Effective Combination Antiretroviral Therapy Research Articles

Effects of combination antiretroviral therapy and nutritional rehabilitation on growth in children aged 6-36 months with severe acute malnutrition in IMPAACT protocol P1092.

Antiretroviral therapy (ART) is known to improve child survival and growth in children living with HIV (CLHIV). We investigated growth outcomes in children with severe non-edematous acute malnutrition (SAM) and without-SAM (mild malnutrition and normal nutrition) after initiation of ART in both groups and nutritional support. IMPAACT P1092 enrolled CLHIV aged 6 to <36 months with WHO-defined SAM or without-SAM across 5 sites in Sub-Saharan Africa and followed them for 48 weeks. The enrollment was conducted in 4 countries Malawi, Tanzania, Uganda, and Zimbabwe. Weight, height, and mid-upper-arm circumference (MUAC) were measured at baseline through 48 weeks. WHO weight-for-length/height Z-scores (WFL/H Z-score) were calculated. SAM children received readily available therapeutic food per WHO guidelines. All participants were initiated on a triple-ART regimen. SAM children entered the study after initial nutritional rehabilitation. Fifty-two CLHIV, 25 in the SAM cohort and 27 in the without-SAM cohort, were enrolled. WFL/HZ-scores and MUAC in the SAM cohort increased significantly at weeks 24 and 48 (WFL/HZ-scores: mean change [95% CI] 2.34 [1.77, 2.91] and 2.73 [2.09, 3.37], both p< 0.001; MUAC: mean change [95% CI] 2.63 [1.98, 3.28] and 3.53 [2.83, 4.24] cm, p<0.001). At Week 48, mean SAM height was 4cm shorter and mean weight 1kg lighter than without SAM (post hoc mean differences -4.11 (95% CI -8.60, 0.38) cm and -0.92 (95% CI -2.22, 0.39) kg). CHLHIV with SAM who undergo WHO nutritional rehabilitation can achieve significant growth and WFL/HZ score improvements but continued intensive anthropometric monitoring is needed as SAM will still be behind those without SAM.

Non-AIDS-defining comorbidities impact health related quality of life among older adults living with HIV.

The life expectancy of people living with HIV receiving effective combination antiretroviral therapy is approaching that of the general population and non AIDS-defining age-related comorbidities are becoming of greater concern. In order to support healthy aging of this population, we set out to explore the association between multimorbidity (defined as presence of 2 or more non AIDS-defining comorbidities) and quality of life (QoL). We performed a cross-sectional analysis using data from the Correlates of Healthy Aging in Geriatric HIV (CHANGE HIV) study, a Canadian cohort of people living with HIV age 65 years and older. Study participants completed two QoL modules, the general QoL and health related QoL (HR-QoL). 433 participants were included in the analysis with a median age of 69 years (interquartile range, IQR 67-72). The median number of comorbidities among study participants was 3 (IQR 2-4), with 78% meeting the definition of multimorbidity. General QoL scores (median 66, IQR 58-76) were lower than HR-QoL scores (median 71, IQR 61-83) and were not associated with multimorbidity after adjusting for age, sex, relationship status, household income, exercise, tobacco smoking history, malnutrition, time since HIV diagnosis, and HIV-related stigma. In contrast, multimorbidity was associated with lower HR-QoL (adjusted β = -4.57, 95% CI -8.86, -0.28) after accounting for the same variables. Several social vulnerabilities (not having a partner, low household income), health behaviours (lower engagement in exercise, smoking), and HIV-related factors (HIV stigma, longer time since HIV diagnosis) were also associated with lower QoL. Overall, our study demonstrated a high burden of multimorbidity among older adults living with HIV in Canada, which has a negative impact on HR-QoL. Interventions aimed at preventing and managing non-AIDS-defining comorbidities should be assessed in people living with HIV to determine whether this can improve their HR-QoL.

