Search Results (445)

Objective: To characterize the profiles of resistance mutations to HIV reverse transcriptase inhibitors in Gabon. Design: Cross-sectional study conducted over 37 months, from October 2019 to October 2022, at the IST/HIV/AIDS Reference Laboratory, a reference center for the biological monitoring of people living with the human immunodeficiency virus (PWHIV) in Gabon. Methods: Plasma from 666 PWHIV receiving antiretroviral treatment was collected, followed by RNA extraction, amplification, and reverse transcriptase gene sequencing. Statistical analyses were performed using Stata^® 14.0 software (USA). Results: Six hundred and sixty-six (666) PWHIV plasma collected from 252 male and 414 female patients were analyzed and 1654 mutations were detected in 388 patients, including 849 (51.3%) associated with nucleoside reverse transcriptase inhibitors (NRTIs) and 805 (48.7%) with non-nucleoside reverse transcriptase inhibitors (NNRTIs). Three of the most prescribed treatment regimens were associated to the appearance of both NRTIs and NNRTIs resistance mutations: TDF + 3TC + EFV (24.02%; 160/666); TDF + FTC + EFV) (17.2%; 114/666) and AZT + 3TC + EFV (14.6%; 97/666). Additionally, stage 3 of CD4 T-lymphocyte deficiency, the higher viral load, and treatment duration are risk factors influencing the appearance of virus mutations. Also, treatment containing TDF-3TC + DTG is more protective against mutations. Conclusions: Drug resistance mutations are common in Gabon and compromise the efficacy of ART. Further study must search for other causes of therapeutic failure in Gabon in PWHIV. Full article

Objectives: Understanding the antibody response in monkeypox virus (MPXV)-infected and uninfected individuals is essential for developing next-generation MPXV vaccines. This study aimed to characterize neutralizing antibody (NAb) and antibody-dependent cellular cytotoxicity (ADCC) responses in both groups, providing insights into immune protection and vaccine design. Methods: A recombinant vaccinia Tian Tan (VTT) virus was utilized to develop high-throughput luciferase-reporter-based neutralization and ADCC assays. These assays were applied to evaluate the presence and levels of poxvirus-specific antibodies in MPXV-infected and uninfected individuals, including those vaccinated with vaccinia-based vaccines. Results: Poxvirus-specific NAbs were detected in MPXV-negative individuals with prior vaccinia vaccination. However, MSM individuals exhibited significantly lower pre-existing NAb levels than non-MSM individuals, potentially contributing to their higher susceptibility to MPXV infection. In individuals with mild MPXV infection, robust NAb and ADCC responses were observed, regardless of vaccination status. Additionally, HIV-positive individuals demonstrated comparable antibody responses following MPXV infection. Conclusions: These findings highlight the potential role of pre-existing NAbs in MPXV susceptibility and the strong immune response elicited by mild MPXV infection. Further research is needed to determine whether MPXV-specific antibodies mitigate disease progression, which could inform the development of effective MPXV vaccines. Full article

Although ART leads to viral suppression, people living with HIV (PLWH) still face an increased risk of comorbidities, such as cancer. The HIV-1 Tat protein may contribute to the promotion of chronic inflammation, oxidative stress, and genomic instability. While the presence of anti-Tat antibodies has been associated with slower disease progression, their potential role in modulating DNA damage remains unclear. Assess the effect of anti-Tat antibodies on cytotoxic and DNA damage in PLWH. A cross-sectional study was conducted in 178 PLWH. Serum anti-Tat IgG antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Cytotoxicity and DNA damage were assessed via serum 8-hydroxy-2′-deoxyguanosine (8-OHdG) and nuclear anomalies (Micronucleus cytome assay) in 2000 buccal cells. Statistical significance was considered at p < 0.05. Anti-Tat antibodies were found in 24.2% of participants. Positive individuals had lower CD4+ T cell counts (p = 0.045) and higher levels of pyknosis (p = 0.0001). No differences in 8-OHdG were found, but 8-OHdG correlated positively with CD4+ counts (rho = 0.334, p = 0.006). Pyknosis negatively correlated with CD4+ counts (rho = −0.272, p = 0.027). Anti-Tat antibodies may not prevent DNA damage but could be related to cytotoxic effects in PLWH. Full article

