ART-treated Patients Research Articles

Defective HIV-1 DNA pol sequences are not associated with HIV-1 DNA levels and drive most APOBEC-context drug resistance mutations.

The specificity of HIV-1 DNA genotypic resistance tests (GRTs) is hampered by the detection of the APOBEC-context drug resistance mutations (AC DRMs), usually harboured by replication-incompetent proviruses. We sought factors associated with defective sequences in the HIV-1 pol region. In addition, AC DRMs and their link with defective sequences were investigated. We included ART-treated patients with viral suppression or plasma viral load (VL) lower than 200 copies/mL, who underwent HIV-1 DNA genotyping, with successful sequencing of protease (PR), reverse transcriptase (RT) and integrase (IN) regions. Sequencing was performed using either the Sanger method or the Sentosa® NGS approach with a 20% cut-off. All hypermutated sequences and/or those containing at least one stop codon were considered defective. A total of 613 HIV-1 DNA GRTs were analysed. Defective sequences were identified for 186 samples (30.3%) including 65 PR sequences, 92 RT sequences and 65 IN sequences. No association, including HIV-1 DNA levels, was found with the detection of defective pol sequences. A total of 226 AC DRMs were recorded in all sequences. Most of these mutations (78%) were harboured by defective sequences. AC DRMs did not emerge in the plasma viral population, and likely do not impact the virological response to ART. Defectives pol sequences were not associated with HIV-1 DNA levels and harboured most of the AC DRMs. Such mutations likely have no clinical impact, and should not be reported in routine practice. Consensus guidelines for reporting HIV-1 DNA GRTs are needed, especially for the assessment and management of AC DRMs.

Prevalence of intestinal parasites and associated factors among patients with HIV/AIDS at the anti-retroviral treatment clinic of Mizan-Tepi University Teaching Hospital, Southwest Ethiopia.

Intestinal parasitic infections remain very common, particularly in areas with a high prevalence of immune-compromised patients, such as HIV/AIDS patients. The purpose of this study was to determine the prevalence of intestinal parasites and associated factors in people living with HIV/AIDS at an ART clinic in Mizan-Tepi University Teaching Hospital, southwest Ethiopia. A cross-sectional survey was conducted from July to September 2021. A total of 191 adult people living with HIV/AIDS participated in this study. Data on socio-demographic, clinical, and other risk factors were collected using a structured questionnaire. Stool samples were collected and processed using a direct wet mount, formol-ether concentration, and modified Ziehl-Nelson staining techniques. The data were analyzed using the Statistical Package for Social Sciences Version 25 software. Among 67 adult individuals living with HIV/AIDS, the prevalence of intestinal parasites was 35.1%. Specifically, 31.5% (45/143) of patients on antiretroviral therapy (ART) and 45.8% (22/48) of ART-naïve patients were infected. The distribution of intestinal parasites was as follows: protozoa were found in 14.7% of ART-treated patients and 22.9% of ART-naïve patients; helminths in 15.4% of ART-treated patients and 16.7% of ART-naïve patients; and opportunistic parasites in 1.4% of ART-treated patients and 6.25% of ART-naïve patients. Significant associations with a higher prevalence of intestinal parasites were observed for a CD4 count <200 cells/mm3 (Adjusted Odds Ratio [AOR] = 3.77; 95% Confidence Interval [CI]: 1.01-13.15; p = 0.04), consumption of unwashed raw vegetables (AOR = 3.29; 95% CI: 1.23-8.86; p = 0.02), and residing in rural areas (AOR = 2.34; 95% CI: 1.27-4.32; p = 0.01). The findings indicate that a significant proportion of adults living with HIV/AIDS are affected by intestinal parasites, with a notably higher prevalence among ART-naïve patients compared to those on ART. Factors such as a low CD4 count, consumption of unwashed raw vegetables, and rural residence are associated with increased risk of intestinal parasite infections. These results underscore the importance of improving hygiene practices and access to healthcare, particularly in rural areas, to reduce the burden of parasitic infections among individuals living with HIV/AIDS.

Predicting adjuvant radiation therapy benefit in cutaneous squamous cell carcinoma with the 40-gene expression profile.