Brief Report: In cART-Treated HIV-Infected Patients, Immunologic Failure Is Associated With a High Myeloid-Derived Suppressor Cell Frequency.

During HIV infection, effective combined antiretroviral therapy suppresses viral replication and restores the number of circulating CD4+ T cells. However, 15%-30% of treated patients show a discordant response to combined antiretroviral therapy. Myeloid-derived suppressor cells (MDSC) are expanded in HIV+ patients; to better understand the role of MDSC on CD4 T-cell recovery, we evaluated the frequency of MDSC in HIV+ patients under combined antiretroviral therapy and its association with immunologic response. We enrolled 60 HIV+ patients, including complete responders (R, n = 44), virologic nonresponders (VNR, n = 5), and immunologic nonresponders (INR, n = 11). The frequency of circulating MDSC and the percentage of activated and naïve CD4 T cells were evaluated by flow cytometry. Plasmatic cytokine levels were analyzed by automated ELISA. As previously observed, polymorphonuclear MDSC (PMN-MDSC) frequency was higher in HIV+ patients compared with healthy donors. Furthermore, PMN-MDSC percentage was higher in INR than R patients, and a significant association between MDSC frequency and immunologic failure was confirmed by a receiver operator characteristic analysis. Accordingly, an inverse correlation was found between the percentages of PMN-MDSC and naïve CD4 T cells. A positive correlation was observed between PMN-MDSC frequency and the percentage of human leucocyte antigen locus DR + CD4 T cells and the plasmatic level of IL-1β and IL-8. Our results show that a high frequency of PMN-MDSC persists in INR, possibly because of immune activation, contributing to CD4 T-cell recovery failure. These findings further highlight the detrimental role of MDSC during HIV infection, suggesting these cells as a possible new therapeutic target.

Novel role of host protein SLC25A42 in the HIV-1 reactivation of latent HIV-1 provirus.

Despite the effectiveness of combination antiretroviral therapy, human immunodeficiency virus (HIV)infection remains incurable. To seek new strategies to overcome HIV type 1 (HIV-1) latency, one of the major barriers to HIV elimination, it is crucial to better understand how this state is maintained. Here, by means of an RNA interference screen employing an HIV-1 latency model using monocytic cell lines, we identified solute carrier family 25 member 42 (SLC25A42) as a potential host factor not previously known to affect HIV-1 latency. SLC25A42 knockdown resulted in increased HIV-1 expression, whereas forced expression of exogenous SLC25A42 suppressed it in SLC25A42-depleted cells. SLC25A42 depletion increased HIV-1 proviral transcriptional elongation but did not cause HIV-1 activation in an HIV-1 Tat-depleted latency model. This suggests that the role of SLC25A42 in HIV-1 transcription depends on HIV-1 Tat. Chromatin immunoprecipitation-qPCR analysis further revealed that SLC25A42 accumulated on or near the HIV-1 5' long terminal repeat promoter region of the HIV-1 provirus, suggesting a possible role in regulating HIV-1 Tat near this promoter region. These results indicate that SLC25A42 plays a novel role in HIV-1 latency maintenance in monocytic HIV-1 reservoirs.

Potential Advantages of a Well-balanced Nutrition Regimen for People Living with Human Immunodeficiency Virus Type -1

This review underscores the important role of nutrition in enhancing the management of Human Immunodeficiency Virus type 1 (HIV-1). Highlighting the efficacy of dietary interventions, including, the importance of omega-3 fatty acids, vitamins D and B-12, and the Mediterranean diet, we delineate how these beneficial nutritional strategies can improve the effectiveness of combined antiretroviral therapy (cART), mitigate its side effects, and ameliorate metabolic disorders in people living with HIV-1 (PLWH). Our review advocates for the integration and implementation of personalized nutritional assessments into the care plan for PLWH, proposing actionable strategies for healthcare providers in HIV-1 field. Summarizing the current standing of the relevance of the nutritional and well-planned diet recommended for the PLWH and emphasizing on the future research directions, this review establishes a foundation for nutrition as a cornerstone in comprehensive HIV-1 management. Our review aims to improve patients’ health outcomes and overall quality of life for PLWH.

