Immunodeficiency Virus-infected Patients Research Articles

Frequency of Human Immunodeficiency Virus Infection in patients at the Hospital National during the period 2021-2023

Introducción: el virus de la inmunodeficiencia humana sigue siendo de los principales problemas para la salud pública a nivel mundial ya que es causante de muertes a nivel global. La generalización del test del VIH en la población es una forma de estrategia de salud pública. Objetivo: determinar la frecuencia de la infección por el VIH en pacientes que acuden a urgencias en el período de marzo 2021 a octubre 2023. Metodología: estudio observacional, descriptivo, fueron incluidos pacientes adultos internados en el servicio de urgencias durante el periodo de marzo 2021 a octubre del año 2023. Para el cálculo del tamaño de la muestra basada en una proporción esperada de 0,1 (1 %) y una amplitud de 0,10 (precisión), nivel de confianza de 95 % lo que arrojó un tamaño de 974 pacientes. Los datos fueron procesados en el paquete estadístico EPI Info (Atlanta- CDC). Resultados: se incluyeron en el estudio 976 pacientes, la frecuencia de la seropositividad del virus de la inmunodeficiencia humana por test de ELISA fue del 12,8 % (n = 126) la media de edad de los pacientes positivos fue de 38,4 ± 13 años, en cuanto a los factores de riesgo 18,25 % (n = 23) refirieron consumo de drogas ilícitas; 16,66 % (n = 21) tatuajes; 11,90 % (n = 15) antecedente de transfusiones de hemoderivados; 7,14 % (n = 9) piercings. Conclusión: la frecuencia de la seropositividad del VIH por test de ELISA fue del 12,8 % en pacientes adultos que acuden a urgencias por cualquier razón.

Difficulties of diagnosis and management tactics of COVID-19 in HIV-infected patients in a non-infectious hospital

The spread of COVID-19 over the past three years has posed difficult tasks for doctors related to rapid diagnosis and provision of highly qualified medical care to patients, including with co-infection ― SARS-CoV-2/human immunodeficiency virus.
 The analysis of the combined course of COVID-19 and human immunodeficiency virus demonstrated the synergistic effect of SARS-CoV-2 and human immunodeficiency virus on the human body. Numerous studies have shown that COVID-19 is more severe and is accompanied by high mortality in older people and in the presence of comorbid pathology. Including important role belongs to diseases accompanied by suppression of cellular immunity, which lead to frequent complications and longer viremia, which can be observed with human immunodeficiency virus infection. The similarity of clinical, laboratory and radiological data does not allow to differentiate COVID-19 and human immunodeficiency virus opportunistic diseases with lung damage (pneumocystic pneumonia, cytomegalovirus and candidiasis etiology), in an early period, especially in patients without an established human immunodeficiency virus status.
 Identification of the features of the course of the disease, alertness towards human immunodeficiency virus infection in patients admitted to the hospital with COVID-19 at a young age, the peculiarities of the epidemiological history will allow early diagnosis and improve management tactics.

Tuberculosis and isoniazid prophylaxis among adult HIV positive patients on ART in Northwest Ethiopia.

Although antiretroviral therapy (ART) can avert tuberculosis (TB) incidence among human immunodeficiency virus (HIV) infected patients, the concomitant use of ART with isoniazid (INH) has a paramount effect. Despite this evidence, there is a paucity of data regarding TB incidence among HIV patients on ART with and without isoniazid prophylaxis and its predictors. Thus, this study sought to assess the incidence and predictors of TB among adult HIV positive patients on ART. This was a hospital based retrospective study including 368 adult HIV positive patients on ART in Gondar comprehensive specialized hospital between January 1, 2016, and April 30, 2019. Data was extracted from clinical laboratory and HIV care ART follow up clinic. The bi-variable and multivariable regression models were used to ascertain predictors of incident TB. Data was analyzed using SPSS version 20 software. A total of 335 adult HIV positive patients were included in the analysis, of whom, 56 (16.7%) were developed incident TB. Being ambulatory and bedridden (AOR: 2.2, 95% CI: 1.1, 4.6), advanced WHO clinical HIV disease stage (III and IV) (AOR: 3.2, 95% CI: 1.6, 6.1), not taking INH (AOR: 2.8, 95% CI: 1.3, 5.9), and baseline CD4+ T cell count ≤ 200 cell/mm3 (AOR: 3.6, 95% CI: 1.8, 7.2) were found to be the predictors of tuberculosis incidence. The study indicated a high TB incidence among HIV positive patients in Gondar. Therefore, scaling up the isoniazid preventive therapy program and its strict compliance is necessary to avert HIV fueled tuberculosis in HIV endemic areas.