Aim: To independently confirm that the 40-gene expression profile (40-GEP) test can identify patients with high-risk cutaneous squamous cell carcinoma who are more or less likely to benefit from adjuvant radiation therapy (ART).Materials & methods: Primary cutaneous squamous cell carcinoma tumors from two academic centers received retrospective 40-GEP testing and were analyzed for 5-year metastasis-free survival and projected time to event.Results: Random sampling of matched patient pairs (n=52 ART-treated; 371no ART) showed a median 50% decrease in 5-year progression rate for ART-treated patients (vs no ART) with 40-GEP Class 2B. Class 2A was associated with a modest ART benefit, but not Class 1.Conclusion: The 40-GEP identified patients most likely to benefit from ART (Class 2B) and those that can consider deferring treatment (Class 1).

HIV-Induced Thymic Insufficiency and Aging-Related Immunosenescence on Immune Reconstitution in ART-Treated Patients.

The mechanisms underlying unsatisfactory immune reconstitution in HIV-1 positive patients under ART have not been fully elucidated, even after years of investigation. Thus, this study aimed to assess the correlation between age and thymic production profile, and its influence on inadequate immunological recovery. Here, 44 ART-treated patients with undetectable plasma HIV-1 load (<40 copies/mL) were classified as 31 immunological responders (IR) and 13 immunological non-responders (INR), according to their CD4+ T-cell count after 18 months of ART. The thymic function was assessed by identifying recent thymic emigrants (RTEs) CD4+ T cells (CD4+/CD45RA+CD31+) in PBMCs using flow cytometry. Clinical data were also analyzed from medical records. The INR group showed a higher age at ART initiation (41 ± 3.0) compared to the IR (33.7 ± 2.1) group (p = 0.041). Evaluating RTE CD4+ T-cells, we observed a lower percentage in the INR group (19.5 ± 6.3) compared to the IR group (29.9 ± 11.5) (p = 0.012). There was a strong negative correlation between age at ART initiation and RTE CD4+ T-cells in INRs (r = -0.784, p = 0.004). Our study has highlighted the thymic insufficiency and aging-related immunosenescence with unsatisfactory immunological recovery during ART in HIV-1 positive patients.

Antiretroviral Therapy Suppresses RNA N6-Methyladenosine Modification in Peripheral Blood Mononuclear Cells from HIV-1-Infected Individuals.

RNA N6-methyladenosine (m6A) modification is important for regulating gene expression and innate immune responses to viral infection. HIV-1 in vitro infection induces a significant increase in m6A modification of cellular RNA; however, whether m6A levels of cellular RNA are affected by HIV-1 replication or by antiretroviral therapy (ART) in infected individuals remains unknown. Using dot blot or enzyme-linked immunosorbent assay, we measured RNA m6A levels of peripheral blood mononuclear cells (PBMCs) from healthy donors or HIV-1-infected individuals with or without ART. Using a reverse transcription-quantitative polymerase chain reaction array, we quantified expression levels of 84 type-I interferon (IFN-I)-responsive genes in PBMCs from some individuals of these three groups. RNA m6A levels in PBMCs from HIV-1 viremic patients (n = 10) were significantly higher (p ≤ .0001) compared with ART-treated individuals (n = 22) or 1.5-fold higher compared with healthy donors (n = 14). However, the increase in RNA m6A levels did not correlate with changes in the expression of 10 m6A-regulatory genes. We found significant upregulation and downregulation in the expression of several IFN-I-responsive genes from HIV-1 viremic patients (n = 4) and ART-treated patients (n = 6) compared with healthy donors (n = 5), respectively. Our results suggest that post-transcriptional m6A modification may contribute to the regulation of IFN-I-responsive gene expression during HIV-1 infection and ART.

Plasma proteomics analysis of Chinese HIV-1 infected individuals focusing on the immune and inflammatory factors afford insight into the viral control mechanism.

