Human Immunodeficiency Virus Infected Patients Research Articles

Biological parameters determining the effectiveness of monitoring of HIV / AIDS infected patients in Morocco.

Human Immunodeficiency Virus (HIV) remains one of the world's most serious health challenges. The development of therapeutic regimens has significantly increased survival and reduced HIV-associated morbidities in HIV-infected individuals. However, some people living with HIV may not respond as expected, resulting in treatment failure. The objective of this study is to identify and characterize, by immunological (T-cell CD4) and virological (viral load) parameters, HIV infected patients with therapeutic failure in Morocco. Prospective cross-sectional studies were conducted over a 5-years period (between January 2015 and December 2019) at the referral center of Ibn Zohr Hospital, Marrakech, Morocco. A total, of 1088 HIV-infected patients diagnosed by the rapid test (Immunochromatography) in addition to Western Blot analysis, was recruited. All patients were under the antiretroviral therapy (ART) for at least six months and followed every six months. Sociodemographic, clinical, and biological data as well as information on patient adherence were collected. Out of 1088 patients, 92.46% were under treatment based on non-nucleoside reverse transcriptase inhibitors (NNRTIs) including 26.20% first line first intention and 66.26% first line second intention, and 7.54% of patients on a protease inhibitor (PI) therapy. Regarding the immunological and virological status, 76% of HIV-infected patients had a CD4 count > 200 cells/µl and 24% had a CD4 count < 200 cells / µl, while 69.5% had an undetectable viral load and 30.05% had a detectable viral load (including 11.86% with viral load < 1000 copies / ml and 18.20% viral load > 1000 copies / ml) (P-values < 0.05). In our study, we showed a therapeutic failure rate of 18.2% in HIV-infected patients under treatment in Marrakech region. These failures were mainly related to poor adherence and low CD4+ rates at the initiation of treatment. We concluded that immunological monitoring alone is insufficient to predict virological suppression and therapeutic success. Consequently, we recommend the HIV plasma viral load test be accessible as a routine exam.

Prevalence of soil-transmitted helminth infections in HIV patients: a systematic review and meta-analysis

Soil-transmitted Helminth (STH) infections have been found associated with people living with human immunodeficiency virus (HIV) but little is known about the overall burden of STH coinfection in HIV patients. We aimed to assess the burden of STH infections among HIV patients. Relevant databases were systematically searched for studies reporting the prevalence of soil-transmitted helminthic pathogens in HIV patients. Pooled estimates of each helminthic infection were calculated. The odds ratio was also determined as a measure of the association between STH infection and the HIV status of the patients. Sixty-one studies were finally included in the meta-analysis, consisting of 16,203 human subjects from all over the world. The prevalence of Ascaris lumbricoides infection in HIV patients was found to be 8% (95% CI 0.06, 0.09), the prevalence of Trichuris trichiura infection in HIV patients was found to be 5% (95% CI 0.04, 0.06), the prevalence of hookworm infection in HIV patients was found to be 5% (95% CI 0.04, 0.06), and prevalence of Strongyloides stercoralis infection in HIV patients was found to be 5% (95% CI 0.04, 0.05). Countries from Sub-Saharan Africa, Latin America & Caribbean and Asia were identified with the highest burden of STH-HIV coinfection. Our analysis indicated that people living with HIV have a higher chance of developing Strongyloides stercoralis infections and decreased odds of developing hookworm infections. Our findings suggest a moderate level of prevalence of STH infections among people living with HIV. The endemicity of STH infections and HIV status both are partially responsible for the burden of STH-HIV coinfections.

Right ventricular function in treatment-naïve human immunodeficiency virus-infected patients.

Right ventricular dysfunction carries a poorer prognosis in human immunodeficiency virus (HIV)-positive patients. The objectives of this study were to ascertain the prevalence of right ventricular systolic and diastolic dysfunction, as well as its predictors, in antiretroviral therapy-naïve HIV-positive patients. Participants in this cross-sectional, descriptive study comprised 60 HIV-positive patients and 60 HIV-negative controls. All participants had transthoracic echocardiography done to assess right ventricular systolic and diastolic function. The HIV-positive patients had their CD4 counts measured. The mean age of the study population was 34.63 ± 8.7 years versus that of the controls (34.45 ± 9.40 years) (p = 1.000). Right ventricular systolic dysfunction was found in 11.6% of the HIV-positive patients versus the controls (3.33%, p = 0.166) while right ventricular diastolic dysfunction was found in 15.0% of HIV-positive patients versus the controls (1.7%, p = 0.021). The CD4 count did not contribute to the frequency and degree of right ventricular systolic or diastolic dysfunction. Right ventricular systolic and diastolic dysfunction was common in treatment-naïve HIV-infected individuals but the frequency and degree were not associated with the CD4 count or other measured parameters.

