory-driven comorbidities, including cardiovascular disease (CVD). The gut microbiome could be one of several driving factors, along with traditional risk factors and HIV-related risk factors such as coinfections, ART toxicity, and past immunodeficiency.ResultsPLWH have an altered gut microbiome, even after adjustment for known confounding factors including sexual preference. The HIV-related microbiome has been associated with cardiometabolic comorbidities, and shares features with CVD-related microbiota profiles, in particular reduced capacity for short-chain fatty acid (SCFA) generation. Substantial inter-individual variation has so far been an obstacle for applying microbiota profiles for risk stratification. This review covers updated knowledge and recent advances in our understanding of the gut microbiome and comorbidities in PLWH, with specific focus on cardiometabolic comorbidities and inflammation. It covers a comprehensive overview of HIV-related and comorbidity-related dysbiosis, microbial translocation, and microbiota-derived metabolites. It also contains recent data from studies in PLWH on circulating metabolites related to comorbidities and underlying gut microbiota alterations, including circulating levels of the SCFA propionate, the histidine-analogue imidazole propionate, and the protective metabolite indole-3-propionic acid.ConclusionsDespite recent advances, the gut microbiome and related metabolites are not yet established as biomarkers or therapeutic targets. The review gives directions for future research needed to advance the field into clinical practice, including promises and pitfalls for precision medicine.E43Wq5ZcF7qWyj5HQEGoJiVideo

Cognitive impairment in children and adolescents living with perinatal HIV disease in the ART era: a meta-analysis

Despite improved survival and overall health outcomes from modern antiretroviral therapy (ART), children and adolescents living with HIV are facing pervasive impairments in neurodevelopment including cognitive impairment, but there remains a lack of consensus on the cognitive domains that are affected in those children and adolescents. The objective of this meta-analysis was to evaluate the impact of perinatal HIV-infection on executive function, working memory, and speed of information processing in the ART era. The PubMed database was searched for studies published between 1997 and 2024, plus additional search with the ScienceDirect, bioRxiv, and medRxiv databases. A meta-analysis was conducted on thirty-five studies published between 2012 and 2023 that encompassed a total of 4066 perinatally-infected HIV patients, 2349 HIV-exposed uninfected (HEU) controls, and 2466 HIV-unexposed, uninfected (HUU) controls. Performance scores on executive function, working memory, and processing speed were pooled using random-effects meta-analysis. Compared to HEU and HUU controls, perinatally HIV-infected children and adolescents presented with significant impairments in processing speed (Hedges g=-0.64, p<0.00001), working memory (Hedges g=-0.69, p<0.00001), and to a lesser degree, executive function (Hedges g=-0.35, p=0.02). Meta-regression analysis suggested that the effect estimate of processing speed impairment negatively correlated with Gross National Income (GNI) per capita of the study countries (CALHIV vs HUU, p=0.0016; CALHIV vs HEU, p=0.0019), even though HIV-infected cases were compared to sociodemographically matched HUU controls from the same countries. Sub-group meta-analyses with participants from high-income or low-/middle-income countries provided further evidence suggesting that the performance gap between HIV-infected cases and HUU/HEU controls may be larger in low-/middle-income countries than high-income countries. In the ART era, cognitive impairment (especially reduced processing speed and working memory) persists in children and adolescents living with HIV. These impairments may be more pronounced among those children and adolescents living with HIV in low-income countries, suggesting that there may be global health inequities in treatment outcomes with perinatal HIV-infection. However, meta-analysis and meta-regression analysis have their limitations, which calls for future collaborative multi-country international studies to directly investigate this important topic. Nevertheless, there is an unmet need to assure equity in timely assessments and interventions to optimize neurocognitive development and outcomes among children and adolescents with perinatal HIV globally. This research was supported in part by NIH R01MH108466, NIH R56NS124422, and NIH R01NS124422.

Transactivator of Transcription (Tat)-Induced Neuroinflammation as a Key Pathway in Neuronal Dysfunction: A Scoping Review.