Long-term non-progressors (LTNPs) with HIV infection can naturally control viral replication for up to a decade without antiretroviral therapy (ART), but the underlying mechanisms of this phenomenon remain elusive. To investigate the relevant immune and inflammatory factors associated with this natural control mechanism, we collected plasma samples from 16 LTNPs, 14 untreated viral progressors (VPs), 17 successfully ART-treated patients (TPs), and 16 healthy controls (HCs). The OLINK immune response panel and inflammation panel were employed to detect critical proteins, and the plasma neutralizing activity against a global panel of pseudoviruses was assessed using TZM-bl cells. The combination of IL17C, IL18, DDX58, and NF2 contributed to discriminating LTNPs and VPs. IL18 and CCL25 were positively associated with CD4+ T cell counts but negatively correlated with viral load. Furthermore, CXCL9 and CXCL10 emerged as potential supplementary diagnostic markers for assessing the efficacy of antiretroviral therapy (ART). Finally, TNFRSF9 displayed positive correlations with neutralization breadth and Geometry Median Titer (GMT) despite the lack of significant differences between LTNPs and VPs. In summary, this study identified a set of biomarkers in HIV-infected individuals at different disease stages. These markers constitute a potential network for immune balance regulation in HIV infection, which is related to the long-term control of HIV by LTNPs. It provides important clues for further exploring the immune regulatory mechanism of HIV.

Inconsistent Associations Between Risk Factor Profiles and Adjuvant Radiation Therapy (ART) Treatment in Patients with Cutaneous Squamous Cell Carcinoma and Utility of the 40-Gene Expression Profile to Refine ART Guidance.

National Comprehensive Cancer Network (NCCN) recommendations for adjuvant radiation therapy (ART) use are similar for High Risk and Very High Risk cutaneous squamous cell carcinoma (cSCC) with negative post-surgical margins. Although studies report reductions in disease progression following ART treatment, ART use is likely inconsistent when guided by available risk factors. This study evaluated the association of ART with clinical risk factors in ART-treated and untreated patients and showed the clinical utility of the 40-gene expression profile (40-GEP) for guiding ART. A multicenter study of 954 patients was conducted with institutional review board (IRB) approval. The 40-GEP test was performed using primary tumor tissue from patients with either a minimum of 3years of follow-up or a documented regional or distant metastasis. Unsupervised hierarchical cluster analysis identified patterns of clinical risk factors for ART-treated patients, then identified untreated patients with matching risk factor profiles. Results were cross-referenced to 40-GEP test results to determine utility of the test to guide ART. Analysis demonstrated inconsistent implementation of ART for eligible patients. Cluster analysis identified four patient profiles based on clusters of risk factors and, notably, matching profiles in ART-treated and untreated patients. Further, the analysis identified patients who received but could have deferred ART on the basis of 40-GEP test result and biologically low risk of metastasis, and untreated patients who likely would have benefitted from ART on the basis of their 40-GEP test result. ART guidance is not determined by the presence of specific clinicopathologic factors, with treated and untreated patients sharing the same risk factor profiles. cSCC risk determination based on NCCN recommendations for clinical factor assessment results in inconsistent use of ART. Including tumor biology-based prognostic information from the 40-GEP refines risk and identifies patients who are most appropriate and likely to benefit from ART, and those that can consider deferring ART.

Prevalence and analysis of acquired and transmitted integrase strand transfer inhibitor-associated HIV-1 drug resistance in Chongqing, China

ABSTRACT In this study, we examined the occurrence of acquired and transmitted drug resistance to integrase strand transfer inhibitor (INSTI) in HIV-1 strains in Chongqing (China) for guiding for the routine testing of INSTI-associated HIV-1 genotype resistance. Plasma samples were obtained from HIV-1 patients at Chongqing Public Health Medical Center from July 2019 to August 2022. Besides, amplification, sequence, and analysis of the portion of the HIV-1 pol gene that encodes the integrase protein were implemented to identify INSTI resistance. Integrase sequence data was harvested for a comprehensive cohort of 1032 patients infected with HIV-1. This cohort consisted of 564 ART-naive patients, 465 ART-treated patients, and 3 patients with an unknown treatment history. Within the study group, we identified INSTI resistance in 21 patients (2.03%, 21/1032), including 17 ART-treated patients (3.66%, 17/465). Among the ART-treated patients, 12 were INSTI-treated (11.76%, 12/102), 5 were INSTI-naive (1.38%, 5/363), and 4 were ART-ineffective patients (0.71%, 4/564). The prevalent major resistance mutation was Q148R (0.48%, 5/1032), while the most prevalent accessory resistance mutation was E157Q (1.65%, 17/1032). In light of the above, it is recommended that the incidence of accessory genotype analysis should be considered before starting any future INSTI-based therapy, especially in patients with drug resistance to NRTIs and NNRTIs and the reduction of INSTI sensitivity should be carefully monitored and investigated. Regular monitoring for resistance should be implemented after the use of INSTIs, and, importantly, ongoing monitoring of the decreasing susceptibility to INSTIs is crucial following the initiation of treatment with INSTIs.