Assessment of right ventricular systolic function using right ventricular fractional area change among human immunodeficiency virus infected patients on highly active antiretroviral therapy and its relationship with viral load and CD4 cell count

Abstract Introduction: Patients with human immunodeficiency virus (HIV) infection are at increased risk of cardiovascular disease compared with the general population, and right ventricular (RV) systolic dysfunction is said to be associated with worse outcomes. HIV infection is an established risk factor for pulmonary hypertension. On the other hand, pulmonary hypertension directly affects RV function through an increase in pulmonary vascular resistance, causing right ventricle hypertrophy, chamber dilatation, and ultimately RV systolic dysfunction. We, therefore, sought to assess RV systolic function (RVSF) using RV fractional area change (RVFAC) among HIV patients on highly active antiretroviral therapy (HAART) and its relationship with viral load and CD4 cell count. Methods: The study was a cross-sectional conducted among HIV patients receiving HAART at the Federal Medical Center, Nguru, Yobe State, North Eastern Nigeria, using RVFAC among HIV patients on HAART and its relationship with viral load and CD4 cell count. Results: One hundred and seven subjects were recruited into the study, comprising 37 (34.6%) males and 70 (65.4%) females. Ninety-six (89.71%) had preserved RVSF, while 11 (10.3%) had reduced RVSF. The mean CD4 cell count of patients with preserved RVSF was significantly higher compared to those with reduced RVSF (838.4 ± 27.5 cells/μL and 301.7 ± 12.4 cells/μL), respectively P ≤ 0.001. The mean viral load of patients with preserved was significantly lower compared to those with reduced RVSF (547.9 ± 10.8 1 copies/mL and 10,293.00 ± 74.8 1 copies/mL), respectively P ≤ 0.001. Conclusion: The prevalence of RV systolic dysfunction among HIV patients on HAART was found to be 10.3% and there was a significant positive correlation between RVFAC with CD4 cell count and a significant negative correlation between RVFAC with HIV viral load.

Opportunistic Infections Among Human Immunodeficiency Virus (HIV) Infected Patients in Turkey: A Systematic Review.

This study aimed to identify opportunistic infections among human immunodeficiency virus (HIV) infected patients in Turkey. Therefore, we conducted a systematic literature review of the studies published up to October 1, 2022, in the Pubmed, Web of Science (WoS), and ULAKBİM TR Dizin databases. We searched for medical subject headings (MeSH) terms of (HIV) OR (AIDS) OR (human immunodeficiency virus) AND (opportunistic infections) AND (Turkey). Fifty-five studies in Pubmed, 68 in WoS, and 212 in ULAKBİM TR Dizin were listed with these keywords. After removing duplicated studies, we included 22 original articles, two poster presentations, one short communication, one letter to the editor, and 17 case reports/series. Out of 1582 patients, we defined 788 patients (49.8%) as late presenters. In addition, we detected tuberculosis (286, 5.5%), candidal infections (207, 4%), and Pneumocystis jirovecii pneumonia (PCP) (113, 2.1%) as the most frequent opportunistic infections. According to our analysis, late presentation is a major problem in our country, and more screening and sensitization campaigns should be carried out to ensure early diagnosis and earlier care of patients.