Efficacy of combined antiretroviral therapy (cART) in Hepatitis B and C associated hepatocellular carcinoma (HCC): a narrative review

Introduction: HCC is the 3rd leading cancers in the world. Majority of HCC are due to chronic viral hepatitis including HBV, HCV, and HDV. Progression to cirrhosis and HCC in HBV and HCV infection is linked to level of replication and high serum viral DNA load. The use of antiviral agents is an effective strategy of treating HBV- and HCV- associated HCC. Aim: To assess the effectiveness of combined antiretroviral therapy on HBV and HCV-associated HCC Method: A narrative review of literature involving RCT and observational studies was performed. Blinding scores was used to evaluate the quality of the studies. This review was informed by one of the author’s experience with hepatitis virus in Africa. Discussion: The five studies were found to be useful in reducing viral load and improving the pathology of HBV- and HCV- associated cirrhosis, HCC, and decompensated liver disease. The combinations are sofosbuvir plus ledipasvir, declatasvir plus asunaprevir, grazoprevir plus elbasvir with or without ribavirin, ombitasvir, paritaprevir, ritonavir plus ribavirin, sofosbuvir plus ribavirin. However, resistance to either drug or both is a problem that needs to be addressed.

EcoHIV-Infected Mice Show No Signs of Platelet Activation.

Platelets express several surface receptors that could interact with different viruses. To understand the mechanisms of HIV-1's interaction with platelets, we chose the EcoHIV model. While EcoHIV is an established model for neuroAIDS, its effects on platelets are ill-defined. Our results indicate that EcoHIV behaves differently from HIV-1 and is cleared from circulation after 48 h post-infection. The EcoHIV course of infection resembles an HIV-1 infection under the effects of combined antiretroviral therapy (cART) since infected mice stayed immunocompetent and the virus was readily detected in the spleen. EcoHIV-infected mice failed to become thrombocytopenic and showed no signs of platelet activation. One explanation is that mouse platelets lack the EcoHIV receptor, murine Cationic Amino acid Transporter-1 (mCAT-1). No mCAT-1 was detected on their surface, nor was any mCAT-1 mRNA detected. Thus, mouse platelets would not bind or become activated by EcoHIV. However, impure virus preparations, generated by Polyethylene Glycol (PEG) precipitation, do activate platelets, suggesting that nonspecific PEG-precipitates may contain other platelet activators (e.g., histones and cell debris). Our data do not support the concept that platelets, through general surface proteins such as DC-SIGN or CLEC-2, have a wide recognition for different viruses and suggest that direct platelet/pathogen interactions are receptor/ligand specific.

HIV and an Ageing Population-What Are the Medical, Psychosocial, and Palliative Care Challenges in Healthcare Provisions.

The continuing increase in patient numbers and improvement in healthcare provisions of HIV services in the UK, alongside the effectiveness of combined antiretroviral therapy (cART), has resulted in increasing numbers of the ageing population among people living with HIV (PLWH). It is expected that geriatricians will need to deal with many older people living with HIV (OPLWH) as life expectancy increases. Therefore, geriatric syndromes in OPLWH will be similar to the normal population, such as falls, cognitive decline, frailty, dementia, hypertension, diabetes and polypharmacy. The increase in the long-term use of cART, diabetes, dyslipidaemia and hypertension may lead to high prevalence of cardiovascular disease (CVD). The treatment of such conditions may lead to polypharmacy and may increase the risk of cART drug-drug interactions. In addition, the risk of developing infection and cancer is high. OPLWH may develop an early onset of low bone mineral density (BMD), osteoporosis and fractures. In this review, we have also provided potential psychosocial aspects of an ageing population with HIV, addressing issues such as depression, stigma, isolation and the need for comprehensive medical and psychosocial care through an interdisciplinary team in a hospital or community setting. OPLWH have a relatively high burden of physical, psychological, and spiritual needs and social difficulties, which require palliative care. The holistic type of palliative care that will improve physical, emotional and psychological wellbeing is discussed in this review.