Humoral immune response to two doses of COVID-19 mRNA-based vaccines in people living with HIV: A systematic review and meta-analysis.

People living with HIV (PLWH) are susceptible to severe COVID-19 infection and hence this fragile population has prioritised vaccination. This systematic review and meta-analysis aimed to assess the humoral immune response after receiving two doses schedule of COVID-19 mRNA vaccinations in this high-risk population. A systematic electronic search on the PubMed database and manual searches were performed for relevant articles until 30 Sep 2022. Two outcomes of interest were seroconversion rates and anti-spike receptor binding domain (anti-S-RBD) antibody titres at the median time of 14-35days following two-dose vaccination among PLWH. Nineteen cohorts and one cross-sectional study were eligible for inclusion in this study. The pooled estimate of seroconversion rate after receiving two doses of mRNA vaccination schedule were 98.4% and 75.2% among PLWH with CD4>500 cells/mm3 and CD4<200 cells/mm3 , respectively. Compared with controls, PLWH with CD4>500 cells/mm3 had a 51% likelihood of having positive anti-Spike-RBD immunoglobulin G (IgG) (OR: 0.509, 95% CI: 0.228, 1.133, p=0.098) post-vaccination and this value was only 1.4% (OR: 0.014, 95% CI: 0.002, 0.078, p=0.000) for PLWH with CD4<200cells/mm3 . There was no significant difference in titres of antibodies on 14-35days post-vaccination between PLWH with CD4>500cells/mm3 and healthy controls (p=0.06). The pooled median of anti-S-RBD IgG values were 1461.93 binding antibody units (BAU)/ml and 457.41 BAU/ml in PLWH with CD4>500cells/mm3 and CD4<200cells/mm3 , respectively. According to these findings, vaccination with both Pfizer-BioNTech and Moderna vaccines induced a robust humoral response in ART-treated HIV patients with preserved CD4 cell count. A diminished humoral immune response to vaccination against COVID-19 in PLWH with unrestored CD4 count implied the need of specific vaccination schemes.

Outcomes in critically Ill HIV-infected patients between 1997 and 2020: analysis of the OUTCOMEREA multicenter cohort

PurposeDespite antiviral therapy (ART), 800,000 deaths still occur yearly and globally due to HIV infection. In parallel with the good virological control and the aging of this population, multiple comorbidities [HIV-associated-non-AIDS (HANA) conditions] may now be observed.MethodsHIV adult patients hospitalized in intensive care unit (ICU) from all the French region from university and non-university hospital who participate to the OutcomeRea™ database on a voluntary basis over a 24-year period.ResultsOf the 24,298 stays registered, 630 (2.6%) were a first ICU stay for HIV patients. Over time, the mean age and number of comorbidities (diabetes, renal and respiratory history, solid neoplasia) of patients increased. The proportion of HIV diagnosed on ICU admission decreased significantly, while the median duration of HIV disease as well as the percentage of ART-treated patients increased. The distribution of main reasons for admission remained stable over time (acute respiratory distress > shock > coma). We observed a significant drop in the rate of active opportunistic infection on admission, while the rate of active hemopathy (newly diagnosed or relapsed within the last 6 months prior to admission to ICU) qualifying for AIDS increased—nonsignificantly—with a significant increase in the anticancer chemotherapy administration in ICU. Admissions for HANA or non-HIV reasons were stable over time. In multivariate analysis, predictors of 60-day mortality were advanced age, chronic liver disease, past chemotherapy, sepsis-related organ failure assessment score > 4 at admission, hospitalization duration before ICU admission > 24 h, AIDS status, but not the period of admission.ConclusionWhereas the profile of ICU-admitted HIV patients has evolved over time (HIV better controlled but more associated comorbidities), mortality risk factors remain stable, including AIDS status.

Healthcare Resource Consumption and Related Costs in Patients on Antiretroviral Therapies: Findings from Real-World Data in Italy.