A Study of the Susceptibility of Candida Species Isolated from Human Immunodeficiency Virus Infected Patients to Antifungal Drugs

Background: On a worldwide scale there is an increase in resistance in fungal infection (resistance,) which is crucial for people with compromised immune systems. One of the most frequent causes of fungal infections in these individuals is Candida fungus infection, which can have fatal consequences. This study aimed to investigate the (medication) antimicrobial sensitivity profile of Candida in HIV seropositive patients.&#x0D; Methods: The study included a total of 674 Candida isolates. Candida was isolated from clinical samples using wet mount, Gram stain, and SDA culture. Germ tube test, cornmeal agar morphology, sugar assimilation, fermentation tests, and BACT/ALERT 3D were used to further speciate the organisms.&#x0D; Results: Six and a half percent (6.5%) of the population was found to contain one or more Candida species. The most prevalent isolate was discovered to be 20 Candida tropicalis (45.45%), followed by 9 Candida albicans (20.45%), 7 Candida glabrata (15.9%), 4 Candida parapsilosis, and 4 Candida krusei. Antifungal susceptibility test performed by disk diffusion method revealed resistance to Amphotericin B in Candida tropicalis (25%), Candida albicans (33.33%) and Candida glabrata (28.5%).&#x0D; Conclusion: The clinician can select the most efficient antifungal drug with the help of a quicker identification of the Candida species in immunocompromised patients, thereby resulting in lower treatment costs and shorter hospital stays.

Epstein-Barr virus variation in people living with human immunodeficiency virus in southeastern China

BackgroundPatients infected with HIV are at high risk of developing Epstein-Barr Virus (EBV)-related diseases. The genotype and viral biological behavior of EBV infection in patients with human immunodeficiency virus-1 (HIV) in China remain unclear. This study analyzed the characteristics of EBV in patients infected with HIV in southeastern China.MethodsA total of 162 HIV-infected patients and 52 patients without HIV were enrolled in this study. EBV viral load in blood was determined by fluorescence quantitative PCR. EBV typing was performed using saliva according to polymorphisms in the EBNA3C region. EBV LMP-1 carboxy terminus (C-ter) was sequenced, and compared with the epidemic strains in the world.ResultsAmong HIV infected patients, the EBV strain variant was mainly EBV-1, while EBV-2 had a higher viral load than EBV-1 (P = 0.001) and EBV-1/2 (P = 0.002). HIV infected patients had higher active virus replication. The EBV LMP-1 variants were mainly the China1 variant. HIV-infected patients had different nucleic acid positions of 30-bp deletion (del30) and had a higher incidence of high 33-bp tandem repeats (rep33) copies than non-HIV-infected patients. There was a difference in the mutations of EBV LMP-1 C-ter del30 and ins15 between HIV infected patients and the control group (P < 0.001).ConclusionIn southeastern China, EBV in HIV-infected patients had higher active virus replication; EBV infection was mainly EBV-1, and EBV-2 infection has higher EBV virus load; hotspot mutations of LMP-1 C-ter were different between HIV-infected patients and non-HIV-infected patients.Trial registration: This study was approved by the ethics committee of the First Affiliated Hospital of Zhejiang University School of Medicine (Approval No. 2018764), and registered in Chinese Clinical Trial Registry on 3 June 2019 (ChiCTR, ChiCTR1900023600, http://www.chictr.org.cn/usercenter.aspx).

Molecular components of the circadian clock regulate HIV-1 replication

Human immunodeficiency virus 1 (HIV-1) causes major health burdens worldwide and still lacks curative therapies and vaccines. Circadian rhythms are endogenous daily oscillations that coordinate an organism's response to its environment and invading pathogens. Peripheral viral loads of HIV-1 infected patients show diurnal variation; however, the underlying mechanisms remain unknown. Here, we demonstrate a role for the cell-intrinsic clock to regulate rhythmic HIV-1 replication in circadian-synchronized systems. Silencing the circadian activator Bmal1 abolishes this phenotype, and we observe BMAL1 binding to the HIV-1 promoter. Importantly, we show differential binding of the nuclear receptors REV-ERB and ROR to the HIV-long terminal repeat at different circadian times, demonstrating a dynamic interplay in time-of-day regulation of HIV-1 transcription. Bioinformatic analysis shows circadian regulation of host factors that control HIV-1 replication, providing an additional mechanism for rhythmic viral replication. This study increases our understanding of the circadian regulation of HIV-1, which can ultimately inform new therapies.

