Antiretroviral Research Articles

Retinal detachment and mortality in patients with cytomegalovirus retinitis: A multicenter study in taiwan.

To characterize patients with cytomegalovirus (CMV) retinitis and identify risk factors for retinal detachment (RD) and mortality in this Taiwanese patient population. This retrospective study included patients diagnosed with CMV retinitis between 2007 and 2019. The diagnosis was confirmed through aqueous polymerase chain reaction (PCR). Relevant data were collected from the Chang Gung Research Database. Univariate Cox regression was performed to identify the associations of RD and mortality risks with various patient characteristics, including demographic features, comorbidities, laboratory results, and medication use patterns. In total, 32 patients with CMV retinitis were included. Among these patients, 78.1% had an immunocompromised status, including 56.3% with high-dose systemic steroid use, 21.9% with HIV infection, 12.5% with hematologic malignancy, and 9.4% with renal transplantation. Approximately 21.9% of patients had RD 2.4 ± 2.1 months after CMV retinitis diagnosis, and 34.4% died within 6.2 [4.2, 38.2] months after diagnosis. Patients with RD had a statistically significant, but likely not clinically significant, later initiation of anti-CMV medications compared to their non-RD counterparts (8 [5, 23] days vs. 2 [1,11] days, p = 0.039). Mortality was significantly associated with older age (hazard ratio [HR]: 1.06; 95% confidence interval [CI]: 1.02-1.10), hematologic malignancy (HR: 5.92; 95% CI: 1.44-24.37), and positivity for CMV on blood PCR (HR: 4.93; 95% CI: 1.49-16.35). Our study suggests that older age, hematologic malignancy, and positivity for CMV on blood PCR are risk factors for mortality in patients with CMV retinitis. What is known Cytomegalovirus (CMV) retinitis is the predominant sight-threatening opportunistic ocular infection in patients with acquired immunodeficiency syndrome (AIDS). What is new In the era of highly active antiretroviral therapy for AIDS, the majority of CMV retinitis patients are those receiving immunomodulatory therapy for underlying diseases. Older age, hematologic malignancy, and positive blood polymerase chain reaction for CMV are potential risk factors for mortality in patients with CMV retinitis.

Experiences and challenges of nurses in initiating antiretroviral drugs among adolescents living with HIV and AIDS in Thaba-Tseka, Lesotho

Background: Lesotho has the second-highest HIV and AIDS prevalence globally and is the country’s second leading cause of death. Despite increasing ART coverage, adolescents remain left behind and face high mortality because of delayed ART initiation. This study aimed to explore the experiences and challenges of nurses when initiating adolescents living with HIV on ART in Thaba-Tseka, Lesotho. Methods: A qualitative descriptive research design and twelve in-depth interviews were conducted among nurses from a hospital in the Thaba-Tseka district. Participants were selected purposively until data saturation was reached. Data were transcribed verbatim and analysed manually using the thematic analysis approach. The findings were presented in themes and sub-themes. Individual face-to-face interviews were conducted in English and Sesotho from May to August 2021. Results: The key findings in this study involved adolescents’ attendance at the health care facility, ART initiation process, HIV stigma influencing the uptake of ART, poor ART follow-up and socio-economic factors affecting adherence to ART. Conclusion: The themes uncovered in this study provide valuable insights into the gaps in ART initiation, and highlight the challenges encountered by nurses during this process among adolescents in Lesotho. The experiences and obstacles shared by nurses during ART initiation cover a range of issues, collectively demonstrating their engagement in HIV and ART care. These findings emphasise the critical role of policymakers and health care providers in devising customised ART initiation interventions for adolescents. Addressing these challenges will be crucial for enhancing ART uptake and adherence among adolescents living with HIV in Lesotho.

Management of low-level HIV viremia during antiretroviral therapy: Delphi consensus statement and appraisal of the evidence

ObjectiveWhile antiretroviral therapy (ART) is highly effective, detection of low levels of HIV-1 RNA in plasma is common in treated individuals. Given the uncertainties on the topic, we convened a...