Background: Immunological strategies for antibody-guided vaccine design intend to enhance viral neutralization and protection and increase efficacy. Here, we discuss advances in antibody-guided vaccine design and current antibody-guided strategies, including epitope-based, nanoparticle-based, and scaffold-based vaccine approaches. We review the challenges and limitations of vaccines against different pathogens, such as influenza A virus, HIV-1 virus, single-celled malaria parasite, respiratory syncytial virus, and SARS-CoV-2. We summarize the available literature guidance, including emerging techniques in immunological vaccine design, to help understand and improve antibody-based immunity. The search strategy we applied is a comprehensive literature review of major databases, with specific search terms related to antibody-mediated vaccine design, viral neutralization, and immune protection. We discuss the how future directions for next-generation vaccine platforms and personalized vaccines based on immunogenetics will help improve vaccine design for increased specificity and potency of antibodies that neutralize pathogens, offering more precise and effective immune responses and, therefore, protection. Full article

Background: Development Assistance for Health (DAH) plays a vital role in health financing across Sub-Saharan Africa, particularly in tackling communicable diseases such as HIV/AIDS, malaria, and tuberculosis. Despite its importance, the efficiency and equity of DAH allocation remain contested. Objectives: The study aims to evaluate the cost-effectiveness of DAH in Sub-Saharan Africa from 1995 to 2018, as well as to explore differences in efficiency across diseases and country contexts. Methods: Data were drawn from the Institute for Health Metrics and Evaluation and applied Generalized Cost-Effectiveness Analysis in conjunction with the Gross Domestic Product-based thresholds. Averted Disability-Adjusted Life Years were analyzed across countries and diseases, and countries were categorized by the Human Development Index (HDI) level to assess differential DAH performance. Results: DAH cost-effectiveness showed similar patterns across HDI groups, with roughly equal proportions of cost-effective and dominated outcomes in both low- and middle-HDI countries. Thirteen countries were identified as very cost-effective, nine as cost-effective, and two as non-cost-effective. Twenty-one countries were dominated, reflecting persistent inefficiencies in aid impact that transcends the various levels of development. Conclusions: Tailoring DAH allocation to specific disease burdens and development levels enhances its impact. The study underscores the need for targeted investment and a strategic shift toward integrated health system strengthening. Additionally, microinsurance is highlighted as a key mechanism for improving healthcare access and financial protection in low-income settings. Full article

Background: Human immunodeficiency virus (HIV) remains a global health challenge despite significant advancements in antiretroviral therapy and prevention strategies. Developing a safe and effective vaccine that protects people worldwide has been a major goal, yet the genetic variability and rapid mutation rate of the virus continue to pose substantial challenges. Methods: In this review paper, we aim to provide a comprehensive review of previous vaccine candidates and the progress made in HIV vaccine clinical trials, spanning from the late 1990s to 2025. PubMed and ClinicalTrials.gov were searched for English-language Phase 1–3 HIV vaccine trials published from 1990 to March 2025. After de-duplication, titles/abstracts and then full texts were screened; trial phase, regimen, immunogenicity, efficacy, and correlates were extracted into a structured spreadsheet. Owing to platform heterogeneity, findings were synthesized narratively and arranged chronologically to trace the evolution of vaccine strategies. Results: Early vaccine trials demonstrated that a protein subunit vaccine failed to protect against infection, revealing the complexity of HIV evasion strategies and shifting the focus to a comprehensive immune response, including both antibody and T-cell responses. Trials evaluating the role of viral vectors in generating cell-mediated immunity were also insufficient, and suggested that targeting T cell response alone was not enough. In 2009, the RV144 trial made a breakthrough by showing partial protection against HIV infection and providing the first indication of efficacy. This partial success influenced subsequent trials, prompting researchers to further explore the complex immune response required for protection and consider combinations of vaccine technologies to achieve robust, long-lasting immunity. Conclusion: Despite setbacks, decades of rigorous efforts have provided significant contributions to HIV vaccine discovery and development, offering hope for preventing and protecting against HIV infection. The field remains active by continuing to advance our understanding of the virus, refining vaccine strategies, and employing novel technologies. Full article

