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1.
J Int Assoc Provid AIDS Care ; 23: 23259582241269919, 2024.
Article in English | MEDLINE | ID: mdl-39234631

ABSTRACT

BACKGROUND: Early initiation of antiretroviral therapy improves human immunodeficiency virus (HIV) outcomes. However, achieving earlier treatment initiation is challenging for many reasons including provider awareness and clinic barriers; this study sought to understand perceptions of an early initiation program. METHODS: We interviewed 10 providers from 3 HIV clinics in North Carolina (October-November 2020). We asked providers about overall perceptions of early initiation and the pilot program. We developed narrative summaries to understand individual contexts and conducted thematic analysis using NVivo. RESULTS: Providers believed earlier initiation would signal an "extra sense of urgency" about the importance of antiretroviral therapy-a message not currently reflected in standard of care. Safety was a consistent concern. Cited implementation barriers included transportation assistance, medication sustainability, and guidance to address increased staff time and appointment availability. CONCLUSION: Our qualitative findings highlight the need for training on the safety of early initiation and addressing staffing needs to accommodate quicker appointments.


Doctor and clinic staff perspectives on a program to immediately start HIV treatment among patients newly diagnosed with HIVTreating human immunodeficiency virus (HIV) is easier than ever. Starting newly diagnosed persons on HIV medication as soon as possible is a now recommended goal. However, starting patients right away can be challenging. This study interviewed doctors and clinic staff to better understand their perspectives prior to implementing a program that would provide newly diagnosed patients with HIV treatment immediately. Results showed that some doctors are worried patients will not return after receiving their medications. Providers want support for linking patients to the clinic and ensuring they will be able to receive their next dose of medication when they come in. Other providers saw the benefits of reducing HIV stigma if the program can more quickly start patients on treatment. Some providers explained that when you go to the doctor and are sick you receive medications immediately, yet for newly diagnosed patients living with HIV, patients can be told to come back a month later to start treatment. Some providers believe shifting this messaging may also help patients take their medications better. Most providers saw the need for clinics to have more same-day appointment availability to meet the needs of the new program. Overall, providers were excited about the opportunity to improve the HIV care by offering HIV medications to newly diagnosed patients immediately.


Subject(s)
Attitude of Health Personnel , HIV Infections , Qualitative Research , Humans , HIV Infections/drug therapy , North Carolina , Male , Female , Anti-HIV Agents/therapeutic use , Adult , Time-to-Treatment/statistics & numerical data , Health Personnel/psychology , Middle Aged
2.
BMC Res Notes ; 17(1): 225, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39148100

ABSTRACT

INTRODUCTION: Opportunistic infections (OIs) are more common and severe among people with suppressed immunity like those living with HIV/AIDS (PLWH). This study aimed to assess the prevalence of OIs and associated factors among PLWH attending antiretroviral therapy (ART) clinics in the Gedeo zone, Southern Ethiopia. METHODS: A facility based retrospective cohort study was conducted from April to June 2018 among PLWH attending ART clinics in Gedeo zone, Ethiopia from November 2016 - November 2017. A simple random sampling method was used to select the both paper based and electronic study participants' charts. Adjusted odds ratios were calculated using multivariable logistic regression analysis for variables statistically significant at 95% confidence interval under bivariable logistic regression analysis, and significance was declared at P < 0.05. RESULTS: a total of 266 PLWH attended the selected ART clinics of Gedeo zone during the one year period were participated in the current study. The majority 104(39.1%) were within the age group 30-39, 106(60.2%) male, 184(69.2%) married, and 167(62.9%) urban residents. The study revealed the prevalence of OIs was 113(42.5%) with oral candidiasis 28(24.5%) the most prevalent followed by pulmonary tuberculosis 22(19.5%) and herpes zoster 15(13.4%). Further, study participants with ambulatory [AOR = 2.40(95% CI: 1.14, 5.03)], and bedridden [AOR = 3.27(95% CI:1.64, 6.52)] working functional status; with lower CD4 count: less than 200cells/mm3 [AOR = 9.14(95% CI: 2.75, 30.39)], 200-350cells/mm3 [AOR = 9.45(95% CI: 2.70,33.06)], 351-500cells/mm3 [AOR = 5.76(95% CI: 1.71, 19.39)]; being poor in ART adherence level [AOR = 10.05(95% CI: 4.31,23.46)]; being in stage III/IV WHO clinical stage of HIV/AIDS [AOR = 2.72(95% CI: 1.42, 5.20)]; and being chewing khat [AOR = 2.84(95% CI: 1.21, 6.65)] were found positively predicting the occurrence of OIs. CONCLUSION: This study speckled a high prevalence of OIs with several predicting factors. Therefore, the study acmes there should be interventional means which tackles the higher prevalence of OIs with focus to the predicting factors like lower CD4 count level, less/bedridden working functional status, poor ART adherence level, advanced stage of HIV/AIDS stage and chewing khat.