O9‐4: The effects of active hexose correlated compound (AHCC) on levels of CD4+ and CD8+ in human immunodeficiency virus (HIV) infected tuberculosis patients

O9‐4: The effects of active hexose correlated compound (AHCC) on levels of CD4+ and CD8+ in human immunodeficiency virus (HIV) infected tuberculosis patients

A cross-sectional study of socio-demographic and clinical profile of HIV patients at ART plus centre, Sawai Man Singh Hospital, Jaipur, India

Background: This study aimed to understand the regional variation in the socio-demographic and clinical profile of human immunodeficiency virus (HIV) infected patients at antiretroviral therapy plus centre of Sawai Man Singh (SMS) hospital, Jaipur, India. 
 Methods: A descriptive cross-sectional study was conducted on HIV patients from January to December 2019. The HIV-positive patients of all age groups and all categories were included in the study. The socio-economic status was assessed by BG Prasad classification-based consumer price index. However, the clinical staging was done according to the World Health Organization (WHO) classification of HIV/AIDS. Data were expressed as mean ± standard deviation.
 Results: Among 525 HIV patients 59.16% were males, 40.26% females and 0.57% intersex. About half (51.0%) in the reproductive age group with mean age 36 ±13 years. The commonest mode of HIV transmission was heterosexual (89.77%). Maximum belonged to social class I (57.84%) and class II (26.05 %) of BG Prasad's socioeconomic status. Each of the non-agricultural laborers and semi-skilled workers constitutes 18.0%, and the housewives were 23.6%. At the time of presentation, baseline CD4+Tcell count was <350 /mm3 in 55.0% of HIV patients. Pulmonary tuberculosis and skin involvement were the most predominant secondary opportunistic infections accounting for 24.8% and 7.8%, respectively. More than half (52.09%) of patients were in WHO clinical stage I of HIV disease.
 Conclusion: Socio-demographic and clinical profile of study participants reflect an impact of early case detection and timely institution of highly active antiretroviral therapy.

The prevalence of and risk factors for peripheral arterial occlusive disease in human immunodeficiency virus-infected omani patients: The first study in GCC

The prevalence of and risk factors for peripheral arterial occlusive disease in human immunodeficiency virus-infected omani patients: The first study in GCC

An RNA-Directed Gene Editing Strategy for Attenuating the Infectious Potential of Feline Immunodeficiency Virus-Infected Cells: A Proof of Concept

Modern antiretroviral therapy for immunodeficiency viruses, although remarkably effective in controlling viral transcription, and overt virus-associated morbidity, has failed to absolutely eradicate retroviruses from their infected hosts as a result of proviral integration in long-lived reservoir cells. Immunodeficiency virus-infected patients are therefore consigned to lifelong antiviral therapy as a means to control viremia, viral transmission, and infection-associated morbidity. Unfortunately, lifelong antiviral therapies can be difficult for patients to continuously maintain and may be associated with therapy-specific morbidities. Patient advocates have argued for new methods to achieve retroviral eradication. As a proof-of-concept study, a lentivirus-delivered RNA-directed gene editing strategy was utilized in a series of in vitro experiments in an attempt to attenuate the feline immunodeficiency virus (FIV) proviral load, viral transcription, and production of infectious virions. We found that a feline T lymphocyte cell line (MCH5-4) treated with an FIV-specific clustered regularly interspersed short palindromic repeats (CRISPR)-associated protein 9 (Cas9) gene editing tool resulted in a reduction of cell-free viral RNA relative to control cells. Decreased infectious potential was demonstrated in a two-step FIV infection study—naïve MCH5-4 cells infected with cell-free FIV harvested from FIV-infected and CRISPR lentivirus-treated cells had less integrated proviral DNA than control cells. This study represents the initial steps towards the development of an effective method of proviral eradication in an immunodeficiency virus-infected host.

