Human Immunodeficiency Virus Comorbidities Research Articles

Transfusion Therapy in HIV: Risk Mitigation and Benefits for Improved Patient Outcomes

Transfusion therapy is a pivotal aspect of healthcare, especially for individuals living with Human Immunodeficiency Virus (HIV). This comprehensive review aims to dissect the intricate landscape of transfusion therapy in HIV patients, emphasizing the delicate balance between risks and benefits to achieve enhanced patient outcomes. With advancements in blood safety measures and antiretroviral therapy (ART), navigating the complexities of transfusion therapy in HIV management becomes paramount for healthcare professionals. The review consolidates current knowledge and emerging trends, encompassing challenges, benefits, risks, and strategies to optimize transfusion therapy for improved patient care. The paper delineates key areas, including blood safety measures such as nucleic acid testing (NAT) and pathogen reduction technologies, emphasizing their role in ensuring safer blood products for transfusion in HIV patients. Furthermore, it explores the impact of HIV on hematological disorders, delving into transfusion-transmitted infections and strategies to mitigate these risks. Additionally, it scrutinizes the therapeutic benefits of transfusion therapy in managing hematologic complications in HIV, while addressing potential risks, including immune reactions and adverse effects. Optimizing transfusion therapy in HIV necessitates personalized approaches, considering the individual patient's HIV status, comorbidities, and specific transfusion needs. The role of ART in reducing transfusion requirements and associated risks is highlighted, alongside emerging trends like novel therapies and alternative transfusion practices. Keywords: Transfusion therapy, HIV, blood safety, antiretroviral therapy, risks, benefits, patient outcomes, transfusion-transmitted infections, personalized treatment, hematology, blood products

Questioning the "Ease" in disease: Was living with HIV a burden or boost during the first wave of Covid-19 in France? A qualitative study (COVIDHIV).

Clinical research has focused on risk factors and treatment for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), particularly in people with a comorbidity including the human immunodeficiency virus (HIV), but little attention has been paid to the care pathway. This article aims to show how living with HIV may have been a biopsychosocial burden or boost in care pathways for Covid-19. People living with HIV (PLHIV) from 9 clinical centers were invited to participate in this qualitative study. The sampling was purposive with a maximum variation in their sociodemographic profiles. Semi-structured interviews were conducted until data saturation, then coded for thematic analysis, using an inductive general approach. We interviewed 34 PLHIV of which 20 had SARS-COV-2 once. They were 24 males, 26 born in France; median age: 55. Twenty had a CD4 number above 500, and all were on antiretroviral therapy (ART). HIV appeared as a burden when Covid-19 symptoms reminded HIV seroconversion, fear of contamination, and triggered questions about ART effectiveness. HIV was not considered relevant when diagnosing Covid-19, caused fear of disclosure when participants sought SARS-COV-2 testing, and its care in hospitals was disrupted by the pandemic. ART-pill fatigue caused avoidance for Covid-19 treatment. As a boost, living with HIV led participants to observe symptoms, to get advice from healthcare professionals, and screening access through them. Some participants could accept the result of screening or a clinical diagnosis out of resilience. Some could consider ART or another drug prescribed by their HIV specialist help them to recover from Covid-19. Living with HIV could function as a burden and/or a boost in the care pathways for Covid-19, according to patients' relationship to their HIV history, comorbidities and representation of ART. Covid-19 in PLHIV needs further qualitative study to gain a more comprehensive assessment of the pandemic's consequences on their lives and coping strategies.