The New Era of Long-Acting Antiretroviral Therapy: When and Why to Make the Switch.

Despite the availability of safe and effective oral combination antiretroviral therapy, barriers to maintaining viral suppression remain a challenge to ending the HIV epidemic. Long-acting injectable antiretroviral therapy was developed as an alternative to daily oral therapy. This review summarizes the current literature on the efficacy of long-acting cabotegravir plus rilpivirine for the treatment of HIV-1, reasons to switch to injectable therapy, and barriers to switching. Long-acting cabotegravir plus rilpivirine is safe and effective in maintaining HIV-1 virologic suppression. Ideal candidates for switching to long-acting cabotegravir plus rilpivirine are virologically suppressed on oral regimens with good adherence and no history of virologic failure or baseline resistance. Indications to switch to injectable therapy include patient preference, the potential for improved adherence, and avoidance of adverse effects. Implementation research is needed to assess and overcome system barriers. Long-acting cabotegravir plus rilpivirine is a novel alternative to oral antiretrovirals, with the potential to improve adherence and quality of life in people with HIV.

Prevalence and characteristics of metabolic syndrome and its components among adults living with and without HIV in Nigeria: a single-center study

BackgroundPersons living with HIV (PLHIV) now live longer due to effective combination antiretroviral therapy. However, emerging evidence indicates that they may be at increased risk for some cardiometabolic disorders. We compared the prevalence of metabolic syndrome (MetS) and its component disorders between persons living with and without HIV in Nigeria.MethodsThis was a cross-sectional analysis of baseline data from a prospective cohort study of non-communicable diseases among PLHIV along with age- and sex-matched persons without HIV (PWoH) at the University of Abuja Teaching Hospital Nigeria. We collected sociodemographic and clinical data, including anthropometric measures and results of relevant laboratory tests. MetS was defined using a modification of the third report of the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III) criteria.ResultsOf the 440 PLHIV and 232 PWoH, women constituted 50.5% and 51.3% respectively. The median age of the PLHIV was 45 years while that of the PWoH was 40 years. The prevalence of MetS was 30.7% (95% CI: 26.4%, 35.2%) and 22.8% (95% CI: 17.6%, 28.8%) among the PLHIV and PWoH respectively (P = 0.026). Independent associations were found for older age (P < 0.001), female sex (P < 0.001), family history of diabetes (P < 0.001), family history of hypertension (P = 0.013) and alcohol use (P = 0.015). The prevalence of component disorders for PLHIV versus PWoH were as follows: high blood pressure (22.3% vs 20.3%), prediabetes (33.8% vs 21.1%), diabetes (20.5% vs 8.2%), high triglycerides (24.5% vs 17.2%), low HDL-Cholesterol (51.1% vs 41.4%), and abdominal obesity (38.4% vs 37.1%). Adjusting for age and sex, prediabetes, diabetes, and low HDL-Cholesterol were significantly associated with HIV status. Duration on antiretroviral therapy, protease inhibitor-based regimen, CD4 count, and viral load were associated with some of the disorders mostly in unadjusted analyses.ConclusionWe found a high burden of MetS and its component disorders, with significantly higher prevalence of dysglycemia and dyslipidemia among PLHIV as compared to PWoH. Integration of strategies for the prevention and management of MetS disorders is needed in HIV treatment settings.

Six-month immune responses to mRNA-1273 vaccine in combination antiretroviral therapy treated late presenter people with HIV according to previous SARS-CoV-2 infection.

Immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in people with HIV (PWH) with a history of late presentation (LP) and their durability have not been fully characterized. In this prospective, longitudinal study, we sought to assess T-cell and humoral responses to SARS-CoV-2 mRNA vaccination up to 6 months in LP-PWH on effective combination antiretroviral therapy (cART) as compared to HIV-negative healthcare workers (HCWs), and to evaluate whether previous SARS-CoV-2 infection modulates immune responses to vaccine. SARS-CoV-2 spike (S)-specific T-cell responses were determined by two complementary flow cytometry methodologies, namely activation-induced marker (AIM) assay and intracellular cytokine staining (ICS), whereas humoral responses were measured by ELISA [anti-receptor binding domain (RBD) antibodies) and receptor-binding inhibition assay (spike-ACE2 binding inhibition activity), before vaccination (T0), 1 month (T1) and 5 months (T2) after the second dose. LP-PWH showed at T1 and T2 significant increase of: S-specific memory and circulating T follicular helper (cTfh) CD4 + T cells; polyfunctional Th1-cytokine (IFN-γ, TNF-α, IL-2)- and Th2-cytokine (IL-4)-producing S-specific CD4 + T cells; anti-RBD antibodies and spike-ACE2 binding inhibition activity. Immune responses to vaccine in LP-PWH were not inferior to HCWs overall, yet S-specific CD8 + T cells and spike-ACE2 binding inhibition activity correlated negatively with markers of immune recovery on cART. Interestingly, natural SARS-CoV-2 infection, while able to sustain S-specific antibody response, seems less efficacious in inducing a T-cell memory and in boosting immune responses to vaccine, possibly reflecting an enduring partial immunodeficiency. Altogether, these findings support the need for additional vaccine doses in PWH with a history of advanced immune depression and poor immune recovery on effective cART.

Propolis consumption by asymptomatic HIV-individuals: Better redox state? A prospective, randomized, double-blind, placebo-controlled trial

Propolis is a natural product has many biological properties of clinical interest, such as anti-inflammatory and antioxidant. Considering that people living with HIV/aids (PLWHA) on effective combined antiretroviral therapy (cART) present early aging due to an intense immune activation, inflammation, and redox imbalance, propolis consumption could offer a benefit to such patients. This double-blind longitudinal study evaluated whether Brazilian green propolis pills intake (500 mg/day for three months) would decrease the oxidative stress of virological suppressed HIV-individuals. To compare each group (propolis, n = 20 versus placebo, n = 20) in both moments (M0, before and M1, after the intervention), the following markers were assessed: plasma malondialdehyde (MDA), carbonylation, total oxide nitric, total antioxidant capacity (TAP), superoxide dismutase, catalase, and NFkB and NRF2 gene expression. Data were analyzed using Poisson, Gamma distribution and ANOVA followed by Tukey-Kramer. The groups were homogeneous regarding age, gender, time of diagnosis/ treatment, cART scheme, CD4+ T cell count, and no changes were observed in the diet food, or patients’ lifestyles. A decreased MDA concentration was seen in the propolis group (M0 = 0.24 ± 0.13, M1 = 0.20 ± 0.10 protein nmol/mg; p = 0.005) as well as a slight but non-significant increase of TAP (M0 = 49.07 ± 13.26, M1 = 52.27 ± 14.86%; p = 0.06). One may conclude that propolis promoted a lower lipid peroxidation and improved the antioxidant system, suggesting that its use may be beneficial to PLWHA in an attempt to contain the intense inflammatory and oxidant activity.

The Natural Stilbenoid (-)-Hopeaphenol Inhibits HIV Transcription by Targeting Both PKC and NF-κB Signaling and Cyclin-Dependent Kinase 9.