Alterations of the gut microbiome in HIV infection highlight human anelloviruses as potential predictors of immune recovery

BackgroundHIV-1 infection is characterized by a massive depletion of mucosal CD4 T cells that triggers a cascade of events ultimately linking gut microbial dysbiosis to HIV-1 disease progression and pathogenesis. The association between HIV infection and the enteric virome composition is less characterized, although viruses are an essential component of the gut ecosystem. Here, we performed a cross-sectional analysis of the fecal viral (eukaryotic viruses and bacteriophages) and bacterial microbiome in people with HIV (PWH) and in HIV-negative individuals. To gain further insight into the association between the gut microbiome composition, HIV-associated immunodeficiency, and immune recovery, we carried out a longitudinal study including 14 PWH who initiated antiretroviral therapy (ART) and were followed for 24 months with samplings performed at baseline (before ART) and at 2, 6, 12, and 24 months post-ART initiation.ResultsOur data revealed a striking expansion in the abundance and prevalence of several human virus genomic sequences (Anelloviridae, Adenoviridae, and Papillomaviridae) in stool samples of PWH with severe immunodeficiency (CD4 < 200). We also noted a decreased abundance of sequences belonging to two plant viruses from the Tobamovirus genus, a reduction in bacterial alpha diversity, and a decrease in Inoviridae bacteriophage sequences. Short-term ART (24 months) was linked to a significant decrease in human Anelloviridae sequences. Remarkably, the detection of Anellovirus sequences at baseline independently predicted poor immune recovery, as did low CD4 T cell counts. The bacterial and bacteriophage populations were unique to each PWH with individualized trajectories; we found no discernable pattern of clustering after 24 months on ART.ConclusionAdvanced HIV-1 infection was associated with marked alterations in the virome composition, in particular a remarkable expansion of human anelloviruses, with a gradual restoration after ART initiation. In addition to CD4 T cell counts, anellovirus sequence detection might be useful to predict and monitor immune recovery. This study confirms data on the bacteriome and expands our knowledge on the viral component of the gut microbiome in HIV-1 infection.3oR8qDfXoWY9s_P5ES648YVideo

Sweden surpasses the UNAIDS 95-95-95 target: estimating HIV-1 incidence, 2003 to 2022.

BackgroundSweden reached the UNAIDS 90-90-90 target in 2015. It is important to reassess the HIV epidemiological situation due to ever-changing migration patterns, the roll-out of PrEP and the impact of the COVID-19 pandemic.AimWe aimed to assess the progress towards the UNAIDS 95-95-95 targets in Sweden by estimating the proportion of undiagnosed people with HIV (PWHIV) and HIV incidence trends.MethodsWe used routine laboratory data to inform a biomarker model of time since infection. When available, we used previous negative test dates, arrival dates for PWHIV from abroad and transmission modes to inform our incidence model. We also used data collected from the Swedish InfCareHIV register on antiretroviral therapy (ART).ResultsThe yearly incidence of HIV in Sweden decreased after 2014. In part, this was because the fraction of undiagnosed PWHIV had decreased almost twofold since 2006. After 2015, three of four PWHIV in Sweden were diagnosed within 1.9 and 3.2 years after infection among men who have sex with men and in heterosexual groups, respectively. While 80% of new PWHIV in Sweden acquired HIV before immigration, they make up 50% of the current PWHIV in Sweden. By 2022, 96% of all PWHIV in Sweden had been diagnosed, and 99% of them were on ART, with 98% virally suppressed.ConclusionsBy 2022, about half of all PWHIV in Sweden acquired HIV abroad. Using our new biomarker model, we assess that Sweden has reached the UNAIDS goal at 96-99-98.