The activity of HIV-1 and its viral proteins within the central nervous system (CNS) is responsible for a wide array of neuropathological effects, resulting in a spectrum of neurocognitive deficits defined as HIV-associated neurocognitive disorders (HAND). Amongst the various viral proteins, the transactivator of transcription (Tat) remains detectable even with effective antiretroviral therapy (ART) and suppressed viremia, highlighting the significance of this protein in the modern ART era. Tat has been extensively researched in both fundamental and clinical settings due to its role in neuroinflammation, neuronal damage, and neurocognitive impairment amongst people living with HIV (PLHIV). To date, numerous fundamental studies have explored Tat-induced neuroinflammation. However, there is no clear consensus on the most frequently studied inflammatory markers or the consistency in the levels of these Tat-induced inflammatory marker levels across different studies. Therefore, we conducted a scoping review of studies investigating Tat-induced neuroinflammation. We conducted searches in PubMed, Scopus, and Web of Science databases using a search protocol tailored specifically to adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for scoping reviews (PRISMA-ScR) guidelines. From the 22 included studies, findings suggest that the HIV-1 Tat protein amplifies levels of neuroinflammatory markers. Amongst the vast array of inflammatory markers explored in the included studies, consistent results point to higher levels of CCL2, IL-6, IL-8, and TNF-α in primary cells and cell lines exposed to or transfected with HIV-1 Tat. These markers are regulated by key inflammatory pathways, such as the extracellularsignal-regulated kinase (ERK)1/2 mitogen-activated protein kinase (MAPK) pathway, the phosphatidylinositol 3-kinase (PI3K) pathway, the p38 MAPK pathway, and nuclear factor-kB (NF-kB). Furthermore, Tat has been shown to induce neuronal apoptosis, both directly and indirectly. With regards to study designs, utilizing full-length Tat101 at concentrations ranging from 100 to 1000 ng/ml and durations of 24 and 48 h appears optimal for investigating Tat-induced neuroinflammation. In this context, we highlight specific inflammatory markers and pathways that are potentially pivotal in Tat-induced neuroinflammation and subsequent neuronal damage. A deeper investigation into these markers and pathways is crucial to better understand their roles in the development of HAND.

Managing Modern Antiretroviral Therapy in the Intensive Care Unit: Overcoming Challenges for Critically Ill People With Human Immunodeficiency Virus.

People with human immunodeficiency virus (HIV) have a 50% excess risk for intensive care unit (ICU) admission, often for non-HIV-related conditions. Despite this, clear guidance for managing antiretroviral therapy (ART) in this setting is lacking. Selecting appropriate ART in the ICU is complex due to drug interactions, absorption issues, and dosing adjustments. Continuing ART in the ICU can be challenging due to organ dysfunction, drug interactions, and formulary limitations. However, with careful consideration, continuation is often feasible through dose adjustments or alternative administration methods. Temporary discontinuation of ART may be beneficial depending on the clinical scenario. Clinicians should actively seek resources and support to mitigate adverse events and drug interactions in critically ill people with HIV. Navigating challenges in the ICU can optimize ART and improve care and outcomes for critically ill people with HIV. This review aims to identify strategies for addressing the challenges associated with the use of modern ART in the ICU.

Incident HIV-Associated Wasting/Low Weight Is Associated with Nearly Doubled Mortality Risk in the Modern ART Era.

