Human Immunodeficiency Virus Load Research Articles

Abstract 4144514: Human Immunodeficiency Virus Associated Cardiomyopathy- A Rare Cause of Heart Failure With Reduced Ejection Fraction in Era of Highly Active Antiretroviral Therapy

Introduction: Human Immunodeficiency Virus Associated Cardiomyopathy (HIVAC) is characterized by left ventricular (LV) systolic or diastolic dysfunction with or without LV dilatation and heart failure symptoms. The introduction of antiretroviral therapy (ART) has changed the fulminant systolic heart failure presentation of HIV myocarditis to diastolic heart failure. We present a unique case of dilated cardiomyopathy in a young patient without advanced HIV illness which has rarely been documented in the literature. This is a rare presentation of HIVAC in the post-ART era. Case Report: A 32-year-old male with a past medical history (PMH) of the human immunodeficiency virus (HIV) presented with complaints of new onset worsening shortness of breath and lower extremity edema for four weeks. He was diagnosed with HIV seven years ago and was not compliant with ART. Laboratory testing showed a cluster of differentiation 4 (CD4) 823 and HIV load 2550. Myocarditis was ruled out by normal troponin levels and no new changes on the electrocardiogram (ECG). Transthoracic echocardiogram (TTE) showed dilated left ventricle (LV), LV global hypokinesis, LV ejection fraction (LVEF) 10-15%, dilated right ventricle, biatrial dilation, moderate to severe mitral regurgitation, severe tricuspid regurgitation, pulmonary artery (PA) systolic pressure 73 mmHg and no pericardial effusion. Coronary angiography was negative for coronary artery disease (CAD). The patient was started on carvedilol and outpatient evaluation for a left ventricular assistance device. Discussion: Systolic dysfunction in patients with HIVAC carried a poor prognosis in the pre-ART era and was common in patients with elevated c-reactive protein (CRP), tobacco use, and previous myocardial infarction (MI). After the advent of ART, systolic dysfunction is rare and replaced by diastolic cardiomyopathy in the setting of ART use. Diagnosis is usually by excluding other etiologies and biopsy is not necessarily required. Management is usually guideline-directed medical therapy (i.e. beta blocker, renin-angiotensin-aldosterone antagonists, sodium-glucose cotransporter-2) and device-based therapy but there is still data lacking to assess its benefit.

A novel humanized mouse model for HIV and tuberculosis co-infection studies.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), continues to be a major public health problem worldwide. The human immunodeficiency virus (HIV) is another equally important life-threatening pathogen. HIV infection decreases CD4+ T cell levels markedly increasing Mtb co-infections. An appropriate animal model for HIV/Mtb co-infection that can recapitulate the diversity of the immune response in humans during co-infection would facilitate basic and translational research in HIV/Mtb infections. Herein, we describe a novel humanized mouse model. The irradiated NSG-SGM3 mice were transplanted with human CD34+ hematopoietic stem cells, and the humanization was monitored by staining various immune cell markers for flow cytometry. They were challenged with HIV and/or Mtb, and the CD4+ T cell depletion and HIV viral load were monitored over time. Before necropsy, the live mice were subjected to pulmonary function test and CT scan, and after sacrifice, the lung and spleen homogenates were used to determine Mtb load (CFU) and cytokine/chemokine levels by multiplex assay, and lung sections were analyzed for histopathology. The mouse sera were subjected to metabolomics analysis. Our humanized NSG-SGM3 mice were able to engraft human CD34+ stem cells, which then differentiated into a full-lineage of human immune cell subsets. After co-infection with HIV and Mtb, these mice showed decrease in CD4+ T cell counts overtime and elevated HIV load in the sera, similar to the infection pattern of humans. Additionally, Mtb caused infections in both lungs and spleen, and induced granulomatous lesions in the lungs. Distinct metabolomic profiles were also observed in the tissues from different mouse groups after co-infections. The humanized NSG-SGM3 mice are able to recapitulate the pathogenic effects of HIV and Mtb infections and co-infection at the pathological, immunological and metabolism levels and are therefore a reproducible small animal model for studying HIV/Mtb co-infection.

