Search Results (401)

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

Extrapulmonary tuberculosis (EPTB) remains diagnostically challenging due to its paucibacillary nature and variable presentation. Xpert and culture are limited in EPTB diagnosis due to sampling challenges, low sensitivity, and long turnaround times. This study evaluated the performance of the MPT64 antigen detection test for diagnosing EPTB, particularly tuberculous lymphadenitis (TBLN) and tuberculous pleuritis (TBP), in a high-TB, low-HIV setting. Conducted at Gulab-Devi Hospital, Lahore, Pakistan, this study evaluated the MPT64 test’s performance against conventional diagnostic methods, including culture, histopathology, and the Xpert MTB/RIF assay. Lymph node biopsies were collected, and cell blocks were made from aspirated pleural fluid from patients clinically presumed to have EPTB. Of 338 patients, 318 (94%) were diagnosed with EPTB. For TBLN, MPT64 demonstrated higher sensitivity (84%) than Xpert (48%); for TBP, the sensitivity was 51% versus 7%, respectively. Among histopathology-confirmed TBLN cases, MPT64 outperformed both culture and Xpert (85% vs. 58% and 47%). Due to the low number of non-TB cases, specificity could not be reliably assessed. The MPT64 test shows promise as a rapid, sensitive diagnostic tool for EPTB, particularly TBLN, in routine settings. While sensitivity is notably superior to Xpert, further studies are needed to evaluate its specificity and broader diagnostic utility. Full article

Background: Pneumocystis jirovecii pneumonia (PJP) remains a serious threat to non-HIV immunocompromised patients, who often experience rapid disease progression, delayed diagnosis, and higher mortality. Standard treatment with high-dose trimethoprim-sulfamethoxazole (TMP-SMX) is based primarily on data from HIV-positive populations, despite differences in immune response and drug tolerability. Objective: This narrative review critically synthesizes the available evidence on lower-dose TMP-SMX strategies for PJP in non-HIV patients and explores the potential role of individualized dosing approaches to improve outcomes. Findings: Emerging retrospective data suggest that lower-dose regimens (<15 mg/kg/day) may provide similar survival outcomes with fewer adverse effects. The intense inflammatory response observed after treatment initiation in non-HIV patients, potentially exacerbated by high-dose therapy, may contribute to clinical deterioration. This raises the possibility that TMP-SMX dosing itself could influence immune-mediated lung injury. While adjunctive corticosteroids are frequently used to temper inflammation, their benefit remains uncertain. Conclusions: Existing data suggest that lower-dose TMP-SMX may be effective and better tolerated in some non-HIV patients with PJP. A personalized approach to dosing, informed by clinical and host-specific factors, represents a promising strategy to optimize outcomes and minimize harm. Future research should prioritize precision medicine frameworks and prospective evaluation of individualized dosing protocols. Full article

Rilpivirine (RPV, R278474) was highlighted in 2005, two years after the death of Dr. Paul Janssen, as the ideal non-nucleoside reverse transcriptase inhibitor (NNRTI) to treat HIV infections. For this purpose, it was subsequently combined with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), darunavir (boosted with ritonavir or cobicistat) or dolutegravir. Its wide-spread use is thanks to its combination with cabotegravir (CAB) in the form of a long-acting intramuscular injection once per month (QM), later twice per month (Q2M), for the treatment of adults, later extended to adolescents and pregnant women, with HIV infections. The long-acting CAB plus RPV should not be administered in patients treated with rifampicin or rifabutin, patients with virological failure or patients with resistance to CAB or RPV, or patients with hepatitis B virus (HBV) infection. Long-acting CAB+RPV may lead to pain at the site of injection which would diminish over time. Full article

Health outcomes for people with HIV (PWH) have improved significantly with combination antiretroviral therapy (ART), yet the risk of lung cancer remains elevated. While a single case cannot establish causality, we describe here an investigation of a 74-year-old male PWH with de novo high-grade neuroendocrine small cell lung carcinoma. To investigate the potential contribution of HIV to cancer development, we performed HIV integration site sequencing on blood, tumor, and non-tumor tissue samples from the patient. We analyzed integration site distribution, clonal expansion, and associated gene disruption. Phosphatase and Tensin Homolog (PTEN) expression was evaluated using immunofluorescence and microscopy. A total of 174 unique HIV integration sites were identified, with 29.9% (52/174) located in clonally expanded cells. The most frequent integration site in clonally expanded cells was within the PTEN gene, representing 4.2% to 16.7% of all HIV-infected cells across samples. PTEN expression was markedly reduced in tumor regions relative to non-tumor tissue. Areas positive for HIV p24 antigen showed minimal PTEN expression. These findings suggest that HIV integration into the PTEN gene, coupled with clonal expansion of HIV-infected cells, may impair anti-tumor immune responses and promote cancer progression in PWH. Full article