HIV-associated wasting (HIVAW) is an underappreciated AIDS-defining illness, despite highly effective antiretroviral therapy (ART). We (a) assessed the association between incident HIVAW/low weight and all-cause mortality and (b) described virologic outcomes after people with HIV (PWH) experienced HIVAW/low weight while on ART. In the Observational Pharmaco-Epidemiology Research & Analysis (OPERA®) cohort, PWH without prior HIVAW/low weight who were active in care in 2016-2020 were followed through the first of the following censoring events: death, loss to follow-up, or study end (October 31, 2021). HIVAW/low weight was a diagnosis of wasting or low body mass index (BMI)/underweight or a BMI measurement <20 kg/m2. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between time-dependent HIVAW/low weight and mortality were estimated with extended Cox regression models. Over a median follow-up of 45 months (interquartile range: 27, 65), there were 4,755 (8%) cases of HIVAW/low weight and 1,354 (2%) deaths among 62,314 PWH. PWH who experienced HIVAW/low weight had a significantly higher risk of death than those who did not (HR: 1.96; 95% CI: 1.68, 2.27) after adjusting for age, race, ethnicity, and changes in viral load (VL) and Veterans Aging Cohort Study Mortality Index scores over follow-up. Among 4,572 PWH on ART at HIVAW/low weight, 68% were suppressed (VL of <200 copies/mL); subsequent virologic failure was uncommon (7%). Among viremic PWH, 70% and 60% achieved suppression and undetectability (VL of <50 copies/mL), respectively, over follow-up. HIVAW remains a challenge for some PWH. Particular attention needs to be paid to HIVAW/low weight and virologic control to restore health and potentially reduce the risk of death.

Prevention and infection control of HIV infection and AIDS

Background: Although the global incidence of human immunodeficiency virus (HIV) has decreased significantly since modern antiretroviral therapy (ART), new HIV infections steadily occur, in the Republic of Korea. Based on the understanding of the risk factors for HIV infection, combined strategic behavioral and biomedical interventions should be implemented to reduce HIV infection. This paper reviews the strategies for the prevention of HIV infection.Current Concepts: While the consistent use of latex condoms is effective for the prevention of HIV transmission, consistent use of condoms is low among sexually active individuals. ART can be initiated, after exposure, to prevent HIV infection (post-exposure prophylaxis) after occupational or sexual exposure, injection drug use, and other nonoccupational exposures to HIV. There is a negligible risk of sexual transmission of HIV when the HIV-infected sexual partner has durably suppressed viral replication with ART. Antiretroviral agents have been shown to be highly effective when administered prophylactically to HIV-uninfected but at-risk individuals (preexposure prophylaxis). A high-risk group, such as men who have sex with men, is required to be included in health insurance care benefits for pre-exposure prophylaxis, in addition to the current partners of HIV-infected individuals, to ensure its efficacy.Discussion and Conclusion: HIV-related deaths are rapidly decreasing, but new HIV infections continue to occur. In an environment where a cure or the development of vaccines is unlikely, a multifaceted and proactive approach is required to minimize new HIV infections.

The Potential of Clostridium butyricum to Preserve Gut Health, and to Mitigate Non-AIDS Comorbidities in People Living with HIV.

A dramatic reduction in mortality among people living with HIV (PLWH) has been achieved during the modern antiretroviral therapy (ART) era. However, ART does not restore gut barrier function even after long-term viral suppression, allowing microbial products to enter the systemic blood circulation and induce chronic immune activation. In PLWH, a chronic state of systemic inflammation exists and persists, which increases the risk of development of inflammation-associated non-AIDS comorbidities such as metabolic disorders, cardiovascular diseases, and cancer. Clostridium butyricum is a human butyrate-producing symbiont present in the gut microbiome. Convergent evidence has demonstrated favorable effects of C. butyricum for gastrointestinal health, including maintenance of the structural and functional integrity of the gut barrier, inhibition of pathogenic bacteria within the intestine, and reduction of microbial translocation. Moreover, C. butyricum supplementation has been observed to have a positive effect on various inflammation-related diseases such as diabetes, ulcerative colitis, and cancer, which are also recognized as non-AIDS comorbidities associated with epithelial gut damage. There is currently scant published research in the literature, focusing on the influence of C. butyricum in the gut of PLWH. In this hypothesis review, we speculate the use of C. butyricum as a probiotic oral supplementation may well emerge as a potential future synergistic adjunctive strategy in PLWH, in tandem with ART, to restore and consolidate intestinal barrier integrity, repair the leaky gut, prevent microbial translocation from the gut, and reduce both gut and systemic inflammation, with the ultimate objective of decreasing the risk for development of non-AIDS comorbidities in PLWH.