Subject(s)
AIDS-Related Opportunistic Infections , HIV Infections , Humans , Ethiopia/epidemiology , Male , Adult , Female , AIDS-Related Opportunistic Infections/epidemiology , Retrospective Studies , HIV Infections/drug therapy , HIV Infections/epidemiology , Prevalence , Middle Aged , Young Adult , Candidiasis, Oral/epidemiology , Acquired Immunodeficiency Syndrome/drug therapy , Acquired Immunodeficiency Syndrome/epidemiology , Adolescent , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/drug therapy , CD4 Lymphocyte Count , Anti-HIV Agents/therapeutic use
3.
Sci Rep ; 14(1): 17820, 2024 08 01.
Article in English | MEDLINE | ID: mdl-39090139

ABSTRACT

The gut and oral microbiome is altered in people living with HIV (PLWH). While antiretroviral treatment (ART) is pivotal in restoring immune function in PLWH, several studies have identified an association between specific antiretrovirals, particularly integrase inhibitors (INSTI), and weight gain. In our study, we explored the differences in the oral and gut microbiota of PLWH under different ART regimens, and its correlation to Body Mass Index (BMI). Fecal and salivary samples were collected from PLWH (n = 69) and healthy controls (HC, n = 80). We performed taxonomy analysis to determine the microbial composition and relationship between microbial abundance and ART regimens, BMI, CD4+T-cell count, CD4/CD8 ratio, and ART duration. PLWH showed significantly lower richness compared to HC in both the oral and gut environment. The gut microbiome composition of INSTI-treated individuals was enriched with Faecalibacterium and Bifidobacterium, whereas non-nucleotide reverse transcriptase inhibitor (NNRTI)-treated individuals were enriched with Gordonibacter, Megasphaera, and Staphylococcus. In the oral microenvironment, Veillonella was significantly more abundant in INSTI-treated individuals and Fusobacterium and Alloprevotella in the NNRTI-treated individuals. Furthermore, Bifidobacterium and Dorea were enriched in gut milieu of PLWH with high BMI. Collectively, our findings identify distinct microbial profiles, which are associated with different ART regimens and BMI in PLWH on successful ART, thereby highlighting significant effects of specific antiretrovirals on the microbiome.


Subject(s)
Gastrointestinal Microbiome , HIV Infections , Humans , HIV Infections/drug therapy , HIV Infections/microbiology , Gastrointestinal Microbiome/drug effects , Male , Female , Middle Aged , Adult , Mouth/microbiology , Body Mass Index , Feces/microbiology , Anti-Retroviral Agents/therapeutic use , Saliva/microbiology
4.
BMC Nephrol ; 25(1): 270, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39179963

ABSTRACT

BACKGROUND: Chronic kidney disease (CKD) affects almost 10% of the global populace including people living with HIV (PLWH). PLWH acquire CKD from both traditional and HIV-specific CKD risk factors. This study aimed to determine the prevalence of CKD and associated factors among antiretroviral therapy (ART) naïve PLWH in Lagos, Nigeria.  METHODS: This is a secondary data analysis among adult (≥ 18 years) ART-naïve PLWH enrolled at a large ART clinic in Lagos over 6 years. CKD was defined as estimated glomerular filtration rates (eGFR) below 60ml/min/1.73m2 over 3 months. Three estimators [Body surface area corrected Cockcroft Gault (BSA-CG), Modification of Diet in Renal Disease (MDRD), Chronic kidney disease Epidemiology Collaboration (CKD-EPI)] were used to determine the burden of CKD with no race correction factor. Age- and sex-standardised prevalence rates were determined. Cohen Kappa and Spearman correlations were used to compare the estimators. Logistic regressions were applied to identify variables associated with prevalent CKD. RESULTS: Among 2 772 PLWH, the mean age was 38 years with males older than females (p < 0.001). The majority of participants were females (62.1%), married (54.8%), employed (85.7%), had underweight or normal body mass index (BMI) (62.2%), and were diagnosed with World Health Organization (WHO) clinical stages 1 and 2 (55.5%). The age- and sex-standardised prevalence of CKD ranged from 10.0 - 17.6% with the highest Spearman's correlation (0.928) observed with MDRD and CKD-EPI equations. Increasing age [AOR (95% CI), equation] was significantly associated with CKD across all equations [1.09 (1.06 - 1.13), BSA-CG; 1.07 (1.05 - 1.10), MDRD; 1.09 (1.06 -1.12), CKD-EPI]. Other variables associated with CKD [AOR (95% CI), equation] were anaemia [2.50 (1.34 - 4.68), BSA-CG; 1.73 (1.04 - 2.86), MDRD], BMI <25 kg/m2 [3.35 (1.55 - 7.26), BSA-CG; 2.02 (1.18 - 3.46), CKD-EPI], and CD4 counts ≤ 200 cells/µL [2.02 (1.06 - 3.87), BSA-CG]. CONCLUSION: There was a high prevalence of CKD among ART-naïve PLWH at enrollment, which highlights the need to evaluate this population for CKD. Aside increasing age and low CD4 counts, none of the traditional or HIV-specific risk factors were related to CKD diagnosis.


