Distinct profile of antiviral drugs effects in aortic and pulmonary endothelial cells revealed by high-content microscopy and cell painting assays.

Antiretroviral therapy have significantly improved the treatment of viral infections and reduced the associated mortality and morbidity rates. However, highly effective antiretroviral therapy (HAART) may lead to an increased risk of cardiovascular diseases, which could be related to endothelial toxicity. Here, seven antiviral drugs (remdesivir, PF-00835231, ritonavir, lopinavir, efavirenz, zidovudine and abacavir) were characterized against aortic (HAEC) and pulmonary (hLMVEC) endothelial cells, using high-content microscopy. The colourimetric study (MTS test) revealed similar toxicity profiles of all antiviral drugs tested in the concentration range of 1 nM-50 µM in aortic and pulmonary endothelial cells. Conversely, the drugs' effects on morphological parameters were more pronounced in HAECs as compared with hLMVECs. Based on the antiviral drugs' effects on the cytoplasmic and nuclei architecture (analyzed by multiple pre-defined parameters including SER texture and STAR morphology), the studied compounds were classified into five distinct morphological subgroups, each linked to a specific cellular response profile. In relation to morphological subgroup classification, antiviral drugs induced a loss of mitochondrial membrane potential, elevated ROS, changed lipid droplets/lysosomal content, decreased von Willebrand factor expression and micronuclei formation or dysregulated cellular autophagy. In conclusion, based on specific changes in endothelial cytoplasm, nuclei and subcellular morphology, the distinct endothelial response was identified for remdesivir, ritonavir, lopinavir, efavirenz, zidovudine and abacavir treatments. The effects detected in aortic endothelial cells were not detected in pulmonary endothelial cells. Taken together, high-content microscopy has proven to be a robust and informative method for endothelial drug profiling that may prove useful in predicting the organ-specific endothelial toxicity of various drugs.

Evaluating experiences of HIV-related stigma among people living with HIV diagnosed in different treatment eras in British Columbia, Canada.

There is mixed evidence on whether experiences of HIV-related stigma are mitigated with lived experience. We sought to examine whether people living with HIV (PLWH) with longer living experience reported varying levels of HIV-related stigma. Between January 2016-September 2018, we used purposive sampling to enrol PLWH aged ≥19 across British Columbia, Canada, where participants completed the 10-item Berger HIV Stigma Scale. We conducted bivariate analyzes examining key sociodemographic characteristics and HIV-related stigma scores. Multivariable linear regression modelled the association between year of HIV diagnosis by treatment era and HIV-related stigma scores. We enrolled 644 participants; median age at enrolment was 50 years (Q1-Q3: 42-56), with 37.4% (n = 241) diagnosed before the year 2000. The median HIV-stigma scores of all participants (19.0, Q1-Q3: 13-25, range 0-40) stratified by treatment era were: 17.0 (pre-1996), 20.0 (1996-1999), 20.0 (2000-2009), 19.0 (2010-2018) (p = 0.03). While there was a significant association at the univariate level, year of HIV diagnosis by treatment era was not associated with stigma scores after controlling for age, gender, HIV key populations, ethnicity, relationship status, social support, and ever having a mental health disorder diagnosis. This suggests that PLWH still experience HIV-related stigma today, compared to those diagnosed in earlier time periods.

Exploring the association between erythema multiforme and HIV infection: some mechanisms and implications.

Erythema multiforme (EM) is an immune-mediated mucocutaneous condition characterized by hypersensitivity reactions to antigenic stimuli from infectious agents and certain drugs. The most commonly implicated infectious agents associated with EM include herpes simplex virus (HSV) and Mycoplasma pneumoniae. Other infectious diseases reported to trigger EM include human immunodeficiency virus (HIV) infection and several opportunistic infections. However, studies focusing on EM and human immunodeficiency virus (HIV) infection are scarce. even though the incidence of EM among HIV-infected individuals have increased, the direct and indirect mechanisms that predispose HIV-infected individuals to EM are not well understood. In turn, this makes diagnosing and managing EM in HIV-infected individuals an overwhelming task. Individuals with HIV infection are prone to acquiring microorganisms known to trigger EM, such as HSV, Mycobacterium tuberculosis, Treponema pallidum, histoplasmosis, and many other infectious organisms. Although HIV is known to infect CD4 + T cells, it can also directly bind to the epithelial cells of the oral and genital mucosa, leading to a dysregulated response by CD8 + T cells against epithelial cells. HIV infection may also trigger EM directly when CD8 + T cells recognize viral particles on epithelial cells due to the hyperactivation of CD8 + T-cells. The hyperactivation of CD8 + T cells was similar to that observed in drug hypersensitivity reactions. Hence, the relationship between antiretroviral drugs and EM has been well established. This includes the administration of other drugs to HIV-infected individuals to manage opportunistic infections. Thus, multiple triggers may be present simultaneously in HIV-infected individuals. This article highlights the potential direct and indirect role that HIV infection may play in the development of EM and the clinical dilemma that arises in the management of HIV-infected patients with this condition. These patients may require additional medications to manage opportunistic infections, many of which can also trigger hypersensitivity reactions leading to EM.