Causative factors of liver fibrosis in HIV-infected patients. A single center study

BackgroundLiver disease is a leading cause of morbidity and mortality among Human Immunodeficiency virus (HIV) infected patients; however no consensus exists on HIV-related risk factors for it. The aim of this study was to identify risk factors for liver fibrosis/cirrhosis in a cohort of Greek HIV-infected patients.MethodsPatients attending the HIV outpatient clinic of Pathophysiology Department at «Laiko» General Hospital in Athens, Greece, between December 2014 and December 2017 were eligible for inclusion. Inclusion criteria were confirmed HIV infection and age > 18 years. Exclusion criteria were Body-Mass index (BMI) > 40, liver metastases of malignant diseases and concurrent or previous chemotherapy.Liver stiffness (LS) was measured using Vibration Controlled Transient Elastography (TE) and laboratory tests were acquired in all patients. Patients were classified in 2 groups: those with mild or no fibrosis (equivalent to Metavir score F0-F2) and those with significant fibrosis (equivalent to Metavir score F3-F4).ResultsA total of 187 consecutive patients were included in this study. Median TE value was 5.1 kilopascals (KPa) (range 2.8–26.3), with 92.5% (173/187) of the patients having no/mild fibrosis and 7.4% (14/187) significant fibrosis.On multivariate logistic regression analysis older patient’s age, abnormal serum aspartate aminotransferase (AST) value, Hepatitis C virus (HCV) infection, alcohol abuse, CD4/CD8 ratio and an increased number of liver related events (LREs) were significantly correlated with liver fibrosis/cirrhosis.ConclusionsIn our cohort of HIV-infected individuals HCV/HIV co-infection, older age, alcohol abuse and CD4/CD8 ratio seem to correlate with fibrogenesis in the liver.

The Prevalence of Human Immunodeficiency Virus Infection in Patients with Sexually Transmitted Diseases.

Background:Human immunodeficiency virus (HIV) transmission pattern in Iran has been changed from injection drug to sexual contact. Lack of accurate assessment of HIV in people with sexually transmitted diseases (STDs) in Iran prompted us to conduct this study to determine the frequency of HIV infection in these patients.Materials and Methods:In this cross-sectional study which conducted in 2016–2017, overall, 190 patients with STDs referring to two hospitals of Hamadan were enrolled in the study. All of the patients were examined for HIV in the first visit by rapid test and then 1 and 4 months later by the 4th generation ELISA. A questionnaire including demographic data, clinical manifestations, and high-risk behaviors was completed for all of the referring people. The collected data were analyzed using appropriate statistical tests.Results:Of 190 patients, 126 (66.3%) were female with a mean age of 34.1 ± 10.1 years and 64 (33.7%) were male with a mean age of 30.8 ± 7.8 years. One hundred twenty-eight (67.4%) got married, 73 (38.4%) and 76 (40%) had a diploma and postgraduate education, respectively, 32 (16.8%) mentioned the history of unsafe sex, and 23 (12.1%) had used condoms continuously during sexual contacts. The most common STDs were reported genital warts, 107 patients (56.3%), vaginal discharge (28, 14.7%), and genital ulcer (33, 17.4%). Two (1%) patients were positive for HIV at the first visit.Conclusion:Patients with STDs should be considered as an important source of HIV transmission, so clinicians should pay more attention to screening these patients for HIV infection.