29 Human Immunodeficiency Virus (HIV) Status, Injection Drug Use, and Cognitive Effects in a Spanish-Speaking Population

Objective:Injection drug use is a significant public health crisis with adverse health outcomes, including increased risk of human immunodeficiency virus (HIV) infection. Comorbidity of HIV and injection drug use is highly prevalent in the United States and disproportionately elevated in surrounding territories such as Puerto Rico. While both HIV status and injection drug use are independently known to be associated with cognitive deficits, the interaction of these effects remains largely unknown. The aim of this study was to determine how HIV status and injection drug use are related to cognitive functioning in a group of Puerto Rican participants. Additionally, we investigated the degree to which type and frequency of substance use predict cognitive abilities.Participants and Methods:96 Puerto Rican adults completed the Neuropsi Attention and Memory-3rd Edition battery for Spanish-speaking participants. Injection substance use over the previous 12 months was also obtained via clinical interview. Participants were categorized into four groups based on HIV status and injection substance use in the last 30 days (HIV+/injector, HIV+/non-injector, HIV/injector, HIV-/non-injector). One-way analysis of variance (ANOVA) was conducted to determine differences between groups on each index of the Neuropsi battery (Attention and Executive Function; Memory; Attention and Memory). Multiple linear regression was used to determine whether type and frequency of substance use predicted performance on these indices while considering HIV status.Results:The one-way ANOVAs revealed significant differences (p’s < 0.01) between the healthy control group and all other groups across all indices. No significant differences were observed between the other groups. Injection drug use, regardless of the substance, was associated with lower combined attention and memory performance compared to those who inject less than monthly (Monthly: p = 0.04; 2-3x daily: p < 0.01; 4-7x daily: p = 0.02; 8+ times daily: p < 0.01). Both minimal and heavy daily use predicted poorer memory performance (p = 0.02 and p = 0.01, respectively). Heavy heroin use predicted poorer attention and executive functioning (p = 0.04). Heroin use also predicted lower performance on tests of memory when used monthly (p = 0.049), and daily or almost daily (2-6x weekly: p = 0.04; 4-7x daily: p = 0.04). Finally, moderate injection of heroin predicted lower scores on attention and memory (Weekly: p = 0.04; 2-6x weekly: p = 0.048). Heavy combined heroin and cocaine use predicted worse memory performance (p = 0.03) and combined attention and memory (p = 0.046). HIV status was not a moderating factor in any circumstance.Conclusions:As predicted, residents of Puerto Rico who do not inject substances and are HIVnegative performed better in domains of memory, attention, and executive function than those living with HIV and/or inject substances. There was no significant difference among the affected groups in cognitive ability. As expected, daily injection of substances predicted worse performance on tasks of memory. Heavy heroin use predicted worse performance on executive function and memory tasks, while heroin-only and combined heroin and cocaine use predicted worse memory performance. Overall, the type and frequency of substance is more predictive of cognitive functioning than HIV status.

Advancing the preclinical study of comorbid neuroHIV and substance use disorders: Current perspectives and future directions

Human immunodeficiency virus (HIV) remains a persistent public health concern throughout the world. Substance use disorders (SUDs) are a common comorbidity that can worsen treatment outcomes for people living with HIV. The relationship between HIV infection and SUD outcomes is likely bidirectional, making clear interrogation of neurobehavioral outcomes challenging in clinical populations. Importantly, the mechanisms through which HIV and addictive drugs disrupt homeostatic immune and CNS function appear to be highly overlapping and synergistic within HIV-susceptible reward and motivation circuitry in the central nervous system. Decades of animal research have revealed invaluable insights into mechanisms underlying the pathophysiology SUDs and HIV, although translational studies examining comorbid SUDs and HIV are very limited due to the technical challenges of modeling HIV infection preclinically. In this review, we discuss preclinical animal models of HIV and highlight key pathophysiological characteristics of each model, with a particular emphasis on rodent models of HIV. We then review the implementation of these models in preclinical SUD research and identify key gaps in knowledge in the field. Finally, we discuss how cutting-edge behavioral neuroscience tools, which have revealed key insights into the neurobehavioral mechanisms of SUDs, can be applied to preclinical animal models of HIV to reveal potential, novel treatment avenues for comorbid HIV and SUDs. Here, we argue that future preclinical SUD research would benefit from incorporating comorbidities such as HIV into animal models and would facilitate the discovery of more refined, subpopulation-specific mechanisms and effective SUD prevention and treatment targets.