Genotype Variation of HIV/HCV Co-infections in Karachi, Pakistan

Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) are among major health issues that affect a large section of the world's population. While HCV affects around 170 million people worldwide, HIV affects 3% of the global population, with 10 million HCV cases documented in Pakistan alone. Co-infection with HIV and HCV results in a variety of genotypic patterns, with significant global heterogeneity in the incidence of spontaneous resolution of hepatitis C and the distribution of HCV genotypes among co-infected individuals. Co-infection is usually transmitted by sexual contact, contaminated blood supplies, and mother-to-child transmission, with high-risk populations like intravenous drug users (IDUs), and men who have sex with men (MSM) having increased vulnerability. This study, conducted in Karachi, Pakistan, aimed to explore the predominant genotypes and viral load of HIV and HCV. The genetic features of the HIV Gag and HCV NS5b genes were examined using genotyping techniques and phylogenetic methodology. The study revealed that out of the 150 individuals examined, 70 were diagnosed with HIV alone, 55 with HCV only, and 25 had both HIV and HCV infections concurrently. Furthermore, genetic analysis demonstrated that HIV-1 subtype A1 was the predominant genotype, with subtype C closely following. In the case of HCV, genotype 3a was the most prevalent in both mono- and co-infected individuals. Notably, individuals with dual infections exhibited limited genotypic variability for each virus. In the case of HIV co-infection, there was an elevation in viral load, while HCV demonstrated lower viremia relative to mono-infection. In conclusion, the study revealed the predominance of HIV-1 subtype A1 and HCV genotype 3a, as well as an elevated level of HIV and a lowered level of HCV in co-infection.

Interplay between HIV and Human Pegivirus (HPgV) Load in Co-Infected Patients: Insights from Prevalence and Genotype Analysis.

Human pegivirus (HPgV) is transmitted through sexual or parenteral exposure and is common among patients receiving blood products. HPgV is associated with lower levels of human immunodeficiency virus (HIV) RNA and better survival among HIV-infected patients. This study aimed to investigate the prevalence of HPgV and determine its subtypes in HIV-infected individuals living in Istanbul, which has the highest rate of HIV infection in Türkiye. Total RNA extraction from plasma, cDNA synthesis, and nested PCR were performed for HPgV on plasma samples taken from 351 HIV-1-infected patients. The HPgV viral load was quantified on HPgV-positive samples. HPgV genotyping was performed by sequencing the corresponding amplicons. In the present study, the overall prevalence of HPgV RNA in HIV-infected patients was 27.3%. HPgV subtypes 1, 2a, and 2b were found, with subtype 2a being the most frequent (91.6%). Statistical analysis of HIV-1 viral load on HPgV viral load showed an opposing correlation between HIV-1 and HPgV loads. In conclusion, these data show that HPgV infection is common among HIV-positive individuals in Istanbul, Türkiye. Further comprehensive studies are needed to clarify both the cellular and molecular pathways of these two infections and to provide more information on the effect of HPgV on the course of the disease in HIV-infected individuals.

Viral Load Dynamics in Plasma and Semen When Antiretroviral Therapy Is Initiated During Early HIV-1 Infection.

We assessed human immunodeficiency virus (HIV) load in plasma and semen during primary HIV infection using serial samples of semen and plasma during the first 24 weeks after diagnosis in untreated participants and those who started antiretroviral therapy (ART) immediately at diagnosis. In the absence of treatment, semen viral load was >1000 copies/mL in almost all specimens (83%) collected 2-10 weeks after the estimated date of HIV acquisition and remained >1000 copies/mL in 35% of untreated participants at the last observed time point. Thus, in the absence of ART, semen viral load remained at a level consistent with transmissibility throughout primary infection.

Knowledge and Attitude of Caregivers in Paediatrics’ HIV Management and Viral Suppression in Lagos State, Nigeria

This study assessed the knowledge, attitude and practices of caregivers of children living with HIV (Human Immuno-Deficiency Virus) in Lagos State, Nigeria. A cross-sectional study was conducted among 500 caregivers of children living with HIV who reside and are receiving treatment in a government health facility in Lagos State. The Sampling technique was purposive sampling based on some inclusion and exclusion criteria, data collection was administered by telephone interview, and the questionnaire was deployed using CAPI (Computer Assisted Personal Interviews) (Kobo Collect) for ease and time management. The study discovered that caring for children living with HIV is demanding. As most of the caregivers are married, and self-employed. The majority of the children living with HIV in this study have been on antiretroviral therapy (ART) for at least 5 years. Most caregivers are parents of the infected child/children living with HIV. Additionally, most caregivers had a good knowledge of HIV transmission and prevention, but they had limited knowledge of paediatric HIV management and had negative attitudes towards HIV. They also reported experiencing stigma and discrimination. These findings suggest that there is a need to improve the knowledge and attitudes of caregivers in order to improve the management of paediatric HIV, Interventions should be designed to address the stigma and discrimination experienced by caregivers. Accurate information should be provided to caregivers about paediatric HIV and paediatric HIV management. The results from this study may not be generalizable to other settings as this study was conducted in Lagos State. In addition, the study relied on self-reported data, which may be subject to bias. Keywords: Attitude, Caregiver, HIV, Knowledge, Practice and Viral Load.