Diagnostic oral biomarkers of immunosuppression in apparently healthy seropositive HIV population, in South Western Uganda

Background: Accurate diagnosis remain key to effective intervention of endemic and pandemic diseases even up to the developed world. Despite availability of many high-quality diagnostic tests for immunosuppression in the developed countries, they are neither available, affordable nor accessible in rural communities of Africa. Clinical diagnostic surrogate biomarkers may be suitable alternative. Objective: To evaluate oral clinical manifestations as biomarkers of immunosuppression in apparently healthy population of Human Immunodeficiency Virus (HIV) infected patients in resource poor Masaka, Mbarara and Rukungiri districts, of South Western Uganda. Methods: Visual oral inspection of 304 apparently health and HIV seropositive patients attending the AIDS Support Organization clinics in study districts of Uganda was done to detect and establish oral biomarkers associated with immunosuppression in HIV disease. Standard methods were used to reconfirm the HIV sero-positivity status and clinical staging of oral manifestations of consenting clients. Result: Figures 1-22 shows representative 304 oral manifestations of research participants. Figures 1-5 depicts 140 (46.1%) pseudomembranous candidiasis. Figures (6-9) depicts representative photographs of 53 (17.4%) erythemathous candidiasis (Figures 7 & 8) and also 63 (20.7%) shows erythemathous candidiasis found co-infecting with pseudomembranouse candidiasis in (Figures 9 & 10). Figure 10 shows linear gingival erythemathouse banding. Figures 11-15 shows Karposi sarcoma developmental stages and Figure 16-18 shows 7 (2.3%) Angular cheilitis. Figure 19 shows 3 (1.0%) aphthous ulceration of anterior portion of the tongue. Figure 20 shows 1 (0.3%) Acute necrotizing ulcerative gingivitis (ANUG) while Figures 21 & 22 shows 10 (3.3%) intra-oral pigmentation. Conclusion: Visual oral inspection of apparently healthy HIV seropositive individuals revealed different oral manifestations that may serve as diagnostic oral biomarkers of immunosuppression in apparently healthy but HIV infected population in Uganda. Poor resources drive the need for available and affordable diagnostic tools for improved and effective intervention.

Distribution and Characteristics of Intrathoracic Lymphadenopathy in TB/HIV Co-Infection.

Intrathoracic Lymphadenopathy (ITLN) in Human Immunodeficiency Virus (HIV) infected patients may have various etiologies and prognoses. Etiologies of ITLN can be distinguished based on the distribution of enlarged lymph nodes. Sometimes tuberculosis (TB) is the first sign of underlying HIV infection. We sought to determine ITLN distribution and associated pulmonary findings in TB/HIV co-infection using Computed Tomography (CT) scan. In this retrospective, observational, cross-sectional study, chest CT scans of 52 patients with TB/HIV co-infection were assessed for enlarged intrathoracic lymph nodes (>10 mm in short axis diameter), lymphadenopathy (LAP) distribution, calcification, conglomeration, the presence of hypodense center and associated pulmonary abnormalities. LAP distribution was compared in TB/HIV co-infection with isolated TB infection. Mediastinal and/or hilar LAP were seen in 53.8% of TB/HIV co-infection patients. In all cases, LAP was multistational. The most frequent stations were right lower paratracheal and subcarinal stations. Lymph node conglomeration, hypodense center and calcification were noted in 25%, 21.4% and 3.5% of patients, respectively. LAP distribution was the same as that in patients with isolated TB infection except for the right hilar, right upper paratracheal and prevascular stations. All patients with mediastinal and/or hilar adenopathy had associated pulmonary abnormalities. All patients with TB/HIV co-infection and mediastinal and/or hilar adenopathy had associated pulmonary abnormalities. Superior mediastinal lymph nodes were less commonly affected in TB/HIV co-infection than isolated TB.

