Antiretroviral Effects Research Articles

Optimizing rosemary oil nanoemulsion loaded with nelfinavir and epigallocatechin gallate: A Design Expert® endorsed approach for enhanced neuroAIDS management

This study focuses on optimizing the delivery of Nelfinavir (NFV), a vital protease inhibitor in antiretroviral therapy, and Epigallocatechin gallate (EGCG), a potent adjunctive anti- human immunodeficiency virus (anti-HIV) agent found in green tea. The challenge lies in NFV's low intrinsic dissolution rate, significant p-gp efflux, and high hepatic metabolism, necessitating frequent and high-dose administration. Our objective was to develop a nanoemulsion loaded with NFV and EGCG to enhance oral delivery, expediting antiretroviral effects for NeuroAIDS treatment. After meticulous excipient screening, we selected Tween 40 as the surfactant and polyethylene glycol 400 (PEG 400) as the co-surfactant. Employing a Quality by Design (QbD) approach with statistical multivariate methods, we optimized the nanoemulsion that exhibited a droplet size of 83.21 nm, polydispersity index (PDI) of 2.289, transmittance of 95.20 %, zeta potential of 1.495 mV, pH of 6.95, refractive index of 1.40, viscosity of 24.00 ± 0.42 mPas, and conductivity of 0.162 μS/cm. Pharmacokinetic studies demonstrated superior in vivo absorption of the optimized nanoemulsion compared to NFV and EGCG suspension. The optimized nanoemulsion showcased higher Cmax of NFV (9.75 ± 1.23 μg/ml) and EGCG (27.7 ± 1.22 μg/ml) in the brain, along with NFV (26.44 ± 1.44 μg/ml) and EGCG (313.20 ± 5.53 μg/ml) in the plasma. This study advocates for the potential of NFV and EGCG-loaded nanoemulsion in combination antiretroviral therapy (cART) for effective NeuroAIDS management.

Long-acting antiretroviral therapy effectiveness and patient satisfaction using patient questionnaires: data from a real-world setting

BackgroundAntiretroviral therapy (ART) for HIV infection has evolved substantially. The development of long-acting drugs, such as cabotegravir (CAB) and rilpivirine (RPV) might improve treatment satisfaction among people living with HIV (PLWH). The real-world effectiveness of long-acting ART and its effect on patient satisfaction needs to be assessed. This study investigated antiviral effectiveness and treatment satisfaction in PLWH who switched from conventional to long-acting ART (CAB + RPV).MethodsThis prospective cohort study included PLWH aged 18 years and older who switched to CAB + RPV and received the injections every 8 weeks between June 2022 and May 2023, after a 4-week oral lead-in phase. The eligibility criteria included viral suppression, absence of hepatitis B virus (HBV) DNA, and no prior RPV resistance mutations. Clinical data, including renal, lipid, and glucose biomarker levels, were monitored from the baseline to 44 weeks after switching. Treatment satisfaction was assessed using the HIV Treatment Satisfaction Questionnaire. A linear mixed-effects model was used to estimate changes in clinical data from baseline.ResultsThirty-eight male participants were enrolled. Some participants had detectable levels of viral replication; however, all participants maintained viral suppression (HIV-RNA < 50 copies/mL) at 44 weeks and no cases of virological failure were detected. The creatinine level decreased by − 0.04 mg/dL (95% confidence interval [CI]: − 0.07 to − 0.01), lipid and glucose profiles remained stable, and treatment satisfaction increased by 6.6 points (95% CI: 2.4 to 10.8) after switching to CAB + RPV.ConclusionsLong-acting ART provides effective viral suppression and enhances treatment satisfaction in PLWH switching from conventional ART. Long-acting ART can improve patient well-being; however, patient selection and monitoring to prevent HBV-related complications are important.

Healthcare practitioners' experiences in managing HIV among young people in Namibia.