Mental Health, Self-Care, and Engagement in Care among Black Women Living with HIV.

Due to sociostructural factors, Black women living with human immunodeficiency virus (HIV) in the United States represent the highest percentage of women with HIV and experience mental health struggles that impact health behaviors. This study examines associations between mental health, self-care, medication adherence, engagement with healthcare, HIV-related healthcare visits, and hospitalization. One hundred and nineteen Black women living with HIV in the Southeastern United States completed measures on scheduled visits (general and HIV-related healthcare), visits attended/missed/rescheduled, mental healthcare engagement (therapy and support groups), hospital visits (emergency room and overnight stays), medication adherence, and a clinician-administered interview assessing mental health. Higher self-care was associated with fewer emergency room visits (β=-0.31, P<.001) and hospitalizations (β=-0.22, P<.05). Higher post-traumatic stress disorder symptoms were associated with hospitalization (β=0.23, P<.05) and missed HIV-related visits (β=0.20, P<.05) but higher outpatient mental healthcare visits for group psychotherapy (β=0.20, P< .05). Higher suicidality was associated with lower HIV-related healthcare visits scheduled (β=-0.26, P<.01). Higher HIV load was associated with higher HIV-related healthcare visits scheduled (β=0.45, P<.001) and hospitalization (β=0.41, P<.001). Higher Wisepill medication adherence (β=-0.28, P<.01) and self-reported adherence (β=-0.33, P<.001) were associated with fewer HIV missed visits. Higher self-reported adherence was associated with fewer emergency room visits (β=-0.38, P<.001) and hospitalizations (β=-0.27, P<.001). Our findings highlight the need for treating mental health symptoms and enhancing self-care among Black women living with HIV to improve engagement in care and health behaviors and decrease emergency room visits and hospitalization.

HIV Latency and Nanomedicine Strategies for Anti-HIV Treatment and Eradication

Antiretrovirals (ARVs) reduce Human Immunodeficiency Virus (HIV) loads to undetectable levels in infected patients. However, HIV can persist throughout the body in cellular reservoirs partly due to the inability of some ARVs to cross anatomical barriers and the capacity of HIV-1 to establish latent infection in resting CD4+ T cells and monocytes/macrophages. A cure for HIV is not likely unless latency is addressed and delivery of ARVs to cellular reservoir sites is improved. Nanomedicine has been used in ARV formulations to improve delivery and efficacy. More specifically, researchers are exploring the benefit of using nanoparticles to improve ARVs and nanomedicine in HIV eradication strategies such as shock and kill, block and lock, and others. This review will focus on mechanisms of HIV-1 latency and nanomedicine-based approaches to treat HIV.

Risk of Myocardial Infarction in HIV Patients: A Systematic Review.

Human immunodeficiency virus (HIV) is a retrovirus that is associated with mortality in the final stage. The advancement of antiretroviral therapy (ART) improved the life expectancy of patients with HIV. However, the long age of such patients is associated with different comorbidities such as cardiovascular diseases. Also, HIV therapy increased the concern about cardiovascular diseases. This systematic review aims to assess the risk of myocardial infarction (MI) among patients with HIV by reviewing the previous studies conducted on this subject. Research gate, Google Scholar, and PubMed databases were explored starting from 2012 till 2022. The keywords used for the searching process included "HIV, MI, AMI, Association, Correlation, and Risk." The inclusion criteria were original articles conducted on HIV patients and reported MI,written in English language, and available in full text. A total of 1,570 articles were obtained, but only seven articles met the inclusion criteria. The included studies were published between 2012 and 2019 and involved a total number of 496,600 participants; there were 266,274 who had HIV infection, with a sample size ranging from 1,147 to 252,150. The incidence of MI is higher among HIV compared to the general population. The risk factors associated with MI among HIV patients, as found in our analysis, included male gender, viral load of HIV, low CD4 count, higher CD8 count, and types of ART.

