Search Results (76)

Oral manifestations of HIV infection can be an early sign of the disease and may indicate progression to AIDS. Although antiretroviral therapies, especially highly active antiretroviral therapy (HAART), have reduced the prevalence of HIV-related oral lesions, ongoing updates in diagnosis and treatment are essential due to the extended life expectancy of individuals living with HIV. Periodontal disease is a significant concern in these patients, influenced by altered immune responses and microbial dynamics, though the mechanisms are not fully understood. This exploratory study aimed to investigate the oral microbiota and periodontal disease prevalence in HIV-positive individuals by analyzing subgingival plaque samples from 24 patients. We identified 12 bacterial species using Polymerase Chain Reaction (PCR) and amplicon sequencing. Seven species were detected, with Filifactor alocis, Tannerella forsythia, and Porphyromonas endodontalis being the most common. Porphyromonas gingivalis was present in only 13.6% of samples, while T. forsythia was found in 58.3%. Genetic diversity was also observed in P. endodontalis and Selenomonas sputigena amplicons, with specific single nucleotide polymorphisms (SNPs) identified in both species. These results highlight the complex microbial interactions in the oral environments of people living with HIV, emphasizing the need for personalized diagnostic and therapeutic strategies for managing oral health in this population. Full article

Backgrounds: The rapid initiation of highly active anti-retroviral therapy (HAART) can control HIV-1 viremia and stabilize the long-term health of people living with HIV-1 (PLWH). Despite this, individuals who are diagnosed late and exhibit poor therapeutic efficacy still pose a great challenge to global HIV management. To address this, we conducted comprehensive multiparametric immune profiling and analyzed its association with disease progression and therapeutic efficacy. Methods: Multicolor flow cytometry was used to characterize the circulating immune cell composition and cellular phenotypes in 40 treatment-naive individuals (16 chronic, 24 newly diagnosed), 26 HAART-treated individuals, and 18 healthy controls. Comparative analyses of T cell subsets, immune activation markers, and viral load signatures were performed, followed by network construction. We carried out principal component analysis and displayed the data by dimensionality reduction. Results: Persistent immune activation, dysregulated regulatory immunity, and aberrant memory differentiation markers were identified in T cells of HIV-1-infected individuals and were associated with disease progression. Additionally, HAART-treated patients which did not fully restore CD4 T cells exhibited higher levels of activated markers, suggesting possible biomarkers of therapeutic efficacy. Conclusions: This study describes changes in immune cell profiles throughout HIV-1 disease progression and explores suitable laboratory predictors for future clinical and therapeutic settings by monitoring pathological immune cell events. Full article

Hypercalcemia represents a rare complication of nontuberculous Mycobacterium (NTM) infections, particularly in individuals with human immunodeficiency virus (HIV) positivity. This systematic review examines NTM infections associated with hypercalcemia, including the presentation of a novel and illustrative case of Mycobacterium simiae. A meticulous literature search identified 24 cases relevant to this phenomenon (11 HIV-positive and 13 non-HIV), which were included in the analysis. Key clinical and laboratory findings reveal significant contrasts between HIV-positive and non-HIV patients. In the HIV-positive cohort, hypercalcemia is commonly developed after the initiation of highly active antiretroviral therapy (HAART) or treatment for NTM infections despite severe underlying immunosuppression. Conversely, in the non-HIV group, a spectrum of immunosuppressive conditions, including chronic renal failure and prolonged use of immunosuppressive drugs, was implicated in the pathogenesis of NTM infections with hypercalcemia. Two distinct mechanistic pathways likely underlie this association. In HIV-positive patients, immune restoration following HAART appears to drive granuloma formation and excessive 1,25-dihydroxyvitamin D production. In non-HIV individuals, prolonged immune suppression may facilitate macrophage activation associated with NTM infections, thereby contributing to hypercalcemia. Treatment strategies varied and included bisphosphonates, corticosteroids, and hemodialysis. Notably, bisphosphonates emerged as a safe and effective option in most cases. Antibiotic therapy was deemed unnecessary when hypercalcemia was the sole symptom of NTM infection. This review underscores the importance of recognizing hypercalcemia as a potential complication of NTM infections and tailoring management strategies to the patient’s underlying immunological status. Full article

Highly active antiretroviral therapy (HAART) has reduced the incidence of VL/HIV dramatically. However, HAART only partially prevents relapses, with one-year relapse rates ranging from 30 to 60%. Consequently, secondary prophylaxis is recommended for patients with <200 CD4+ cells/μL. In clinical practice, characterizing cellular immune response could help estimate the risk of relapse in VL/HIV coinfected patients. In this study, the lymphoproliferative response after stimulation with soluble Leishmania antigen was assessed in 2022 and 2023 in three cases of VL/HIV coinfection with long-term follow-up (17, 8 and 19 years). PCR and rK-39 results for Leishmania, HIV viral load, CD4 cell count, proliferation index, IFN-γ, IL-2, IP-10, IL-10 and TNF-α were determined. Heterogeneous results were obtained, with only one patient having developed specific cellular immunity against Leishmania. No cases of relapse were observed. The heterogeneity of lymphoproliferative test results in the three cases described highlights the need to identify surrogate markers of cure to guide maintenance or withdrawal of prophylaxis. Full article