Subject(s)
HIV Infections , Renal Insufficiency, Chronic , Humans , Nigeria/epidemiology , Male , Female , Adult , Renal Insufficiency, Chronic/epidemiology , Prevalence , HIV Infections/epidemiology , HIV Infections/drug therapy , Middle Aged , Glomerular Filtration Rate , Risk Factors , Young Adult , Cross-Sectional Studies
5.
Vaccines (Basel) ; 12(7)2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39066423

ABSTRACT

While SARS-CoV-2 has transitioned to an endemic phase, infections caused by newly emerged variants continue to result in severe, and sometimes fatal, outcomes or lead to long-term COVID-19 symptoms. Vulnerable populations, such as PLWH, face an elevated risk of severe illness. Emerging variants of SARS-CoV-2, including numerous Omicron subvariants, are increasingly associated with breakthrough infections. Adapting mRNA vaccines to these new variants may offer improved protection against Omicron for vulnerable individuals. In this study, we examined humoral and cellular immune responses before and after administering adapted booster vaccinations to PLWH, alongside a control group of healthy individuals. Four weeks following booster vaccination, both groups exhibited a significant increase in neutralizing antibodies and cellular immune responses. Notably, there was no significant difference in humoral immune response between PLWH and the healthy controls. Immune responses declined rapidly in both groups three months post vaccination. However, PLWH still showed significantly increased neutralizing antibody titers even after three months. These findings demonstrate the efficacy of the adapted vaccination regimen. The results suggest that regular booster immunizations may be necessary to sustain protective immunity.

6.
Viruses ; 16(7)2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39066329

ABSTRACT

Natural Killer (NK) cells have the potential to eliminate HIV-1-infected cells by antibody-dependent cellular cytotoxicity (ADCC). NK cell activation is tightly regulated by the engagement of its inhibitory and activating receptors. The activating receptor CD16 drives ADCC upon binding to the Fc portion of antibodies; NK cell activation is further sustained by the co-engagement of activating receptors NTB-A and 2B4. During HIV-1 infection, Nef and Vpu accessory proteins contribute to ADCC escape by downregulating the ligands of NTB-A and 2B4. HIV-1 also evades ADCC by keeping its envelope glycoproteins (Env) in a "closed" conformation which effectively masks epitopes recognized by non-neutralizing antibodies (nnAbs) which are abundant in the plasma of people living with HIV. To achieve this, the virus uses its accessory proteins Nef and Vpu to downregulate the CD4 receptor, which otherwise interacts with Env and exposes the epitopes recognized by nnAbs. Small CD4-mimetic compounds (CD4mc) have the capacity to expose these epitopes, thus sensitizing infected cells to ADCC. Given the central role of NK cell co-activating receptors NTB-A and 2B4 in Fc-effector functions, we studied their contribution to CD4mc-mediated ADCC. Despite the fact that their ligands are partially downregulated by HIV-1, we found that both co-activating receptors significantly contribute to CD4mc sensitization of HIV-1-infected cells to ADCC.


Subject(s)
Antibody-Dependent Cell Cytotoxicity , HIV Antibodies , HIV Infections , HIV-1 , Killer Cells, Natural , Signaling Lymphocytic Activation Molecule Family , Humans , Antibody-Dependent Cell Cytotoxicity/immunology , HIV-1/immunology , Killer Cells, Natural/immunology , HIV Antibodies/immunology , HIV Infections/immunology , HIV Infections/virology , Signaling Lymphocytic Activation Molecule Family/immunology , Signaling Lymphocytic Activation Molecule Family/metabolism , CD4 Antigens/immunology , CD4 Antigens/metabolism , Human Immunodeficiency Virus Proteins/immunology , Human Immunodeficiency Virus Proteins/metabolism , nef Gene Products, Human Immunodeficiency Virus/immunology , nef Gene Products, Human Immunodeficiency Virus/metabolism , Viral Regulatory and Accessory Proteins/metabolism , Viral Regulatory and Accessory Proteins/immunology , Viral Regulatory and Accessory Proteins/genetics , Antibodies, Neutralizing/immunology , Viroporin Proteins
7.
J Virus Erad ; 10(2): 100377, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38983868

ABSTRACT

Introduction: Healthcare professionals working in infectious disease units are often engaged in the care of patients with HIV infection. A cocoon vaccination strategy may protect those who are immunocompromised from a severe course of COVID-19. Methods: The research was conducted between January 2021 and June 2022. The study participants were 450 healthcare workers (HCWs) from the Hospital for Infectious Diseases in Warsaw who were vaccinated against COVID-19 with the BNT162b2 mRNA vaccine (Pfizer-BioNTech) -, thefirst available type of vaccine in Poland. Sera were collected according to the schedule of the study. Statistical analyses were performed with non-parametric tests: Wilcoxon's test was used to compare dependent numerical variables, and Fisher's exact test and the Chi-squared test to compare categorical variables. A p value of <0.05 was considered statistically significant. Results: Among the 450 HCWs working in the Hospital for Infectious Diseases in Warsaw 412 (91,5 %) were vaccinated against COVID-19. In total 170 (41,3 %) vaccinated HCWs were included in the final analysis. Their median age was 51 years [interquartile range (IQR): 41-60 years] and median body mass index (BMI) was 25.10 [IQR: 22.68-29.03]. Most of the cohort consisted of women (n = 137, 80.59 %), with the majority working directly with patients (n = 137, 73.21 %). It was found that as early as 14 days after the second dose of the vaccine, 100 % of the study participants achieved a positive result for SARS CoV-2 S-RBD antibodies. There were 168 subjects who had had a COVID-19 diagnosis before entering study and after vaccination 65 HCWs was diagnosed with COVID-19. Conclusions: Due to the fact that people living with HIV with severe immunodeficiency may have an incomplete immune response to COVID vaccination and be at risk of a severe course of the disease, the cocoon strategy of vaccinating medical personnel may be beneficial for these patients.