Despite effective combination antiretroviral therapy (cART), people living with HIV (PLWH) continue to harbor replication-competent and transcriptionally active virus in infected cells, which in turn can lead to ongoing viral antigen production, chronic inflammation, and increased risk of age-related comorbidities. To identify new agents that may inhibit postintegration HIV beyond cART, we screened a library of 512 pure compounds derived from natural products and identified (-)-hopeaphenol as an inhibitor of HIV postintegration transcription at low to submicromolar concentrations without cytotoxicity. Using a combination of global RNA sequencing, plasmid-based reporter assays, and enzyme activity studies, we document that hopeaphenol inhibits protein kinase C (PKC)- and downstream NF-κB-dependent HIV transcription as well as a subset of PKC-dependent T-cell activation markers, including interleukin-2 (IL-2) cytokine and CD25 and HLA-DRB1 RNA production. In contrast, it does not substantially inhibit the early PKC-mediated T-cell activation marker CD69 production of IL-6 or NF-κB signaling induced by tumor necrosis factor alpha (TNF-α). We further show that hopeaphenol can inhibit cyclin-dependent kinase 9 (CDK9) enzymatic activity required for HIV transcription. Finally, it inhibits HIV replication in peripheral blood mononuclear cells (PBMCs) infected in vitro and dampens viral reactivation in CD4+ cells from PLWH. Our study identifies hopeaphenol as a novel inhibitor that targets a subset of PKC-mediated T-cell activation pathways in addition to CDK9 to block HIV expression. Hopeaphenol-based therapies could complement current antiretroviral therapy otherwise not targeting cell-associated HIV RNA and residual antigen production in PLWH.

Nanodelivery of antiretroviral drugs to nervous tissues.

Despite the development of effective combined antiretroviral therapy (cART), the neurocognitive impairments associated with human immunodeficiency virus (HIV) remain challenging. The presence of the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCFB) impedes the adequate penetration of certain antiretroviral drugs into the brain. In addition, reports have shown that some antiretroviral drugs cause neurotoxicity resulting from their interaction with nervous tissues due to long-term systemic exposure. Therefore, the research into the effective therapeutic modality that would cater for the HIV-associated neurocognitive disorders (HAND) and ART toxicity is now receiving broad research attention. Thus, this review explores the latest information in managing HAND using a nanoparticle drug delivery system (NDDS). We discussed the neurotoxicity profile of various approved ART. Also, we explained the applications of silver nanoparticles (AgNPs) in medicine, their different synthesis methods and their interaction with nervous tissues. Lastly, while proposing AgNPs as useful nanoparticles in properly delivering ART to enhance effectiveness and minimize neurocognitive disorders, we hypothesize that the perceived toxicity of AgNPs could be minimized by taking appropriate precautions. One such precaution is using appropriate reducing and stabilizing agents such as trisodium citrate to reduce silver ion Ag + to ground state Ag0 during the synthesis. Also, the usage of medium-sized, spherical-shaped AgNPs is encouraged in AgNPs-based drug delivery to the brain due to their ability to deliver therapeutic agents across BBB. In addition, characterization and functionalization of the synthesized AgNPs are required during the drug delivery approach. Putting all these factors in place would minimize toxicity and enhance the usage of AgNPs in delivering therapeutic agents across the BBB to the targeted brain tissue and could cater for the HIV-associated neurocognitive disorders and neurotoxic effects of antiretroviral drugs (ARDs).

Characterization of Circulating Fibrocytes in People Living with HIV on Stable Antiretroviral Therapy.