This real-world analysis conducted on administrative databases of a sample of Italian healthcare entities was aimed at describing the role of therapeutic pathways and drug utilization in terms of adherence, persistence, and therapy discontinuation in HIV-infected patients under antiretroviral therapies (ART) and Tenofovir Alafenamide (TAF)-based regimens on healthcare resource consumption and related direct healthcare costs. Between 2015 and 2019, adults (≥18 years) prescribed with TAF-based therapies were identified and characterized in the year prior to the first prescription (index-date) for TAF-based therapies and followed-up until the end of data availability. Overall, 2658 ART-treated patients were included, 1198 of which were under a TAF-based regimen. TAF-based therapies were associated with elevated percentages of adherence (83.3% patients with proportion of days covered, PDC > 95% and 90.6% with PDC > 85%) and persistence (78.5%). The discontinuation rate was low in TAF-treated patients, ranging from 3.3% in TAF-switchers to 5% in naïve. Persistent patients had lower overall mean annual healthcare expenditures (EUR 11,106 in persistent vs. EUR 12,380 in non-persistent, p = 0.005), and this trend was statistically significant also for costs related to HIV hospitalizations. These findings suggest that a better therapeutic management of HIV infection might result in positive clinical and economic outcomes.

Thymic Exhaustion and Increased Immune Activation Are the Main Mechanisms Involved in Impaired Immunological Recovery of HIV-Positive Patients under ART.

Decades of studies in antiretroviral therapy (ART) have passed, and the mechanisms that determine impaired immunological recovery in HIV-positive patients receiving ART have not been completely elucidated yet. Thus, T-lymphocytes immunophenotyping and cytokines levels were analyzed in 44 ART-treated HIV-positive patients who had a prolonged undetectable plasma viral load. The patients were classified as immunological non-responders (INR = 13) and immunological responders (IR = 31), according to their CD4+ T cell levels. Evaluating pre-CD4+ levels, we observed a statistically significant trend between lower CD4+ T cell levels and INR status (Z = 3.486, p < 0.001), and during 18 months of ART, the CD4+ T cell levels maintained statistical differences between the INR and IR groups (WTS = 37.252, p < 0.001). Furthermore, the INRs were associated with an elevated age at ART start; a lower pre-treatment CD4+ T cell count and a percentage that remained low even after 18 months of ART; lower levels of recent thymic emigrant (RTE) CD4+ T cell (CD45RA + CD31+) and a naïve CD4+ T cell (CD45RA + CD62L+); higher levels of central memory CD4+ T cells (CD45RA-CD62L+); and higher immune activation by CD4+ expressing HLA-DR+ or both (HLA-DR+ and CD38+) when compared with IRs. Our study demonstrates that thymic exhaustion and increased immune activation are two mechanisms substantially implicated in the impaired immune recovery of ART-treated HIV patients.

Non-AIDS-Defining Events in Human Immunodeficiency Virus Controllers Versus Antiretroviral Therapy-Controlled Patients: A Cohort Collaboration From the French National Agency for Research on AIDS CO21 (CODEX) and CO06 (PRIMO) Cohorts.

Low-grade chronic inflammation may persist in spontaneous human immunodeficiency virus controllers (HICs), leading to non-AIDS-defining events (nADEs). Two hundred twenty-seven antiretroviral therapy (ART)-naive HICs (known human immunodeficiency virus type 1 [HIV-1] infection ≥5 years and at least 5 consecutive viral loads [VLs] <400 HIV RNA copies/mL) were compared with 328 patients who initiated ART ≤1 month after primary HIV infection diagnosis and had undetectable VL within 12 months following ART initiation for at least 5 years. Incidence rates of first nADEs were compared between HICs and ART-treated patients. Determinants of nADEs were assessed by using Cox regression models. All-cause nADEs incidence rates were 7.8 (95% confidence interval [CI], 5.9-9.6) and 5.2 (95% CI, 3.9-6.4) per 100 person-months among HICs and ART patients, respectively (incidence rate ratio [IRR], 1.5 [95% CI, 1.1-2.2]; adjusted IRR, 1.93 [95% CI, 1.16-3.20]). After adjustment for the cohort, demographic, and immunological characteristics, the only other factor associated with all-cause nADE occurrence was age ≥43 (vs <43) years at the beginning of viral control (IRR, 1.69 [95% CI, 1.11-2.56]). The most frequent events observed in the 2 cohorts were non-AIDS-related benign infections (54.6% and 32.9% of all nADEs, respectively, for HICs and ART patients). No differences in cardiovascular or psychiatric events were observed. HICs experienced 2 times more nADEs than virologically suppressed patients on ART, mainly non-AIDS-related benign infections. Older age was associated with nADE occurrence, independent of immune or virologic parameters. These results do not argue in favor of expanding the ART indication for HICs but rather a case-by-case approach considering clinical outcomes such as nADEs besides immune activation.