8.
Infect Drug Resist ; 17: 3133-3143, 2024.
Article in English | MEDLINE | ID: mdl-39050836

ABSTRACT

Background: Sichuan Province was severely affected by the HIV, and there was a scarcity of data regarding the survival time and influencing factors for People Living with HIV/AIDS (PLWH) in Sichuan Province who have received Antiretroviral Therapy (ART). Therefore, it is necessary to conduct a survival analysis for PLWH receiving ART. Methods: A retrospective cohort study was conducted on PLWH who had received ART≥6 months in Sichuan Province from January 1, 2003, to December 31, 2022. The Kaplan-Meier method was used to calculate median survival time and plot survival curves, while a Cox proportional hazards regression model was applied to analyze factors affecting survival time. Bilateral tests were performed, with P≤0.05 considered statistically significant. Results: The cumulative survival rates at 1, 3, 5, and 10 years for the 223,386 subjects were 94.54%, 89.07%, 84.82%, and 76.44%, respectively. Multivariate analysis using the Cox regression model indicated lower mortality risks for females (HR=0.59, 95% CI: 0.54-0.65), homosexual transmission (HR=0.43, 95% CI: 0.33-0.55), and baseline BMI≥24 (HR=0.81, 95% CI: 0.72-0.90). Higher mortality risks were associated with age≥50 years at diagnosis (HR=3.21, 95% CI: 2.94-3.50), being unmarried or divorced (HR=1.23, 95% CI: 1.11-1.37), living separately (HR=1.32, 95% CI: 1.22-1.43), baseline BMI <18.5 (HR=1.27, 95% CI: 1.13-1.41), presence of single-drug resistance (HR=1.25, 95% CI: 1.15-1.36), baseline WHO stage IV (HR=1.27, 95% CI: 1.09-1.47), and a diagnosis-to-treatment interval >12 months (HR=1.27, 95% CI: 1.15-1.41). Compared to those with CD4(+) T cell count of 200-350cells/µL, 350-500cells/µL, and >500cells/µL at baseline, individuals with <200cells/µL had higher mortality risks (HR=0.73, 95% CI: 0.67-0.79; HR=0.57, 95% CI: 0.51-0.64; and HR=0.58, 95% CI: 0.51-0.66, respectively). Conclusion: The survival rate for PLWH receiving ART in Sichuan Province was relatively high. Male gender, age over 50 at diagnosis, being unmarried, divorced, or living separately, presence of single-drug resistance, low baseline BMI, baseline CD4+ T cell <200cells/µL, baseline WHO stage IV, and a diagnosis-to-treatment interval >12 months were risk factors for the survival of PLWH.

9.
Clin Immunol ; 266: 110323, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39029640

ABSTRACT

The African continent reported the least number of COVID-19 cases and deaths of all the continents, although the exact reasons for this are still unclear. In addition, little is known about the immunological profiles associated with COVID-19 mortality in Africa. The present study compared clinical and immunological parameters, as well as treatment outcomes in patients admitted with COVID-19 in Pretoria, South Africa, to determine if these parameters correlated with mortality in this population. The in-hospital mortality rate for the cohort was 15.79%. The mortality rate in people living with HIV (PLWH) was 10.81% and 17.16% in people without HIV (p = 0.395). No differences in age (p = 0.099), gender (p = 0.127) or comorbidities were found between deceased patients and those who survived. All four of the PLWH who died had a CD4+ T-cell count <200 cells/mm3, a significantly higher HIV viral load than those who survived (p = 0.009), and none were receiving antiretroviral therapy. Seven of 174 (4%) patients had evidence of auto-antibodies neutralizing Type 1 interferons (IFNs). Two of the them died, and their presence was significantly associated with mortality (p = 0.042). In the adjusted model, the only clinical parameters associated with mortality were: higher fraction of inspired oxygen (FiO2) (OR: 3.308, p = 0.011) indicating a greater need for oxygen, high creatinine (OR: 4.424, p = 0.001) and lower platelet counts (OR: 0.203, p = 0.009), possibly secondary to immunothrombosis. Overall, expression of the co-receptor CD86 (p = 0.021) on monocytes and percentages of CD8+ effector memory 2 T-cells (OR: 0.45, p = 0.027) was lower in deceased patients. Decreased CD86 expression impairs the development and survival of effector memory T-cells. Deceased patients had higher concentrations of RANTES (p = 0.003), eotaxin (p = 0.003) and interleukin (IL)-8 (p < 0.001), all involved in the activation and recruitment of innate immune cells. They also had lower concentrations of transforming growth factor (TGF)-ß1 (p = 0.40), indicating an impaired anti-inflammatory response. The immunological profile associated with COVID-19 mortality in South Africa points to the role of aberrate innate immune responses.