HIV-Hypertension Comorbidity, Associated Factors and Treatment Option Among HIV Patients Attending Katsina General Hospital, Katsina State Nigeria

People living with human immunodeficiency virus (HIV) are facing an increased burden of non-communicable diseases (NCDs) comorbidity. There is however, paucity of information on the magnitude of HIV-hypertension comorbidity, its associated factors, and how the health system responds to the burden in Nigeria. This study aimed to determine the magnitude of comorbidity HIV and hypertension and associated factors among HIV-positive adults receiving antiretroviral therapy (ART) in Katsina General Hospital, Katsina. Two hundred (200) HIV infected adults (aged ≥ 18) who had been on antiretroviral therapy for at least six months Katsina General Hospital, Katsina were recruited. Participants’ demographics, HIV characteristics, the presence of non-communicable diseases via self-report, from clinic folders and from measurement of their blood pressure on the day of interview and serum lipid profile, were evaluated. The magnitude of HIV and hypertension comorbidity was 28.5%. Old age, higher BMI, higher viral load, alcohol and duration on antiretroviral therapy were found to be factors associated with development of hypertension among HIV-positive adults. The prevalence of hypertension measured on the day of interview was greater than that found on self-report or reported in the clinic folder. Regular screening for the incidences of hypertension, addressing modifiable risk factors, and providing integrated care in the center would help improve the quality of life of comorbid patients.

Opioid abuse and SIV infection in non-human primates.

Human immunodeficiency virus (HIV) and drug abuse are intertwined epidemics, leading to compromised adherence to combined antiretroviral therapy (cART) and exacerbation of NeuroHIV. As opioid abuse causes increased viral replication and load, leading to a further compromised immune system in people living with HIV (PLWH), it is paramount to address this comorbidity to reduce the NeuroHIV pathogenesis. Non-human primates are well-suited models to study mechanisms involved in HIV neuropathogenesis and provide a better understanding of the underlying mechanisms involved in the comorbidity of HIV and drug abuse, leading to the development of more effective treatments for PLWH. Additionally, using broader behavioral tests in these models can mimic mild NeuroHIV and aid in studying other neurocognitive diseases without encephalitis. The simian immunodeficiency virus (SIV)-infected rhesus macaque model is instrumental in studying the effects of opioid abuse on PLWH due to its similarity to HIV infection. The review highlights the importance of using non-human primate models to study the comorbidity of opioid abuse and HIV infection. It also emphasizes the need to consider modifiable risk factors such as gut homeostasis and pulmonary pathogenesis associated with SIV infection and opioid abuse in this model. Moreover, the review suggests that these non-human primate models can also be used in developing effective treatment strategies for NeuroHIV and opioid addiction. Therefore, non-human primate models can significantly contribute to understanding the complex interplay between HIV infection, opioid abuse, and associated comorbidities.

Chronic binge alcohol-induced hippocampal plasticity in SIV-infected female rhesus macaques

Human immunodeficiency virus (HIV) infection is detrimental to central nervous system (CNS) function and may result in HIV-associated neurocognitive disorder (HAND) over time. HIV-associated cognitive deficits are further exacerbated by chronic alcohol use. With the rising prevalence of alcohol use disorder (AUD) in females and people living with HIV (PLWH), understanding the neurobiological impact of chronic alcohol exposure in these populations is increasingly important. As the hippocampus plays a prominent role in cognition, examining neuroadaptations in this brain region in the context of comorbid HIV infection and alcohol exposure is critical for understanding the mechanisms of neurocognitive impairment. We hypothesized that simian immunodeficiency virus (SIV)-infected female rhesus macaques with a history of chronic binge alcohol (CBA) administration (n=7-8 per group) would exhibit increased phosphorylation of mitogen-activated protein kinase (MAPK) family members, indicative of increased hippocampal activity and potential hyperexcitability. We also measured cognitive performance in macaques via the novel object recognition (NOR) task and further hypothesized a manifestation of cognitive deficits in the CBA-treated group. Finally, we incorporated additional groups of ovariectomized (OVX) females in the design as we hypothesized that the loss of ovarian hormones would reduce cognitive performance. Data were analyzed via two-way ANOVA with CBA treatment and OVX as factors. Western blot analyses demonstrated that CBA significantly increased phosphorylation of MAPK-family members extracellular signal-regulated kinase (ERK; F=8.278, p=0.0093) and p38 mitogen-activated protein kinase (p38 MAPK; F=4.414, p=0.0485). Furthermore, CBA significantly increased both phosphorylated and total levels of Jun N-terminal kinase (JNK; F=5.989, p=0.0233; F=7.158, p=0.0145). While analysis of the NOR task revealed a significant reduction in latency to approach the novel versus familiar object on test day across all groups (F = 11.97, p=0.0013), no significant difference was seen between CBA and control groups. Interestingly, no main effects of OVX or interactive CBA/OVX effects were observed for either molecular or behavioral outcomes. We are currently considering alternative cognitive tasks that may better reveal CBA-associated cognitive deficits, as well as neuroadaptations in nuclear signaling downstream of MAPK activity. Together, these data suggest that chronic alcohol use results in profound changes in hippocampal plasticity, potentially facilitating cognitive decline and other CNS symptoms observed in PLWH. This research was supported by grant # T32AA007577 and #P60AA009803 from the NIAAA at the National Institutes of Health. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Pattern of HCV Genotypes in HIV/HCV Co-Infected Patients on Antiretroviral Therapy in Nigeria