Low viral load suppression rates among older adolescents and young adults with HIV are a global challenge, including in Namibia. Healthcare providers struggle with managing these age groups due to their unique demographic characteristics. Monitoring viral load suppression is vital for evaluating antiretroviral treatment effectiveness, making it essential to identify and address existing gaps. This study aimed to explore and describe healthcare practitioners' understanding and experiences in managing older adolescents and younger adults living with HIV in seven high-burden districts of Namibia. Qualitative descriptive phenomenological research was followed in this study. Healthcare practitioners directly managing older adolescents and younger adults living with HIV were purposively recruited. Telephonic individual interviews were conducted, and data saturation was achieved with the 29th participant. Colaizzi's seven-step analysis was used to analyse the data. Two themes emerged from the study: (1) healthcare practitioners' knowledge of viral load management and (2) the strategies employed to manage high viral load in these age groups. These strategies included implementing differentiated service delivery, adopting interprofessional and Ubuntu approaches, psychosocial support, community engagement, enhancing adherence counselling, and support from implementing partners. The findings revealed inadequate knowledge among healthcare practitioners regarding viral load management, which negatively impacts the provision of quality care and an effective HIV response within the spirit of Ubuntu.Contribution:This study enhances healthcare practitioners' capacity in viral load management and guides policy makers in supporting this unique population, thus improving their health outcomes.

Exploring the interplay between antiretroviral therapy and the gut-oral microbiome axis in people living with HIV

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.

Broadly neutralizing antibodies for HIV prevention: a comprehensive review and future perspectives.

SUMMARYThe human immunodeficiency virus (HIV) epidemic remains a formidable global health concern, with 39 million people living with the virus and 1.3 million new infections reported in 2022. Despite anti-retroviral therapy's effectiveness in pre-exposure prophylaxis, its global adoption is limited. Broadly neutralizing antibodies (bNAbs) offer an alternative strategy for HIV prevention through passive immunization. Historically, passive immunization has been efficacious in the treatment of various diseases ranging from oncology to infectious diseases. Early clinical trials suggest bNAbs are safe, tolerable, and capable of reducing HIV RNA levels. Although challenges such as bNAb resistance have been noted in phase I trials, ongoing research aims to assess the additive or synergistic benefits of combining multiple bNAbs. Researchers are exploring bispecific and trispecific antibodies, and fragment crystallizable region modifications to augment antibody efficacy and half-life. Moreover, the potential of other antibody isotypes like IgG3 and IgA is under investigation. While promising, the application of bNAbs faces economic and logistical barriers. High manufacturing costs, particularly in resource-limited settings, and logistical challenges like cold-chain requirements pose obstacles. Preliminary studies suggest cost-effectiveness, although this is contingent on various factors like efficacy and distribution. Technological advancements and strategic partnerships may mitigate some challenges, but issues like molecular aggregation remain. The World Health Organization has provided preferred product characteristics for bNAbs, focusing on optimizing their efficacy, safety, and accessibility. The integration of bNAbs in HIV prophylaxis necessitates a multi-faceted approach, considering economic, logistical, and scientific variables. This review comprehensively covers the historical context, current advancements, and future avenues of bNAbs in HIV prevention.

Risk of Cardiovascular Events in People with HIV (PWH) Treated with Integrase Strand-Transfer Inhibitors: The Debate Is Not Over; Results of the SCOLTA Study.