Efficacy of Lamivudine and Dolutegravir simplification therapy compared with triple therapy in Northeast Brazil (LAMDO Study)

Background: Modern antiretroviral therapy provides numerous effective and well-tolerated treatment options for individuals living with HIV. However, due to medication tolerability, toxicity, and cost optimization associated with the emergence of highly potent drugs, dual therapy has emerged as a new therapeutic alternative for patients with viral suppression. Observational studies worldwide are being conducted to assess the effectiveness of dual therapy in people living with HIV/AIDS. A real-world study is important to validate the findings obtained in controlled studies. Objective: Assess the effectiveness of dual therapy with lamivudine and dolutegravir compared to triple therapy in real-life settings. Methods: The study was conducted at São José Infectious Diseases Hospital, a tertiary referral hospital in the state of Ceará, northeast Brazil, for the treatment of PLWHA. Results: A total of 521 patients were taking double therapy with lamivudine plus dolutegravir and 450 patients were in triple therapy, mostly in the use of association with dolutegravir, were analyzed. Patients on dual therapy had a higher median age compared to those on triple therapy. A statistically significant higher viral suppression was observed in patients on dual therapy compared to triple therapy (p &lt; 0,001). Viral suppression on dual therapy under 200 copies was 97.2%. There was a statistically significant higher percentage of patients with higher CD4/CD8 ratio using triple therapy compared to dual therapy. Conclusion: The current study suggests a higher effective response to dual therapy compared to triple therapy in PLWHA in the real-world, supporting therapy simplification as a sustainable option to maintain virological suppression in patients experiencing toxicity or comorbidities.

Demographic and clinical characteristics of HIV-infected patients in Ekaterinburg

Aim. To study the demographic and clinical characteristics of patients with HIV infection during registration in the period from 2016 to 2020 in the city of Ekaterinburg.Materials and methods. The study was conducted on the basis of the Sverdlovsk Regional Center for the Prevention and Control of AIDS, Ekaterinburg. The data of 4222 patients with HIV infection registered in the period from 2016 to 2020 were analyzed retrospectively.Results and discussion. This study included a large number of patients with HIV infection registered for 5 years, which made it possible to comprehensively assess the portrait of a patient with HIV infection at the present stage, reflecting the demographic and clinical parameters of the cohort. A downward trend in the detection of HIV infection from 2016 to 2020 was noted; reducing the time from the detection of HIV infection to the start of dispensary observation and the appointment of antiretroviral therapy (ART); increase in the proportion of patients of older age groups. The maximum terms of registration were noted in the group of injecting drug users. The proportion of patients with comorbidities is 75–86%, which requires expanding the possibilities for choosing an ART regimen. Most of naïve patients receive «non-nucleoside reverse transcriptase inhibitor (NNRTI) and two nucleoside reverse transcriptase inhibitors (NIOT)» and «protease inhibitor (PI) and two NIOT», as a first line treatment, integrase inhibitors account for 6.9%.Conclusion. Despite the positive dynamics of indicators regarding the start of medical examination and treatment of patients with HIV infection in the period from 2016 to 2020, in order to reduce the time for involving patients, additional research and subsequent interventions are required in the identified gender, age and clinical risk groups, as well as ensuring accessibility modern ART and an increase in the proportion of fixed combinations of ARV drugs in it. The increase in the average age of patients, high polypharmacy and the need to reduce the risk of possible drug interactions argue in favor of the need to increase the proportion of integrase inhibitors.In order to determine the patient’s responsibility for monitoring and treating their disease, the Federal Law of March 30, 1995 No. 38-FL «On the Prevention of the Spread in the Russian Federation of a Disease Caused by the Human Immunodeficiency Virus (HIV)» needs to be brought into line with the Federal Law dated November 21, 2011 No. 323-FL «On the fundamentals of the health of citizens in the Russian Federation».