At least 33 million people worldwide are living with human immunodeficiency virus (HIV) infection, and about 20-30% of these are also infected with hepatitis C virus (HCV). Co-infection with HIV and HCV is a major public health concern. Co-infected persons develop cirrhosis and end-stage liver disease more quickly than individuals infected with HCV only. The particular HCV strain or genotype is a major factor for HCV prognosis. The pattern of HCV genotypes in a cohort of HIV/HCV co-infected patients was investigated. One hundred (100) adult patients were recruited from the Nigerian Institute of Medical Research (NIMR), Yaba, Lagos, with age ranging from 18 to 65 years (58% male). Upon recruitment, they were placed on appropriate antiretroviral drugs; 300 mg tenofovir (TDF), 200 mg emtricitabine (FTC) plus 600 mg efavirenz (EFV) once daily dosage. HCV genotyping was done using the Linear Array hepatitis C virus genotyping kit (Roche Molecular Systems, Inc. USA). HCV genotyping revealed prevalence of genotypes 1 (65.6%) and 4 (34.4%), respectively. These are the hard-to-treat genotypes that previously required a long duration of HCV therapy until newer drugs were introduced. The nature of HCV genotypes in HIV/HCV co-infected people has serious implications for further HCV therapy. These findings are pertinent for decisions about the best possible time for and kind of HCV treatment in the setting of co-morbid HIV infection.

Prevalence of depressive symptoms and quality of life among patients with diabetes mellitus with and without HIV infection: A South African study.

BackgroundDiabetes mellitus (DM) and human immunodeficiency virus (HIV) infection are both associated with increased risk of mood disorders and poorer quality of life (QOL). This association has not been explored in patients living with comorbid DM and HIV.AimTo describe the prevalence of depressive symptoms and impact on the QOL in patients with DM living with and without HIV attending a public sector hospital in South Africa.SettingA medical outpatient clinic at a state regional hospital.MethodsA cross-sectional questionnaire pilot survey was conducted amongst 101 patients with DM attending a specialist medical outpatient service. The assessment was conducted using a structured socio-demographic and clinical questionnaire, the patient health questionnaire 9 (PHQ-9) for depressive symptoms and the World Health Organization QOL scale. The HIV status was confirmed from the clinical records. The correlates of depressive symptomatology in the participants with DM living with and without HIV were identified using t-tests.ResultsThe prevalence of depressive symptoms in the participants with DM was 36%. Moderate to severe depression was associated with female gender (p = 0.03) and low educational level (p = 0.02) but not with HIV comorbidity or clinical characteristics of DM. The QOL was influenced by moderate to severe depressive symptoms (QOL in physical p < 0.218 and environmental p < 0.001 domains), but not HIV status (p = 0.218).ConclusionA substantial proportion of people with DM reported depressive symptoms, which is slightly higher than the average reported in other out-patient studies. The association of depression with poor QOL highlights the need for integrated mental health access in medical outpatient services. The lack of association between comorbid HIV status and DM with depression or QOL needs to be further explored.

Correlates and cascade of HIV care in patients with psychiatric disorders in the Eastern Cape province, South Africa.