Cardiovascular disease (CVD) is common in people with HIV (PWH), and has great impact in terms of morbidity and mortality. Several intertwined mechanisms are believed to play a role in determining the increased risk of CVD, including the effect of certain antiretrovirals; among these, the role of integrase strand-transfer inhibitors (INSTIs) is yet to be fully elucidated. We conducted a multicenter, observational study comprising 4984 PWH evaluating the antiretroviral therapy (ART)-related nature of CVD in real life settings, both in naïve vs. treatment-experienced people. A comparison was conducted between INSTIs vs. either protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) considering demographic, baseline clinical characteristics, incidence of CVD in both 2-year and complete follow-up periods. Among 2357 PWH exposed to INSTIs, 24 people experienced CVD; the corresponding figure was 12 cases out of 2599 PWH exposed to other ART classes. At univariate and multivariate analysis, a tendency towards an increased risk of CVD was observed in the 2-year follow-up period in PWH exposed to INSTIs in the absence, however, of statistical significance. These findings leave open the hypothesis that INSTIs may play a role, albeit minimal, in determining an increased risk of CVD in PWH.

Understanding Anemia among Women of Reproductive Age and Children in Namibia: A Comprehensive Review

Anemia is one of the leading causes of death globally, not only among children and women; however, there have been records of deaths among men too. Anemia disproportionately affects young children and expecting mothers with increased morbidity and mortality. Who estimates that anemia affects 30% of women aged 15 to 49, 37% of pregnant women, and 40% of children aged 6 to 59 months globally. The goal of lowering anemia among women of reproductive age has not been met, and 25.2% of women between the ages of 15 and 49 are now affected in Namibia. Namibia with a current prevalence rate of 46.1% of children under 5 years, is a severe global public health issue. According to the morphological classification of anemia, normocytic normochromic anemia (86.3%) was the most common kind in Namibia, with a moderate frequency of iron deficiency anemia whereas the highest prevalence of vitamin b12 deficient anemia was found in some regions. Anemia indicates both poor nutrition and poor health and is often categorized based on its cause. Iron deficiency, pregnancy, antiretroviral therapy side effects, and hereditary blood abnormalities increase the risk of anemia. Depending on the hemoglobin levels in the blood, anemia can be either short-term or long-term. For pregnant women and children under the age of 5, mild anemia is defined as a level of hemoglobin concentration between 10.0 and 10.9g/dl, moderate anemia is defined as a level between 7.0 and 9.9g/dl, and severe anemia is defined as a level below 7.0g/dl. Medical professionals follow different standards such as typical treatment recommendations, World Health Organization recommendations, and reference materials while dealing with individuals who have suspected anemia.

Qualitative Description of Exercise Perceptions and Experiences Among People With Human Immunodeficiency Virus in the High-Intensity Exercise to Attenuate Limitations and Train Habits Study.

The benefits of physical activity (PA), specifically exercise, among older adults in general are well known. Yet globally, there is concern regarding limited engagement in PA, increased obesity, and frailty among older people with human immunodeficiency virus related to low levels of PA. We conducted in-depth interviews among 30 older, sedentary people with human immunodeficiency virus participating in the ongoing High-Intensity Exercise to Attenuate Limitations and Train Habits (HEALTH study, NCT04550676) between February 2021 and August 2022. A semistructured interview guide, informed by two minds theory, which frames behavior change as an intention-behavior gap between 2 neurocognitive systems, was used to elicit data from participants. Interviews explored general exercise perceptions, self-efficacy for exercise, mobile health intervention tailoring, outcome expectations, and PA goals. Thirty interviews from 33 participants were recorded and transcribed verbatim, and deductive and inductive thematic analysis were used using Dedoose. Physical activity was defined as maintaining daily living activities and addressing health goals. Previous experiences with PA varied among participants and were influenced by chronic illnesses, including human immunodeficiency virus; motivation; work commitments; interest; and social support. Reported barriers to PA included antiretroviral adverse effects, comorbidities, aging, and the COVID-19 pandemic. Changes in health status, body changes, and relationships were identified as benefits of PA. Conversations with healthcare providers supporting exercise goals were perceived to be important but rarely received by the participants. Understanding how older people with human immunodeficiency virus perceive PA is crucial to developing tailored strategies and structuring service delivery within the healthcare setting to promote a physically active life.