Hepatoprotective effect of methanol fruit extract of Punica granatum L in highly active antiretroviral therapy-induced toxicity in Wistar rats.

Prolonged use of Highly Active Antiretroviral Therapy (HAART) has been linked to toxicity, particularly hepatotoxicity. There are few effective drugs for HAART patients that promote hepatic cell regeneration and prevent liver injury. Therefore, the purpose of this study was to investigate the hepato-protective activity of Methanol fruit extract of Punica granatum (MFEPG) in HAART-administered rats. Thirty rats weighing between 150-200 g were randomly divided into six groups and each group comprised of five rats. Distilled water was given to the rats in group one. Only HAART was given to the rats in group two. MFEPG at doses of 100 and 400 mg/kg was given to the rats in groups three and four. MFEPG dosages of 100 and 400 mg/kg along with HAART were given to the rats in groups five and six, respectively. All treatments were via oral gavage daily for 40 days. Under halothane anesthesia, all rats were sacrificed on day 41. Liver tissues were utilized for lipid peroxidation marker; Malondialdehyde (MDA), antioxidant enzymes; Superoxide dismutase (SOD) and Catalase (CAT) and histological evaluation, while blood samples were examined for biochemical parameters (AST, ALT, ALP, Total cholesterol, Total protein, and Albumin). The HAART-treated group exhibited a significantly higher amount of the lipid peroxidation end product; MDA, and significantly lower levels of antioxidant enzymes; SOD, and CAT. Liver enzymes and total cholesterol were significantly increased with a significant reduction in Total protein and Albumin levels in the HAART-treated group. Conversely, the liver function biomarkers were returned to normal levels in the HAART and MFEPG-treated groups. Histopathological studies revealed that when HAART-exposed rats were treated with MFEPG, both the biochemical and histological results significantly improved. Thus, the antioxidant activity of MFEPG provides protection against HAART-induced liver oxidative damage. More research is needed to determine the safety of using MFEPG in humans.

The Complex Dysregulations of CD4 T Cell Subtypes in HIV Infection.

Human immunodeficiency virus (HIV) infection remains an important global public health problem. About 40 million people are infected with HIV, and this infection caused about 630,000 deaths in 2022. The hallmark of HIV infection is the depletion of CD4+ T helper lymphocytes (Th cells). There are at least seven different Th subtypes, and not all are the main targets of HIV. Moreover, the effect of the virus in a specific subtype can be completely different from that of the others. Although the most compromised Th subtype in HIV infection is Th17, HIV can induce important dysregulations in other subtypes, such as follicular Th (Tfh) cells and regulatory Th cells (Treg cells or Tregs). Several studies have shown that HIV can induce an increase in the immunosuppressive activity of Tregs without causing a significant reduction in their numbers, at least in the early phase of infection. The increased activity of this Th subtype seems to play an important role in determining the immunodeficiency status of HIV-infected patients, and Tregs may represent a new target for innovative anti-HIV therapies, including the so-called "Kick and Kill" therapeutic method whose goal is the complete elimination of the virus and the healing of HIV infection. In this review, we report the most important findings on the effects of HIV on different CD4+ T cell subtypes, the molecular mechanisms by which the virus impairs the functions of these cells, and the implications for new anti-HIV therapeutic strategies.

Effect of genetic variations in drug transporters, metabolizing enzyme and regulatory genes on the development of HIV-associated lipodystrophy.