Subject(s)
COVID-19 , HIV Infections , Immunity, Innate , SARS-CoV-2 , Humans , COVID-19/immunology , COVID-19/mortality , South Africa/epidemiology , Male , Female , Immunity, Innate/immunology , HIV Infections/immunology , HIV Infections/mortality , HIV Infections/drug therapy , Middle Aged , Adult , SARS-CoV-2/immunology , CD4 Lymphocyte Count , Hospital Mortality , Viral Load , Aged
10.
Cell Rep ; 43(6): 114344, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38850529

ABSTRACT

A heterologous Ad26/MVA vaccine was given prior to an analytic treatment interruption (ATI) in people living with HIV-1 (mainly CRF01_AE) who initiated antiretroviral treatment (ART) during acute HIV-1. We investigate the impact of Ad26/MVA vaccination on antibody (Ab)-mediated immune responses and their effect on time to viral rebound. The vaccine mainly triggers vaccine-matched binding Abs while, upon viral rebound post ATI, infection-specific CRF01_AE binding Abs increase in all participants. Binding Abs are not associated with time to viral rebound. The Ad26/MVA mosaic vaccine profile consists of correlated non-CRF01_AE binding Ab and Fc effector features, with strong Ab-dependent cellular phagocytosis (ADCP) responses. CRF01_AE-specific ADCP responses (measured either prior to or post ATI) are significantly higher in individuals with delayed viral rebound. Our results suggest that vaccines eliciting cross-reactive responses with circulating viruses in a target population could be beneficial and that ADCP responses may play a role in viral control post treatment interruption.


Subject(s)
AIDS Vaccines , HIV Infections , HIV-1 , Phagocytosis , Viral Load , Humans , HIV-1/immunology , HIV Infections/immunology , HIV Infections/virology , HIV Infections/drug therapy , Male , AIDS Vaccines/immunology , AIDS Vaccines/administration & dosage , Adult , Female , HIV Antibodies/immunology , Middle Aged , Treatment Interruption
11.
Biomedicines ; 12(6)2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38927468

ABSTRACT

BACKGROUND: DNA methylation may be a link between HIV, aging, and the increased risk of lung comorbidities. We investigated whether bronchoalveolar lavage (BAL) cells of people living with HIV (PLWH) demonstrate epigenetic disruptions and advanced epigenetic aging. METHODS: BAL cell DNA methylation from 25 PLWH and 16 HIV-uninfected individuals were tested for differential methylation of Alu and LINE-1 sites, markers of aging. We used a weighted gene correlation network analysis to identify HIV- and age-associated co-methylation networks. We tested the effect of HIV on DNA methylation using a robust linear model (false discovery rate < 0.10). RESULTS: The BAL cells of PLWH were marked by global hypomethylation in both Alu and LINE-1 elements. Six co-methylated CpG networks were identified that were significantly associated with age; of these, the red module was significantly differentially methylated in PLWH and enriched pathways (e.g., Ras signaling and T-cell receptors). We identified 6428 CpG sites associated with HIV. CONCLUSIONS: We have shown here for the first time that alterations in the DNA methylation of BAL cells in the lung with HIV show a pattern of advanced aging. This study strongly supports that HIV may contribute to an increased the risk of lung comorbidities through the epigenetics of aging.

12.
Front Aging ; 5: 1414866, 2024.
Article in English | MEDLINE | ID: mdl-38895099

ABSTRACT

Despite effective control of HIV replication by antiretroviral therapy (ART), a significant number of people living with HIV (PLWH) fail to achieve complete immune reconstitution and thus are deemed immune non-responders (INRs). Compared with immune responders (IRs) who have restored their CD4 T cell numbers and functions, CD4 T cells from these INRs exhibit prominent mitochondrial dysfunction and premature aging, which play a major role in increasing the incidence of non-AIDS, non-communicable diseases (NCDs). To date, there are no reliable biomarkers that can be used to typify and manage PLWH, especially INRs with non-AIDS NCDs. Growth differential factor-15 (GDF-15) is a transforming growth factor-ß (TGF-ß) family member known to regulate several biological processes involved in cell aging and stress responses. Since PLWH exhibit premature aging and metabolic dysregulation, here we measured the plasma levels of GDF-15 by ELISA and metabolic proteins by proteomic array and correlated the results with clinical parameters in ART-controlled PLWH (including INRs and IRs) and healthy subjects (HS). We found that GDF-15 levels were significantly elevated in PLWH compared to HS. GDF-15 levels were positively correlated with age and negatively associated with body mass and LDL cholesterol levels in the study subjects. Also, elevated GDF-15 levels were correlated with differential dysregulation of multiple metabolic proteins in PLWH. These results suggest that GDF-15 protein may serve as a biomarker of metabolic dysregulation and aging, and this biomarker will be useful in clinical trials targeting aging and metabolic disorders in ART-treated PLWH.

13.
Respir Res ; 25(1): 240, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38867225

ABSTRACT

BACKGROUND: Despite the success of antiretroviral therapy (ART), people living with HIV (PLWH) suffer from a high burden of pulmonary diseases, even after accounting for their smoking status. Cytotoxic CD8 T-cells are likely implicated in this phenomenon and may act as a double-edged sword. While being essential in viral infection control, their hyperactivation can also contribute to lung mucosal tissue damage. The effects of HIV and smoking on pulmonary mucosal CD8 T-cell dynamics has been a neglected area of research, which we address herein. METHODS: Bronchoalveolar lavage (BAL) fluid were obtained from ART-treated PLWH (median duration of supressed viral load: 9 years; smokers: n = 14; non-smokers: n = 21) and HIV-uninfected controls (smokers: n = 11; non-smokers: n = 20) without any respiratory symptoms or active infection. Lymphocytes were isolated and CD8 T-cell subsets and homing markers were characterized by multiparametric flow cytometry. RESULTS: Both smoking and HIV infection were independently associated with a significant increase in frequencies of total pulmonary mucosal CD8 T-cell. BAL CD8 T-cells were primarily CD69 + expressing CD103 and/or CD49a, at least one of the two granzymes (GzmA/GzmB), and little Perforin. Higher expression levels of CD103, CD69, and GzmB were observed in smokers versus non-smokers. The ex vivo phenotype of GzmA + and GzmB + cells revealed increased expression of CD103 and CXCR6 in smokers, while PLWH displayed elevated levels of CX3CR1 compared to controls. CONCLUSION: Smoking and HIV could promote cytotoxic CD8 T-cell retention in small airways through different mechanisms. Smoking likely increases recruitment and retention of GzmB + CD8 Trm via CXCR6 and CD103. Heightened CX3CR1 expression could be associated with CD8 non-Trm recruitment from the periphery in PLWH.