Acute kidney injury and its predictors among HIV-positive patients in Africa: Systematic review and meta-analysis.

cute kidney injury(AKI) is a rapid loss of the kidney's excretory function, resulting in an accumulation of end products of nitrogen metabolism. The causes of AKI in HIV-positive patients are not well investigated, but it may be associated with antiretroviral drug side effects and HIV itself. Even though there were studies that reported the prevalence of AKI among HIV-positive patients in Africa, their findings were inconsistent across the studies. We searched on PubMed, Embas, Ebsco, OVID, Cochrane Library, and other supplementary search engines, including Google and Google Scholar. Articles published upto July 2023 were included in this review study. The quality of the study was assessed using the Newcastle-Ottawa Scale for cross-sectional, case-control, and cohort studies. The data were extracted using a Microsoft Excel spreadsheet and exported to Stata version 14 for analysis. A random effect meta-analysis model was used to estimate the pooled prevalence of AKI among HIV-positive patients. Heterogeneity was evaluated using Cochrane Q statistics and I squared (I2). Furthermore, the graphic asymmetric test of the funnel plot and/or Egger's tests were computed to detect publication bias. Sensitivity analysis was computed to see the effect of a single study on the summary effects. To treat the publication bias, a trim and fill analysis was carried out. The protocol of this review has been registered in an international database, the Prospective Register of Systematic Reviews (PROSPERO),with reference number CRD42023446078. A total of twenty-four original articles comprising 7913HIV-positive patients were included in the study. The pooled prevalence of AKI among HI-positive patients was found to be 23.35% (95% CI: 18.14-28.56%, I2 = 97.7%, p-value <0.001). Low hemoglobin (Hgb <8mg/dl) was found to be the determinant factor for AKI among HIV-positive patients (AOR = 2.4; 95% CI:1.69-3.4, I2 = 0.0%, p-value = 0.40). In meta-regression analysis, sample size was the possible source of variation among the included studies (AOR = 3.11, 95%CI: 2.399-3.83). The pooled prevalence of AKI among HIV-positive patients was high. HIV-positive patients with low hemoglobin levels are at risk of developing AKI. Hence, regular monitoring of kidney function tests is needed to prevent or delay the risk of AKI among HIV-positive patients. Healthcare workers should provide an integrated healthcare service to HIV-positive patients on the prevention, treatment, and reduction of the progression of AKI to advanced stages and complications.

Revolutionizing HIV-1 Viral Load Monitoring in India: The Potential of Dried Blood Spot Analysis for Expanding Access and Improving Care.

India continues to grapple with a significant burden of HIV infections. Despite notable progress in prevention and treatment efforts, multiple challenges, such as high-risk populations, inadequate testing facilities, and limited access to healthcare in remote areas, persist. Though the Government of India offers HIV-1 plasma viral load testing at various medical centers, aiding treatment decisions and monitoring antiretroviral therapy effectiveness, enhancing care for individuals living with HIV under the National AIDS Control Program (NACP), the nation's large population and diverse demographics further complicate its outreach and response. Hence, strategic interventions and alternative methods of testing remain crucial to curbing HIV transmission and improving the quality of life for those affected. Dried blood spot (DBS) sampling has emerged as a convenient and cost-effective alternative for HIV-1 viral load testing, revolutionizing the landscape of diagnostic and monitoring strategies for HIV infection. Though the plasma-based viral load remains the gold standard for monitoring HIV-1, DBS-based HIV-1 viral load testing holds immense promise for improving access to care, particularly in resource-limited settings where traditional plasma-based methods may be logistically challenging. DBS entails the collection of a small volume of blood onto filter paper, followed by drying and storage. This approach offers numerous advantages, including simplified sample collection, transportation, and storage, reducing the need for cold-chain logistics. Recent studies have demonstrated the feasibility and accuracy of DBS-based HIV-1 viral load testing, revealing a strong correlation between DBS and plasma measurements. Its implementation can enhance the early detection of treatment failure, guide therapeutic decisions, and ultimately contribute to better clinical outcomes for HIV-infected individuals. Hence, this review explores the principles, advancements, feasibility, and implications of DBS-based HIV-1 viral load testing.