Adipocytes play a crucial role in the metabolism of lipids and sugars. Their response varies depending on the circumstances or other factors influenced by physiological and metabolic stresses. People living with HIV (PLWH) experience different effects of HIV and highly active antiretroviral therapy (HAART) on their body fat. Some patients respond well to antiretroviral therapy (ART), while others taking similar regimens do not. The genetic makeup of patients has been strongly linked to the variable responses to HAART among PLWH. The cause of HIV-associated lipodystrophy syndrome (HALS) is not well understood, but it may be influenced by genetic variations in the host. The metabolism of lipid effectively modulates plasma triglyceride and high-density lipoprotein cholesterol levels in PLWH. Genes related to drug metabolism and transport play an important role in the transportation and metabolism of ART drugs. Genetic variation in metabolizing enzyme genes of antiretroviral drugs, lipid transport and transcription factor-related genes could interfere with fat storage and metabolism, contributing to the development of HALS. Hence we examined the impact of genes associated with transport, metabolism and various transcription factors in metabolic complications, and their impact on HALS. A study using databases such as PubMed, EMBASE and Google Scholar was conducted to understand the impact of these genes on metabolic complications and HALS. The present article discuss the changes in the expression and regulation of genes and their involvement in the lipid metabolism, lipolysis and lipogenesis pathways. Moreover, alteration of the drug transporter, metabolizing enzyme and various transcription factors can lead to HALS. Single-nucleotide polymorphisms in genes that play an essential role in drug metabolism and drug and lipid transportation may also contribute to individual differences in the emergence of metabolic and morphological alterations during HAART treatment.

Trend over time of HIV-1 drug resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and their drivers: A cohort study from Antiviral Response Cohort Analysis (ARCA).

The rise of HIV-1 drug resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) threatens the long-term success of NNRTI-based therapies. Our study aims to describe the circulation of major resistance-associated mutations (RAMs) for NNRTIs in people living with HIV (PLWH) in Italy from 2000 to 2020. We included 5982 naïves and 28 505 genotypes from 9387 treatment-experienced PLWH from the Antiviral Response Cohort Analysis (ARCA) cohort. Transmitted drug resistance (TDR) was found in 12.5% and declined from 17.3% in 2000-2003 to 10.9% in 2016-2020 (p = 0.003). Predictors of TDR were viral subtype B [vs. non-B, adjusted odds ratio (aOR) = 1.94, p < 0.001], zenith viral load (VL) (per 1 log10 higher, aOR = 0.86, p = 0.013), nadir CD4 cell count (per 100 cells/µL increase aOR = 0.95, p = 0.013). At least one RAM for NNRTIs among treatment experienced PLWH was detected in 33.2% and pre-treatment drug resistance (PDR) declined from 43.4% in 2000-2003 to 20.9% in 2016-2020 (p < 0.001). Predictors of PDR were sexual transmission route (vs. others, aOR = 0.78, p < 0.001), time since HIV diagnosis (per 1 month longer, aOR = 1.002, p < 0.001), viral subtype B (vs. non B, aOR = 1.37, p < 0.001), VL (per 1 log10 higher, aOR = 1.12, p < 0.001), nadir CD4 count (per 100 cells/µL increase, aOR = 0.91, p < 0.001), previous exposure to any NNRTI (aOR = 2.31, p < 0.001) and a more recent calendar year sequence (any time span > 2008 vs. 2000-2003, any aOR <1, p < 0.001). Circulation of RAMs to NNRTIs declined during the last 20 years in Italy. NNRTIs remain pivotal drugs for the management of HIV-1 due to safety concerns and long-acting options.

Prevalence and factors associated with late diagnosis among older adults living with HIV in liuzhou, China: 2010-2020.

This paper aimed to quantify and characterize the prevalence and associated factors for late diagnosis in older adults living with human immunodeficiency virus (HIV) in Liuzhou, China, from 2010 to 2020. The characteristics of older adults living with HIV were described separately in time, space and population. Multivariate logistic regression analysis evaluates the factors influencing late diagnosis in HIV-positive adults ≥ 50 years of age. The majority of older adults living with HIV were over 60 years old, male, and with CD4 counts < 200 cells/µl at diagnosis, with most late diagnoses being more likely to report heterosexual transmission. These two factors may potentially provide a positive influence on late diagnosis: older and CD4 counts < 500 cells/µl. In contrast, females and those with homosexual or other transmission provide a negative. These results suggest that late diagnosis of HIV-positive adults ≥ 50 years of age remains a severe and growing epidemiological issue.

Successful virologic outcomes over time among HAART-treated HIV-infected patients.