MASLD in persons with HIV is associated with high cardiometabolic risk as evidenced by altered advanced lipoprotein profiles and targeted metabolomics

BackgroundMetabolic dysfunction associated steatotic liver disease (MASLD) is associated with increased cardiovascular disease (CVD) risk in persons with HIV (PWH). The lipidomic and metabolomic alterations contributing to this risk are poorly understood. We aimed to characterize the advanced lipoprotein and targeted metabolomic profiles in PWH and assess if the presence and severity of MASLD influence these profiles.MethodsThis is a cross-sectional analysis of a prospectively enrolled multicenter cohort. PWH without alcohol abuse or known liver disease underwent vibration-controlled transient elastography for controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). Lipidomic and metabolomic profiling was undertaken with nuclear magnetic resonance (NMR) spectroscopy. Hepatic steatosis was defined as CAP ≥ 263 dB/m and clinically significant fibrosis (CSF) as LSM ≥ 8 kPa. Logistic regression models assessed associations between MASLD, CSF and lipidomic and metabolic parameters.ResultsOf 190 participants (71% cisgender male, 96% on antiretroviral therapy), 58% had MASLD and 12% CSF. Mean (SD) age was 48.9 (12.1) years and body mass index (BMI) 29.9 (6.4) kg/m2. Compared to PWH without MASLD (controls), PWH with MASLD had lower HDL-C but higher total triglyceride, VLDL-C, branched-chain amino acids, GlycA, trimethylamine N-oxide levels, Lipoprotein-Insulin Resistance and Diabetes Risk Indices. There were no significant differences in these parameters between participants with MASLD with or without CSF. In a multivariable regression analysis, MASLD was independently associated with changes in most of these parameters after adjustment for age, gender, race/ethnicity, type 2 diabetes mellitus, BMI, and lipid lowering medications use.ConclusionsMASLD in PWH is independently associated with altered advanced lipoprotein and targeted metabolic profiles, indicating a higher CVD risk in this population.

Antiretroviral Therapy with Ritonavir-Boosted Atazanavir- and Lopinavir-Containing Regimens Correlates with Diminished HIV-1 Neutralization.

The impact of virion maturation on neutralizing antibody responses in HIV treatment is not fully understood. This study examines whether antiretroviral regimens (ART) with boosted protease inhibitors (b-PI), which increase exposure to immature virions, affect neutralization capacity compared to Non-b-PI regimens. Neutralization activity was assessed in 45 HIV-infected individuals on b-PI regimens and 56 on Non-b-PI regimens, adjusting for factors like infection duration, ART initiation, and immune markers. Individuals on b-PI regimens had significantly lower neutralization scores [mean: 6.1, 95% Confidence Interval (CI): 5.3-6.9] than those on Non-b-PI regimens (mean: 8.9, 95% CI: 8.0-9.9; p < 0.0001). This difference was not explained by infection duration or CD4+ counts. CD4+/CD8+ ratios were positively associated with neutralization, while b-PI use was negatively associated. A regression model indicated that b-PI use significantly predicted lower neutralization scores (beta = -0.30, p = 0.049). These findings suggest that exposure to immature virions via b-PI use reduces neutralizing antibody responses, highlighting the importance of virion maturation in antibody induction. ART regimens promoting exposure to mature virions may enhance neutralization, with potential implications for HIV vaccine design. Further research is needed to explore implications for HIV vaccine design, especially using virus-like particles.

Expanding Treatment Opportunities: Reviewing the Current State of Injectable Antiretrovirals for Treatment of HIV.

Antiretroviral therapy has evolved significantly over the last 20-30years, from requiring multiple tablets multiple times per day to single-tablet regimens and most recently, in 2021, long-acting injectable antiretrovirals. These long-acting antiretrovirals have expanded the treatment options for individuals with HIV who may have difficulty adhering to daily oral medications, difficulty taking oral medications, and/or individuals with multidrug-resistant HIV. This article reviews the currently available long-acting injectable antiretrovirals, including cabotegravir/rilpivirine, lenacapavir, and ibalizumab. The available data supporting these agents and current place in therapy will be discussed. Data supporting the use of additional long-acting injectable agents, broadly neutralizing antibodies, currently in the pipeline will be reviewed as well.