Subject(s)
HIV Infections , Humans , Male , HIV Infections/drug therapy , HIV Infections/immunology , Female , Middle Aged , Adult , Respiratory Mucosa/immunology , Respiratory Mucosa/metabolism , Respiratory Mucosa/drug effects , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/metabolism , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Cytotoxic/drug effects , T-Lymphocytes, Cytotoxic/metabolism , Smoking/adverse effects , Bronchoalveolar Lavage Fluid/immunology , Anti-Retroviral Agents/therapeutic use , Anti-HIV Agents/therapeutic use , Lung/immunology , Lung/drug effects , Lung/metabolism
14.
Curr HIV Res ; 22(3): 202-211, 2024.
Article in English | MEDLINE | ID: mdl-38747228

ABSTRACT

INTRODUCTION: The prevalence of sleep disorders in people living with HIV (PLWH) is higher than in the general population. Even if viral suppression is achieved with Antiretroviral Therapy (ART), the chronic immune activation and increased inflammation due to immune reconstitution persist. The aim of our study was to determine the prevalence of poor quality of sleep (QoS) and associated risk factors in PLWH and to investigate the relationship between poor QoS and CD4 T lymphocyte count and CD4 reconstitution. METHODS: PLWH ≥18 years old, attending for routine HIV monitoring were recruited. PLWH with conditions that may affect their QoS (pregnant, hospitalized, malignancy, substance-alcohol abuse, psychiatric disease or treatment, sleeping pill) were excluded. Pittsburgh Sleep Quality Index (PSQI, score ≥5 indicates poor QoS), Epworth Sleepiness Scale (ESS, score ≥11 indicates daytime sleepiness), and Beck Depression Scale (BDS, score ≥10 indicates clinical depression) were applied. CD4+ T lymphocyte reconstitution (current-baseline CD4+ count) and CD4+ T lymphocyte reconstitution rate [(current-baseline CD4+ count)/duration of HIV infection in years] were calculated for PLWH on ART. Student t-test and Pearson's chi-squared test were used for analysing the data, and p<0.05 was considered significant. RESULTS: A total of 131 (15 newly diagnosed, 116 on ART for at least six months) PLWH were enrolled. Poor QoS was detected in 60.3% of PLWH. When compared, the ratio was higher in newly diagnosed PLWH (vs PLWH on ART, p>0,05). Daytime sleepiness in PLWH with poor Qos (p=0.04) was significantly increased (vs good QoS). Clinical depression (p=0.001) was significantly more common in PLWH with poor QoS (vs good QoS). Although statistically nonsignificant (p>0,05), younger age, female sex, being single, homosexüel sexual preference, high income and living with the family were associated with poor QoS. No association was found between the ART regime and QoS. PLWH with poor QoS had a higher CD4+ T lymphocyte count (p>0,05), a higher number of CD4+ T lymphocyte reconstitution (p<0.05), and a higher reconstitution rate than PLWH with good QoS (p<0.05). CONCLUSION: Prevalence of poor QoS was high in our cohort. Poor QoS was associated with CD4+ T lymphocyte reconstitution and reconstitution rate.


Subject(s)
HIV Infections , Sleep Quality , Sleep Wake Disorders , Humans , Male , Female , Adult , Cross-Sectional Studies , HIV Infections/complications , HIV Infections/epidemiology , HIV Infections/immunology , HIV Infections/drug therapy , Risk Factors , Middle Aged , Prevalence , CD4 Lymphocyte Count , Turkey/epidemiology , Sleep Wake Disorders/epidemiology , CD4-Positive T-Lymphocytes/immunology , Young Adult
15.
Curr HIV Res ; 22(3): 195-201, 2024.
Article in English | MEDLINE | ID: mdl-38798214

ABSTRACT

INTRODUCTION: People living with HIV (PLWH) are more susceptible to acquiring and having serious consequences from COVID-19. The objective of this study was to examine the correlation between COVID-19 infection and other risk factors in these patients. METHODS: This is a descriptive-analytical study recruiting 160 PLWH referred to the Behavioral Disease Counselling Centre of Imam Khomeini Hospital in Tehran in 2021. The patients were selected through convenient sampling. A checklist was used to collect the necessary data. Descriptive statistical tests, such as mean and standard deviation, were employed alongside inferential statistics, including chi-square, Fisher, independent t-tests, and logistic regression, all evaluated at a significance level of p<0.05 using the R software. RESULTS: The patients' average age was 43.15 ± 11.23. Forty-four women and 116 men were present. A notable association was observed between the incidence of COVID-19 and variables such as hepatitis C and the duration of time since HIV diagnosis (p<0.001). Moreover, a strong correlation was found between the amount of COVID-19 vaccination doses given to patients and their probability of acquiring the disease. The first vaccination dose was linked to a 5.45 percent increase in COVID-19 incidence in patients, whereas the second and third doses (t=2.95, t=7.57) reduced the risk of getting COVID-19. Furthermore, no discernible link (p>0.05) was found between the use of various antiretroviral medications and COVID-19 infection. CONCLUSION: This study finds that vaccine type does not impact COVID-19 outcomes in HIV-positive patients, but receiving more doses decreases the probability of occurrence of COVID-19, advocating for multiple vaccinations. However, PLWH, especially those non-compliant with antiretrovirals, need strict adherence to health protocols due to heightened vulnerability to viral illnesses.