Background/Objectives: Highly active antiretroviral therapy (HAART) effectively suppresses viral load and aids immunological recovery in HIV patients, but may still lead to subclinical myocardial dysfunction. This study assesses left and right ventricular functions in patients on HAART containing abacavir, dolutegravir, and lamivudine using Tissue Doppler Imaging (TDI). Methods: This observational cross-sectional study involved 118 HIV-positive adults on HAART and 80 age- and gender-matched healthy controls. Comprehensive echocardiographic assessments, including TDI, were conducted to evaluate myocardial performance index (MPI) and isovolumic acceleration (IVA). Results: Conventional echocardiographic parameters showed no significant differences; however, TDI indicated significant impairments in ventricular functions in the HAART group, with increased MPI and decreased IVA (p < 0.001). Pulmonary artery pressures were also higher in the HIV group (p = 0.012). There was a strong positive correlation between MPI and HAART duration (r = 0.675, p = 0.002), and a negative correlation with CD4 count (r = −0.545, p = 0.006). Conclusions: TDI reveals significant subclinical ventricular dysfunction in HIV patients on HAART, correlating with therapy duration and immune status. These findings underscore the utility of TDI in detecting myocardial deterioration before clinical symptoms appear. Full article

Background: HIV-1 RT inhibitors were the first drugs approved to treat AIDS and remain key components of highly active antiretroviral therapy (HAART). While HAART effectively suppresses viral replication and slows disease progression, it has limitations, including long-term side effects and the emergence of drug-resistant strains, highlighting the need for new treatments. Objectives: Based on our previous experience, and insights from existing inhibitors of HIV-1 RT and RNase H, we aim to design and synthesize safer, multifunctional molecules. Methods: Using molecular docking studies, these compounds will incorporate pharmacophores targeting multiple stages of the HIV life cycle to enhance efficacy, reduce resistance, and improve pharmacokinetics. The compounds were synthesized via a one-pot three component reaction. The synthesized compounds were identified using spectroscopy and tested in vitro for activity against key HIV targets, including RNA-dependent DNA polymerase (RDDP) and RNAse H. Results: Among the synthesized compounds, several demonstrated strong inhibitory activity, with compound 11 showing IC₅₀ values comparable to the reference drug Nevirapine, and compound 4 exhibiting dual inhibition of both RT and RNase H activities. Conclusions: These findings emphasize the importance of a multidisciplinary approach, combining computational modeling with experimental validation, to identify promising leads for therapeutic development. Full article

Cardiovascular involvement in patients with human immune deficiency (HIV) has gained significant attention as the improved life expectancy of individuals with HIV has changed the paradigm regarding the long-term impact of the virus on cardiovascular health. We reviewed current literature on the prevalence, diagnosis, and unique characteristics of cardiovascular disease (CVD) in HIV patients, including those treated with protease inhibitors (PIs) and complementary therapies. The incidence of infectious, immunosuppressive, and nutritionally related pathologies in HIV patients has declined, largely due to advancements in highly active antiretroviral therapies (HAART) and supportive care. However, issues related to autoimmunity and chronic inflammation persist. Elevated levels of high-sensitivity C-reactive protein, along with activated cytokines and other pro-inflammatory molecules, are common in HIV patients and contribute significantly to the increased risk for endothelial dysfunction, coagulation disorders, and accelerated atherogenesis. The advent of HAART has significantly improved the prognosis for HIV patients, leading to prolonged life expectancy and a reduction in AIDS-related complications. However, this success has also resulted in a shift in the clinical presentation, with HIV patients showing more chronic and insidious cardiovascular manifestations. Full article

Background: The interaction between HIV infection, nutrition and immune system functioning is intricate, leading, in many cases, to a cycle of poor health outcomes. Despite the widespread use of highly active antiretroviral therapy (HAART) since the late 1990s and the concomitant increase in the life expectancy of people living with HIV (PLHIV), malnutrition and HIV-associated wasting continue to pose significant challenges, particularly in developing countries. Additionally, metabolic adverse effects associated with HAART, such as alterations in bone and lipid metabolism, as well as the impact on cardiovascular health, add further complexity to patient care. Methods: We conducted a comprehensive literature review of relevant studies involving adults diagnosed with HIV. The studies, published between 2000 and 2023, were identified using the Medline/PubMed, Scopus and Google Scholar databases. Results: Accumulating evidence in the literature indicates that careful monitoring and appropriate nutritional interventions can significantly enhance clinical outcomes in malnourished HIV-positive persons. The importance of addressing the prevalent deficiencies in certain micronutrients discussed in many of the studies is clearly underlined. However, challenges remain, particularly in low-income settings, where limited resources and infrastructure can impede effective implementation. Conclusions: There are critical research gaps with regard to the interaction between ART and nutrition, as well as the development of tailored nutritional approaches that aim to improve patient outcomes. Future research directions and policy strategies should focus on the development of sustainable programmes aimed at enhancing the quality of life for PLHIV. Full article