Stigma, support, and messaging for people recently diagnosed with HIV: a qualitative study.

Background Despite advances in antiretroviral treatment and the message of undetectable equals untransmittable (U=U), there remain challenges related to stigma and quality of life for people living with HIV. This study aimed to understand the experiences of people recently diagnosed with HIV at a clinical service, to guide insights into how to improve care and support in the contemporary treatment era. Methods This qualitative study involved semi-structured interviews with individuals diagnosed with HIV between 2016 and 2021 at RPA Sexual Health service (a sexual health clinic in Sydney, Australia), or who were referred to the clinic directly after diagnosis. Participants were recruited through a short survey questionnaire between May 2022 and May 2023, and interviews were transcribed and analysed thematically. Results Fourteen participants were interviewed for the study, eight of whom were born outside of Australian or Aotearoa New Zealand. We found that diagnosis was still a shocking event requiring careful support; that there was ongoing stigma, shame, and reduced sexual confidence following diagnosis; and that beyond initial diagnosis, some people would benefit from ongoing support and education about key concepts regarding HIV treatment. Conclusion Our study suggests that HIV diagnosis remains disruptive, and sexual stigma is a key issue negatively impacting quality of life. Health providers can mitigate these issues by supporting the ongoing psychosocial needs of people with HIV in the early period of adjusting to HIV diagnosis, and referring to peer-based and other services. Initiating conversations about sex and dating and checking understandings of key health messages over time may promote improved care.

A Prospective Study of the Medication Regimen Complexity Index and Hospitalization Due to Adverse Drug Reactions Among People Living with HIV.

Background and Objective: The complexity of antiretroviral therapy (ART) regimens in people living with HIV (PLHIV) poses significant challenges for medication management, impacting adherence and overall health outcomes. The Medication Regimen Complexity Index (MRCI) is a tool that quantifies regimen complexity, yet its correlation with hospitalization rates and adverse drug reactions (ADRs) in PLHIV remains underexplored. Materials and Methods: This prospective study, which was conducted at a government-funded antiretroviral treatment center, investigated the relationships among MRCI scores, hospitalization due to ADRs, and the ADR rates in 285 PLHIV participants over 18 months. Results: The study revealed a significant association between higher baseline MRCI scores and hospitalization due to ADRs, with a threshold MRCI score of 8 indicating increased risk. There was no significant association between average MRCI scores and overall ADR rates or non-ADR-related hospitalizations. Conclusions: These findings emphasize the importance of monitoring medication regimen complexity in PLHIV, particularly in the context of preventing hospitalizations related to ADRs. Further research is needed to understand the multifactorial influences on ADR occurrence and to optimize ART regimens for better patient outcomes.

Transmitted drug resistance and molecular transmission network among treatment-naive HIV-1 patients in Wenzhou, China, 2020–2023

BackgroundTransmitted drug resistance (TDR) increases the risk of antiretroviral therapy (ART) failure in HIV-1 patients. This study investigated the molecular epidemiology of TDR and its transmission networks among newly diagnosed HIV-1 patients in Wenzhou, China.MethodsWe enrolled 1878 ART-naive HIV-1 patients from January 2020 to October 2023. TDR was evaluated using the Stanford University HIV Drug Resistance Database. We performed phylogenetic analysis, genotyping, transmission clustering, and population-based TDR-related factor analysis.ResultsAmong 1782 patients with successful genotyping, TDR prevalence was 5.7%. Multivariable analysis identified CRF08_BC subtype (adjusted odds ratio [aOR] 18.59, 95% CI 3.79-336.18, p = 0.004), CD4 > 500 cells/mm³ (aOR 2.19, 95% CI 1.16–4.03, p = 0.013), and year 2023 (aOR 1.83, 95% CI 1.11–4.89, p = 0.039) as factors associated with higher TDR risk. The most prevalent NNRTI mutations were K103N, E138A, and V179E. Seven TDR transmission clusters were identified, notably one with V179D that expanded during 2020–2023.ConclusionsWhile TDR prevalence in Wenzhou remained lower than in other Chinese regions, an upward trend was observed. Most resistant individuals were in transmission clusters, predominantly middle-aged and elderly. NNRTI resistance was severe and concentrated in efavirenz, nevirapine, and rilpivirine. Enhanced HIV surveillance and wider free antiretroviral options are crucial to control drug-resistant HIV spread in Wenzhou.