Prevalence of Hepatitis b and c viral infections among human immunodeficiency virus (HIV) infected patients on highly active anti-retroviral therapy (haart) in the university of port harcourt teaching hospital

Prevalence of Hepatitis b and c viral infections among human immunodeficiency virus (HIV) infected patients on highly active anti-retroviral therapy (haart) in the university of port harcourt teaching hospital

Clinical outcomes of ventricular assist device support by HIV infection status: An STS-INTERMACS analysis

Cardiovascular disease remains the leading cause of mortality in human immunodeficiency virus-infected (HIV-positive) patients. Ventricular assist device therapy is rarely offered to these patients and data on outcomes are sparse. We investigated outcomes following ventricular assist device implants for HIV-positive as compared to non-HIV-infected (HIV-negative) patients. We analyzed 22,065 patients from the Interagency Registry for Mechanically Assisted Circulatory Support registry for outcomes by HIV status. A propensity-matched analysis adjusting for 21 preimplant risk factors was also conducted. Compared with 21,980 HIV-negative device recipients, the 85 HIV-positive recipients were younger (median age 58 years vs 59 years, p=0.02), had lower body mass index (26kg/m2 vs 29kg/m2, p=0.001), and had higher rates of prior stroke (8% vs 4%, p=0.02). In the matched HIV-positive and HIV-negative cohorts, there was significantly higher mortality in HIV-positive patients in earlier implant years, however, this association was not seen in later implant years (2018-2020). In both unmatched and matched cohorts, no significant differences in postimplantation stroke, major bleeding, or major infection were noted. With recent advancements in mechanical circulatory support and HIV treatment, ventricular assist device therapy is a viable therapeutic option for HIV-positive patients with end-stage heart failure.

The value of bone marrow examinations performed in the investigation of HIV infected patients with cytopenias.

Bone marrow examination (BME) is a reliable and effective tool in the diagnosis of many haematological and non-haematological diseases and may be used to investigate unexplained cytopenia in human immunodeficiency virus (HIV) infected patients. The objective of this study was to determine the diagnoses made, diagnostic yield and unique diagnostic yield of BMEs performed to investigate cytopenias in HIV infected patients. A retrospective cross-sectional descriptive study was performed involving all BMEs performed on HIV-infected adult patients with the main indication of unexplained cytopenia over a period of 5 years and 4 months. Data was extracted from the National Health Laboratory Service's laboratory information system and clinicians' BME request forms. The study included 128 BMEs, performed on 124 patients. The diagnostic yield was 32% and the unique diagnostic yield was 30.5%. The most common diagnosis was pure red cell aplasia (10.9%), followed by immune thrombocytopenic purpura (ITP) (7%), iron deficiency anaemia (6.3%), malignancy (4.7%) and disseminated infection (3.9%). BME is a useful investigation for unexplained cytopenia in HIV-infected patients. Less invasive investigations to exclude haematinic deficiencies, haemolysis and sepsis are recommended on an individualised basis prior to BME. In HIV-infected patients with therapy refractory ITP or ITP with atypical clinicopathological findings, BME is strongly recommended. As Mycobacterial and other infections are common in this group of patients, staining and culture of specimens are advised if BME is undertaken.

Evaluation of serum calcitonin gene related peptide (CGRP) Level in HIV infected patients as an indicator of disease activity

Human immunodeficiency virus (HIV) infection is under global attention due to its rapid spread and high rate of morbidity and mortality. HIV gets an access into the mucosa of genital epithelium through binding to Langerhans cells. While viral load and CD4+ cell count are the main parameters to detect disease activity, new biomarkers are introduced as a potential parameter for monitoring of disease activity in HIV infected patients. Calcitonin Gene Related Peptide (CGRP) is a neuropeptide that is secreted by peripheral neurons at genital epithelia and plays an important role in limitation of HIV transmission and spread to infected CD4+ cells through its effect onto Langerhans cells. This study aimed to evaluate the serum level of CGRP in HIV infected patients and to determine whether CGRP can serve as an indicator of HIV infection activity. The study included 104 HIV patients and 24 normal controls. Patients were divided into four groups. Serum levels of CGRP were measured by ELISA and correlated to viral load and CD4+ cells count for patients in the four groups: primary HIV infection (PHI), chronic HIV infection (CHI) before combinational antiretroviral therapy (cART-naïve), chronic HIV infection after one year of cART-initiation, and chronic HIV infection after two years of cART. Serum levels of CGRP were also measured in sera of controls and compared to patients' groups. Serum levels of CGRP were significantly lower in cART naïve PHI and CHI patients in comparison with normal controls (p < 0.05), Also, serum CGRP levels were positively correlated with CD4+ cells count (p < 0.01), but negatively correlated with viral load (p>0.05). In conclusion, CGRP could be proposed as an indicator of disease activity in HIV patients.