Myocardial infarction in patients with HIV infection: incidence, risk factors, pathogenesis, clinical performance and treatment

HIV infection increases the risk of premature myocardial infarction (MI) and other atherosclerotic cardiovascular diseases, which are the main noncommunicable cause of death in HIV-infected patients. The review presents the analysis of recent literature on the incidence, prevalence and risk factors of MI in HIV-infected people. It established that MI is associated with the combined effects of traditional cardiovascular risk factors, HIV infection and the cardiometabolic effects of antiretroviral therapy. Pathogenetic features of acute coronary syndrome in HIV infection under conditions of systemic immune-mediated inflammation, hypercoagulation and direct exposure to the virus are highlighted. The clinical features and coronary damage in MI are described. Methods of treating MI are compared. We concluded that the volume and quality of care for patients with HIV and MI is insufficient. From the perspective of possible drug interactions with antiretroviral therapy, effectiveness and safety of methods for secondary prevention of MI was analyzed.

In vitro anti-HIV, cytotoxicity and nutritional analysis of Trianthema portulacastrum L. (Aizoaceae)

The development of antiretroviral therapy has brought a tremendous relief to the world as it minimizes mortality, reduces HIV transmission, and suppresses progression in infected patients. However, the orthodox antiretroviral therapy is faced with limitations which have necessitated a continuous search for more novel plant-based antiviral compounds, which can bypass the existing barriers created by drug resistance and target more viral proteins. Despite the edibility and enormous pharmacological benefits of T. portulacastrum, little is known about its nutrient profiles and potential use as a natural source of antiviral drug. This study focuses on the full feed analysis and anti-HIV potential of two biotypes of T. portulacastrum. Ethanolic extracts of both biotypes of T. portulacastrum (T01 and T02) had significant inhibitory effects on the level of replication of the HIV-1. Both extracts induced the inhibition of at least 50% of the HIV-1 viral load at considerably low IC50 values of 1.757 mg/mL (T01) and 1.205 mg/mL (T02) which is comparable to the AZT standard. The protein composition ranged between 8.63-22.69%; fat (1.84-4.33%); moisture (7.89-9.04%); fibre (23.84-49.98%); and carbohydrate content (38.54-70.14%). Mineral contents of tested T. portulacastrum varied considerably in different parts of the plant. Nitrogen N mineral ranged between 13.8-36.3 mg/g; sodium Na (2.0-14.0 mg/g); potassium K (14.0-82.0 mg/g); magnesium Mg (2.8-7.1 mg/g); calcium Ca (9.1-24.7 mg/g); phosphorus P (1.3-3.6 mg/g); iron Fe (193.5-984.0 ppm); zinc Zn (42.5-96.0 ppm); manganese Mn (28.5-167.5 ppm); and copper Cu (2.0-8.5 ppm). These mineral values are comparable or higher than values quoted for common vegetables, suggesting that T. portulacastrum is a nutrient-dense vegetable that could provide alternative sources of antiviral nutrients to HIV-infected individuals. Further studies are recommended to unravel key metabolites responsible for high nutrient profiles and antiretroviral effects in T. portulacastrum.

Barriers and Enablers to Retention in HIV Care and Adherence to Antiretroviral Therapy: Evidence from Dar es Salaam, Tanzania.