Nucleoside reverse transcriptase inhibitors (NRTIs) are the backbone of highly active antiretroviral therapy (HAART)—the current standard of care for treating human immunodeficiency virus (HIV) infection. Despite their efficacy, NRTIs cause numerous treatment-limiting adverse effects, including a distinct peripheral neuropathy, called antiretroviral toxic neuropathy (ATN). ATN primarily affects the extremities with shock-like tingling pain, a pins-and-needles prickling sensation, and numbness. Despite its negative impact on patient quality of life, ATN remains poorly understood, which limits treatment options and potential interventions for people living with HIV (PLWH). Elucidating the underlying pathophysiology of NRTI-induced ATN will facilitate the development of effective treatment strategies and improved patient outcomes. In this article, we will comprehensively review ATN in the setting of NRTI treatment for HIV infection. Full article

Extensive research on tuberculosis (TB) and HIV co-infection reveals the diverse prevalence and co-epidemic patterns across populations, necessitating tailored public health strategies. Co-infection is bidirectional; individuals with HIV are more susceptible to TB, and vice versa. Antiretroviral therapy (ART) and antituberculosis treatment (ATT) are critical for managing these conditions, but pose risks due to drug–pathogen and drug–drug interactions, potentially leading to immune reconstitution inflammatory syndrome (IRIS) in patients with HIV/AIDS. IRIS, often triggered by highly active antiretroviral therapy (HAART), can exacerbate HIV progression, increase drug resistance, and deteriorate patients’ quality of life. Approximately one-third of the global population with HIV is also infected with TB, with extensive drug-resistant (XDR) and multidrug-resistant (MDR) strains posing significant challenges. Latent TB infection (LTBI) further complicates the scenario, as it can progress to active TB, particularly in individuals with both conditions. The global and Indian mortality rates for TB-HIV co-infection remain high, emphasizing the need for new strategies. Additionally, unreported cases and inadequate post-treatment monitoring contribute to the high mortality rate, particularly among patients with LTBI. The complexity of managing HIV-TB co-infection, especially with LTBI, underscores the urgency of addressing these challenges to improve the outcomes for the affected populations. Full article

Body weight is impacted by several individual host and environmental factors. In a person living with HIV (PLWH), weight is also influenced by the disease stage. Wasting syndrome is derived from disease progression, and it can be reversed by the effective use of highly active antiretroviral therapy (HAART). Body weight alterations have been studied and compared in several clinical ART trials, and they differ according to antiviral regimens. The newer integrase strand transfer inhibitors (INSTIs), such as bictegravir and dolutegravir, especially when co-administered with tenofovir alafenamide fumarate (TAF), seem to lead to greater weight increases compared to regimens that include tenofovir disoproxil fumarate (TDF), which seem to have an attenuating effect on weight gain. Nevertheless, despite the established association between INSTI and TAF and the negative impact on weight, more recent data suggest a more cautious approach when HAART treatment decisions are taken. In this manuscript, we review weight changes among PLWH receiving HAART and the relevant underlying pathogenic mechanisms described in recent literature. We try to provide a more critical appraisal of the available data and to underline the challenges in assessing the role of HAART in weight changes in both ART initiation and setting switching. Full article

Intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin are cell adhesion molecules that play a significant role in inflammation and are implicated in the pathophysiology of preeclampsia development and HIV infection. More specifically, the immune expression of ICAM-1, VCAM-1, and E-selectin within cyto- and syncytiotrophoblast cells are dysregulated in preeclampsia, indicating their role in defective placentation. This study investigates the associations of ICAM-1, VCAM-1, and E-selectin gene variants (rs3093030, rs3783605, and rs1805193, respectively) with preeclampsia comorbid with HIV infection in women of African ancestry. It also examines the susceptibility to preeclampsia development and the effect of highly active antiretroviral therapy (HAART). A total of 405 women were enrolled in this study. Out of these women, 204 were preeclamptic and 201 were normotensive. Clinical characteristics were maternal age, weight, blood pressure (systolic and diastolic), and gestational age. Whole blood was collected, DNA was extracted, and genotyping of the ICAM-1 (rs3093030 C>T), VCAM-1(rs3783605 A>G), and E-selectin (rs1805193 A>C) gene polymorphisms was performed. Comparisons were made using the Chi-squared test. Our results demonstrated that preeclamptic women exhibited a higher frequency of analyzed variants, in contrast to those with the duality of preeclampsia and HIV infection. Additionally, the C allele of the ICAM-1 (rs3093030 C>T) and G allele of the VCAM-1 (rs3783605 A>G) genes were found to have a greater role in the co-morbidity and may be considered as a risk factor for preeclampsia development in women of African ancestry. In contrast, the SNP of rs1805193 of the E-selectin gene indicated that A>C was only significantly associated with HIV infection and not with preeclampsia. These findings highlight a strong association of the rs3093030 SNP of the ICAM-1 gene and of the VCAM-1 rs3783605 gene with the development of preeclampsia, indicating their role in the defective trophoblast invasion of preeclampsia. Sub-group analysis further reveals an association of the AA genotype with late-onset preeclampsia, a less severe form of disease indicating differing genetic predispositions between early and late-onset forms. Full article

More than 80 million people worldwide have been infected with the human immunodeficiency virus (HIV). There are now approximately 39 million individuals living with HIV/acquired immunodeficiency syndrome (AIDS). Although treatments against HIV infection are available, AIDS remains a serious disease. Combination antiretroviral therapy (cART), also known as highly active antiretroviral therapy (HAART), consists of treatment with a combination of several antiretroviral drugs that block multiple stages in the virus replication cycle. However, the increasing usage of cART is inevitably associated with the emergence of HIV drug resistance. In addition, the development of persistent cellular reservoirs of latent HIV is a critical obstacle to viral eradication since viral rebound takes place once anti-retroviral therapy (ART) is interrupted. Thus, several efforts are being applied to new generations of drugs, vaccines and new types of cART. In this review, we summarize the antiviral therapies used for the treatment of HIV/AIDS, both as individual agents and as combination therapies, and highlight the role of both macrophages and HIV cellular reservoirs and the most recent clinical studies related to this disease. Full article

Background: Highly Active Antiretroviral Therapy (HAART) for HIV infection and Direct-Acting Antivirals (DAA) for HCV infection currently represent the main treatment options for HIV/HCV co-infected patients. However, HAART has been associated with increased lipids. This study aimed to evaluate lipid profile changes after the DAA cycle in HIV/HCV co-infected patients undergoing HAART/DAA therapy. Methods: A prospective, longitudinal, observational study among HIV/HCV co-infected patients undergoing HAART/DAA treatment was conducted at the Infectious Diseases Unit of the University Hospital of Salerno. Inclusion criteria were age > 18 years, written informed consent, completion of the DAA cycle, and virologic suppression on HAART. Changes in the lipid profile were analyzed from baseline during and after DAA therapy at 12, 24, and 48 weeks after the sustained virologic response (SVR). A t-test was used to compare continuous variables. An analysis of variance was performed for each antiretroviral drug and genotype. Results: Fifty-four HIV/HCV patients (men/women n. 34/20 [68/32%], median age 56 years), all naïve to HCV therapy, were enrolled. HCV infection was caused by genotype 1 in 55% of cases and by genotype 3 in 29%. An increase in total cholesterol was recorded after the DAA treatment (from 165.03 ± 46.5 to 184.7 ± 44.9 mg/dL, p < 0.0001), after 12, 24, and 48 weeks, and in LDL-C at 24 weeks follow-up (at baseline 86.7 ± 34 mg/dL to 103.4 ± 41.38 mg/dL, p < 0.0001). Conclusions: Changes in the lipid profile after combined DAA/HAART treatment represent an important prognostic index. Further evaluation of cardiovascular-associated risk is necessary to implement appropriate prevention strategies. Full article

Infections with human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) represent one of the greatest health burdens worldwide. The complex pathophysiological pathways that link highly active antiretroviral therapy (HAART) and HIV infection per se with dyslipidemia make the management of lipid disorders and the subsequent increase in cardiovascular risk essential for the treatment of people living with HIV (PLHIV). Amongst HAART regimens, darunavir and atazanavir, tenofovir disoproxil fumarate, nevirapine, rilpivirine, and especially integrase inhibitors have demonstrated the most favorable lipid profile, emerging as sustainable options in HAART substitution. To this day, statins remain the cornerstone pharmacotherapy for dyslipidemia in PLHIV, although important drug–drug interactions with different HAART agents should be taken into account upon treatment initiation. For those intolerant or not meeting therapeutic goals, the addition of ezetimibe, PCSK9, bempedoic acid, fibrates, or fish oils should also be considered. This review summarizes the current literature on the multifactorial etiology and intricate pathophysiology of hyperlipidemia in PLHIV, with an emphasis on the role of different HAART agents, while also providing valuable insights into potential switching strategies and therapeutic options. Full article