The use of azithromycin and pyrimethamine for treatment of cerebral toxoplasmosis in human immunodeficiency virus-infected patients: a systematic review.

Toxoplasma gondii is a parasite that is widely distributed around the globe and can cause brain inflammation, particularly in immunosuppressed patients such as those diagnosed with human immunodeficiency virus (HIV). This paper reviews the efficacy of azithromycin and pyrimethamine combination therapy for cerebral toxoplasmosis in patients with HIV. The scope of the studies included in this review was limited from 1992 to 2022, with studies primarily being randomized, controlled clinical trials available on online scientific journal databases. The authors screened eligible records for review, removing those that did not fit the inclusion and exclusion criteria. The risk of bias of the extracted data was analyzed through the Cochrane risk-of-bias tool for randomized trials. A broad search of major online databases such as PubMed, Medline, Google Scholar, and Cochrane using keywords, limit fields, and Boolean operators yielded 3,130 articles. After thoroughly screening the search results, two studies were included in this review. Results from the studies included in the review demonstrate that the combination therapy of azithromycin and pyrimethamine is favorable for cerebral toxoplasmosis. However, the net response is less effective than the standard treatment regimen (pyrimethamine and sulfadiazine). The combination therapy of azithromycin and pyrimethamine is less effective than the standard treatment regimen for maintenance therapy for cerebral toxoplasmosis; thus, administering these medications for this indication must be met with caution.

Low CD4 Counts and History of Sore Throat Predict High SARS-CoV-2 Seropositivity among Human Immunodeficiency Virus-Infected Patients in Mwanza, Tanzania

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic. Despite the fact that it affects all ages and profiles, some evidence shows that patients with comorbidities, including diabetes, obesity, and hypertension, are likely to be most affected. For chronic diseases, such as human immunodeficiency virus (HIV), information is scarce, with a few studies from high-income countries. This study reports predictors of SARS-CoV-2 seropositivity (IgG + IgM) among unvaccinated people living with HIV attending Bugando Medical Centre in Mwanza, Tanzania. Methodology: A cross-sectional, hospital-based study involving 150 HIV-infected patients was conducted at Bugando Medical Centre between June and July 2022. A pretested questionnaire was used to collect the participants’ information. Blood samples were collected and used for the detection of SARS-CoV-2 (IgM/IgG) antibodies by immunochromatographic assay. Data were analyzed using STATA version 15. Results: The mean age of the enrolled participants was 46.4 ± 11.1 years. The overall seropositivity (IgG + IgM) of SARS-CoV-2 antibodies was 79/150 (52.7%) [95% CI: 44.4–60.9]. Seropositivity of IgM only was 8/150 (5.3) [95% CI: 1.7–8.8], while that of IgG only was 61/150 (40.6%) [95% CI: 32.7–48.4]. Seropositivity of both IgG and IgM was observed in 10/150 (6.7%) patients. In a multivariate logistic regression analysis, history of sore throat (OR: 6.34, 95% CI: 2.305–18.351, p &lt; 0.001), low CD4 count (OR: 0.99, 95% CI: 0.995–0.999, p = 0.004), and use of pit latrines (OR: 2.30, 95% CI: 1.122–4.738, p = 0.023) were independently associated with SARS-CoV-2 seropositivity. Conclusion: HIV-infected individuals with history of sore throat, low CD4 count, and use of pit latrines were more likely to be SARS-CoV-2 IgG seropositive. There is a need to routinely screen for SARS-CoV-2 infection among HIV-infected individuals to obtain comprehensive data regarding the interactions of the pathogens.