Background and Objectives: This study explores the immunogenetic associations of human leukocyte antigens (HLAs) and cytokine levels in people living with HIV/AIDS (PLWH) who exhibit HIV-related skin disorders. HIV-related skin disorders, including inflammatory eruptions, atopic and seborrheic dermatitis, psoriasis, and pruritic papular eruption, are common among PLWH. These conditions may be influenced by genetic and immunological factors. This study aims to investigate the associations between HLA class II alleles, cytokine levels, and the presence of HIV-related dermatoses, providing insights into genetic susceptibility and immune mechanisms. Materials and Methods: This study included 115 PLWH with HIV-related skin disorders and a control group of 80 healthy individuals. HLA allele frequencies were analyzed, and cytokine levels (IL-1β, IL-10, IFN-y) were measured in blood samples. Statistical analyses were performed to identify significant differences in allele frequencies and cytokine responses between the groups. Results: Risk alleles (DQB1*0201:0301, OR = 19.4 and DQA1*0101:0501, OR = 4.2) and protective alleles (DRB1*07:13, OR = 0.19, DRB1*01:13, OR = 0.09, DRB1*04:11, OR = 0.07, and DQA1*0501:0501, OR = 0.24) showed statistically significant differences in frequency (p < 0.05) between PLWH and healthy controls. The protective DQA1*0501:0501 allele was associated with elevated levels of IL-1β (p < 0.001, r = 0.79) and IL-10 (p = 0.010, r = 0.63). Increased IL-1β levels may enhance immune responses, while higher IL-10 levels may exert anti-inflammatory effects, potentially reducing susceptibility to HIV-related dermatoses. Regression analysis revealed that IL-1β (Exp(B) = 0.76, p < 0.001) and IFN-γ (Exp(B) = 1.06, p = 0.043) are significant predictors for the likelihood of developing HIV-related dermatoses. An increase in IL-1β levels reduced this likelihood by 24%, while an increase in IFN-γ levels increased it by 6%. Conclusions: The findings emphasize the interaction between HLA class II alleles and cytokine profiles in determining genetic risk and clinical outcomes in PLWH with HIV-related skin disorders. Protective alleles, such as DQA1*0501:0501, may contribute to immune regulation, offering potential targets for therapeutic interventions in PLWH with dermatoses. Our results highlight the importance of IL-1β and IFN-γ as key modulators in the progression of HIV infection and the development of HIV-related dermatoses. Further research is needed to explore the mechanisms underlying these associations, particularly in the Latvian population, to inform targeted therapeutic strategies. Full article

Inflammation is a crucial component of the immune response essential for host defense and tissue repair. However, when the immune response becomes dysregulated, it can contribute to the pathogenesis of chronic diseases. While acute inflammation is a short-lived, protective response, chronic inflammation is sustained over time and can lead to immune dysfunction, tissue damage, and disease progression. The chronic inflammation theory of disease suggests that persistent immune activation/inflammation underlies both infectious and non-infectious conditions and serves as a unifying mechanism across distinct pathological states. In this review article, we argue that human immunodeficiency virus (HIV) infection represents a prime model for studying chronic inflammation, and that despite effective viral suppression with antiretroviral therapy (ART), people living with HIV (PLWH) exhibit persistent immune activation, systemic inflammation, and an increased risk of cardiovascular, metabolic, and neurodegenerative diseases. Here, the interplay between microbial translocation, immune dysregulation, and metabolic reprogramming fuels a state of chronic inflammation that accelerates disease progression beyond HIV itself. Key factors such as T-cell exhaustion, persistent monocyte/macrophage activation, and immunometabolic dysfunction contribute to such a sustained inflammatory state. This review explores the molecular and cellular mechanisms driving chronic inflammation in HIV infection with a focus on immunometabolism and its implications for broader inflammatory diseases. By understanding such pathways, we can identify novel therapeutic targets to mitigate inflammation-driven disease progression not only in HIV but across a spectrum of chronic inflammatory conditions. Full article