Correlation Between CD4 Cell Count, HIV Viral Load, and Chest CT Findings of AIDS-associated Pulmonary Cryptococcosis

Background: The computed tomography (CT) features of acquired immune deficiency syndrome (AIDS)-associated pulmonary cryptococcosis (PC) are correlated with the viral load of human immunodeficiency virus (HIV). An increase in CD4-positive T lymphocyte (CD4) cell count in peripheral blood after a highly active antiretroviral therapy (HAART) can reflect the morphological changes of lung lesions. Objectives: This study aimed to evaluate the correlation between CT features and HIV viral load and to determine a cut-off value for CD4 cell count increment to investigate the prognosis of PC. It also aimed to examine the morphology of PC lesions and their prognosis following HAART. Patients and Methods: Sixty-two patients with AIDS-associated PC, confirmed by pathology or follow-up, were enrolled in this study. The CT findings were recorded and classified as nodular, cavitary, and consolidation groups and their subtypes. Forty HIV patients who had undergone HAART were screened in this study, and the outcomes of lung lesions were recorded in a follow-up of 3 - 6 months. The participants were divided into improvement and progression groups. The correlation analysis and the receiver operator characteristic (ROC) curve analysis were used to examine the correlation between CT morphology and HIV viral load and to determine the cut-off value for CD4 cell count increment. The intraclass correlation coefficient (ICC) for inter-observer agreement was also calculated. Results: In the nodular group, patients with miliary nodules had the highest HIV viral load in peripheral blood (miliary nodules vs. solitary nodules, P = 0.009; miliary nodules vs. multiple nodules; P = 0.024). In the cavitary group, thick-walled cavity lesions had a higher HIV viral load than thin-walled cavity lesions (thin-walled vs. thick-walled cavity lesions, P = 0.036). Changes in the morphology of lesions, indicating the progression or improvement of PC, had a positive correlation with the CD4 cell count increment (F = 4.260, P = 0.045). The cut-off value for CD4 cell count increment to differentiate the two outcomes (progression and improvement) was 44/µL. The area under the curve (AUC) was 0.851, and sensitivity, specificity, and accuracy were estimated at 0.815, 0.714, and 0.764, respectively. Conclusion: In AIDS-associated PC, different types of lesions were related to the HIV viral load, and CD4 cell count increment following HAART was associated with the morphological changes of lesions. This finding can be helpful for clinicians and radiologists to make an accurate diagnosis and evaluate the treatment outcomes, as well as disease progression.

Virological responses to tenofovir-alafenamide-containing antiretroviral therapy in people living with HIV co-infected with lamivudine-resistant or lamivudine-susceptible hepatitis B virus

BackgroundData on the effectiveness of tenofovir alafenamide (TAF) against lamivudine-resistant (LAM-R) hepatitis B virus (HBV) among patients co-infected with human immunodeficiency virus (HIV) and HBV are limited. MethodsBetween April and December 2018, HIV-positive patients co-infected with LAM-R or lamivudine-susceptible (LAM-S) HBV who switched from tenofovir-disoproxil-fumarate-containing antiretroviral therapy (ART) to TAF-containing ART were followed for 96 weeks. Plasma HBV and HIV loads, HBV serological markers, and liver function before and after the switch were analysed. ResultsIn total, 182 patients co-infected with HIV and HBV were included in this study: 45 with LAM-R HBV and 137 with LAM-S HBV. At baseline, 28.9% and 7.4% of patients in the LAM-R and LAM-S groups, respectively, tested positive for hepatitis B virus envelope antigen (HBeAg) (P<0.001), and the respective percentages of patients who had achieved plasma HBV DNA <20 IU/mL were 95.5% and 97.1%. At weeks 48 and 96, 100% and 94.9% of patients in the LAM-R group, respectively, and 97.1% and 95.6% of patients in the LAM-S group, respectively, maintained plasma HBV DNA <20 IU/mL. Lamivudine resistance of HBV and baseline hepatitis B virus surface antigen (HBsAg) level were associated with HBsAg decrement at week 96 at a degree of 0.25 log10 IU/mL [95% confidence interval (CI) 0.059–0.246] and 0.22 log10 IU/mL (per 1-log10IU/mL increase, 95% CI 0.018–0.101), respectively. At week 96, 2.2% (4/182) of patients had HBsAg loss; no patients in the LAM-R group and 25.0% (2/8) of patients in the LAM-S group had HBeAg seroconversion. ConclusionsSwitching to TAF-containing regimens maintained high rates of HBV viral suppression in patients co-infected with either LAM-R or LAM-S HBV. The decrease in HBsAg was minimal, and HBsAg seroconversion occurred infrequently.