Subject(s)
COVID-19 , HIV Infections , SARS-CoV-2 , Humans , COVID-19/epidemiology , Female , Male , Adult , Cross-Sectional Studies , HIV Infections/epidemiology , HIV Infections/complications , HIV Infections/drug therapy , Risk Factors , Middle Aged , Incidence , Iran/epidemiology , COVID-19 Vaccines/administration & dosage
16.
HIV Res Clin Pract ; 25(1): 2351258, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38726811

ABSTRACT

BACKGROUND: Recently, injectable cabotegravir/rilpivirine (ICAB/RPV) became available for HIV treatment. However, there are no real-life data on the impact of switching to ICAB/RPV on sleep disturbances (SD). Therefore, we aimed at assessing and investigating this aspect in our cohort. METHODS: A SD multidimensional assessment (Epworth Sleepiness scale, Insomnia severity Index, Berlin Questionnaire, and Pittsburg Sleep Quality Index, PSQI) was performed to all people who consented before starting ICAB/RPV and 12 wk after the switch. Demographics, life-style habits, laboratory, and clinical data were collected from medical health records. RESULTS: To June 2023, 46 people were included, 76.1% males, with a median age of 48.5 (IQR: 41-57), 50% had multimorbidity, 13% was on polypharmacy. Median age with HIV and CD4 + T cell count nadir were 10 (5-19.5) years and 360 (205-500) cell/mm3, respectively. The reason to start a long-acting strategy was person's choice in all cases. Baseline antiretroviral regimens were mostly: tenofovir alafenamide/emtricitabine/rilpivirine (39.1%) and dolutegravir/lamivudine (32.6%). No significant changes were observed in any of the scores for each questionnaire, but for a worsening PSQI. 37% people reported a subjectively improved sleep quality, even if statistically significant changes were not observed in almost all the sleep parameters. CONCLUSIONS: To the best of our knowledge, this is the first study exploring impact of switching to ICAB/RPV on SD. Despite integrase inhibitor have been associated with SD, we did not observed a negative impact on sleep quality after the switch to ICAB/RPV. More studies and with larger number of people are necessary to confirm our results.


Subject(s)
Anti-HIV Agents , HIV Infections , Pyridones , Rilpivirine , Sleep Wake Disorders , Humans , Rilpivirine/therapeutic use , Rilpivirine/administration & dosage , Male , Female , Adult , HIV Infections/drug therapy , HIV Infections/complications , Middle Aged , Pyridones/therapeutic use , Pyridones/administration & dosage , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/administration & dosage , Sleep Wake Disorders/drug therapy , Cohort Studies , Drug Substitution/statistics & numerical data , Tenofovir/therapeutic use , Tenofovir/administration & dosage , Diketopiperazines
17.
SAGE Open Med ; 12: 20503121241253960, 2024.
Article in English | MEDLINE | ID: mdl-38784122

ABSTRACT

Objectives: To map the evidence on the barriers to and facilitators of diagnosing noncommunicable diseases among people living with HIV in low- and middle-income countries in Africa. Introduction: Noncommunicable diseases are increasing among people living with HIV. Thus, strengthened and sustained diagnosis of noncommunicable diseases through integrated noncommunicable diseases and HIV care is needed to improve patient outcomes. However, there is paucity of evidence on the barriers and facilitators diagnosing noncommunicable diseases among people living with HIV in low- and middle-income countries. Methods: The Arksey and O'Malley methodological framework was used. A comprehensive systematic search of academic databases (MEDLINE, Academic Search Complete, APA PsycInfo, CAB, and Health Source/Nursing) was performed via EBSCO search and PubMed. The articles were reviewed independently by three reviewers. The results were structured using Capability-Opportunity-Motivation-Behavior model and Theoretical Domains Framework. Results: A total of 152 articles were retrieved for full-text review. Forty-one articles met the inclusion criteria. The identified barriers were relevant to all the Capability-Opportunity-Motivation-Behavior constructs and 14 Theoretical Domains Framework domains. A lack of knowledge and awareness of noncommunicable diseases, fear of stigma, financial problems and out-of-pocket payments were the most cited patient-level barriers. Healthcare providers (knowledge and awareness gaps, skill and competence deficiencies, unwillingness, burnout, low motivation, and apathy) were frequently cited. Lack of equipment, noncommunicable disease medications and supply chain challenges, lack of integrated noncommunicable disease and HIV care, and shortage of trained healthcare providers were identified as health-system-level barriers. Conclusion: This scoping review is the first to identify barriers and facilitators using a theoretical framework. The most cited barriers include a lack of integrated HIV and noncommunicable disease care, equipment and logistics chain challenges for noncommunicable diseases, patients' and healthcare providers' lack of knowledge and awareness of noncommunicable diseases, and healthcare provider's skill and competency deficiencies. Addressing these issues is crucial for improving patient outcomes and reducing the burden on healthcare providers and health systems.