Few large studies evaluated the effects of time trends on virologic suppression in people living with HIV/AIDS (PLWHA) in China. To address this, An retrospective observational longitudinal study was conducted. We examined annual trends in the rate of virologic suppression, the viral load at the time of virologic suppression, and other determinants of virologic suppression in Zhejiang Province, China in PLWHA between January 2013 and July 2018. Patients who received a treatment regimen for at least 24 weeks were included. Virologic suppression was defined as VL ≤50 copies/mL. Generalized estimating equation logistic regression models were used to adjust for covariates. We included 16,265 patients with 45023 tests. The proportion of patients who experienced an unsuccessful virologic outcome decreased continuously throughout the observation period (18.14% to 6.64%). Time was significantly negatively associated with detectable VL (all ORs <1). Other factors were positively associated with detectable VL, including patients <30 years of age, single, non-adherent to treatment, and with a follow-up CD4 count <200 cells/µL. Patients infected through homosexual transmission and those with a longer ART duration were more likely to reach virologic suppression. We demonstrated outstanding time trend improvements in the virological outcomes of PLWHA in China.

Isolated collagenoma in an HIV-positive patient on ART: a case report.

BACKGROUND: Collagenomas are rare connective tissue hamartomas composed of dermal collagen. Patients infected with human immunodeficiency virus (HIV) can present with HIV-related lipodystrophy or lipomas. There are no known associations between HIV and collagenomas. CASE PRESENTATION: Here we describe a case of an isolated collagenoma in an HIV patient on ART. The lesion was a seven by four-centimeter subcutaneous nodule with no epidermal changes located on the occipital scalp. This lesion was excised, and histopathology showed thick and randomly arranged collagen bundles, consistent with a collagenoma. CONCLUSION: This case represents an isolated collagenoma presenting in a patient with HIV. It is unclear whether HIV or ART contributed to the development of this collagenoma. Treatment of collagenomas include surgical excision and intralesional corticosteroids. In addition to lipoma or lipodystrophy, it is important to keep collagenoma in the differential diagnosis in a patient presenting with an isolated large indurated subcutaneous nodule.

Clinical features and treatment effect of HIV-associated immune thrombocytopenia-single center Ten-Years data summary.

Thrombocytopenia represents one of the most prevalent hematologic complications observed in patients infected with the human immunodeficiency virus (HIV). In this study, we sought to analyze the clinical characteristics and treatment outcomes of patients with coexisting HIV and thrombocytopenia. Specifically, we retrospectively examined the medical records of 45 patients diagnosed with HIV/AIDS and thrombocytopenia at the Yunnan Infectious Diseases Specialist Hospital between January 2010 and December 2020, all of whom received highly active antiretroviral therapy (HAART) with/without glucocorticoids. The median follow-up period was 79 days, ranging between 14 and 368 days, the total platelet count was higher after receiving treatment than before (Z = -5.662, P < .001). Among the cohort, 27 patients (60.0%) responded to treatment, with 12 patients (44.44%) experiencing relapse during the follow-up period. The response rate (80.00%) of newly diagnosed ITP were significantly higher than of persistent ITP (28.57%) and chronic ITP (38.46%) (\x 2 = 9.560, P = .008) and the relapse rate of the newly diagnosed ITP (30.00%) was significantly lower than the persistent ITP and chronic ITP (100.00%, 80.00%) (\x2 = 6.750, P = .034). Notably, we found that the number of CD4+ T cells, duration of HIV infection, selection of HAART and type of glucocorticoids administered displayed no statistically significant effect on platelet count, treatment response, or relapse rate. However, we observed a significant decrease in platelet count in hepatitis C virus-positive individuals coinfected with HIV compared to those with HIV alone (Z = -2.855, P = .003). Our findings suggest that patients diagnosed with HIV and thrombocytopenia exhibit a low response rate to treatment and have an increased likelihood of relapse.

The impact of the COVID-19 pandemic on routine HIV care and cervical cancer screening in North-Central Nigeria.

INTRODUCTION: Cervical cancer is the fourth most diagnosed cancer among women globally, with much of the burden being carried by women in limited-resource settings often worsened by the high prevalence of HIV. Furthermore, the COVID-19 pandemic disrupted organized screening efforts and HIV management regimens worldwide, and the impact of these disruptions have not been examined in these settings. The purpose of this paper is to describe whether uptake of cervical cancer screening and HIV management changed before, during, and since the COVID-19 pandemic in North-Central Nigeria. METHODS: Longitudinal healthcare administration data for women who obtained care between January 2018 and December 2021 were abstracted from the AIDS Prevention Initiative Nigeria (APIN) clinic at Jos University Teaching Hospital. Patient demographics, pap smear outcomes, and HIV management indicators such as viral load and treatment regimen were abstracted and assessed using descriptive and regression analyses. All analyses were conducted comparing two years prior to the COVID-19 pandemic, the four quarters in 2020, and the year following COVID-19 restrictions. RESULTS: We included 2304 women in the study, most of whom were between 44 and 47 years of age, were married, and had completed secondary education. About 85% of women were treated with first line highly active retroviral therapy (HAART). Additionally, 84% of women screened using pap smear had normal results. The average age of women who sought care at APIN was significantly lower in Quarter 3, 2020 (p = 0.015) compared to the other periods examined in this study. Conversely, the average viral load for women who sought care during that period was significantly higher in adjusted models (p < 0.0001). Finally, we determined that the average viral load at each clinic visit was significantly associated with the period in which women sought care. CONCLUSIONS: Overall, we found that COVID-19 pandemic mitigation efforts significantly influenced women's ability to obtain cervical cancer screening and routine HIV management at APIN clinic. This study buttresses the challenges in accessing routine and preventive care during the COVID-19 pandemic, especially in low-resource settings. Further research is needed to determine how these disruptions to care may influence long-term health in this and similar at-risk populations.