The impact of dolutegravir-based combination antiretroviral therapy on the spermatozoa and fertility parameters of men living with human immunodeficiency virus.

The factors responsible for this reported fertility decline among human immunodeficiency virus (HIV) positive men is yet to be determined. This study is aimed at investigating the impact of HIV or combination antiretroviral therapy (cART) on sperm cells, reproductive hormones, oxidative stress markers, apoptosis, and sperm DNA fragmentation of men living with HIV. Twenty-one men living with HIV gave their written informed consent to participate in this study. Only 11 of the participants successfully donated blood and semen before and after 3 months of their treatment with cART. Semen, reproductive hormones, oxidative stress biomarkers, and DNA fragmentation were analysed. Data were subjected to Wilcoxon matched pairs signed rank test (ethical approval: CMUL/HREC/09/19/614). There was a significant decrease in viral load of HIV (p < 0.01), and a marked increase in progressive and total sperm motility. Total sperm count, morphology, and vitality had no significant change after 3 months of treatment with cART however, there was a significant increase (p < 0.05) in testosterone from 2.48 to 3.68 ng/ml, but luteinizing hormone decreased significantly (p < 0.05) from 9.6 to 6.5mIU/ml. In addition, sperm DNA fragmentation increased significantly (p < 0.01). Conversely, viral load, and catalase decreased significantly, but no significant difference in malondialdehyde. This study showed that HIV depleted testosterone and impaired sperm motility which may negatively affect the fertility potential of men living with HIV. It also showed that adherence to cART (a combination of tenofovir, lamivudine, and dolutegravir) reduces the viral load and reverses the deleterious effects of cART albeit, cART appears to be toxic at subcellular spermatogenic levels.

BLOOD AND CEREBROSPINAL FLUID HIV LOAD INPATIENTS WITH HIV-ASSOCIATED NEUROLOGICAL DISORDERS

Relevance. The issues of replication and concentration of the human immunodeficiency virus (HIV) in various tissues and body fluids remain insufficiently studied. Solving this problem is hindered by the lack of simple, cheap and accessible methods for quantitative determination of HIV in various tissue samples.&#x0D; Objective is to establish a relationship between the presence of HIV-associated damage of the central nervous system (CNS), the number of CD4+ lymphocytes in the blood, and the level of HIV load in blood plasma and cerebrospinal fluid. The difference between the level of HIV viral load in different tissues and biological fluids may reflect the formation of several independent reservoirs of HIV replication in the human body.&#x0D; Materials and methods. 87 patients with HIV infection with clinical signs of central nervous system damage who had no experience of taking antiretroviral drugs (ARVP) were examined. Paired samples of blood and cerebrospinal fluid were analyzed to determine the level of viral load in both biological fluids, as well as the number of CD4+ lymphocytes in the blood.&#x0D; Results. It was established that the patient's presence of clinical signs of CNS damage was reliably correlated with the level of HIV load in the cerebrospinal fluid (logistic regression, P&lt;0.001) and was not associated with the content of CD4+ lymphocytes or the level of HIV load in the blood (logistic regression, P &gt;0.05).&#x0D; The level of HIV load in the cerebrospinal fluid (CSF) was on average 1.5 lg RNA copies/ml higher (P&lt;0.001) in patients with neurological disorders despite the fact that the mean CD4+-lymphocyte count and HIV load in blood in both groups of patients did not differ. The difference between the HIV load in blood and cerebrospinal fluid of patients with neurological disorders was only 0.8 lg RNA copies/ml.&#x0D; Despite the similar indicators of the content of CD4+ lymphocytes and the amount of HIV in the blood, in HIV-infected patients with clinical signs of CNS damage, the level of HIV load in CSF is 1.5 lg RNA copies/ml higher, compared with patients without symptoms of CNS dysfunction (P &lt;0.001). The difference between HIV load in blood and cerebrospinal fluid in the presence of neurocognitive disorders was reduced to 0.7 lg RNA copies/ml compared to 1.8 lg RNA copies/ml in the group of individuals without signs of CNS damage. The presence of HIV-associated damage to the central nervous system is not statistically related to the content of CD4+ lymphocytes or the level of HIV load in the blood.&#x0D; Statistical analysis showed that a CSF HIV load equal to or greater than 4.00 lg RNA copies/mL (10,000 RNA copies/mL) indicated a significant likelihood of HIV-associated CNS involvement in patients (P&lt;0.001) .&#x0D; Conclusion. The method of determining the level of HIV load in cerebrospinal fluid samples can be used to optimize the diagnostic algorithm of HIV-associated lesions of the central nervous system, differential diagnosis with neurocognitive disorders of non-infectious etiology. The threshold for making a clinical decision is the level of HIV load in the CSF sample, which is equal to or exceeds 4.00 lg RNA copies/ml, which indicates a significant probability of the presence of an HIV-associated lesion of the CNS in the patient.