Evaluating the iatrogenic effects of polypharmacy and drug interactions in HIV-positive patients admitted to the intensive care unit: a single-center retrospective study

Background. Polypharmacy and drug interactions are of particular concern in people living with HIV/AIDS, especially those who receive antiretroviral therapy (ARVs). Polypharmacy and drug-drug interactions (DDIs) can impact the efficacy and toxicity of HIV treatment. ARVs used in HIV treatment are often prone to drug interactions if administered with other non-ARV drugs because many of them are metabolized through the cytochrome P450 system. The pharmacological management of HIV patients in the intensive care unit (ICU) is usually complex and typically involves the administration of several classes of drugs. This patient group may be at higher risk for potential DDIs due to polypharmacy in the ICU. The main objective of this study was to assess the iatrogenic effects of polypharmacy in HIV patients treated in the ICU and to describe the DDI profile between ARVs and other non-ARV medications prescribed in the ICU. Methods and materials. Between 2018 and 2020, we conducted a single-center, retrospective study evaluating the medical records of 59 HIV patients admitted to the ICU for more than 24 hours at the Infectious Disease Clinical Hospital No. 2, Moscow, Russia. We evaluated the impact of polypharmacy on renal, hepatic and haemopoietic function. The Liverpool HIV Drug Interaction database was used to identify DDIs in ART-treated HIV patients. Results. All patients received more than 5 different medications matching the definition of polypharmacy. The average number of concurrent medications prescribed was 156.713 (maximum 40, minimum 6). All drug interactions recorded were between ARVs and antibiotics: 30 cases of potential interactions in 65.5% patients who received ARV. Of such patients, 94% were exposed to at least two potential interactions. Tenofovir (TDF) and the antibiotic vancomycin underlaid the most common potential interaction (49.2%), followed by lopinavir ritonavir (LPV/RTV) and ciprofloxacin (30.3%). A significant difference in average creatinine levels was found in patients with TDF/vancomycin potential interactions (p 0.05). Conclusion. This study demonstrated that potential DDIs frequently occur in ICU patients in line with previous investigations. It is necessary to implement collaborations among clinical pharmacologists and infectious disease/HIV specialists, as well as frequent clinical and laboratory monitoring, aimed at developing effective and actionable strategies that could reduce potential DDIs in HIV patients in the ICU.

Clinical Application of Cardiac Magnetic Resonance in ART-Treated AIDS Males with Short Disease Duration.

Cardiac complications are common in antiretroviral therapy-treated (ART-treated) acquired immune deficiency syndrome (AIDS) patients, and the incidence increases with age. Myocardial injury in ART-treated AIDS patients with a relatively longer disease duration has been evaluated. However, there is no relevant study on whether patients with a short AIDS duration have cardiac dysfunction. Thirty-seven ART-treated males with AIDS and eighteen healthy controls (HCs) were prospectively included for CMR scanning. Clinical data and laboratory examination results were collected. The ART-treated males with AIDS did not have significantly reduced biventricular ejection fraction, myocardial edema, or late gadolinium enhancement. Compared with the HCs, the biventricular volume parameters and left ventricle myocardial strain indices in ART-treated males with AIDS were not significantly reduced (all p > 0.05). ART-treated males with AIDS were divided into subgroups according to their CD4+ T-cell counts (<350 cells/μL and ≥350 cells/μL) and duration of disease (1–12 months, 13–24 months, and 25–36 months). There was no significant decrease in left or right ventricular volume parameters or myocardial strain indices among the subgroups (all p > 0.05). In Pearson correlation analysis, CD4+ T-cell counts were not significantly correlated with biventricular volume parameters or left ventricular myocardial strain indices. In conclusion, ART-treated males with AIDS receiving ART therapy with a short disease duration (less than 3 years) might not develop obvious cardiac dysfunction as evaluated by routine CMR, so it is reasonable to appropriately extend the interval between cardiovascular follow-ups to more than 3 years.