BackgroundThe cascade of human immunodeficiency virus (HIV) care in patients with psychiatric disorders is poorly understood.AimThis study determined the prevalence of HIV and described its cascade of care among patients with psychiatric disorders in the Eastern Cape province, South Africa. The study also examined the correlates of HIV comorbidity with psychiatric disorders in the cohort.MethodsIn this cross-sectional study, a total of 368 individuals attending the Psychiatric Outpatients’ Department of Cecilia Makiwane Hospital in Eastern Cape were interviewed with a structured questionnaire. Relevant items on demographics and clinical information were extracted from the medical records. Virologic suppression was defined as viral load < 1000 RNA copies/mL.ResultsThe HIV prevalence after the intervention was 18.8% and a significant proportion of participants already knew their status (n = 320; 87.0%). Linkage to care and antiretroviral therapy initiation occurred in 61 participants, of those diagnosed with HIV (88.4%), with 84.1% being eligible for viral load monitoring (n = 58) and 53.4% having achieved virologic suppression. Being female (AOR = 5.48; 95% CI 2.61–11.51) and black (adjusted odds ratio [AOR] = 3.85; 95% confidence interval [CI] 1.06–14.03) were independent predictors of HIV comorbidity in individuals living with psychiatric disorders.ConclusionThis study found a moderately high prevalence (close to 19%) of HIV in individuals with psychiatric disorders, with a significant correlation with being female and being black people. This study also found a significant gap in the linkage to antiretroviral therapy (ART) initiation and a low rate of virologic suppression of 53.4%. Clinicians, therefore, should monitor and provide interventions for patients with concomitant HIV infection along this cascade of care.

Abstract PO-045: Experiences of oncologists treating cancer patients living with HIV: Opportunities to improve care and reduce disparities

Abstract Introduction: Prior database studies have demonstrated that cancer patients with comorbid human immunodeficiency virus (HIV) have higher cancer-specific mortality and are less likely to receive cancer treatment. People living with HIV (PLWH) who achieve viral suppression have near normal life expectancy, highlighting the critical importance of reducing cancer treatment disparities. The purpose of this study is to understand how oncologists make treatment decisions for cancer patients living with HIV and to elicit recommendations for improving care in this population. Methods: We conducted in-depth interviews with 25 attending medical, radiation, and surgical oncologists from Duke University, University of Utah, and community practices in Florida, Georgia, Louisiana, Pennsylvania, and Virginia who had recently engaged in a consultation with PLWH and cancer. In semi-structured interviews, we explored three domains: (1) care coordination with other healthcare professionals, (2) knowledge and attitudes regarding patients with comorbid HIV and cancer, and (3) recommendations for improvements in care delivery. Two analysts coded the data using ATLAS.ti. We utilized applied thematic analysis to identify inductive themes across the three domains. Results: Many participants (n=11) reported always communicating with a patient's Infectious Disease (ID) doctor, and others (n=5) said they only communicate with ID if the patient's HIV is not well-controlled. Ten medical oncologists noted they found it helpful to speak to an HIV pharmacist, particularly about drug-drug interactions. Participants also discussed efforts to connect patients with supportive services, such as transportation, payment assistance, and mental health counseling. Many participants described concerns in discussing the patient care plan in the presence of caregivers, given the possibility that patients have not disclosed their HIV status. None of the participants had formal training in management of comorbid cancer and HIV, and most noted that they learned through their own clinical practice. Participants made suggestions for improving treatment decision-making for PLWH, including: more evidence of the risk-benefit ratio of treatment (e.g. treatment goals, life expectancy calculators), greater access to social work and mental health resources, streamlined access to communication with HIV providers, and multidisciplinary HIV cancer rounds. Conclusions: This is the first physician-focused qualitative study interviewing oncologists caring for PLWH. Communication among multiple healthcare providers, particularly oncologist and ID doctor, are noted to be common but not universal in the care of comorbid HIV and cancer. Formal training in cancers in PLWH is lacking in medical training. Future steps to reduce disparities in cancer treatment and outcomes for PLWH may include the establishment of multidisciplinary HIV cancer rounds, facilitating connection and communication between healthcare providers, and enhancing supportive care resources for patients. Citation Format: Ashley Khouri, Jeanette Young, Patrick Galyean, Brandon Knettel, Emily M. Cherenack, Anthony Ariotti, Noelani Ho, Susan Zickmund, Melissa Watt, Kathryn Pollak, Peter Ubel, Angela Fagerlin, Gita Suneja. Experiences of oncologists treating cancer patients living with HIV: Opportunities to improve care and reduce disparities [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-045.