18.
Cancer ; 130(18): 3180-3187, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38718047

ABSTRACT

BACKGROUND: Antiretroviral therapy has reduced the incidence and mortality of AIDS-defining malignancies (ADM); however, non-AIDS-defining malignancies (NADM) are a major cause of death among people living with HIV (PLWH) today. Though current guidelines suggest that PLWH should receive the same treatment as the general population, there are limited studies focused on how HIV status affects the prognosis of cancers. The present study aimed to investigate the characteristics and prognosis of malignant diseases among PLWH in Japan. METHODS: Patients with HIV diagnosed with malignant diseases at our institution between 2011 and 2021 were retrospectively reviewed. RESULTS: There were 205 patients who were diagnosed with malignancies. Of these, 87 (42.4%) were diagnosed with ADM and 118 (57.6%) were diagnosed with NADM. Among 69 patients who received chemotherapy for ADM, 24 (34.8%) developed AIDS-defining opportunistic infections during treatment. In contrast, only one (1.8%) of the 56 patients administered chemotherapy for NADM developed AIDS-defining opportunistic infections. Complications of opportunistic infections at diagnosis of malignancies, low CD4+ T-cell count, positive HIV RNA, and nonadministration of antiretroviral therapy were associated with 5-year overall survival among patients with malignant lymphomas. However, the variables associated with HIV did not affect NADM prognosis. CONCLUSIONS: In this analysis, HIV status had a small impact on the prognosis of malignant diseases in PLWH. Few patients with NADM developed AIDS-defining opportunistic infections after receiving chemotherapy.


Subject(s)
HIV Infections , Neoplasms , Humans , Male , Female , Japan/epidemiology , HIV Infections/drug therapy , HIV Infections/complications , Middle Aged , Prognosis , Neoplasms/complications , Neoplasms/epidemiology , Neoplasms/mortality , Adult , Retrospective Studies , Aged , CD4 Lymphocyte Count , AIDS-Related Opportunistic Infections/epidemiology
19.
Oral Oncol ; 154: 106859, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38781626

ABSTRACT

Cancer patients living with HIV (CPLWH) may experience increased mortality risk. Furthermore, they have been historically excluded from clinical trials due to safety concerns. Our patient with squamous cell carcinoma of the lower lip received radiotherapy and platinum-based chemotherapy but declined by multiple centers due to his accidental HIV status. Genomic profiling revealed CDKN2A/B, PBRM1, TP53, and TERT alterations corresponding to UV signature, and high tumor mutational burden with positive PD-L1 staining. Accordingly, we report a durable radiologic and molecular complete response upon nivolumab plus IVC and antiretroviral therapy (ART). We demonstrated the safety and efficacy of ICIs, and feasibility of managing adverse events caused by antitumor, antiviral, and integrative therapies.


Subject(s)
HIV Infections , Nivolumab , Squamous Cell Carcinoma of Head and Neck , Humans , Nivolumab/therapeutic use , Male , HIV Infections/drug therapy , HIV Infections/complications , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/therapy , Squamous Cell Carcinoma of Head and Neck/diagnostic imaging , Middle Aged , Head and Neck Neoplasms/drug therapy
20.
Infection ; 2024 May 03.
Article in English | MEDLINE | ID: mdl-38700658

ABSTRACT

BACKGROUND: Our Hospital in Northern Italy assists 3817 people living with HIV (PLWH) and has faced the impact of COVID-19. Little is known about the impact of HIV infection on the risk of post-COVID-19 conditions (PCCs) onset. We aim to assess the incidence of PCC in PLWH and the factors associated with its occurrence. METHODS: We performed a retrospective, observational study including all PLWH > 18 years registered in the Brescia Health Protection Agency database, assessing SARS-CoV-2 burden, vaccination status, socio-demographic, and viro-immunological parameters from February 2020 until May 2022. Persistence of self-reported symptoms (clustered into gastrointestinal, respiratory, osteo-muscular, and neuro-behavioral symptoms) was evaluated after 3 months by a telephone-administered questionnaire. We estimated the associations between all variables and outcomes through univariate and multivariable logistic models. RESULTS: In the study period, 653 PLWH were diagnosed with SARS-CoV-2 infection (17.1%). We observed 19 (2.9%) reinfections, 71 (10.9%) hospitalizations, and 3 (0.5%) deaths. We interviewed 510/653 PLWH (78%), and 178 (PCCs prevalence 34.9%; CI 95% 30.7-39.2) reported persistent symptoms. Asthenia/fatigue was the most reported symptom (60/178), followed by muscular pain (54/178). In the multivariate regression model, there was a lower risk of PCCs in males respect to females (adjusted OR = 0.64; CI 95% 0.99-3.66), while hospitalization during acute infection was associated with an increased the risk of PCCs (adjusted OR = 1.9; CI 95% 0.99-3.66). Notably, no viro-immunological variable modified the PCCs risk onset. CONCLUSIONS: Our study highlights a substantial prevalence of PCCs among PLWH, three months post-SARS-CoV-2 infection, independent of viro-immunological features or vaccination status.

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