HIV-Associated Neurocognitive Disorder (HAND) and Alzheimer's Disease Pathogenesis: Future Directions for Diagnosis and Treatment.

HIV-associated neurocognitive disorder (HAND) and Alzheimer's disease (AD) are two neurocognitive disorders with overlapping clinical presentations and pathophysiology. The two have been thought to be two separate entities. However, the introduction and widespread use of antiretroviral therapy (ART) has altered the clinical manifestations of HAND, shifting from a pattern of subcortical dementia to one more akin to cortical dementia, resembling AD. Thus, the line between the two disease entities is not clear-cut. In this review, we discuss the concept of Alzheimer's disease-like dementia (ADLD) in HIV, which describes this phenomenon. While the mechanisms of HIV-associated ADLD remain to be elucidated, potential mechanisms include HIV-specific pathways, including epigenetic imprinting from initial viral infection, persistent and low viral load (which can only be detected by ultra-sensitive PCR), HIV-related inflammation, and putative pathways underlying traditional AD risk factors. Importantly, we have shown that HIV-specific microRNAs (miRs) encapsulated in extracellular vesicles (EV-miRs) play an important role in mediating the detrimental effects in the cardiovascular system. A useful preclinical model to study ADLD would be to expose AD mice to HIV-positive EVs to identify candidate EV-miRs that mediate the HIV-specific effects underlying ADLD. Characterization of the candidate EV-miRs may provide novel therapeutic armamentaria for ADLD.

Epidemiologic characteristics of people living with human immunodeficiency virus in South Korea: a nationwide cohort study

Recent information regarding the characteristics of people living with human immunodeficiency virus (HIV) (PLWH) is lacking. Therefore, we examined the incidence of HIV infection and epidemiologic characteristics of PLWH in South Korea using recent National Health Insurance Service database data. The HIV infection rate was 4.13 per 100,000 in 2017, 4.19 per 100,000 in 2018, 6.61 per 100,000 in 2019, 5.98 per 100,000 in 2020, 8.81 per 100,000 in 2021, and 4.14 per 100,000 in 2022. In 2016, the mean age of PLWH was 45.7 years (SD: 13.8 years), and it gradually increased to 49.0 years (standard deviation: 13.7 years) in 2022 over 7 years in South Korea. The proportion of male individuals among PLWH was 90.7% (19,970/22,026) in 2016, and it gradually increased to 92.3% (22,943/24,857) in 2022 over 7 years in South Korea. The proportion of anti-retroviral therapy (ART) users among PLWH in South Korea was 92.6% (20,388/22,026) in 2016, and it gradually increased to 97.9% (24,328/24,857) in 2022 over 7 years. In this population-based cohort analysis, we presented the HIV infection incidence and epidemiologic features of PLWH in South Korea. This study’s results may influence future infection prevention strategies and policies for PLWH.

Long-Term Follow-Up of Persons Living with Perinatally Acquired HIV Infection at a Large HIV Treatment Clinic in Trinidad.