Neck of femur (NOF) fractures are a critical orthopaedic emergency with a high morbidity and mortality prevalence, particularly in people living with Human Immunodeficiency Virus (PLWHIV). A combination of HIV infection, combined antiretroviral therapy (cART), and compromised bone health further increases the risk of fragility fractures. Additionally, HIV-related immune dysfunction, cART-induced osteoporosis, and perioperative infection risks further pose challenges in ongoing surgical management. Despite the rising global prevalence of PLWHIV, no specific guidelines exist for the perioperative and post-operative care of PLWHIV undergoing NOF fracture surgery. This narrative review synthesises the current literature on the surgical management of NOF fractures in PLWHIV, focusing on pre-operative considerations, intraoperative strategies, post-operative complications, and long-term outcomes. It also explores infection control, fracture healing dynamics, and ART’s impact on surgical outcomes while identifying key research gaps. A systematic database search (PubMed, Embase, Cochrane Library) identified relevant studies published up to February 2025. Inclusion criteria encompassed studies on incidence, risk factors, ART impact, and NOF fracture outcomes in PLWHIV. Data were analysed to summarise findings and highlight knowledge gaps. Pre-operative care: Optimisation involves assessing immune status (namely, CD4 counts and HIV-1 viral loads), bone health, and cART to minimise surgical risk. Immunodeficiency increases surgical site and periprosthetic infection risks, necessitating potential enhanced antibiotic prophylaxis and close monitoring of potential start/switch/stopping of such therapies. Surgical management of neck of femur (NOF) fractures in PLWHIV should be individualised based on fracture type (intracapsular or extracapsular), age, immune status, bone quality, and functional status. Extracapsular fractures are generally managed with internal fixation using dynamic hip screws or intramedullary nails. For intracapsular fractures, internal fixation may be appropriate for younger patients with good bone quality, though there is an increased risk of non-union in this group. Hemiarthroplasty is typically favoured in older or frailer individuals, offering reduced surgical stress and lower operative time. Total hip arthroplasty (THA) is considered for active patients or those with pre-existing hip joint disease but carries a higher infection risk in immunocompromised individuals. Multidisciplinary evaluation is critical in guiding the most suitable surgical approach for PLWHIV. Importantly, post-operative care carries the risk of higher infection rates, requiring prolonged antibiotic use and wound surveillance. Antiretroviral therapy (ART) contributes to bone demineralisation and chronic inflammation, increasing delayed union healing and non-union risk. HIV-related frailty, neurocognitive impairment, and socioeconomic barriers hinder rehabilitation, affecting recovery. The management of NOF fractures in PLWHIV requires a multidisciplinary, patient-centred approach ideally comprising a team of Orthopaedic surgeon, HIV Physician, Orthogeriatric care, Physiotherapy, Occupational Health, Dietitian, Pharmacist, Psychologist, and related Social Care. Optimising cART, tailoring surgical strategies, and enforcing strict infection control can improve outcomes. Further high-quality studies and randomised controlled trials (RCTs) are essential to develop evidence-based guidelines. Full article

AIDS-related malignant lymphomas (ARLs) are the lymphomas that develop in association with HIV infection. According to the introduction of combination antiretroviral therapy (cART), the life expectancy of People Living with HIV (PLWH) has markedly improved; however, approximately one-third of PLWH have passed away from the complications of malignancies, even in well-controlled PLWH. HIV itself is not tumorigenic, and most of these tumors are due to co-infection with oncogenic viruses. γ-herpes viruses (Epstein–Barr virus: EBV and Kaposi sarcoma-associated herpesvirus: KSHV) are the most significant risk factors for ARLs. Immunodeficiency, chronic inflammation, accelerated aging, and genetic instability caused by HIV infection, as well as HIV accessory molecules, are thought to promote lymphomagenesis. The prognosis of ARLs is comparable to that of non-HIV cases in the cART era. Intensive chemotherapy with autologous stem cell transplantation is also available for relapsed/refractory ARLs. Since the early stage of HIV infection has no symptoms, significant numbers of HIV-infected individuals have not noticed HIV infection until the onset of AIDS (so-called Ikinari AIDS). Since the ratio of these patients is more than 30% in Japan, hematologists should carefully consider the possibility of HIV infection in cases of lymphoma. Even in an era of cART, ARL remains a critical complication in PLWH, warranting continuous surveillance. Full article