Abstract P3122: Latent Mouse Model Of HIV-1

Background: Antiretroviral therapy (ART) significantly improves the life span of people living with HIV/AIDS (PLWHA). However, HIV- associated cardiovascular diseases (CVDs) remain one of the leading causes of heart failure and comorbidity in PLWHA. Modern ART regimens reduce viral loads to undetectable levels in HIV+ patients while being less toxic. Nevertheless, HIV proteins are present in the plasma of PLWHA. The HIV protein, Nef, has been found circulating in the plasma of ART-treated patients within extracellular vesicles and in association with immune cells. We hypothesized that circulating HIV Nef proteins may cause an adverse effect on various organ functions. To further understand the effect of Nef on differing organ functions, we have generated a transgenic mouse model which expresses the Nef protein in the presence of Cre recombinase. Methods and Results: Nef transgenic mouse model was generated by cloning HIV-1 Nef ORF in CAG-Lox-CAT vector. Transgenic mice lines were crossed with the alpha myosin heavy chain promoter Cre mice to express Nef protein in the heart. Western blot data validated Nef protein expression in the adult mouse heart. Histological evaluation of the effect of Nef protein expression on heart morphology revealed cardiac hypertrophy. Furthermore, heart function analysis shows that Nef expressing mouse lines have depressed heart function. Conclusion: Our study suggests that Nef causes cardiac dysfunction that mimics cardiomyopathy secondary to latent HIV in PLWHA. Further, this mouse model could be useful in studying the effect of Nef protein in different organs or cells using cell-specific Cre recombinase. Moreover, Nef transgenic mice could be useful in generating new therapeutic tools to control comorbidity in PLWHA.

HIV-1 Drug Resistance Profiles of Low-Level Viremia Patients and Factors Associated With the Treatment Effect of ART-Treated Patients: A Cross-Sectional Study in Jiangsu, China.

ObjectivesEvaluating the drug resistance (DR) profiles of LLV patients and the influencing factors of treatment effects in Jiangsu Province.MethodThe Pol gene (Reverse transcriptase and protease) was amplified and sequenced to identify the genotypes and DR profiles among LLV patients in 2021. Questionnaire survey was conducted among HIV/AIDS patients to investigate the potential influence factors of treatment effects.Results242 Pol genes were amplified from 345 specimens, and ten genotypes were detected. The DR rate was 40.5%, with 66, 86, and 14 being resistant to NRTIs, NNRTIs, and PIs, respectively. Patients treated with the 2NRTIs+PIs regimen were detected with more DR; and drug resistance was less detected in married or cohabiting patients than unmarried patients. Non-smokers were less likely to develop LLV at follow-up than smokers; patients with stage II clinical stage at diagnosis and using 2NRTIs+PIs regimen were also more likely to develop LLV at follow-up.ConclusionDrug resistance profiles in LLV patients are severe and differ in treatment regimens and marital statuses. Meanwhile, smoking history, clinical stage, and treatment regimen may influence the therapeutic effect. It is necessary to include LLV people in the free drug resistance testing program.

Plasma Phage Load is Positively Related to the Immune Checkpoints in Patients Living with Human Immunodeficiency Virus.

Microbial Translocation (MT) and altered gut microbiota are involved in immune activation and inflammation, whereas immune checkpoint proteins play an important role in maintaining immune self-tolerance and preventing excessive immune activation. This study aims to investigate the relationship between plasma phage load and immune homeostasis in people living with HIV(PLWH). We recruited 15 antiretroviral therapy (ART)-naive patients, 23 ART-treated (AT) patients, and 34 Healthy Participants (HP) to explore the relationship between the plasma phage load and immune checkpoint proteins. The Deoxyribonucleic Acid (DNA) load of the lambda (λ) phage was detected using fluorescence quantitative Polymerase Chain Reaction (PCR). The Immune Checkpoints (ICPs) were detected using multiplex immunoassay. Our study demonstrated that the plasma phage load was increased in people living with HIV (PLWH) (P<0.05), but not in the ART-naive and AT groups (P>0.05). Plasma ICPs, including cluster of differentiation 27 (CD27), soluble glucocorticoid-induced Tumor Necrosis Factor (TNF) receptor (sGITR), soluble cluster of differentiation 80 (sCD80), sCD86, soluble glucocorticoidinduced TNF receptor-related ligand (sGITRL), soluble induced T-cell Costimulatory (sICOS), sCD40, soluble toll-like receptor 2 (sTLR2), and sCD28, were markedly decreased among the ARTnaive group (P<0.05) but not in the AT and HP groups (P>0.05). The plasma phage load was positively correlated with ICP and C-reactive protein (CRP) levels in PLWH (P<0.05). Our study indicated that the plasma phage load in PLWH was positively related to the expression of ICPs and inflammation, which may be used as a promising marker for the immune level of PLWH.