Correlation between recurrence of anorectal condyloma acuminatum and human papilloma virus subtype.

Anorectal condyloma is the representative venereal disease caused by human papilloma virus (HPV), which has more 180 subtypes. Although there are various known risk factors for recurrence, few studies have investigated the influence of HPV subtypes. We aimed to investigate the correlation between the recurrence of anorectal condyloma and HPV subtypes. We analyzed the clinical and histopathological information of 143 patients who underwent surgery for anorectal condyloma at the National Medical Center between March 2016 and September 2020. PCR analyses were performed to confirm the HPV subtype in 24 patients. Recurrence was confirmed in 63 patients through outpatient follow-up over a median of 31.7months (range: 0-56.2) after surgery. Recurrence was significantly associated with anorectal condyloma severity (p < 0.001), but there were no differences between the primary and recurrent groups, CD4-positive cell counts, or human immunodeficiency virus loads. The high-risk HPV subtype was associated with a high recurrence rate. Furthermore, the overall recurrence rate in anorectal condyloma patients was 44.1%. These results suggest that recurrence of anorectal condyloma has a significant association with high-risk HPV subtypes. Therefore, it is necessary to check for recurrences during follow-up after surgery.

Protocol for Optimizing the Use of Kidneys From Donors With Seropositivity for Hepatitis C Virus in Seronegative Recipients

The rapid identification of the viral load from hepatitis C virus (HCV) in seropositive donors enables the determination of their infection capacity and the subsequent design of a strategy to optimize the use of direct-action antivirals (DAA) in seronegative recipients. In 2017, we designed an optimization protocol; this study aims to assess its efficacy and safety. This is a prospective, multicenter observational study that complies with the Declarations of Helsinki and Istanbul. Donors were HCV seropositive. The HCV and human immunodeficiency virus loads were immediately determined in the donors. For viremic donors, recipients were treated with DAA for 8 weeks. For nonviremic donors, DAA was started if a viral load was detected during the follow-up period. The minimum follow-up period was 6 months posttransplant. This study recruited 28 donors. Just over half of the donors (n=15; 53.5%) had a nonactive history of injection drug use. Eight (22.4%) donors were viremic, and 20 (87.6%) were nonviremic; 13 (65%) had been treated previously. Nine grafts were ineligible for the protocol. We performed a total of 47 transplants. Procedure I (viremic donors) was performed in 13 recipients (27.7%). Posttransplant viremia was observed in 6 participants. Posttransplant viremia was low (<100 IU/mL) in 4 participants but high (36,000 and 138,000 IU/mL) in 2 participants who had initiated DAA after the transplant; all these patients had a sustained viral response. Seroconversion was observed in 11 of 13 (84.6%) patients. Procedure II (nonviremic donors) was undertaken in 34 (82.3%) patients. No positive viral loads were observed. Seroconversion occurred in 7 of 34 (20.5%) recipients. All recipients maintained kidney function at 6 months posttransplant, except 1 patient with a graft that had never been functional and another patient who died of pancreatitis. Both patients had received kidneys from nonviremic donors. Our experience supports the efficacy and safety of this protocol.

Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in people living with HIV-1

ObjectivesThe immunogenicity and safety of the Pfizer-BioNTech BNT162b2 mRNA vaccine in people living with human immunodeficiency virus type 1 (PLWH) are unknown. We aimed to assess the immunogenicity and safety of this vaccine in PLWH. MethodsIn this prospective open study, we enrolled 143 PLWH, aged ≥18 years, who attended our clinic and 261 immunocompetent health-care workers (HCWs). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain (RBD) IgG and neutralizing antibodies were measured. Adverse events, viral load and CD4 cell counts were monitored. ResultsAt a median of 18 days (interquartile range 14–21 days) after the second dose, anti-RBD-IgG was positive in 139/141 (98%) PLWH. Among HCWs, 258/261 (98.9%) developed anti-RBD-IgG at a median of 26 days (interquartile range 24–27 days) after the second dose. Following the second dose, immune sera neutralized SARS-CoV-2 pseudo-virus in 97% and 98% of PLWH and HCWs, respectively. Adverse events were reported in 60% of PLWH, mainly pain at the injection site, fatigue and headache. AIDS-related adverse events were not reported. Human immunodeficiency virus load increased in 3/143 (2%) patients from <40 copies/mL to ≤100 copies/mL. CD4+ T-cell count decreased from a geometric mean of 700 cells/μL (95% CI 648–757 cells/μL) to 633.8 cells/μL (95% CI 588–683 cells/μL) (p < 0.01). ConclusionsBNT162b2 mRNA vaccine appears immunogenic and safe in PLWH who are on antiretroviral therapy with unsuppressed CD4 count and suppressed viral load.

Clinical efficacy of laser therapy in the prevention of retinal detachment in patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis.

The aim of the present study was to evaluate the clinical efficacy of laser therapy in the prevention of retinal detachment in patients with acquired immunodeficiency syndrome (AIDS) and cytomegalovirus retinitis (CMVR). A total of 96 eyes from 80 patients with AIDS and CMVR who received anticytomegalovirus (anti-CMV) treatment in the ophthalmology and infection centers of Beijing YouAn Hospital, between June 2016 and August 2018 were retrospectively investigated. The patients were randomly divided into a nonlaser group (50 eyes from 43 patients), who were treated with anti-CMV therapy, and a laser group (46 eyes from 37 patients), who were treated with a fundus laser method to close the retinopathy area after commencing the maintenance stage of anti-CMV treatment. Both groups were followed up for 24 months. The safety of laser therapy was observed, and the efficacy of the therapy was determined by evaluating the incidence of retinal detachment. The percentage of retinal detachment in the nonlaser group was 24% compared with 6.5% in the laser group (P=0.018). There was no significant difference between the two groups in the number of CD4+ T cells, the load of human immunodeficiency virus, or the time between the detachment and the end of the induction period. After laser therapy, 39.13% of patients exhibited keratic precipitates (KP), 30.43% had anterior chamber flare (±), 50% had anterior chamber flare (+), and 19.57% had anterior chamber flare (++). Intraocular pressure (IOP) increased in 3 eyes within 2 weeks of laser therapy. The retinal pigment reaction was not obvious in 8 eyes. The use of laser therapy in the main maintenance period of anti-CMV treatment can effectively reduce the incidence of retinal detachment in patients with AIDS and CMVR, and the therapy is safe and reliable.

Infant Exposure to Dolutegravir Through Placental and Breast Milk Transfer: A Population Pharmacokinetic Analysis of DolPHIN-1.

BackgroundRapid reduction in human immunodeficiency virus (HIV) load is paramount to prevent peripartum transmission in women diagnosed late in pregnancy. We investigated dolutegravir population pharmacokinetics in maternal plasma, umbilical cord, breast milk, and infant plasma samples from DolPHIN-1 participants (NCT02245022) presenting with untreated HIV late in pregnancy (28–36 weeks gestation).MethodsPregnant women from Uganda and South Africa were randomized (1:1) to daily dolutegravir (50 mg/d) or efavirenz-based therapy. Dolutegravir pharmacokinetic sampling (0–24 hours) was undertaken 14 days after treatment initiation and within 1–3 weeks after delivery, with matched maternal and cord samples at delivery. Mothers were switched to efavirenz, and maternal and infant plasma and breast milk samples were obtained 24, 48, or 72 hours after the switch. Nonlinear mixed-effects modeling was used to describe dolutegravir in all matrices and to evaluate covariates.ResultsA total of 28 women and 22 infants were included. Maternal dolutegravir was described by a 2-compartment model linked to a fetal and breast milk compartment. Cord and breast milk to maternal plasma ratios were 1.279 (1.209–1.281) and 0.033 (0.021–0.050), respectively. Infant dolutegravir was described by breast milk–to–infant and infant elimination rate constants. No covariate effects were observed. The median predicted infant dolutegravir half-life and median time to protein-adjusted 90% inhibitory concentration (0.064 mg/L) for those above this threshold were 37.9 (range, 22.1–63.5) hours and 108.9 (18.6–129.6) hours (4.5 [0.8–5.4] days) (n = 13), respectively.ConclusionsBreastfeeding contributed relatively little to infant plasma exposure, but a median of 4.5 days of additional prophylaxis to some of the breastfed infants was observed after cessation of maternal dolutegravir (3–15 days postpartum), which waned with time postpartum as transplacental dolutegravir cleared.