Background/Objectives: This study aims to investigate the influence of demographic, behavioral, anthropometric, and comorbid factors on brain atrophy in people living with HIV (PLWH). Methods: We conducted a cross-sectional study involving 121 HIV-positive patients, stratified into two groups, those with and without brain atrophy (BA). For each participant, we recorded demographic data, smoking status, physical activity levels, disease and treatment duration, and comorbidities. BA was quantitatively assessed using MRI-derived volumetric measurements of 47 cerebral substructures. Results: Patients with BA exhibited significantly reduced gray matter (GM) and white matter (WM) volumes alongside increased cerebrospinal fluid volumes, both in absolute and percentage measurements. WM atrophy was most pronounced in the frontal, parietal, and temporal lobes, with relative sparing of the occipital lobe. GM atrophy predominantly affected the basal ganglia (notably, the thalamus and putamen) and cortical regions, including the hippocampus, frontal, and parietal lobes. Significant positive correlations were observed between BA and both smoking status (pack–years) and disease duration, while physical activity demonstrated an inverse relationship (higher atrophy risk in those with less than 30 min of daily continuous walking). Non-adherence to antiretroviral therapy (ART) was also associated with BA. Among comorbidities, type 2 diabetes and HIV-associated neurocognitive disorders (HAND) showed the strongest associations with BA. Conclusions: Brain atrophy in PWH is correlated with smoking, physical inactivity, and the duration of HIV infection. Comorbid conditions, such as type II diabetes and HAND, amplify the risk for BA. We consider that early lifestyle interventions and optimized ART may mitigate the neurodegeneration process. Full article

Background/Objectives: In addition to classical transmission routes, hepatitis A (HA) outbreaks were, for the first time, linked to sexual activity in the late 1970s, particularly among men who have sex with men (MSM). Since then, outbreaks have continued to emerge globally among adults engaging in high-risk sexual behaviors, reinforcing the ongoing public health significance of this transmission route. Although the COVID-19 pandemic temporarily reduced HA cases, outbreaks reemerged following the relaxation of pandemic measures. This study aims to report the HA outbreak registered at Romania’s tertiary infectious diseases hospital during the first half of 2022. Methods: We retrospectively analyzed all HA cases admitted to the National Institute for Infectious Diseases from 1 January to 1 August 2022. Results: Among 51 cases, eight children (under 14) were excluded from further analyses. Of the 43 remaining cases, 37 (86%) were male, with 20/37 (54.05%) identified as MSM. Twenty-two of the males (59.45%) were previously or concomitantly diagnosed with sexually transmitted diseases (STDs), notably syphilis and HIV. A marginal finding: 14 out of 29 patients screened for hepatitis E tested positive for IgM. The MSM patients exhibited significantly higher transaminase levels (ALT median level 3404 U/L [IQR 2608–5448] vs. 2066 U/L [IQR 1393–3682]) and more severe liver impairment (INR median level 1.37 [IQR 1.18–1.78] vs. 1.18 [IQR 1.11–1.43] compared to non-MSM patients. While direct bilirubin levels were higher in MSM (7.4 mg/dL vs. 5.5 mg/dL), the difference was not statistically significant. Conclusions: An HA outbreak occurred at the beginning of 2022 among Romanian young MSM, with a more severe acute liver injury. High-risk sexual practices may be a potential risk factor for severe HA. This emphasizes the need to screen for STDs in young males with HA and review vaccination policies for at-risk individuals. Full article