Coreceptor-Based Hematopoietic Stem Cell Gene Therapy for HIV Disease

Combination antiretroviral therapy (cART) has significantly reduced the mortality rate and morbidity, and has increased the life expectancy of the human immunodeficiency virus (HIV) infected patients. However, the current cART is incapable of eradicating viruses from the human body, and HIV remains one of the most notorious viruses mankind has ever faced. HIV-1 enters target cells through the binding of gp120 viral protein to a CD4 receptor and then to a coreceptor, C-C chemokine receptor 5 (CCR5) or C-X-C chemokine receptor type 4 (CXCR4). Individuals homozygous for a 32-bp deletion in the CCR5 allele, CCR5Δ32, are almost completely resistant to HIV-1 acquisition. Moreover, several of natural CXCR4 mutants which have been identified can reduce HIV-1 entry without impairing either ligand binding or signaling. In order to get rid of indefinite treatment for HIV patients, there is a growing interest in creating an HIV-resistant immune system through the use of CCR5 and CXCR4-modified hematopoietic stem cells (HSCs). Proof of concept for this approach has been provided in the instance of "Berlin patient" transplanted with allogeneic stem cells from a donor with homozygosity for the CCR5Δ32 deletion. Here, we review the progress of coreceptor-based HSC gene therapy for HIV disease and present new strategies.

Long-term performance of the IGRA to predict and prevent active tuberculosis development in HIV-infected patients.

<sec id="st1"> <title>OBJECTIVE</title> To estimate the long-term performance of the interferon-gamma release assay (IGRA) in predicting active tuberculosis (ATB) development among human immunodeficiency virus (HIV) infected patients in an intermediate TB burden country. </sec> <sec id="st2"> <title>DESIGN</title> A retrospective cohort study was conducted. HIV-infected patients with 1 IGRA result but no current or previous ATB who had been retained in care for 1 year were enrolled and observed for ATB development from 2006 to 2016. </sec> <sec id="st3"> <title>RESULTS</title> Sixty-two IGRA-positive and 354 IGRA-negative patients were observed for a median period of 4.03 years. ATB incidence in IGRA-positive vs. negative patients was respectively 15.24/1000 person-years (py) (95%CI 4.15-39.02) vs. 0.67/1000 py (95%CI 0.01-3.68) (P = 0.001). The sensitivity, specificity and positive and negative predictive values of the IGRA were respectively 80.0% (28.4-99.5%), 85.9% (82.1-89.1%), 6.5% (4.0-10.2%) and 99.7% (98.4-99.9%). Among the 62 IGRA-positive patients, 25 were treated for latent tuberculous infection (LTBI) and 37 were not. Patients with LTBI treatment did not develop ATB, while four cases of ATB occurred among patients without LTBI treatment. Among the 257 IGRA-negative patients who received a follow-up IGRA, 34 (12.9%) patients converted to positive. No ATB developed in IGRA converters. </sec> <sec id="st4"> <title>CONCLUSION</title> Screening for LTBI using IGRAs and LTBI treatment can be useful to prevent ATB in an intermediate TB burden country. </sec>.

English

Screening of Hepatitis C virus (HCV) infection by molecular test is not routinely performed for the care of human immunodeficiency virus (HIV) infected patients in most countries of Sub-Saharan Africa such as Benin. The aim of this study was to assess the extent of HCV infection in patients infected with HIV in Cotonou. This study was conducted from February to June 2017 on HIV infected patients from the National Reference Center for Research and Management of HIV infection in Cotonou.  Blood samples were collected from patients to detect anti-HCV antibody and HCV viral load. A total of 205 patients were tested, out of which 67.3% were females. Seroprevalence of anti-HCV antibody was 7.8% and HCV viral load was detectable in 3.4% of cases with a median of 2.200.000 IU/mL (6.3 Log10). Three out of seven patients (42.8%) had negative HCV serology with positive HCV RNA detection. In conclusion, the prevalence of HCV infection among HIV infected patients is not negligible in Cotonou. Universal access to molecular tests is needed in the country to detect HCV infection in these patients.   Keywords: HCV, HIV, prevalence.