Perinatal outcomes of twenty-five human immunodeficiency virus-infected pregnant women: Hacettepe University experience

Objective:To evaluate perinatal outcomes in human immunodeficiency virus (HIV) infected pregnant women in Turkey.Material and Methods:Maternal characteristics, pregnancy complications, laboratory findings including HIV load, CD4 cell count, CD4/CD8 ratio, neonatal features and final HIV status of the baby were retrospectively analyzed.Results:The sample included 26 singleton pregnancies, from 25 HIV-infected women. The ethnicities were Turkish (n=18), East European (n=4), Asian (n=2) and African (n=2). The majority (76.9%) was aware of their HIV status before becoming pregnant. Four cases (15.3%) were diagnosed during pregnancy and two (7.8%) at the onset of labor. The results for median HIV viral load, CD4 count, and CD4/CD8 ratio at birth were 20 copies/mL (0-34 587), 577/mm3 (115-977), and 0.7 (0.1-1.9), respectively. The HIV viral load rate was 5.5% in eighteen women taking anti-retroviral treatment. The rates of gestational diabetes mellitus, gestational hypertension, intrauterine growth restriction, and preterm delivery were 3.8%, 3.8%, 7.6%, and 8% (numbers are 1;1;2;2), respectively. The mean gestational week at birth was 38 weeks and mean birthweight is 2972±329 g. Two babies were congenitally infected with HIV (infection rate of 8.3%). There was one needle-related accident during surgery.Conclusion:Timely diagnosis of HIV infection during pregnancy is important for preventing mother to child transmission. HIV infected women may give birth to HIV negative babies with the help of a multidisciplinary team, composed of perinatology, infectious diseases, and pediatrics specialists.

Assessment of Key Elements in the Innate Immunity System Among Patients with HIV, HCV, and Coinfections of HIV/HCV

Coinfection of Hepatitis C virus (HCV) with human immunodeficiency virus (HIV) has a higher risk of mortality than HCV or HIV monoinfection. HCV and HIV infections are specified by systemic inflammation, but the inflammation process in HCV/HIV coinfection is much complicated and is not well characterized. The aim of this study was to analyze the expression of TLR-3, TLR-7, IL-10, IFN-1 (IFN-α, IFN-β), and TNF-α in HIV, HCV and HIV/HCV co-infected patients. Forty-five patients including HIV group (n=15), HCV group (n=15), HIV/HCV coinfection group (n=15) and healthy control group (n=15) participated. Peripheral blood mononuclear cells (PBMCs) were obtained. PBMC-RNA, HCV and HIV RNA were extracted from all subjects and cDNA was synthesized. The viral load analyzed by reverse transcription-quantitative PCR (RT-qPCR), and the expression levels of IFN-α, IFN-β, TLR-3, TLR-7, TNF, and IL-10 mRNA were quantified in PBMCs. The levels of IFN-I, IL-10, and TNF-α were overexpressed in all patients' groups (p<0.05), TLR-7 was upregulated in all groups, but this upregulation was not statistically significant (p>0.05). TLR-3 showed a decrease in all patient groups (p<0.05). The statistical analysis demonstrated that TLR-3 has a negative correlation with HIV load, whereas other genes positively correlated with HIV load. In addition, TLR-3, TNF-α, and IFN-I were negatively correlated with HCV load, whereas TLR-7 and IL-10 s were positively correlated with HCV load. Our results showed a significant relationship between the expression level of innate immunity genes and inflammation in HCV, HIV, and HIV/HCV coinfected patients.