Genetic diversity of capsid protein (p24) in human immunodeficiency virus type-1 (HIV-1) variants circulating in the Russian Federation

The human immunodeficiency virus (HIV) protein p24 plays an important role in the life cycle of the virus, and also is a target for diagnostic tests and for new antiretroviral drugs and therapeutic vaccines. The most studied variant of HIV-1 in the world is subtype B. In Russia, the most common variant is A6, the spread of recombinant forms (CRF63_02A6, CRF03_A6B) is observed as well as circulation of G and CRF02_AG variants. However, a detailed study of the p24 protein in these variants has not yet been conducted. The aim was to study the features of the p24 protein in HIV-1 variants circulating in Russia and estimate the frequency of occurrence of pre-existing mutations associated with resistance to lenacapavir, the first antiretroviral drug in the class of capsid inhibitors. The objects of the study were the nucleotide sequences obtained from the Los Alamos international database and clinical samples from HIV infected patients. The features of HIV-1 variants circulating in Russia have been determined. V86A, H87Q, I91F are characteristic substitutions in A6 genome. It is shown that the presence of preexisting mutations associated with resistance to lenacapavir is unlikely. Features of the p24 protein in HIV-1 variants circulating in Russia allow them to be distinguished from others variants and among themselves. The prognosis for the use of lenacapavir in Russia is generally favorable. The results obtained could be taken into account in developing and using antiretroviral drugs and therapeutic vaccines.

Intracranial tuberculoma in human immunodeficiency virus-infected patient: a case report

Intracranial tuberculoma is one of the most devastating forms of Mycobacterium tuberculosis infection, presenting in 1% of all tuberculosis cases. This condition is significantly associated with high morbidity and mortality and frequently occurs in immunocompromised patients such as patient with human immunodeficiency virus (HIV) infection. Symptoms of intracranial tuberculoma include headache, nausea, vomiting, ataxia, diplopia, hemiparesis, and seizure. We reported a 34-years-old male patient presented with progressive left side weakness for 1 month prior to admission. Patient also complained of intermittent fever, headache, productive cough, night sweats, and unintentional weight loss. On neurological examination, power of left upper and lower limb was 3. Patient had a positive test result for HIV serologic examination. Chest X-ray showed infiltrate in the apical segment of right lower lobe of the lung. Mycobacterium tuberculosis was found on sputum gene expert examination. Head computed tomography (CT) scan showed multiple hypodense lesions with contrast enhancement in right caudate nucleus and right lentiform nucleus, suggestive for tuberculoma. Patient was treated with fixed-dose combination of antituberculosis, corticosteroid, and other symptomatic medication and showed a significant clinical improvement.

Toxoplasma gondii, HBV, and HCV co-infection and their correlation with CD4 cells among Iranian HIV-positive patients.

Human immunodeficiency virus (HIV/AIDS) infected patients have a higher risk of opportunistic infections (OIs) depending on their immunological status, especially CD4 + cell count. Toxoplasma gondii, hepatitis C virus (HCV), and hepatitis B virus (HBV) are important OIs among Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) patients. However, little is known about co-infection of these pathogens among HIV-infected individuals and their correlation with the patient's CD4 + cell count. Hence, this study aimed to investigate the serological and molecular status of T. gondii infection among HIV-infected individuals who had co-infection with HBV and HCV infections. A total of 100 HIV/AIDS patients in two cities in the southwest of Iran was tested for T. gondii Immunoglobulin G (IgG) and Immunoglobulin M (IgM) antibodies as well as DNA detection by polymerase chain reaction (PCR) targeting the RE gene. HBV and HCV were detected by hepatitis B surface antigen (HBsAg) test, hepatitis C antibody (HCV Ab) test, and Real-Time PCR. The number of CD4 + cell counts was determined by Flow cytometry. Anti-T. gondii IgG was positive in 22% of the patients, but anti-T. gondii IgM and PCR were negative in all samples. HBV and HCV were positive in 8% and 33% of the patients, respectively. Co-infections were as followed: HIV + HCV (16%), HIV + HCV + T. gondii (11%), HIV + T. gondii (5%), HIV + HBV (1%), HIV + HBV + T. gondii (1%), HIV + HBV + HCV (1%), and HIV + HBV + HCV + T. gondii (5%). A significant decline in CD4 + cell counts was found in such co-infection groups (HIV + T. gondii, HIV + HCV + T. gondii, and HIV + HBV + HCV + T. gondii) compared with the HIV mono-infection group. Our study showed that co-infections of T. gondii, HCV, and HBV were common among HIV-infected patients and co-infections had a negative correlation with CD4 + cell counts of the patients.