Data on persons with perinatally acquired HIV infection in the Caribbean are limited; thus, a chart review was conducted among these clients at an adult HIV treatment clinic in Trinidad over the period January 01, 2011-June 30, 2023. Sociodemographic, clinical, and laboratory data were extracted and analyzed using RStudio version 2021.09.0. Fifty-four study participants were followed up, age range 18-29 years, and there were 27 (50%) males. Eighteen participants (33.3%) were institutionalized until the age of 18 years, while 36 (66.7%) lived with caregivers/relatives and attended outpatient pediatric clinic. The transition from the sheltered environment of pediatric care to the adult HIV clinic was turbulent for some participants as they experienced HIV-related stigma, which may result in poor HIV outcomes. At the initial clinic visit, 28 (51.9%) study participants were virally suppressed (HIV viral load <1,000 copies/mL), which included 12 (66.7%) of 18 who were institutionalized as compared to 16 (44.4%) of 38 who lived with caregivers/relatives (p = 0.387). Data from their last clinic visit showed 31 (57.4%) participants were virally suppressed; 13 (24.1%) were lost to follow-up from care, and there were 6 (11.1%) deaths; 29 (53.7%) were on antiretroviral therapy single-tablet regimens (STRs) and 25 (46.3%) on complex multiple-tablet regimens (MTRs). Institutionalized clients and those on STRs were more likely to be virally suppressed than those living with relatives (p = 0.043) and those on MTR (p < 0.001), respectively. Reported deaths were higher among clients who lived with caregivers/relatives and those on MTR. Participants of younger age were less likely to achieve viral suppression (p = 0.02). Comprehensive programs that include STRs, the engagement of caregivers/relatives and health workers, life skills, and enhanced psychosocial interventions for youths living with perinatally acquired HIV are important to support the transition to adult care and reduce the complex challenges of living with a stigmatizing disease.

Susceptibility of HPV-18 Cancer Cells to HIV Protease Inhibitors.

Cervical cancer cases continue to rise despite all the advanced screening and preventative measures put in place, which include human papillomavirus (HPV) vaccination. These soaring numbers can be attributed to the lack of effective anticancer drugs against cervical cancer; thus, repurposing the human immunodeficiency virus protease inhibitors is an attractive innovation. Therefore, this work was aimed at evaluating the potential anticancer activities of HIV-PIs against cervical cancer cells. The MTT viability assay was used to evaluate the effect of HIV protease inhibitors on the viability of cervical cancer cells (HeLa) and non-cancerous cells (HEK-293). Further confirmation of the MTT assay was performed by confirming the IC50s of these HIV protease inhibitors on cervical cancer cells and non-cancerous cells using the Muse™ Count and Viability assay. To confirm the mode of death induced by HIV protease inhibitors in the HPV-associated cervical cancer cell line, apoptosis was performed using Annexin V assay. In addition, the Muse™ Cell Cycle assay was used to check whether the HIV protease inhibitors promote or halt cell cycle progression in cervical cancer cells. HIV protease inhibitors did not affect the viability of non-cancerous cells (HEK-293), but they decreased the viability of HeLa cervical cancer cells in a dose-dependent manner. HIV protease inhibitors induced apoptosis in HPV-related cervical cancer cells. Furthermore, they also induced cell cycle arrest, thus halting cell cycle progression. Therefore, the use of HIV drugs, particularly HIV-1 protease inhibitors, as potential cancer therapeutics represents a promising strategy. This is supported by our study demonstrating their anticancer properties, notably in HPV-associated cervical cancer cell line.

Trends in viral load suppression among HIV patients on antiretroviral therapy (ART) at Asante Mampong Municipal Hospital, Ghana: 2019–2023