Perinatally Human Immunodeficiency Virus-Infected Adolescents and Young Adults Demonstrate Distinct BNT162b2 Messenger RNA Coronavirus Disease 2019 Vaccine Immunogenicity.

BackgroundImmunization of vulnerable populations with distinct immunity often results in suboptimal immunogenicity, durability, and efficacy.MethodsSafety and immunogenicity profiles of BNT162b2 messenger RNA coronavirus disease 2019 (COVID-19) vaccine, among people living with human immunodeficiency virus (HIV), were evaluated in 28 perinatally HIV-infected patients under antiretroviral therapy (ART) and 65 healthy controls (HCs) with no previous history of COVID-19. Thus, we measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific humoral and CD4+ T cell responses. Samples were collected before vaccination (baseline, day [D] 0), at the second dose (D21), and at 4 weeks (D28) and 6 months (D180) after D0. Proteomic profiles at D0 and D28 were assessed with a multiplexed proximity extension assay (Olink) on plasma samples.ResultsAll HIV-infected patients mounted similar anti–SARS-CoV-2 humoral responses to those of HCs, albeit with lower titers of anti-trimeric S at D28 (P = .01). Only peripheral blood mononuclear cells of HIV-infected patients demonstrated at D28 an impaired ability to expand their specific (CD40L+) CD4+ T-cell populations. Similar humoral titers were maintained between the 2 groups at 6-months follow-up. We additionally correlated baseline protein levels to either humoral or cellular responses, identifying clusters of molecules involved in immune response regulation with inverse profiles between the 2 study groups.ConclusionsResponses of ART-treated HIV-infected patients, compared to those of HCs, were characterized by distinct features especially within the proteomic compartment, supporting their eligibility to an additional dose, similarly to the HC schedule.

Has modern human immunodeficiency virus therapy decreased complications following total knee arthroplasty?

BackgroundAnti-retroviral therapy (ART) remains the cornerstone of decreasing morbidity and mortality in human immunodeficiency virus (HIV) patients. However, a large study comparing HIV patients taking ART prior to total knee arthroplasty (TKA) is lacking. We sought to examine: (1) readmissions; (2) post-operative complications; and (3) revisions in ART-treated or untreated HIV patients compared with a non-HIV population. MethodsWe queried a national, all-payer database to identify TKA patients from 2010-2020 (n = 1,393,357). The presence or absence of ART was identified and matched with non-HIV patients based on age, sex, diabetes, obesity, and tobacco status resulting in 889 patients in each cohort. Readmissions, post-operative complications, and revisions were assessed. ResultsReadmissions were higher among all HIV patients and even higher in those not taking ART, as compared to the matching cohort (4.8 versus 1.6%, p < 0.01). Prosthetic joint infections (PJIs) at 1-year were higher among HIV patients who were either taking ART (4.0%; OR, 1.41 [0.82–2.45]) or not taking ART (5.1%; OR, 2.44 [1.42–4.21]) as compared to non-HIV patients (2.1%, all p < 0.03). Revision rates at 1-year trended higher in HIV patients who were taking ART (2.6%; Odds Ratio (OR), 1.94 [0.96–3.93]) and who did not take ART (3.1%; OR, 2.38 [1.20–4.70]), compared to non-HIV patients (1.3%, all p < 0.09). ConclusionsART-treated HIV patients are associated with lower readmissions, post-operative complications, and revisions when compared to HIV patients not taking ART. The findings of this study underscore the utility of ART and patient optimization to reduce risk in HIV patients.