Mortality Risk in COVID-19 Patients with HIV-Comorbidity: Meta-Analysis

Background: Coronavirus disease 2019 or known as COVID-19 is a disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2). Comorbidities that are risk factors for COVID-19 death include hypertension, diabetes, heart disease, COPD, HIV (Human Immunodeficiency Virus), kidney failure, and cancer. This study aims to estimate the magnitude of the risk of death in COVID-19 patients with comorbid HIV, with a meta-analysis of the primary studies conducted by the previous authors. Subjects and Method : This study is a systematic review and meta-analysis with the following PICO, population: COVID-19 patients. Intervention: HIV comorbidity. Comparison: without co-morbid HIV. Outcome: Mortality. The articles used in this study were obtained from four data­bases, namely PubMed, Google Scholar, Springerlink, and Science direct, using the search keys "HIV/AIDS" AND "Mortality" OR "death" AND "COVID-19 OR SARS-CoV-2. The included article is a full-text English language with a cohort study design from 2020 to 2021 and reports the adjusted Odds Ratio (aOR) in a multivariate analysis. Article selection is done by using PRISMA flow diagram. Articles were analyzed using the Review Manager 5.3 application. Results: A total of 9 cohort studies involving 3,397,186 COVID-19 patients from America, Europe, and Africa were selected for a systematic review and meta-analysis. The data collected showed that COVID-19 patients with HIV comorbidities had a mortality risk of 3.30 times compared to COVID-19 patients without HIV comorbidities (aOR = 3.30; 95% CI = 2.87 to 3.81; p&lt;0.001). Conclusion: HIV increases mortality risk in COVID-19 patients. Keywords: HIV, COVID-19, SARS-CoV-2, mortality Correspondence: Nindita Arum Veibiani. Masters Program in Public Health, Universitas Sebelas Maret, Jl. Ir. Sutami 36A, Surakarta 57126, Central Java. Email: nindita.veibiani@gmail.com. Mobile: 085800­216969. Journal of Epidemiology and Public Health (2022), 07(04): 431-440 https://doi.org/10.26911/jepublichealth.2022.07.04.02 .

Human Immunodeficiency Virus Co-morbidities: How Lipid Homeostasis Alterations Lead to Cardiovascular and Neurological Disorders

Although human immunodeficiency virus (HIV) is still prevalent worldwide, life-saving antiretroviral drugs can now prevent an infection from progressing into acquired immunodeficiency syndrome (AIDS). Nevertheless, people who are HIV-positive are still at increased risk of developing neurological disorders and cardiovascular diseases, known as co-morbidities. Professor Michael Bukrinsky from the George Washington University in Washington DC works to understand the underlying biological mechanisms that lead to these disorders. His research has produced interesting results that demonstrate the role of altered lipid (cholesterol) homeostasis in HIV-infected cells and how this comes to pass.

Sirtuins as Interesting Players in the Course of HIV Infection and Comorbidities.

The sirtuins (SIRTs) are a family of enzymes from the group of NAD+-dependent deacetylases. Through the reaction of splitting the acetyl group of various transcription factors and histones they regulate many processes in the organism. The activity of sirtuins is linked to metabolic control, oxidative stress, inflammation and apoptosis, and they also affect the course of viral infections. For this reason, they may participate in the pathogenesis and development of many diseases, but little is known about their role in the course of human immunodeficiency virus (HIV) infection, which is the subject of this review. In the course of HIV infection, comorbidities such as: neurodegenerative disorders, obesity, insulin resistance and diabetes, lipid disorders and cardiovascular diseases, renal and bone diseases developed more frequently and faster compared to the general population. The role of sirtuins in the development of accompanying diseases in the course of HIV infection may also be interesting. There is still a lack of detailed information on this subject. The role of sirtuins, especially SIRT1, SIRT3, SIRT6, are indicated to be of great importance in the course of HIV infection and the development of the abovementioned comorbidities.

New insights into pathogenesis point to HIV-1 Tat as a key vaccine target.