Staged HIV transmission and treatment in a dynamic model with long-term partnerships.

The transmission dynamics of HIV are closely tied to the duration and overlap of sexual partnerships. We develop an autonomous population model that can account for the possibilities of an infection from either a casual sexual partner or a long-term partner who was either infected at the start of the partnership or has been newly infected since the onset of the partnership. The impact of the long-term partnerships on the rate of infection is captured by calculating the expected values of the rate of infection from these extended contacts. The model includes three stages of infectiousness: acute, chronic, and virally suppressed. We calculate HIV incidence and the fraction of new infections attributed to casual contacts and long-term partnerships allowing for variability in condom usage, the effect of achieving and maintaining viral suppression, and early intervention by beginning HAART during the acute phase of infection. We present our results using data on MSM HIV transmission from the CDC in the U.S. While the acute stage is the most infectious, the majority of the new infections will be transmitted by long-term partners in the chronic stage when condom use is infrequent as is common in long-term relationships. Time series analysis of the solution, as well as parameter sensitivity analysis, are used to determine effective intervention strategies.

Incidence of complications and revision surgery in HAART compliant HIV patients undergoing primary total hip and knee arthroplasty: an institutional review.

INTRODUCTION: Human immunodeficiency virus (HIV) positive patients are at high risk for osteonecrosis along with age-related osteoarthritis, resulting in a high number of joint reconstruction surgeries at younger ages in these immunosuppressed patients. Few previous studies have reported on patient outcomes in HAART (highly active antiretroviral therapy) compliant patients undergoing primary arthroplasty. The aim of this study is to report one institution's overall rate of complications and revision in HAART-compliant patients after primary hip and knee arthroplasty. METHODS: A retrospective chart review was performed spanning a 4 year period. This study included 50 primary joint arthroplasty patients diagnosed with HIV including 13 TKA (total knee arthroplasty) and 37 THA (total hip arthroplasty) with a prior diagnosis of HIV infection. Preoperative CD4 count and viral loads were recorded. Charts were reviewed for post-operative complications including infection and revision. RESULTS: The were a total of 11 postoperative complications (22%). There were 3 cases (6%) of soft tissue infection, 3 cases (6%) of implant loosening, 2 cases (4%) of dislocation, 1 case (2%) of lower extremity weakness, 1 case (2%) of venous thrombosis, and 1 case (2%) of arthrofibrosis. Of all patients, there were 6 cases of revision in this cohort (12%), 5 of which were aseptic etiology. All 3 infected patients had a history of IVDU. Two of these infected patients resolved with IV antibiotics while 1 underwent two-stage revision (2%). Patients that experienced post-operative complications had significantly elevated preoperative CD4 levels (983 versus 598, p = 0.003). CONCLUSION: Arthroplasty is a viable option for HAART-compliant patients. Most previous studies showing a higher risk for deep tissue infection and revision in HIV patients have not accounted for modern HAART. Our results show that compliance with HAART has vastly improved the outcomes of arthroplasty in these patients, while a history of IVDU is likely the largest risk factor for infection in this population.

Prevalence and Aetiology of Visual Impairment and Blindness in Persons with HIV/AIDS on Highly Active Anti-Retroviral Therapy in Benin City, Nigeria.