The global impact of HIV is especially significant when diagnoses are made in advanced stages. While strategies exist to mitigate late presentations, Ecuador’s 2018–2022 strategic plan has not yet been evaluated. This study assesses the prevalence and implications of late and advanced HIV presentations in Ecuador, using data from a reference hospital in Quito. A cross-sectional analysis of 436 medical records of people living with HIV from the “Hospital de Especialidades Eugenio Espejo” was conducted between November 2015 and February 2020. The data were divided into “Pre-Plan” and “Post-Plan” periods for comparative analysis. The mean CD4 T count showed a non-statistically significant increase in the post-plan period (January 2018–February 2020). Notably, 65.1% of patients presented late, and 39.4% had advanced disease. Demographic data indicated that 89.9% were men, and 54.1% were under 30 years of age. No characteristics were identified that were associated with advanced late presentation of HIV infection. Sexual orientation data revealed that 69.1% identified as homosexual or bisexual. A predominance of late and advanced presenters was identified in the post-plan period, associated with being employed (p < 0.05) and being drug users (p < 0.001). There was also a greater incidence of late presenters among immigrants in the post-plan period (p = 0.045). Despite the implementation of Ecuador’s 2018–2022 strategic plan for HIV, substantial challenges in reducing late presentations remain. This study suggests that early diagnoses have not significantly improved. Employed patients and drug users were more likely to present late, with drug users also accounting for many advanced cases. This study highlights the need for more focused and targeted strategies to supplement the existing plan. Full article

Diagnosis of histoplasmosis is challenging. A rapid, sensitive, and specific method is essential. Serum is a non-invasive and easy sample to obtain in any hospital. The diagnostic accuracy of different techniques that use serum has been evaluated. Forty-one serum samples from patients with proven or probable histoplasmosis were analyzed. Different diagnostic techniques based on the detection of antibodies (ID Fungal Antibody System), antigens (Histoplasma GM EIA and Platelia^TM Aspergillus Ag), and DNA (“in-house” real-time PCR (RT-PCR) were tested and compared. Additionally, the quantification of cytokines and biomarkers related to histoplasmosis was performed. Global results from 27 samples in which all the tests were performed showed that the sensitivity of the Histoplasma GM EIA kit was 87.5% in patients with disseminated infection and HIV as an underlying disease; in immunocompetent (IC) patients, it was 54.5%. The detection of Histoplasma spp. with the ID Fungal Antibody System was positive in 90.9% of IC and in 62.5% of HIV patients. The Platelia-Asp kit had a low performance in both groups of patients (37.5% in HIV and 9% in non-HIV), and, finally, RT-PCR was better in immunosuppressed patients (44% in HIV vs. 27% in non-HIV). The combination of diagnostic techniques increased the detection of Histoplasma infection in inmunosupressed patients. Overall, patient groups infected with H. capsulatum (Hc) showed higher IL-8, IL-6, IL-1β, TNF-α, and IL-18 median values compared to non-Hc-infected controls. The effectiveness of diagnostic techniques on serum samples is highly influenced by the patient’s clinical presentation and underlying condition. Consequently, a thorough assessment of the patient’s clinical presentation and disease phenotype is crucial in selecting the most suitable diagnostic method. Full article

In this study, we investigated the proportion of transmitted drug resistance (TDR) mutations and human immunodeficiency virus (HIV)-1 subtypes among 487 antiretroviral therapy (ART)-naïve individuals in South Korea from 2021 to 2024 to inform more effective treatment strategies. Consistent with previous reports, subtype B was most prevalent among HIV-1 subtypes at 50.7%; however, its proportion decreased annually (p = 0.047). Various subtypes of circulating recombinant forms (CRFs) were analyzed in this study, resulting in high genetic diversity. The subtype distributions of Korean and non-Korean patients differed, with subtype B (53.7%) and CRF01_AE (34.4%) being dominant in the former and latter, respectively. TDR across antiretroviral drug classes was approximately 3.5% in South Korea. Non-nucleoside reverse transcriptase inhibitors elicited the greatest drug resistance, which increased from 2021 to 2023, with a slight decrease in 2024. The integrase strand transfer inhibitor drugs, elvitegravir and raltegravir, most frequently exhibited high resistance scores. We provide a comprehensive overview of the HIV-1 genetic distribution and TDR patterns in South Korea from 2021 to 2024. Within the broader context of HIV-1 epidemiology in Asia and the Pacific, the findings contribute to a comprehensive understanding of the global distribution of HIV-1 resistance and genotypes, enabling the development of effective interventions. Full article