HIV/AIDS infection in critical care: epidemiological profile and risk factors for mortality in a Colombian cohort

Outcomes of human immunodeficiency virus (HIV) infected patients admitted to intensive care units (ICU) have improved with antiretroviral therapy (ART). However, whether the outcomes have improved in low- and middle-income countries, paralleling those of high-income countries is unknown. The objective of this study was to describe a cohort of HIV-infected patients admitted to ICU in a middle-income country and identify the risk factors associated with mortality. A cohort study of HIV-infected patients admitted to five ICUs in Medellín, Colombia, between 2009 and 2014 was done. The association of demographic, clinical and laboratory variables with mortality was analyzed using a Poisson regression model with random effects. During this time period, 472 admissions of 453 HIV-infected patients were included. Indications for ICU admission were: respiratory failure (57%), sepsis/septic shock (30%) and central nervous system (CNS) compromise (27%). Opportunistic infections (OI) explained 80% of ICU admissions. Mortality rate was 49%. Factors associated with mortality included hematological malignancies, CNS compromise, respiratory failure, and APACHE II score ≥ 20. Despite advances in HIV care in the ART era, half of HIV-infected patients admitted to the ICU died. This elevated mortality was associated to underlying disease severity (respiratory failure and APACHE II score ≥ 20), and host conditions (hematological malignancies, admission for CNS compromise). Despite the high prevalence of OIs in this cohort, mortality was not directly associated to OIs.

Introduction of Mutant APOBEC3G Into CD4+ T-Cells to Resist HIV-1

Introduction: Human immunodeficiency virus 1 (HIV-1) is a potentially lethal retrovirus with high genetic diversity and replication ability. HIV-1 mainly targets human CD4+ T-cells, causing a rapid decline in CD4+ T-cell count after infection. Apolipoprotein B mRNA Editing Enzyme Catalytic Subunit 3G (APOBEC3G or A3G) is a human anti-viral enzyme that blocks early stages of HIV-1 replication by deaminating the cytosine residues to uracil in the viral minus-strand DNA during reverse transcription. Nevertheless, HIV-1 overcomes A3G anti-viral activity by employing Vif accessory protein to degrade A3G. Due to a proline/aspartate point mutation in residue 129 (P129D), an artificial A3G mutant, also known as A3G-P129D, was found to be resistant against diverse Vif variants, including HIV-1 Vif, thereby shedding light on a potential A3G-mediated gene therapy for HIV-1. Methods: We propose that, using CRISPR-Cas9 tools, the P129D mutation will be introduced into A3G expressed by human hematopoietic stem cells. Engineered stem cells will be transplanted into Non-Obese Diabetic Severe Combined Immunodeficient Gamma (NSG) mice, which will later be infected with HIV-1. Following infection, flow cytometry will be used to compare the CD4+ T-cell count in mice that express A3G-P129D versus control mice transplanted with unmodified human CD4+ T-cells. Results: We expect a notably higher CD4+ T-cell count in mice carrying the P129D mutation than in the control group, which would be attributed to the efficient inhibition of HIV-1 replication by the mutant A3G. Discussion: Transforming human A3G to A3G-P129D will prevent Vif-mediated degradation of A3G, allowing A3G to efficiently target HIV-1. Thus, this treatment would ultimately block HIV-1 replication and prevent CD4+ T-cell depletion. Conclusion: Overall, our novel gene therapy approach could open the door to a potential one-time treatment for HIV-1 infected patients.

Changing Mortality and Patterns of Death Causes in HIV Infected Patients - China, 2013-2022.

The advent of antiretroviral therapy (ART) has markedly decreased mortality rates among patients infected with human immunodeficiency virus (HIV). Globally, there has been a 43% reduction in acquired immunodeficiency syndrome (AIDS)-related deaths from 2010 to 2022. Additionally, prior research indicates that the initiation of ART at an early stage within China has substantially lowered mortality rates. Over the previous decade, following the implementation of China's universal ART access strategy, the patterns of mortality causes among HIV-infected individuals across the country have undergone significant alterations. In 2022, the all-cause mortality rate among this population was reported at 2.7%, with the non-AIDS-related mortality rate at 1.8%. However, it is important to consider that the accuracy of death reporting could contribute to potential misclassification of the underlying causes of death. Efforts to enhance health outcomes should persist in emphasizing the advancement of ART strategies, with a particular focus on mitigating non-AIDS-related mortality in the future.