BACKGROUND: The use of Highly Active Anti-Retroviral Therapy (HAART) has revolutionized the course and pattern of eye diseases in persons with HIV/AIDS which ultimately affects the visual status. OBJECTIVE: To determine the prevalence and etiology of visual impairment and blindness in people with HIV/AIDS on HAART in Benin City, Nigeria. METHODOLOGY: This was a descriptive hospital-based study on all HIV/AIDS patients on HAART in the United States President's Emergency Plan for AIDS Relief (PEPFAR) clinics of University of Benin Teaching Hospital seen from July to August 2018 and Central Hospital, Benin City in October 2019. Demographic data and other relevant questions related to the disease were obtained from participants and recorded in an interviewer administered questionnaire. Participants were examined and ocular findings recorded. The IBM SPSS software version 21 was used for data analysis and level of significance set at p<0.05. RESULTS: There were 451 persons comprising 104 (23.1%) males and 347 (76.9%) females. More participants, 176(39%) were within the age group 41-50 years, with a mean age of 46.6± 10.78 years, and age range of 14-75 years. Visual impairment was present in 105 (23.3%), blindness in 10 (2.2%) and 336(74.5%) had normal visual acuity. Refractive error was the most common cause of mild 34 (29.6%) and moderate 23(20%) visual impairment. Cataract 4(3.5%) was the predominant cause of blindness. There was no case of severe visual impairment recorded. CONCLUSION: The major causes of visual impairment and blindness in persons with HIV are not HIV-related diseases which may be an indication of improved management protocols.

CONTEXTE: L'utilisation de la thérapie antirétrovirale hautement active (HAART) a révolutionné le cours et le modèle des maladies oculaires chez les personnes atteintes du VIH/SIDA, ce qui affecte finalement l'état visuel. OBJECTIF: Déterminer la prévalence et l'étiologie de la déficience visuelle et de la cécité chez les personnes atteintes du VIH/SIDA sous HAART à Benin City, au Nigeria. MÉTHODOLOGIE: Il s'agissait d'une étude descriptive en milieu hospitalier sur tous les patients atteints du VIH/sida sous HAART dans les cliniques du Plan d'urgence du président des États-Unis pour la lutte contre le sida (PEPFAR) de l'hôpital universitaire de Benin vu de juillet à août 2018 et de l'hôpital central de Benin City en octobre 2019. Les données démographiques et d'autres questions pertinentes liées à la maladie ont été obtenues des participants et enregistrées dans un questionnaire administré par un enquêteur. Les participants ont été examinés et les résultats oculaires enregistrés. Le logiciel IBM SPSS version 21 a été utilisé pour l'analyse des données et le niveau de signification fixé à p<0,05. RÉSULTATS: 451 personnes ont été recensées, dont 104 (23,1%) hommes et 347 (76,9%) femmes. La plupart des participants, 176 (39%) étaient dans la tranche d'âge 41-50 ans, avec un âge moyen de 46,6± 10,78 ans, et une fourchette d'âge de 14-75 ans. La déficience visuelle était présente chez 105 (23,3%), la cécité chez 10 (2,2%) et 336 (74,5%) avaient une acuité visuelle normale. L'erreur de réfraction était la cause la plus fréquente de déficience visuelle légère (34, 29,6%) et modérée (23, 20 %). La cataracte, 4 (3,5 %), était la cause prédominante de cécité. Aucun cas de déficience visuelle grave n'a été enregistré. CONCLUSION: Les principales causes de déficience visuelle et de cécité chez les personnes séropositives ne sont pas des maladies liées au VIH, ce qui peut indiquer une amélioration des protocoles de prise en charge. Mots clés: Déficience Visuelle, Cécité, VIH/SIDA, HAART.

Tympanometric findings among adult HIV patients undergoing a short-term treatment with high active antiretroviral therapy (HAART) in port harcourt.

Background: In our practice as ENT specialists, people living with Human immunodeficiency Virus/acquired immunodeficiency syndrome (HIV/AIDS) have presented at the clinics with symptoms suggestive of otitis media with effusion such as the sensation of fluid in the ear, aural fullness and hearing loss. Eustachian tube dysfunction which is often the beginning of middle ear pathology could be caused by nasal allergy, upper respiratory tract infection, or obstruction by a nasal pharyngeal lesion such as lymphoid hyperplasia which is a common feature in people living with HIV/AIDS. Tympanometric findings give a measure of the objective assessment of middle ear function. Aim and Objective: This study was designed to determine tympanometric findings among adult patients undergoing short-term treatment with HAART in Port Harcourt. Patients and Methods: A hospital-based study involving 150 HIV-positive patients that received the same HAART treatment over 6 months and a control group of 150 HIV-negative individuals in Port Harcourt. The data extracted includes; the patient's ear symptoms, otoscopic findings, and tympanogram. Data were analyzed using SPSS version 20 and statistical significance was set at P > 0.05. Results: There was a high proportion of type B-Typanogram at baseline (Rt ear 24[16.0%], left ear 23 [15.3%]) and at repeat (Rt ear 23 (15.3%), Lt ear 21 (14%) evaluations. Also, there was a relatively high proportion of type C- tympanogram at baseline {right ear 18 (12%), left ear 15 (10%)} and at repeat Rt ear 14 (9.3%), Lt ear 10 (6.7%)} evaluations. Conclusion: One out of every eight patients living with HIV infection may likely have Eustachian tube dysfunction while one out of every five may have developed otitis media with effusion already. There was no significant change in tympanometric findings after treatment with HAART.