Long-term tolerability and effectiveness of raltegravir in Japanese patients: Results from post-marketing surveillance.

Antiretroviral agents are approved in Japan based on non-clinical and clinical data reported from overseas. Neither the long-term tolerability nor the effectiveness of raltegravir or other integrase strand transfer inhibitors in Japan is known. This study reports on the long-term tolerability and effectiveness of raltegravir in Japanese clinical practice using data collected through approximately 9 years of post-marketing surveillance. This observational survey used data on human immunodeficiency virus (HIV) infected patients initiated treatment with raltegravir between 2008 and 2017 in the HIV-related drug (HRD) cooperative survey to assess the safety and effectiveness of raltegravir in real world clinical practice. There were totally 1,303 patients prescribed raltegravir across 30 institutions; 1,293 patients and 1,178 patients were included for the safety and effectiveness analyses, respectively. The overall risk of adverse drug reaction was 17.25%, with abnormal hepatic function and hyperlipidaemia (<1.5%) having the highest proportion. Median HIV-1 RNA viral loads rapidly decreased below 40 copies/mL after 3 months of raltegravir use in treatment-naïve patients, and consistently sustained below 40 copies/mL after the start of raltegravir use in treatment-experienced patients. Among the patients who were treated for 7 years, 92.00% (95% CI: 73.97–99.02) maintained HIV-1 RNA viral load below 50 copies/mL. Additionally, CD4+ cell counts exceeded >500 cells/μL in treatment-naïve and treatment-experienced patients after 3 years and 4 years of treatment, respectively. In Japanese HIV patients, long-term treatment with raltegravir is well-tolerated and effective at viral suppression as measured by HIV-1 RNA levels and subsequent change in CD4+ cell counts. Such benefits can be expected for not only treatment-naïve but also treatment-experienced patients.

Factors affecting first month adherence due to antiretroviral therapy among HIV-positive adults at Felege Hiwot Teaching and Specialized Hospital, north-western Ethiopia; a prospective study

BackgroundNon-adherence to Highly Active Antiretroviral Therapy (HAART) is one of the factors for treatment failure in human immunodeficiency virus (HIV) infected patients in developing countries. The main objective of this study was to identify factors for treatment failure among adult HIV patients based on the assessment of first month adherence in the study area.MethodsThe study was conducted using secondary data from antiretroviral unit at Felege Hiwot Teaching and Specialized Hospital. A prospective study was undertaken on 792 randomly selected adult HIV positive patients who have started HAART. The variable of interest, adherence to HAART was categorized as non-adherence if a patient had taken less than 95% of the prescribed medication and this was measured using pill counts. Descriptive statistics, Chi-square tests of association, independent samples t-test and binary logistic regression were used for data analysis.ResultsIn first month therapy, 68.2% of the patients belong to adherence group to HAART. As age increases, a patient without cell phone was less likely to be adherent to HAART as compared to patients with cell phone (AOR = 0.661, 95% CI: (0.243, 0.964)). Compared to urban patients, rural patients were less likely to adhere to HAART (AOR = 0.995, 95% CI: (0.403, 0.999)). A patient who did not disclose his/her disease to families or communities had less probability to be adherent to HAART (AOR = 0.325, 95% CI: (0.01, 0.64)). Similarly, a patient who did not get social support (AOR = 0.42, 95% CI: (0,021, 0.473)) had less probability of adherence to HAART. The main reasons for patients to be non-adherent were forgetfulness, side effects, feeling sick and running out of medication.ConclusionThis study indentified certain groups of patients who are at higher risk and who need counseling. Such groups should be targeted and tailored for improvement of adherence to HAART among HIV positive adults. The health care providers should advise the community to provide social support to HIV positive patients whenever their disease is disclosed. On the other hand, patients should disclose their disease to community to get integrated supports. HIV infected patients who are directed to start HAART should adhere the prescribed medication. For the adherence to be effective, patients who have cell phone should use them as reminder to take pills on time.