To explore the enabling factors, barriers, and strategies to improve retention in HIV care and adherence to antiretroviral therapy (ART) among adults (18 years and above) living with HIV in Dar es Salaam, Tanzania. We conducted a descriptive qualitative study to better understand and explore enablers, barriers, and strategies to improve retention in HIV care and adherence to antiretroviral therapy (ART) among PLHIV in Dar es Salaam, Tanzania. Focus group discussions (FGD) were conducted with a semi-structured discussion guide between December 2021 and June 2022. A non-random purposive sampling technique was used to select PLHIV and people involved in provision of healthcare and socioeconomic support to PLHIV. Thematic analysis was used to identify and interpret the themes. Three major themes with 10 sub-themes emerged. Participants indicated that family and partner support, peer-support group/adherence clubs, and healthcare provider counselling on medication adherence facilitated retention and adherence to ART. In contrast, stigma and discrimination, financial constraints, disease outbreaks such as the COVID-19 pandemic, myths and misconceptions about HIV, and side effects of antiretrovirals were mentioned as barriers. Strengthening community and patient education about HIV and ART through peer support groups and financial support for poor PLHIV were the proposed mitigation. Addressing the challenges to ART adherence may require a more holistic approach. We recommend the implementation of peer support groups and financial support through small microfinance groups as interventions to increase retention in HIV care and adherence to ART in the study area.

Comprehensive Review of Antiretroviral Therapy Effects on Red Blood Cells in HIV Patients

Antiretroviral therapy (ART) has revolutionized the landscape of HIV treatment, substantially reducing morbidity and mortality rates in affected individuals. However, while ART effectively suppresses viral replication and restores immune function, its impact on red blood cells (RBCs) and associated hematological parameters has drawn increasing attention in clinical research. This paper aims to provide a comprehensive overview of the effects of ART on RBCs among HIV patients, encompassing alterations in RBC indices, hemoglobin levels, and potential clinical implications. A systematic review of literature and clinical studies was conducted to analyze observed changes in RBC parameters in individuals receiving ART. The clinical implications arising from ART-induced changes in RBCs, particularly the occurrence of anemia and erythrocyte disorders, highlight the importance of vigilant monitoring and tailored management strategies. Addressing these hematological complications is pivotal for optimizing treatment outcomes and enhancing patient wellbeing. In conclusion, while ART has significantly improved HIV management, its effects on RBCs signify the need for tailored monitoring and interventions to manage hematological complications effectively. Keywords: Antiretroviral Therapy, Red Blood Cells, HIV

3 The Relationship Between Apolipoprotein-E4 Genotype, Memory, and the Medial Temporal Lobe and How These Relationships Vary by Race in Middle-Aged Persons with HIV

Objective:Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.Participants and Methods:The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (&lt;50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, andrelevant imaging covariates (i.e., intracranial volume or mean cortical thickness).Results:APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps&gt;0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps&lt;0.05). There were no APOE by race interactions for any MTL structures (ps&gt;0.10).Conclusions:Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.

41 Examining the independent and additive effects of family history of dementia and apolipoprotein e4 on neurocognitive performance among people with HIV