Risk factors of severe hepatotoxicity among HIV-1 infected individuals initiated on highly active antiretroviral therapy in the Northwest Region of Cameroon.

BACKGROUND: Hepatotoxicity due to highly active antiretroviral therapy (HAART) has gained prominent attention since it can be affected by many factors. The aim of this study was to determine the prevalence of hepatotoxicity and related risk factors of severe hepatotoxicity following HAART initiation. METHODS: A total of 100 drug-naive patients aged between 18 and 61 years were recruited. They were put on Tenofovir/Lamivudine/Efavirenz [TDF/3TC/EFV] (64), Zidovudine/ Lamivudine/Efavirenz [AZT/3TC/EFV] (22), and Zidovudine/Lamivudine/Nevirapine AZT/3TC/NVP (14) and monitored for 6months and blood samples drawn.Alanine aminotransferases (ALT), aspartate aminotransferases (AST), and alkaline phosphatase (ALP) wereanalyzed by enzymatic methods and used to classify levels of hepatotoxicity. RESULTS: A total of 37(37%) and 49(49%) patients presented with hepatotoxicity while 15% and 28% had severe hepatotoxicity at 4 and 24 weeks respectively. Serum levels of all enzymes increased significantly (p = 0.001) with increased treatment duration. Univariate analysis revealed that the risk factor of developing severe hepatotoxicity was significantly greater in patients < 30years (p = 0.02), males(p = 0.04), low BMI (p = 0.02), low monthly income (p = 0.01) earners, and patients on AZT + 3TC + NVP regimen (p = 0.01). While multivariate analysis at p < 0.09 showed that age 30-40 years, low BMI, low monthly income, and the use of AZT + 3TC + NVP regimen were independent risk factors. CONCLUSIONS: Low BMI, age group of 30-40years, low monthly income, and the use of AZT + 3TC + NVP regimen identified as risk factors for the development of severe hepatotoxicity should be considered as an important strategy by clinicians in preventing the hepatotoxicity.

Stroke among highly active antiretroviral therapy-naive people living with the human immunodeficiency virus in China: a retrospective study of the characteristics, risk factors, and prognosis.

BACKGROUND: We aimed to clarify the characteristics, risk factors, and prognosis of stroke among HAART-naive people living with HIV (PLWH) in China. METHODS: We selected HAART-naive PLWH admitted to Beijing Ditan Hospital, Capital Medical University, from 1 January 2009 to 31 December 2019. Demographic and clinical data were obtained by searching an anonymous electronic case system. Descriptive analysis and logistic regression and Cox proportional hazard models were used to determine the characteristics and predictors of stroke among all HAART-naive PLWH and evaluate the risk factors of mortality in HAART-naive PLWH with stroke. RESULTS: Stroke was diagnosed in 105 cases (3.7%) of 2867 HAART-naive PLWH. Multivariate logistic regression indicated that age of 30-55 years (OR 1.903, 95% CI 1.005-3.603, p = 0.048), age of ≥ 55 years (OR 4.104, 95% CI 1.928-8.737, p < 0.001), and CD4 count of < 200 cells/µL (OR 2.005, 95% CI 1.008-3.985, p = 0.047) were associated with increased odds of stroke. Diabetes (OR 3.268, 95% CI 1.744-6.125, p < 0.001), hypertension (OR 2.301, 95% CI 1.425-3.717, p = 0.001), syphilis (OR 2.003, 95% CI 1.300-3.089, p = 0.002), and complicated AIDS-defining CNS diseases (OR 7.719, 95% CI 4.348-13.703, p < 0.001) were risk factors for stroke. Of the 105 stroke patients, 12 (11.4%) died during hospitalisation, and the risk factors for mortality among patients with stroke were age of > 65 years (AHR: 8.783, 95% CI 1.522-50.668, p = 0.015), complicated severe pneumonia (AHR: 3.940, 95% CI 1.106-14.029, p = 0.034), and AIDS-defining CNS diseases (AHR: 19.766, 95% CI 3.586-108.961, p = 0.001). CONCLUSIONS: For HAART-naive people living with HIV (PLWH), stroke occurred in various age groups, and early screening for stroke, timely intervention for risk factors among patients in various age groups, and controlling the CD4 count are extremely important in reducing the burden of stroke.