Despite over 30 years of enormous effort and progress in the field, no preventative and/or therapeutic vaccines against human immunodeficiency virus (HIV) are available. Here, we briefly summarize the vaccine strategies and vaccine candidates that in recent years advanced to efficacy trials with mostly unsatisfactory results. Next, we discuss a novel and somewhat contrarian approach based on biological and epidemiological evidence, which led us to choose the HIV protein Tat for the development of preventive and therapeutic HIV vaccines. Toward this goal, we review here the role of Tat in the virus life cycle as well as experimental and epidemiological evidence supporting its key role in the natural history of HIV infection and comorbidities. We then discuss the preclinical and clinical development of a Tat therapeutic vaccine, which, by improving the functionality and homeostasis of the immune system and by reducing the viral reservoir in virologically suppressed vaccinees, helps to establish key determinants for intensification of combination antiretroviral therapy (cART) and a functional cure. Future developments and potential applications of the Tat therapeutic vaccine are also discussed, as well as the rationale for its use in preventative strategies. We hope this contribution will lead to a reconsideration of the current paradigms for the development of HIV/AIDS vaccines, with a focus on targeting of viral proteins with key roles in HIV pathogenesis.

Clinical characteristics and impacts of HIV infection in people with bipolar disorders

People with bipolar disorders (BD) may be at increased risk of Human Immunodeficiency Virus (HIV) infection but our understanding of the impacts of HIV infection on psychiatric outcomes is poor. This study aimed to examine the prevalence, temporal relationship, and clinical impact of HIV infection in people with BD. In this retrospective case-control study, anonymised electronic case records of patients with BD who had been under the care of South London and Maudsley mental health services were used for data extraction. 54 HIV+ people with BD were identified and compared to a matched control group of 54 HIV- people with BD. The prevalence of HIV co-morbidity in the BD population was around 1%. 76% of HIV+ BD men identified as men who have sex with men (MSM). 65% of the HIV+ BD group were diagnosed with BD before becoming HIV+. The HIV+ BD group experienced significantly higher rates of stimulant, GBL/GHB and psychedelic use compared to the HIV- BD group. 85% of the HIV+ BD group were recorded as taking antiretroviral medications. Retrospective and cross-sectional study design, and a relatively small sample size CONCLUSIONS: The prevalence of HIV comorbidity in BD was comparable to the local general population. HIV infection in BD is associated with MSM status and stimulant, GHB/GBL and psychedelics use suggesting that HIV prevention strategies should particularly target these groups. Lower use of antiretroviral medications by people with BD underlines the importance of engaging HIV+ BD people in HIV services.

Screening of Mycobacterium tuberculosis genes as putative drug targets for treatment of HIV-TB and lung cancer-TB comorbidities: An in silico analysis

This study focuses on insilico analysis to understand the mechanism between tuberculosis (TB) associated comorbidities such as Human Immunodeficiency Virus (HIV) and lung cancer. Initially, gene expression studies of samples associated with HIV-TB and lung cancer-TB were analyzed and differentially expressed genes were identified. Further, gene networks for the up-regulated genes were constructed and the functionally associated genes were identified. Functional enrichment analysis was also performed for the genes associated. Differentially- regulated genes could be possible drug targets for treatment of TB associated comorbidities. In this regards, Rv2949c which was found to be highly expressed in HIV patients with TB and it could be a candidate drug target for treatment of patients with HIV comorbidity. Similarly, pgsA1 is highly expressed in lung cancer patients with TB, is a candidate drug target for treatment of patients with lung cancer comorbidity. Suitable inhibitors for Rv2949c and pgsA1 have been found through molecular docking studies. Thus the insights gained through this study will be helpful in designing suitable drug candidates for treatment of TB related comorbidities.

Preliminary Evidence for a Relationship between Elevated Plasma TNFα and Smaller Subcortical White Matter Volume in HCV Infection Irrespective of HIV or AUD Comorbidity.