Update on Peripherically Inserted Central Catheters in Patients with HIV in a tertiary hospital

Literature on patients with HIV and Peripherally Inserted Central Catheter “PICC“ published on MEDLINE database in English and Spanish have thoroughly been studied, revised and updated. We reviewed the medical records of all Human Immunodeficiency Virus (HIV) infected patients with Peripherally Inserted Central Catheter “PICC” implanted from 2010 to 2016. In view of changes over the past in the intravenous management of patients with AIDS and infectious disease, we performed at Policlinico Gemelli Hospital a retrospective study of the last six years, in which we had reviewed all HIV infected patients with PICCs. Retrospectively we have evaluated the clinical severity of patients enrolled using Charlson-Deyo comorbidity score. Our hospital has 1500 beds. There are two departments of infectious diseases for a total of 40 beds. There is an outpatient service where HIV patients are followed and a Day Hospital where chemotherapy is administered. All HIV- infected patients who had PICC were identified about the occurrence of one of the following events: catheter related complication, catheter requiring removal in all cases, or death. All statistical procedures were performed using the SPSS software package (SPSS Inc. Version 15.0, Chicago).

Case-control study of PD-1, PD-L1, and B7-H3 expression in human immunodeficiency virus infected (HIV+) and uninfected patients with head and neck cancers.

e23194 Background: HIV+patients are typically excluded from immunotherapy trials but there are limited data on co-signaling molecule expression in these patients, including in head and neck squamous cell carcinoma (HNSCC). Methods: A case control study was conducted to evaluate tumor tissue sections for PD-L1, PD-1, and B7-H3 expression in HIV+HNSCC patients (n = 12) and HNSCC controls (n = 12). Cases and controls were matched for age at diagnosis, race, gender, TNM stage, and primary site. Smoking status, HIV RNA viral load (VL), and CD4 count were also recorded. Immunostained tumor sections were analyzed for percent of tumor cells expressing PD-L1 (PD-L1%) and B7-H3(B7-H3%) (Abcam), and percent of tumor infiltrating lymphocytes (TIL) expressing PD-1 (TIL-PD-1%) and PD-L1 (TIL-PD-L1%) (Abcam). Statistical analysis used the non-parametric Mann-Whitney test, chi-square test and Spearman’s rank correlation, Rs. Results: The 12 HIV+ HNSCC cases were predominantly male (67%), black race (67%) and cigarette smokers (100%), with a median age of 50.4 years, median viral load (VL) of 52399 copies/mL, median CD4 count (CD4) of 236cells/uL, predominantly locally advanced (75% Stage III/IVa/IVb), and oropharyngeal primary site (42%). Defining positive expression as &gt; 5%, 42% of HIV+ HNSCC patients tumors were positive for PD-L1, 100% for B7-H3, and 92% had TILs that expressed PD-1 and PD-L1. HIV+ patients had significantly higher B7-H3% (Median 60% vs. 20%, p = 0.03) and TIL-PD-L1% (Median 15% vs. 10%, p = 0.045) compared to controls. There were no differences in PD-L1% or TIL-PD-1%. In HIV+ cases, increased VL correlated with increased TIL-PD-1% (Rs = 0.73, p = 0.011) and increased CD4 count correlated with increased tumor PD-L1% (Rs = 0.62, p = 0.04). There were no other significant correlations between CD4 count or VL and co-signaling molecule expression. Conclusions: HIV+ HNSCC patients had significantly higher tumor B7-H3 and TIL PD-L1 expression, with similar tumor PD-L1 and TIL PD-1 expression, compared to HIV negative HNSCC control patients. These findings support inclusion of HIV+ HNSCC patients in immunotherapy trials with checkpoint inhibitors.

Allogeneic hematopoietic cell transplant (alloHCT) for hematologic malignancies in human immunodeficiency virus infected (HIV) patients (pts): Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0903)/AIDS Malignancy Consortium (AMC-080) trial.