Highly effective combination antiretroviral therapy has reduced HIV infection to a manageable chronic disease, shifting the clinical landscape toward management of noninfectious comorbidities in people living with HIV (PLWH). These comorbidities are diverse, generally associated with accelerated aging, and present within multiple organ systems. Mechanistically, immune dysregulation and chronic inflammation, both of which persist in PLWH with well-controlled virally suppressive HIV infection, are suggested to create and exacerbate noninfectious comorbidity development. Persistent inflammation often leads to fibrosis, which is the common end point pathologic feature associated with most comorbidities. Fibrocytes are bone marrow-derived fibroblast-like cells, which emerged as key effector cells in tissue repair and pathologic fibrotic diseases. Despite their relevance to fibrosis, the circulating fibrocyte concentration in PLWH remains poorly characterized, and an understanding of their functional role in chronic HIV is limited. In this study, utilizing PBMCs from a cross-sectional adult HIV cohort study with matched uninfected controls (HIV-), we aimed to identify and compare circulating fibrocytes in blood. Both the percentage and number of fibrocytes and α-smooth muscle actin+ fibrocytes in circulation did not differ between the HIV+ and HIV- groups. However, circulating fibrocyte levels were significantly associated with increasing age in both the HIV+ and HIV- groups (the percentage and number; r = 0.575, p ≤ 0.0001 and r = 0.558, p ≤ 0.0001, respectively). Our study demonstrates that circulating fibrocyte levels and their fibroblast-like phenotype defined as collagen I and α-smooth muscle actin+ expression are comparable between, and strongly associated with, age irrespective of HIV status.

Lymphomas in People Living with HIV

Lymphomas in people living with HIV (PLWH) are associated with Epstein Barr virus (EBV) and Kaposi-sarcoma-associated herpesvirus (KSHV). They include primary effusion lymphoma, large B-cell lymphoma arising in multicentric Castleman disease, plasmablastic lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, and Hodgkin lymphoma (HL). Inclusion of these lymphomas in the WHO classification of tumors of hematopoietic and lymphoid tissues and the increasing recognition of these disorders have resulted in established clinical management that has led to improved outcomes. In this review, we report on the current management in lymphomas occurring in PLWH with an emphasis on KSHV-associated disorders and EBV-related HL. We also report on the simultaneous occurrence of KSHV- and EBV-associated disorders and highlight preventive measures that have been planned for tumor prevention in PLWH. In conclusion, it is recommended that treatment choice for PLWH affected by lymphoma, and receiving effective combined antiretroviral therapy (cART), should not be influenced by HIV status. Moreover, there is an urgent need (1) to reduce the current large disparities in health care between HIV-infected and HIV-uninfected populations, (2) to disseminate effective treatment, and (3) to implement preventive strategies for PLWH.

Spotlight on the September 6 Issue

![Graphic][1]</img>#### Notable in Neurology this week This issue features an article that investigates the longitudinal effects of combination antiretroviral therapy on cognition and neuroimaging biomarkers in treatment-naïve people with HIV; another looks at the association of ultraprocessed food consumption with the risk of dementia. A Historical Neurology article examines views on the memory and treatment of cognitive impairment in 17th-century Spain through the work conducted by Juan Gutiérrez de Godoy. ### Association of Structural Measurements of Brain Reserve With Motor Progression in Patients With Parkinson Disease ![Graphic][2]</img> This study investigated the association between baseline structural measurements of brain reserve … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif

Brain Differences in Adolescents Living With Perinatally Acquired HIV Compared With Adoption Status Matched Controls: A Cross-sectional Study.

Background and ObjectivesDespite effective combination antiretroviral therapy (cART), adolescents with perinatally acquired HIV (PHIV) exhibit cognitive impairment, of which structural changes could be the underlying pathophysiologic mechanism. Prior MRI studies found lower brain volumes, higher white matter (WM) hyperintensity (WMH) volume, lower WM integrity, and differences in cerebral blood flow (CBF). However, these findings may be confounded by adoption status, as a large portion of adolescents with PHIV have been adopted. Adoption has been associated with malnutrition and neglect, which, in turn, may have affected brain development. We investigated the long-term effects of PHIV on the brain, while minimizing the confounding effect of adoption status.MethodsWe determined whole-brain gray matter (GM) and WM volume with 3D T1-weighted scans; total WMH volume with fluid-attenuated inversion recovery; CBF in the following regions of interest (ROIs): WM, GM, and subcortical GM with arterial spin labeling; and whole-brain WM microstructural markers: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) with diffusion tensor imaging in cART-treated adolescents with PHIV visiting our outpatient clinic in Amsterdam and controls matched for age, sex, ethnic origin, socioeconomic status, and adoption status. We assessed differences in neuroimaging parameters between adolescents with PHIV and controls using linear regression models adjusted for age and sex and applied multiple comparison correction.ResultsThirty-five adolescents with PHIV and 38 controls were included with a median age of 14.9 (interquartile range [IQR]: 10.7–18.5) and 15.6 (IQR: 11.1–17.6) years, respectively, with a similar rate of adoption. We found a lower overall FA (beta = −0.012; p < 0.014, −2.4%), a higher MD (beta = 0.014, p = 0.014, 1.3%), and a higher RD (beta = 0.02, p = 0.014, 3.3%) in adolescents with PHIV vs adoption-matched controls, but no differences in AD. We found comparable GM, WM, and WMH volume and CBF in ROIs between adolescents with PHIV and controls. We did not find an association between cognitive profiles and WM microstructural markers in adolescents with PHIV.DiscussionIrrespective of adoption status, adolescents with PHIV exhibited subtle lower WM integrity. Our findings may point toward early-acquired WM microstructural alterations associated with HIV.