BackgroundThe Joint United Nations Programme on Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) (UNAIDS) aims to eradicate AIDS by 2030 through 95:95:95 targets: identifying 95% of persons living with HIV (PLHIV), initiating 95% of those identified on antiretroviral therapy (ART), and ensuring that 95% of those initiated on ART are virally suppressed. Virally suppressed patients pose minimal risk of HIV transmission. ART aims to suppress the HIV-viral load (VL) and increase immunity, reducing morbidity and mortality. This study aimed to determine the trends in VL suppression among HIV patients on ART from 2019 to 2023 at Asante Mampong Municipal Hospital.MethodsThis study adopted a retrospective Hospital-based design in which secondary data from 842 patients on ART from 2019 to 2023 were used. The study design specifically involved conducting serial cross-sectional studies to measure the prevalence of VL suppression each year from 2019 to 2023. This approach allowed the researchers to analyse the annual prevalence of VL suppression among study participants without following individual participants longitudinally throughout the entire period. The data were analysed via STATA version 17.0. Chi-square and logistic regressions were used to determine the associations between VL suppression and the independent variables at p < 0.05 and 95% confidence intervals (CIs).ResultsIn 2019, VL suppression was 79.6%, decreasing to 40.0% in 2020 and then rising to 82.7% in 2021, dropping to 67.8% in 2022 and 66.7% in the first quarter of 2023. Clients aged 40–49, 50–59, and 60–69 years were more likely to have VL suppression [aOR = 4.4 (1.36–14.25), p = 0.013], [aOR = 5.5 (1.65–18.39), p = 0.006] and [aOR = 5.0 (1.42–17.46), p = 0.012], respectively. Clients who were consistently on the same type of ART for more than a year were more likely to have VL suppression [aOR = 10.6 (4.18–26.76), p < 0.001].ConclusionVL suppression was low among patients. Advanced age and being on the same ART for more than 12 months were significantly associated with VL suppression. Health promotion activities are needed for people who have been suppressed to maintain and achieve a lifetime undetectable VL, targeting the younger age group.

Efficacy and Safety of Dolutegravir Plus Emtricitabine Versus Combined Antiretroviral Therapy for the Maintenance of HIV Suppression: Results Through Week 144 of the SIMPL’HIV Trial

Abstract The SIMPL’HIV study investigated whether switching to DTG+FTC was noninferior to continuing cART for maintaining HIV-1 suppression at 144 weeks. The study demonstrated that viral suppression, CD4 gains, adverse events, quality of life, and patient satisfaction were comparable between groups, confirming DTG+FTC's safety and efficacy for long-term management of HIV-1 infection. Clinical Trials Registration NCT03160105.

The Autonomic Nervous System (ANS)-Immune Network in People Living With HIV.

Pre-clinical studies have demonstrated direct influences of the sympathetic and vagal/parasympathetic branches of the autonomic nervous system (ANS) on the immune system. The relevance of these pathways to the development of inflammatory disorders in humans remains unknown. We hypothesized that a comprehensive examination of the ANS-immune network in patients with HIV, would reveal that the type and severity of autonomic neuropathy (AN) would predict immune phenotypes with distinct clinical and demographic characteristics. This is a cross-sectional study of 79 adult people with a history of well-controlled HIV on stable combination antiretroviral treatment (CART) recruited from a primary care clinic network within the Mount Sinai Health System in New York City. All participants underwent a standardized battery of autonomic function tests summarized as the Composite Autonomic Severity Score (CASS) and vagal and adrenergic baroreflex sensitivity (BRS-V and BRS-A). Immune profiling included: 1) measurement of interleukin-6 (IL-6) as part of the Olink assay Target 96 Inflammation Panel, 2) non-negative matrix factorization (NMF) clustering analyses on Olink immune biomarkers, and 3) mass cytometry (CyTOF) on a subset of participants with and without autonomic neuropathy (N = 10). Reduced activity of caudal vagal circuitry involved in the cholinergic anti-inflammatory pathway (CAP) predicted higher levels of IL-6 (Spearman's rho = -0.352, p=0.002). The comprehensive assessment of the ANS-immune network showed four immunotypes defined by NMF analyses. A pro-inflammatory immunotype defined by elevations in type 1 cytokines (IL-6, IL-17) and increased numbers of CD8+ T-cells was associated with autonomic neuropathy (AN). This association was driven by deficits in the cardiovascular sympathetic nervous system and remained strongly significant after controlling for the older age and greater burden of co-morbid illness among participants with this immunotype (aOR=4.7, p=0.017). Our results provide novel support for the clinical relevance of the CAP in patients with chronic inflammatory AN. These data also provide insight regarding the role of the sympathetic nervous system and aging in the progression and development of co-morbidities in patients with chronic HIV and support future research aimed at developing therapies focused on modulation of the sympathetic and parasympathetic/vagal nervous system.