Objective:Among people with HIV (PWH), the apolipoprotein e4 (APOE-e4) allele, a genetic marker associated with Alzheimer’s disease (AD), and self-reported family history of dementia (FHD), considered a proxy for higher AD genetic risk, are independently associated with worse neurocognition. However, research has not addressed the potential additive effect of FHD and APOE-e4 on global and domain-specific neurocognition among PWH. Thus, the aim of the current investigation is to examine the associations between FHD, APOE-e4, and neurocognition among PWH.Participants and Methods:283 PWH (Mage=50.9; SDage=5.6) from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study completed comprehensive neuropsychological and neuromedical evaluations and underwent APOE genotyping. APOE status was dichotomized into APOE-e4+ and APOE-e4-. APOE-e4+ status included heterozygous and homozygous carriers. Participants completed a free-response question capturing FHD of a first- or second-degree relative (i.e., biologic parent, sibling, children, grandparent, grandchild, uncle, aunt, nephew, niece, half-sibling). A dichotomized (yes/no), FHD variable was used in analyses. Neurocognition was measured using global and domain-specific demographically corrected (i.e., age, education, sex, race/ethnicity) T-scores. t-tests were used to compare global and domain-specific demographically-corrected T-scores by FHD status and APOE-e4 status. A 2x2 factorial analysis of variance (ANOVA) was used to model the interactive effects of FHD and APOE-e4 status. Tukey’s HSD test was used to follow-up on significant ANOVAs.Results:Results revealed significant differences by FHD status in executive functioning (t(281)=-2.3, p=0.03) and motor skills (t(278)=-2.0, p=0.03) such that FHD+ performed worse compared to FHD-. Differences in global neurocognition by FHD status approached significance (t(281)=-1.8, p=.069). Global and domain-specific neurocognitive performance were comparable among APOE-e4 carriers and noncarriers (ps&gt;0.05). Results evaluating the interactive effects of FHD and APOE-e4 showed significant differences in motor skills (F(3)=2.7, p=0.04) between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups such that the FHD+/APOE-e4- performed worse than the FHD-/APOE-e4+ group (p=0.02).Conclusions:PWH with FHD exhibited worse neurocognitive performance within the domains of executive functioning and motor skills, however, there were no significant differences in neurocognition between APOE-e4 carriers and noncarriers. Furthermore, global neurocognitive performance was comparable across FHD/APOE-e4 groups. Differences between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups in motor skills were likely driven by FHD status, considering there were no independent effects of APOE-e4 status. This suggests that FHD may be a predispositional risk factor for poor neurocognitive performance among PWH. Considering FHD is easily captured through self-report, compared to blood based APOE-e4 status, PWH with FHD should be more closely monitored. Future research is warranted to address the potential additive effect of FHD and APOE-e4 on rates of global and domain-specific neurocognitive decline and impairment over time among in an older cohort of PWH, where APOE-e4 status may have stronger effects.

High prevalence of low high-density lipoprotein cholesterol and insulin resistance among children and adolescents living with HIV in Uganda: harbinger for metabolic syndrome?

Antiretroviral therapy-associated adverse effects and comorbidities are still pervasive in people living with HIV, especially metabolic syndrome (MetS). We investigated the age-dependent prevalence of components of MetS and insulin resistance in children and adolescents living with HIV (CALWH). A cross-sectional pilot study of CALWH treated at the Baylor Uganda Clinical Centre of Excellence in Kampala, Uganda, May to August 2021. The primary outcome of MetS was defined by both the International Diabetes Federation (IDF) and the Adult Treatment Panel (ATP III) criteria. We estimated the prevalence of MetS and its components for all participants and by the stratification factors. We enrolled 90 children and adolescents, aged 6 to <10 years (n = 30), 10 to <16 years (n = 30), and ≥ 16 to <19 years (n = 30). Fifty-one percent were females. The estimated prevalence of MetS was 1.11% (1 of 90) using either IDF or ATPIII criteria for all participants, and 3.33% in the oldest age group. Notably, while only one among study participants met the criterion based on having central obesity or blood pressure, over 55% of participants had one or more IDF component, with 47% having low high-density lipoprotein (HDL) cholesterol. Two participants (6.67%) in the group aged 10 to <16 years met one of the definitions for insulin resistance (IR) using the Homeostatic Model Assessment (HOMA-IR) index. For every 1-year increase in age, HOMA-IR index increased by 0.04 (95% confidence interval: 0.01-0.08; p = 0.02). With increasing survival of CALWH into adulthood, lifetime exposure to ART, the frequency of MetS in this population may rise, increasing the lifetime risk for associated health problems. There is a need to study the natural history of MetS in CALWH to inform preventative and treatment interventions as needed.

Highly active antiretroviral therapy-related effects on morphological connectivity in HIV.