Cancer of the uterine cervix (cervical cancer) is a leading cancer among women worldwide, although its incidence has been reducing in many developing nations. In the majority of cervical cancer cases, the presence of high-risk human papillomavirus (HPV) is usually detected. However, a growing body of evidence currently considers that exclusive HPV infection may not be sufficient for cancer development. Apart from certain common risk factors for cervical cancer, like poor nutritional status and smoking, many studies documented an association with other viral infections, such as human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV-2). Similarly, vaginal bacterial populations perhaps play a key role in cervical cancer. It may be worth mentioning that different bacterial species can immensely influence (either protecting or adversely) the biochemical characteristics of the cervicovaginal environment—for example, Lactobacillus crispatus, Gardnerella vaginalis, and Chlamydia trachomatis. As a result, chronic infections with unfavorable microorganisms (other than HPV) may affect the pathological processes of malignancy. On the other hand, the cervix is an estrogen-sensitive organ like the corpus uteri (i.e., the body of the uterus). Estrogen and different estrogen receptors are implicated in the development and promotion of various cancers, including endometrial cancer. A number of reports also suggest a close association between estrogen and HPV in the development of cervical cancer. Furthermore, estrogen is linked with the characteristics of the vaginal microenvironment including bacteria. Therefore, several of the abovementioned factors (some are preventable) could play an important role in the progression of cervical neoplastic lesions. Full article

Background: This study investigates the survival outcomes of individuals with HIV receiving different treatment regimens compared to a control group. Utilizing a cohort dataset with demographic and clinical information, this research aims to assess the impact of various factors, including age, education, and travel time, on survival while controlling for confounding effects using propensity score adjustment. Methods: A total of 380 patients with HIV were included in this study, categorized into an intervention group receiving a specific treatment regimen and a control group. The primary outcome measured was the time to death or censoring. Survival analysis was performed using the Cox proportional hazards model, adjusted for potential confounders, including treatment (intervention and control), age, education, travel time, and gestational age at enrollment. Propensity scores were also incorporated to adjust for treatment selection bias. Results: The Cox model revealed a significant protective effect of the intervention on survival (hazard ratio (HR) = 0.583, p = 0.045), indicating that the treatment improved survival outcomes compared to the control group. After adjusting for propensity scores, the relationship between the intervention and survival remained significant (HR = 0.631, p = 0.106), suggesting the robustness of the treatment’s effect even after accounting for confounding variables. Other covariates, such as age, education, and travel time, did not show significant independent effects on survival, likely due to their correlation with the treatment variable. Conclusions: This study highlights the crucial role of the intervention in enhancing survival among individuals with HIV. The use of propensity score adjustment improves the validity of these findings by mitigating confounding bias in observational data. These results highlight the importance of ART (antiretroviral therapy) in HIV management and demonstrate the utility of statistical methods like propensity scores in clinical research. Further studies with diverse populations and advanced methodologies are recommended to validate these findings across different settings. Full article

Monkeypox virus (Mpox virus) is a zoonotic orthopoxvirus that has gained increased global attention due to recent outbreaks. The current review reports the latest update of Mpox cases from 25 February 2022 to 29 April 2025. It also evaluates the possible major complications in human life caused by Mpox. In early 2022, more than 40 countries reported Mpox outbreaks. As of 12 June 2024, the global case count for the 2022–2023 Mpox outbreak was 97,281 confirmed cases, in 118 countries. The World Health Organization (WHO) declared the Mpox virus, a zoonotic disease, a public health emergency of international concern (PHEIC) on 14 August 2024. Mpox symptoms include fever, headache, muscle pain, and face-to-body rashes. The review also highlights Mpox virus replication, genomics, pathology, transmission, diagnosis, and antiviral therapies. The 2022 outbreak is also discussed in detail. The coinfection of HIV in patients infected with Mpox is also discussed. The evolving Mpox epidemiology has raised concerns about the disease’s increasing spread in non-endemic countries, emphasizing the urgent need for control and prevention. The discussion on preventive measures, including vaccination, suggests that cross-protection against Mpox may be possible using orthopoxvirus-specific antibodies. Although there are no specific antiviral drugs available, certain drugs, such as tecovirimat, cidofovir, and ribavirin, are worth considering. Full article