HIV and Global Cardiovascular Health.

Because of effective combination antiretroviral therapy, people living with HIV (PLWH) are living longer but developing chronic age-related conditions including cardiovascular disease (CVD), the leading cause of death globally. This review aims to discuss the epidemiology, mechanisms, and clinical considerations of CVD in PLWH from a global perspective. PLWH are at greater risk for CVD at chronologically younger ages than those without HIV. Potential underlying mechanisms for CVD in PLWH include systemic inflammation, comorbidities, immune-mediated, or treatment-related mechanisms. There is also risk factor variation based on geographical location, including non-traditional CVD risk factors. CVD is prevalent in PLWH and increasing on a global scale. Further understanding the unique epidemiology, risk factors, and treatment of CVD in this population will improve the care of PLWH.

Longitudinal Effects of Combination Antiretroviral Therapy on Cognition and Neuroimaging Biomarkers in Treatment-Naive People With HIV.

While combination antiretroviral therapy (cART) has dramatically increased the life expectancy of people with HIV (PWH), nearly 50% develop HIV-associated neurocognitive disorders. This may be due to previously uncontrolled HIV viral replication, immune activation maintained by residual viral replication or activation from other sources, or cART-associated neurotoxicity. The aim of this study was to determine the effect of cART on cognition and neuroimaging biomarkers in PWH before and after initiation of cART compared with that in HIV-negative controls (HCs) and HIV elite controllers (ECs) who remain untreated. We recruited 3 groups of participants from the University of Rochester, McGovern Medical School, and SUNY Upstate Medical University: (1) ART treatment-naive PWH; (2) age-matched HCs; and (3) ECs. Participants underwent brain MRI and clinical and neuropsychological assessments at baseline, 1 year, and 2 years. PWH were also assessed 12 weeks after initiating cART. Volumetric analysis and fractal dimensionality (FD) were calculated for cortical and subcortical regions. Mixed effect regressions examined the effect of group and imaging variables on cognition. We enrolled 47 PWH, 58 HCs, and 10 ECs. At baseline, PWH had worse cognition and lower cortical volumes than HCs. Cognition improved after initiation of cART and remained stable over time. Greater cortical thickness was associated with better cognition at baseline; greater FD of parietal, temporal, and occipital lobes was associated with better cognition at baseline and longitudinally. At baseline, ECs had worse cognition, lower cortical thickness, and lower FD in all 4 lobes and caudate than PWH and HCs. Greater cortical thickness, hippocampal volumes, and FD of frontal, temporal, and occipital lobes were associated with better cognition longitudinally. Initiation of cART in PWH is associated with improvement in brain structure and cognition. However, significant differences persist over time when compared with HCs. Similar trends in ECs suggest that results are due to HIV infection rather than treatment. Stronger associations between cognition and FD suggest this imaging metric may be a more sensitive marker of neuronal injury than cortical thickness and volumetric measures.