Aspergillus Tracheobronchitis With Mediastinal Lymphadenopathy in a Patient With Well‐Controlled HIV Infection

Background: Aspergillus tracheobronchitis (AT) is an uncommon yet severe form of invasive pulmonary aspergillosis, with a notably low incidence among individuals living with HIV infection—accounting for merely 4.5% (7 out of 156 cases) in recent reviews. The advent of modern antiretroviral therapy (ART) has significantly altered the landscape of opportunistic infections in HIV, rendering conditions like AT rare in well‐controlled cases.Case Presentation: We present the case of a woman in her mid‐20s with well‐managed HIV infection who experienced a 4‐week history of fever and dyspnea. Diagnostic procedures, including bronchoscopy, revealed granulation tissue obstructing her right main bronchus. Cultures confirmed infection with Aspergillus fumigatus, leading to a diagnosis of AT. Despite initial positive response to voriconazole treatment, the patient developed severe hemoptysis and unfortunately succumbed to the complication.Conclusion: This case underscores the critical need for healthcare providers to consider AT in the differential diagnosis of respiratory symptoms in HIV‐positive patients, even when HIV is well‐controlled with ART. Early recognition and prompt antifungal therapy are essential for improving outcomes. Clinicians should remain vigilant for severe complications like hemoptysis, which can occur despite appropriate therapy. This report highlights the ongoing necessity for vigilance and proactive intervention in the care of individuals living with HIV.

Alzheimer’s pathology in older people with HIV in South Africa: protocol of a case‐control study examining mechanisms of inflammation and infection

AbstractBackgroundDue to the success of modern antiretroviral therapy, people with HIV in South Africa are now living into older age. This provides an opportunity to study Alzheimer’s pathology in the context of chronic inflammation and infection. Here we present the protocol of a large case‐control study examining Alzheimer’s pathogenesis.Method250 South African people over 70 years of age will be recruited from a low‐income area of Cape Town with high HIV prevalence. Half will be living with HIV and half will be HIV‐negative and sociodemographically similar. Our primary outcome is CSF biomarkers of amyloidopathy. We have power to detect a 1.5‐fold increase in CSF amyloid positivity from 40% to 60%. Secondary analyses will compare clinical diagnoses of Alzheimer’s disease, and correlate indicators of HIV‐related neuroinflammation with degree of amyloidopathy.ResultProtocol presentation only. Funding is from the Race Against Dementia.ConclusionThis unique cohort will provide a valuable resource for mechanistic studies of Alzheimer’s pathogenesis.

Survival and prognostic factors of progressive multifocal leukoencephalopathy in people living with HIV in modern ART era.

The incidence of progressive multifocal leukoencephalopathy (PML) in people living with HIV (PLWH) is 2%-4%. Currently, there is no effective therapeutic strategy for the treatment of PML in PLWH, resulting in a mortality of up to 50%. This study aimed to identify risk factors of death and prognostic markers in people living with HIV with PML. A retrospective cohort study of AIDS-related PML individuals was conducted from January 1, 2015, to October 1, 2022, in Shanghai, China. PLWH who were diagnosed with PML for the first time were included. Kaplan-Meier curve and Cox regression were used to analyze the survival and its predictors. Levels of inflammatory markers and immune checkpoint inhibitors in blood and cerebrospinal fluid (CSF) were measured in the prestored samples using bead-based multiplex assay Indolamine 2,3-dioxygenase was determined using ELISA. Twenty of 71 subjects had initiated antiretroviral therapy (ART) before PML onset and no patients discontinued ART during this period. In total, 34 patients (47.9%) had opportunistic infections (OIs), the median CD4+ T cell count was 73.0 (33.0-149.0) cells/μL. The estimated probability of survival at six months was 78% (95% confidential intervals [CIs]:0.63-0.85). OIs, low CD4+ T cell count were associated with lower estimated six-month survival (hazard ratio 8.01, 95% CIs: 1.80-35.00, P=0.006 and 5.01, 95% CIs:1.57-16.03, p=0.007). Indolamine 2,3-dioxygenase activity in CSF of non-survivors group were higher than survivors group (p<0.05). The survival rate of AIDS-related PML in the modern ART era was higher than the survival rate a decade ago. Low CD4+T cell count, OIs, were all associated with death of individuals with AIDS-related PML. The role of IDO in AIDS-related PML warrant further investigation.