Background and Objectives: Malaria poses significant threats to pregnant women, particularly in endemic regions. Preventive measures against it include insecticide-treated bed nets, intermittent preventive treatment, and various supplements. We aimed to assess and compare the safety and effectiveness of malaria preventive measures in pregnant women, considering their HIV status. Methods: We conducted a systematic search of PubMed, the Cochrane Library, Scopus, Embase, and Web of Science through January 2024. A network meta-analysis was performed using R 4.3.3 software on 35 studies (50,103 participants). Results: In HIV-positive pregnant women, Co-trimoxazole with dihydroartemisinin significantly reduced malaria incidence compared to Co-trimoxazole alone (RR = 0.45, 95% CI [0.30; 0.68]) and sulfadoxine–pyrimethamine (SP) (RR = 0.14, 95% CI [0.04; 0.48]). Mefloquine was also effective compared to controls and SP. In HIV-negative women, azithromycin–piperaquine significantly reduced infections compared to SP, bed nets, and controls (RR = 0.03, 95% CI [0.00; 0.83]; RR = 0.03, 95% CI [0.00; 0.86]; and RR = 0.03, 95% CI [0.00; 0.77], respectively). Conclusion: Different combinations of preventive measures show varying effectiveness based on HIV status. Co-trimoxazole with dihydroartemisinin and mefloquine are effective for HIV-infected pregnant women, while azithromycin–piperaquine and mefloquine work well for those without HIV. Customized prevention strategies considering HIV status are crucial for optimal protection. Full article

Influenza (flu) is a highly prevalent respiratory illness caused by influenza viruses, representing a significant global health burden due to its substantial morbidity and mortality rate. Vaccination remains the most effective strategy for influenza prevention, and well-characterized animal models of influenza infection serve as essential tools for evaluating vaccine protective efficacy. However, animal models utilizing live influenza virus strains pose significant biosafety concerns, and many such strains are not readily available for research. To address these challenges, we established a novel visual mouse infection model using an HIV-based vector system. This model employs influenza pseudoviruses carrying a luciferase reporter gene, enabling real-time monitoring of viral load and in vivo tracking of viral distribution during infection. Using this infection model, we assessed the in vivo protective efficacy of an influenza vaccine and cross-validated the pseudovirus-based evaluation results against a live virus-infected mouse model. Our study thus establishes a safer and more convenient platform for evaluating influenza vaccine efficacy, including the assessment of broad-spectrum neutralization capacity. Full article

An increase in immunoglobulin G4 (IgG4) levels is typically associated with immunological tolerance states and develops after prolonged exposure to antigens. Accordingly, IgG4 is considered an anti-inflammatory antibody with a limited ability to trigger efficient immune responses. Additionally, IgG4 reduces allergic reactions by blocking immunoglobulin E (IgE) activity. In the case of COVID-19, it has been reported that the repeated administration of some vaccines induces high IgG4 levels. The latest research data have revealed a surprising IgE anti-receptor binding domain response after both natural infection and several SARS-CoV-2 vaccines. The presence of IgG4 and IgE in COVID-19 disease suggests that the virus may induce an “allergic-like” response to evade immune surveillance, leading to a shift from T helper 1 (Th1) to T helper 2 (Th2) cells, which promotes tolerance to the virus and potentially contributes to chronic infection. The spike protein from vaccines could also induce such a response. Interestingly, “allergen-like” epitopes and IgE responses have been reported for other viruses, such as influenza, human immunodeficiency virus (HIV), and respiratory syncytial virus (RSV). The impact of this viral-induced tolerance will be discussed, concerning long COVID and the protective efficacy of vaccines. Full article

Measles remains an important cause of morbidity and mortality worldwide. Most HIV-infected adults are immune against measles, so titres of measles antibodies should be determined prior to vaccination. A measles vaccine can be administered to HIV-positive patients who do not have protective antibody levels and who have a CD4 lymphocyte count ≥ 200 cells/mm³. We describe the case of an HIV-infected patient, diagnosed with complicated measles at our Infectious Diseases Hospital in April 2024. Full article