Suboptimal concentration of the antiretroviral drug is insufficient to inhibit HIV destruction on brain structure and function due to the resistance of blood brain barrier. We aimed to investigate highly active antiretroviral therapy (HAART)-related effects on the morphological connectivity in people with HIV (PWH). Case-control study. Fifty-five HAART-treated for more than 3 months and 54 untreated PWH, as well as 66 demographically matched healthy controls underwent a high-resolution 3D T1-weighted MRI. Individual-level morphological brain network based on gray matter volume of 90 brain regions was constructed and network topological properties were analyzed. Network-based statistics (NBS) was performed to identify sub-networks showing significant differences in morphological connectivity. Correlation and mediation analyses were employed to evaluate associations between the morphological properties and clinical variables of PWH. Although PWH exhibited small-world architecture in their morphological brain networks, untreated PWH demonstrated altered network properties while HAART-treated PWH showed relatively similar network properties compared to healthy controls. Furthermore, HAART-related effects were mainly involved the bilateral putamen and left thalamus. The findings of NBS further indicated the cortico-striatum-thalamic-cortical loop was involved in the therapeutic-associated morphological network. The positive correlations between the HAART treatment and nodal degree and efficiency of the putamen were mediated by the number of CD4 + T lymphocytes. The topological properties are recovered to normal in PWH after HAART and the effects induced by HAART are mostly within the cortical-subcortical circuit.

Provider perspectives on antiretroviral therapy adherence among psychiatric inpatients in Botswana

Background: Optimal adherence to antiretroviral therapy (ART) is crucial for the effective management of HIV. Mental disorders often co-occur with HIV infection which often compromises ART adherence. Little is known about ART adherence in psychiatric settings in sub-Saharan Africa. Aims: This study aimed at exploring the health care providers’ perspectives on ART adherence among psychiatric inpatients. The study further assessed the facilitators and strategies enhancing ART adherence in hospitalised psychiatric patients. Methods: In-depth interviews were conducted with 25 health care providers at the Sbrana Psychiatric Hospital in Botswana. Interviews were focused on barriers and facilitators to psychiatric inpatients’ adherence to ART, and strategies and recommendations to support adherence. Data were manually analysed using a thematic analysis approach. Results: Key barriers were lack of insight, HIV-related stigma, lack of HIV-related knowledge, antiretroviral side effects and delays in re-initiating ART. Facilitators of ART adherence included motivation to be discharged from the hospital, fear of being sick, peer support, longer duration of hospitalisation, good provider-patient relationships, good diet, privacy and confidentiality and a single-tablet regimen. Health care providers described the various strategies currently used to support adherence, including directly observed therapy and family support, and recommended potential approaches to enhance psychiatric inpatient adherence to ART, including the use of injectable antiretrovirals and the introduction of halfway house centres. Conclusions: Findings from this study revealed unique insights into the numerous factors that influence ART adherence among psychiatric inpatients, and underscore the need to implement tailored strategies to support ART adherence in this population with complex health needs.

Lipid profile levels in HIV-AIDS patients on treatment with efavirenz and atazanavir. Cohort study.

Antiretroviral treatment for HIV generates dyslipidemia, which is associated with cardiovascular risk and atherosclerosis. To compare antiretroviral agents effects on lipids in patients with HIV-AIDS. Retrospective cohort. The lipid profiles of patients receiving efavirenz (EFV) vs. atazanavir (ATV) with a zidovudine + lamivudine backbone for 36 months were compared. 212 patients were included in the study. From baseline to month 36, HDL increase in the group of patients treated with ATV was higher in comparison with that of patients on EFV (8.33 vs. 4.26; p < 0.01); a difference in triglycerides was observed between groups, with a decrease of 19.06 mg/dL in patients on ATV and an increase of 40.62 mg/dL in those who received EFV (p < 0.001). Mean difference in total and LDL-cholesterol change between both treatments was not significant (p = 0.32 and p = 0.951, respectively). ATV-containing regimens were associated with more favorable changes in triglyceride and HDL levels than EFV regimens. This benefit could be associated with a reduction in long-term cardiovascular risk; this relationship requires further study.