Abnormal spirometric patterns and respiratory symptoms in HIV patients with no recent pulmonary infection in a periurban hospital in Ghana.

Human immunodeficiency virus (HIV) infection is associated with chronic airway obstruction, even in patients who have achieved viral suppression from combination antiretroviral treatment (cART). Spirometry is a supplementary test that aids in diagnosing pulmonary dysfunction in people living with HIV. To compare the prevalence of spirometric abnormalities among cART-treated HIV patients and cART-naïve HIV patients with non-HIV controls with no recent history of pulmonary infection in a peri-urban hospital in Ghana. In a case-control design, spirometry was performed in 158 cART-treated HIV patients, 150 cART-naïve HIV patients and 156 non-HIV controls. Clinical, sociodemographic data and respiratory symptoms were collected using a structured questionnaire. Spirometric abnormalities were categorised as obstructive (OSP) or restrictive (RSP) spirometric patterns based on the Cameroonian reference equation. The prevalence of OSP was higher in the cART-treated and cART-naïve HIV patients compared to non-HIV controls (13.9% vs 10.7% vs 5.1% respectively, p = 0.026), whereas that of RSP was similar among the study groups. Respiratory symptoms were common among cART-treated and cART-naïve HIV patients compared to non-HIV controls (48.1% vs 40% vs 19.2% respectively, p < 0.001). The major factors associated with OSP were female gender [OR (95% CI) = 2.46 (1.09-5.13), p = 0.031], former cigarette smoking [1.92 (1.04-3.89), p < 0.001], exposure to medium-to-high levels of biomass [3.07 (1.16-8.73), p = 0.019], presence of a respiratory symptom [1.89 (1.11-5.08), p = 0.029] and unemployment [3.26 (1.19-8.95), p = 0.042]. The major determinants of RSP were age, female gender [1.74 (1.05-4.29), p = 0.041], former cigarette smoking [2.31 (1.27-6.77), p < 0.001] and medium-to-high biomass exposure [1.58 (1.06-5.37), p = 0.043]. In HIV patients without any recent pulmonary infection in a peri-urban area of Ghana, there was a higher prevalence of OSP among cART-treated and cART naïve HIV patients compared to the non-HIV control. However, the prevalence of RSP was similar among HIV patients and non-HIV controls.

Relationship between social capital and post-partum antiretroviral therapy adherence among women living with HIV in the Eastern Cape, South Africa

Background: Adherence to antiretroviral therapy (ART) is crucial for preventing vertical transmission of HIV and maternal deaths. While the literature is replete with studies on ART adherence, the role of social capital in adherence to ART is less studied. Drawing from the social cognitive theory, this study examines the relationship between social capital and post-partum adherence to ART. Methods: We analysed data from 481 post-partum women with HIV in the Eastern Cape, South Africa. Adherence to ART was measured using a validated scale, capturing self-reported medication-taking behaviours. Social capital was assessed using a pre-validated tool, encompassing indicators of social engagement, support networks and community connectedness. We used logistic regression models to examine social capital and ART adherence associations, while controlling for relevant covariates. Results: Participants mean age was 32.9 (SD ± 5.76) years. After adjusting for age, education level, alcohol use, status disclosure to partner, marital status, desire for more children, employment status and living arrangements, social capital was significantly associated with higher odds of ART adherence (p = 0.004, AOR 1.09; 95% CI 1.03–1.16). Conclusion: We found evidence in support of the role of social capital in ART adherence. Strengthening social support networks and addressing psychosocial factors could improve adherence to ART. As such, policymakers and programme managers should consider the role of social capital in designing interventions to improve ART adherence. Future research should explore the mechanisms through which social capital impacts ART adherence.