Background: The rise in antimicrobial-resistant (AMR) strains of Neisseria gonorrhoeae is internationally recognised as a critical public health concern, with limited treatment options available. The urgency of this issue prompted the European Centre for Disease Prevention and Control to establish ‘EURO-GASP’ to monitor trends in resistance and address developments. Comprehensive data on AMR strains in people living with HIV (PLHIV) is limited, especially in Cyprus. Objectives: To analyse trends in rates of resistant N. gonorrhoeae infections and identify any correlations between patient factors that may contribute to such in PLHIV in The Republic of Cyprus. Methods: We conducted a retrospective chart review study on N. gonorrhoea resistance among PLHIV from the Gregorios HIV reference clinic in Larnaca, Cyprus, between 2015 and 2023. Antimicrobial susceptibility was assessed via disc diffusion or gradient strip method on GC II agar against a non-homogenous panel of antibiotic preparations, based on standard laboratory practice variation. Demographic and clinical data, including antibiograms, treatments and test of cure, were recorded. Statistical analysis was performed using Stata v16, with significance set at p < 0.05. The study received approval from the Cyprus National Bioethics Committee. Results: A total of 45 isolates from 39 patients were analysed, with 62% of these demonstrating resistance to at least one antibiotic. Resistance rates were not shown to change over time. We identified a statistically significant linear association between a person having a history of an STI and the number of antibiotics which the isolate is resistant to (β = 1.2; p: 0.004). Notably, a single isolate demonstrated resistance to ceftriaxone, the first-line treatment currently recommended in both Europe and the United States. This finding is particularly alarming given the critical role of ceftriaxone in the management of gonorrhoea. Conclusions: Whilst there has been no increase in resistance rates over time, the detection of ceftriaxone-resistant N. gonorrhoeae is a significant public health concern. Given that having a history of an STI makes a person more likely to develop a resistant infection, PLHIV or those who engage in risky sexual behaviours are particularly vulnerable. There is a pressing need to enhance surveillance and implement routine susceptibility testing in Cyprus, given the country’s role as a major international hub for travel and migration. Molecular analysis can further improve our understanding. Additionally, the global public health community must urgently prioritise the development of novel therapeutic agents for the treatment of gonorrhoea. Full article

Neuropathic pain is a chronic disorder that arises from damaged or malfunctioning nerves. Hypersensitivity to stimuli, also known as hyperalgesia, can cause a person to experience pain from non-painful stimuli, termed allodynia. Cannabis-based medicines (CBMs) may provide new treatment options to manage neuropathic pain. A review of the relevant studies was conducted to evaluate the effectiveness of CBMs in treating neuropathic pain. Scientific literature was systematically searched from January 2003 to December 2024 using the Web of Science Core Collection, PubMed, and MEDLINE. A total of 22 randomized controlled trials (RCTs) were identified that considered the use of 1′,1′-dimethylheptyl-Δ⁸-tetrahydrocannabinol-11-oic acid (CT-3), Δ⁹-tetrahydrocannabinol (Δ⁹-THC), cannabidiol (CBD), combinations of Δ⁹-THC with CBD, and cannabidivarin for treatment of neuropathic pain. Significant reductions in pain were reported in 15 studies focused on the treatment of multiple sclerosis, spinal cord injuries, diabetic neuropathy, postherpetic neuralgia, HIV-associated sensory neuropathy, peripheral neuropathic pain, complex regional pain syndrome, chronic radicular neuropathic pain, and peripheral neuropathy of the lower extremities. These positive outcomes often adopted personalized and adjusted dosing strategies. By contrast, seven RCTs observed no significant pain relief compared to placebo, although some had minor improvements in secondary outcomes, such as mood and sleep. Collectively, CBM treatments may improve pain scores, but study limitations such as small sample sizes and study durations, high placebo response rates, and trial unblinding because of the psychoactive effects of cannabinoids all hinder data interpretation and the extrapolation to chronic pain conditions. Hence, future RCTs will need to have larger numbers and be more extended studies that explore optimal dosing and delivery methods and identify patient subgroups that are most likely to benefit. While CBMs show potential, their current use balances modest benefits against possible adverse effects and variable outcomes. 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