7006 Background: AlloHCT has been regarded as risky in HIV pts, with concern about fatal infection. We set out to assess feasibility and safety of alloHCT in this first prospective multicenter trial. Methods: The primary endpoint was 100-day non-relapse mortality (NRM). Pts had drug-susceptible HIV; age ≥ 15 yr; adequate organ function; acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL), high risk myelodysplastic syndrome (MDS), or Hodgkin (HL) or non-Hodgkin lymphoma (NHL) beyond first CR; an 8/8 HLA-matched related or at least a 7/8 unrelated donor. Pts received myeloablative (MA) or reduced intensity (RI) regimens. HIV outgrowth assays (VOA) were performed with resting CD4+T-cells in pts who had clinically undetectable HIV plasma RNA at 1 yr. Results: Between 5/2012 and 12/2015, 17 pts underwent alloHCT. Pts were: male (17); white (11), African American (3), Other/Unknown (3); median age 47 yrs (25-64). Associated malignancies were AML (9), ALL (2), MDS (2), HL (1), NHL (3). Median CD4 was 224 (55-833). Conditioning was MA (8) and RI (9). At 100 days there was no NRM, 13 pts were in CR, 4 pts had relapsed/progressive disease; and 8 pts achieved complete chimerism. The cumulative incidence of Grades (Gr) II-IV acute Graft vs Host Disease (GvHD) was 41 % (95%CI: 18 %, 64%). At 6 mo, OS was 82 % (95% confidence interval [CI]: 55%, 94%); 9 pts achieved complete chimerism. At 1 year, OS was 57 % (CI: 31%, 77 %); 8 deaths were from relapsed/progressive disease (5), acute GvHD (1), adult respiratory distress syndrome (1) and liver failure (1). Infections were reported in 11 pts (3 Gr 2, 8 Gr 3). Infectious HIV was detected by VOA in 2 of 3 pts who were mixed chimeras but 0 of 2 who were 100% donor. Median follow up of survivors is 24 mo (7 to 27 ). Conclusions: HIV pts with heme malignancies underwent MA or RI alloHCT without any100-day NRM and there were no infectious deaths at 1 year. AlloHCT should be considered the standard of care for HIV pts who meet usual eligibility criteria. Clinical trial information: NCT01410344.

Steady-state pharmacokinetics of tenofovir disoproxil fumarate in human immunodeficiency virus-infected Chinese patients

ABSTRACTBackground: The pharmacokinetic (PK) profile of tenofovir disoproxil fumarate in Chinese adults infected with HIV is unknown.Methods: A pilot, prospective, open-label study was performed to investigate the steady-state PK profile of tenofovir disoproxil fumarate in 15 Chinese HIV-infected patients among whom eight patients were treated with 300 mg tenofovir disoproxil fumarate, 300 mg lamivudine and 400/100 mg lopinavir/ritonavir, and seven with 300 mg tenofovir disoproxil fumarate, 300 mg lamivudine and 400 mg nevirapine. The plasma concentrations of tenofovir over the 24-h dosing interval were determined by HPLC. The PK parameters were calculated using the non-compartmental model in WinNonlin software.Results: The PK parameters of tenofovir in the 15 patients were determined as follows (mean ± SD): AUC(0-24 h), 4074.7 ± 1551.9 ng•h/mL; Cmax,ss, 447.1 ± 217.4 ng/mL; Ctrough,ss, 98.7 ± 36.7 ng/mL; tmax,ss, 1.3 ± 0.4 h; plasma t1/2, 21.8 ± 7.6 h; and CLss/F, 45.8 ± 13.0 L/h.Conclusion: Tenofovir demonstrated slower elimination rate and increased plasma concentration in Chinese patients compared to previously published data from Caucasian or African subjects, which may be associated with the higher incidences of renal and bone resorption dysfunction observed in our patient population. Clinicians should be cautious of the differing PK characteristics of tenofovir among people of different races.