Characteristics and outcomes of patients admitted to a tertiary academic hospital in Pretoria with HIV and severe pneumonia: a retrospective cohort study.

BACKGROUND: Human immunodeficiency virus (HIV) contributes significantly to morbidity and mortality in South Africa. Pneumonia and opportunistic infections remain a major cause for hospital admission among those living with HIV, even in the era of the widespread availability of antiretroviral therapy. METHODS: In this retrospective cohort study, the records of patients admitted with HIV and severe pneumonia, requiring high care/intensive care admission, during a period of 12 months (February 2018 to January 2019) were reviewed. Demographic details, antiretroviral use, HIV viral load, CD4 count, sputum culture results and radiological imaging of patients were recorded. Data was analysed to determine variables associated with mortality. RESULTS: One hundred and seventeen patient records were reviewed for this study. The patients were young (mean age 38.3 years), had advanced disease with low CD4 counts (mean 120.2 cells/mm3) and high HIV viral loads (mean 594,973.7 copies/mL). Only 36.9% (42/117) were on highly active antiretroviral therapy (HAART) on presentation to the hospital. Mycobacterium tuberculosis (M. tuberculosis) was found to be the cause for pneumonia in 35% (41/117), whilst Pneumocystis jirovecii (P. jirovecii) was found in 21.4% (25/117). Bacterial pneumonia was the cause in 17.1% (20/117) of patients while no specific aetiology was found in 26.6% (31/117) of patients in the cohort. Mortality among the cohort studied was high (40.1%) and the average length of stay in hospital in excess of two weeks. The need for ICU admission, ventilation and CMV viremia was associated with increased mortality. Chest X-ray findings did not correlate with the aetiology of pneumonia, but multiple B-lines on lung ultrasound correlated with P. jirovecii as an aetiology and there was a signal that pleural effusion with fibrin stranding predicts tuberculosis. CONCLUSIONS: Patients studied presented with advanced HIV and were often naïve to antiretroviral therapy. Mortality in this cohort of young patients was high, which emphasis the need for earlier diagnosis and treatment of HIV at a primary care level. Lung ultrasound may have clinical utility in the management of patients with HIV and pneumonia, particularly to diagnose P. jirovecii as an aetiology.

Off-label use of combined antiretroviral therapy, analysis of data collected by the Italian Register for HIV-1 infection in paediatrics in a large cohort of children.

BACKGROUND: Early start of highly active antiretroviral therapy (HAART) in perinatally HIV-1 infected children is the optimal strategy to prevent immunological and clinical deterioration. To date, according to EMA, only 35% of antiretroviral drugs are licenced in children < 2 years of age and 60% in those aged 2-12 years, due to the lack of adequate paediatric clinical studies on pharmacokinetics, pharmacodynamics and drug safety in children. METHODS: An observational retrospective study investigating the rate and the outcomes of off-label prescription of HAART was conducted on 225 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018. RESULTS: 22.2% (50/225) of included children were receiving an off-label HAART regimen at last check. Only 26% (13/50) of off-label children had an undetectable viral load (VL) before the commencing of the regimen and the 52.0% (26/50) had a CD4 + T lymphocyte percentage > 25%. At last check, during the off label regimen, the 80% (40/50) of patients had an undetectable VL, and 90% (45/50) of them displayed CD4 + T lymphocyte percentage > 25%. The most widely used off-label drugs were: dolutegravir/abacavir/lamivudine (16%; 8/50), emtricitbine/tenofovir disoproxil (22%; 11/50), lopinavir/ritonavir (20%; 10/50) and elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (10%; 10/50). At logistic regression analysis, detectable VL before starting the current HAART regimen was a risk factor for receiving an off-label therapy (OR: 2.41; 95% CI 1.13-5.19; p = 0.024). Moreover, children < 2 years of age were at increased risk for receiving off-label HAART with respect to older children (OR: 3.24; 95% CI 1063-7.3; p = 0.001). Even if our safety data regarding off-label regimens where poor, no adverse event was reported. CONCLUSION: The prescription of an off-label HAART regimen in perinatally HIV-1 infected children was common, in particular in children with detectable VL despite previous HAART and in younger children, especially those receiving their first regimen. Our data suggest similar proportions of virological and immunological successes at last check among children receiving off-label or on-label HAART. Larger studies are needed to better clarify efficacy and safety of off-label HAART regimens in children, in order to allow the enlargement of on-label prescription in children.