Classical inflammation in response to bacterial, parasitic, or viral infections such as HIV includes local recruitment of neutrophils and macrophages and the production of proinflammatory cytokines and chemokines. Proposed biomarkers of organ integrity in Alcohol Use Disorders (AUD) include elevations in peripheral plasma levels of proinflammatory proteins. In testing this proposal, previous work included a group of human immunodeficiency virus (HIV)-infected individuals as positive controls and identified elevations in the soluble proteins TNFα and IP10; these cytokines were only elevated in AUD individuals seropositive for hepatitis C infection (HCV). The current observational, cross-sectional study evaluated whether higher levels of these proinflammatory cytokines would be associated with compromised brain integrity. Soluble protein levels were quantified in 86 healthy controls, 132 individuals with AUD, 54 individuals seropositive for HIV, and 49 individuals with AUD and HIV. Among the patient groups, HCV was present in 24 of the individuals with AUD, 13 individuals with HIV, and 20 of the individuals in the comorbid AUD and HIV group. Soluble protein levels were correlated to regional brain volumes as quantified with structural magnetic resonance imaging (MRI). In addition to higher levels of TNFα and IP10 in the 2 HIV groups and the HCV-seropositive AUD group, this study identified lower levels of IL1β in the 3 patient groups relative to the control group. Only TNFα, however, showed a relationship with brain integrity: in HCV or HIV infection, higher peripheral levels of TNFα correlated with smaller subcortical white matter volume. These preliminary results highlight the privileged status of TNFα on brain integrity in the context of infection.

How Should We Organize Care for Patients With Human Immunodeficiency Virus and Comorbidities? A Multisite Qualitative Study of Human Immunodeficiency Virus Care in the United States Department of Veterans Affairs.

With human immunodeficiency virus (HIV) now managed as a chronic disease, health care has had to change and expand to include management of other critical comorbidities. We sought to understand how variation in the organization, structure and processes of HIV and comorbidity care, based on patient-centered medical home (PCMH) principles, was related to care quality for Veterans with HIV. Qualitative site visits were conducted at a purposive sample of 8 Department of Veterans Affairs Medical Centers, varying in care quality and outcomes for HIV and common comorbidities. Site visits entailed conduct of patient interviews (n=60); HIV care team interviews (n=60); direct observation of clinic processes and team interactions (n=22); and direct observations of patient-provider clinical encounters (n=45). Data were analyzed using a priori and emergent codes, construction of site syntheses and comparing sites with varying levels of quality. Sites highest and lowest in both HIV and comorbidity care quality demonstrated clear differences in provision of PCMH-principled care. The highest site provided greater team-based, comprehensive, patient-centered, and data-driven care and engaged in continuous improvement. Sites with higher HIV care quality attended more to psychosocial needs. Sites that had consistent processes for comorbidity care, whether in HIV or primary care clinics, had higher quality of comorbidity care. Provision of high-quality HIV care and high-quality co-morbidity care require different care structures and processes. Provision of both requires a focus on providing care aligned with PCMH principles, integrating psychosocial needs into care, and establishing explicit consistent approaches to comorbidity management.

Food Insecurity and T-cell Dysregulation in Women Living With Human Immunodeficiency Virus on Antiretroviral Therapy.

Food insecurity is associated with increased morbidity and mortality in people with human immunodeficiency virus (HIV) on antiretroviral therapy, but its relationship with immune dysregulation, a hallmark of HIV infection and comorbidity, is unknown. In 241 women participating in the Women's Interagency HIV Study, peripheral blood mononuclear cells were characterized by flow cytometry to identify cell subsets, comprising surface markers of activation (%CD38+HLADR+), senescence (%CD57+CD28-), exhaustion (%PD-1+), and co-stimulation (%CD57- CD28+) on CD4+ and CD8+ T cells. Mixed-effects linear regression models were used to assess the relationships of food insecurity with immune outcomes, accounting for repeated measures at ≤3 study visits and adjusting for sociodemographic and clinical factors. At the baseline study visit, 71% of participants identified as non-Hispanic Black, 75% were virally suppressed, and 43% experienced food insecurity. Food insecurity was associated with increased activation of CD4+ and CD8+ T cells, increased senescence of CD8+ T cells, and decreased co-stimulation of CD4+ and CD8+ T cells (all P < .05), adjusting for age, race/ethnicity, income, education, substance use, smoking, HIV viral load, and CD4 count. In stratified analyses, the association of food insecurity with CD4+ T-cell activation was more pronounced in women with uncontrolled HIV (viral load >40 copies/mL and CD4 <500 cells/mm3) but remained statistically significant in those with controlled HIV. Food insecurity may contribute to the persistent immune activation and senescence in women with HIV on antiretroviral therapy, independently of HIV control. Reducing food insecurity may be important for decreasing non-AIDS-related disease risk in this population.