Physicians' communication with patients about adherence to HIV medication in San Francisco and Copenhagen: a qualitative study using Grounded Theory

BACKGROUND: Poor adherence is the main barrier to the effectiveness of HIV medication. The objective of this study was to explore and conceptualize patterns and difficulties in physicians' work with patients' adherence to HIV medication. No previous studies on this subject have directly observed physicians' behavior. METHODS: This is a qualitative, cross-sectional study. We used a Grounded Theory approach to let the main issues in physicians' work with patients' adherence emerge without preconceiving the focus of the study. We included physicians from HIV clinics in San Francisco, U.S.A. as well as from Copenhagen, Denmark. Physicians were observed during their clinical work and subsequently interviewed with a semi-structured interview guide. Notes on observations and transcribed interviews were analyzed with NVivo software. RESULTS: We enrolled 16 physicians from San Francisco and 18 from Copenhagen. When we discovered that physicians and patients seldom discussed adherence issues in depth, we made adherence communication and its barriers the focus of the study. The main patterns in physicians' communication with patients about adherence were similar in both settings. An important barrier to in-depth adherence communication was that some physicians felt it was awkward to explore the possibility of non-adherence if there were no objective signs of treatment failure, because patients could feel "accused." To overcome this awkwardness, some physicians consciously tried to "de-shame" patients regarding non-adherence. However, a recurring theme was that physicians often suspected non-adherence even when patients did not admit to have missed any doses, and physicians had difficulties handling this low believability of patient statements. We here develop a simple four-step, three-factor model of physicians' adherence communication. The four steps are: deciding whether to ask about adherence or not, pre-questioning preparations, phrasing the question, and responding to the patient's answer. The three factors/determinants are: physicians' perceptions of adherence, awkwardness, and believability. CONCLUSION: Communication difficulties were a main barrier in physicians' work with patients' adherence to HIV medication. The proposed model of physicians' communication with patients about adherence – and the identification of awkwardness and believability as key issues – may aid thinking on the subject for use in clinical practice and future research

Antiviral Effect of Ribavirin against HCV Associated with Increased Frequency of G-to-A and C-to-U Transitions in Infectious Cell Culture Model

Abstract Ribavirin (RBV) is a broad-spectrum antiviral active against a wide range of RNA viruses. Despite having been used for decades in the treatment of chronic hepatitis C virus (HCV) infection, the precise mechanism of action of RBV is unknown. In other viruses, it inhibits propagation by increasing the rate of G-to-A and C-to-U transitions. Here, we utilized the J6/JFH1 HCV cell-culture system to investigate whether RBV inhibits HCV through the same mechanism. Infected Huh7.5 cells were treated with increasing concentrations of RBV or its phosphorylated forms. A fragment of the HCV NS5B-polymerase gene was amplified, cloned, and sequenced to estimate genetic distances. We confirm that the antiviral effect of all three RBV-drug forms on HCV relies on induction of specific transitions (G-to-A and C-to-U). These mutations lead to generation of non-infectious virions, reflected by decreased spread of HCV in cell culture despite relatively limited effect on virus genome titers. Moreover, treatment experiments conducted on a novel Huh7.5 cell line stably overexpressing adenosine kinase, a key enzyme for RBV activation, yielded comparable results. This study indicates that RBV action on HCV in hepatoma cell-culture is exerted through increase in mutagenesis, mediated by RBV triphosphate, and leading to production of non-infectious viruses

Thirty Years with HIV Infection—Nonprogression Is Still Puzzling: Lessons to Be Learned from Controllers and Long-Term Nonprogressors

In the early days of the HIV epidemic, it was observed that a minority of the infected patients did not progress to AIDS or death and maintained stable CD4+ cell counts. As the technique for measuring viral load became available it was evident that some of these nonprogressors in addition to preserved CD4+ cell counts had very low or even undetectable viral replication. They were therefore termed controllers, while those with viral replication were termed long-term nonprogressors (LTNPs). Genetics and virology play a role in nonprogression, but does not provide a full explanation. Therefore, host differences in the immunological response have been proposed. Moreover, the immunological response can be divided into an immune homeostasis resistant to HIV and an immune response leading to viral control. Thus, non-progression in LTNP and controllers may be due to different immunological mechanisms. Understanding the lack of disease progression and the different interactions between HIV and the immune system could ideally teach us how to develop a functional cure for HIV infection. Here we review immunological features of controllers and LTNP, highlighting differences and clinical implications

Early Infant Diagnosis of HIV in Three Regions in Tanzania; Successes and Challenges.

By the end of 2009 an estimated 2.5 million children worldwide were living with HIV-1, mostly as a consequence of vertical transmission, and more than 90% of these children live in sub-Saharan Africa. In 2008 the World Health Organization (WHO), recommended early initiation of Highly Active Antiretroviral Therapy (HAART) to all HIV infected infants diagnosed within the first year of life, and since 2010, within the first two years of life, irrespective of CD4 count or WHO clinical stage. The study aims were to describe implementation of EID programs in three Tanzanian regions with differences in HIV prevalences and logistical set-up with regard to HIV DNA testing. Data were obtained by review of the prevention from mother to child transmission of HIV (PMTCT) registers from 2009-2011 at the Reproductive and Child Health Clinics (RCH) and from the databases from the Care and Treatment Clinics (CTC) in all the three regions; Kilimanjaro, Mbeya and Tanga. Statistical tests used were Poisson regression model and rank sum test. During the period of 2009 - 2011 a total of 4,860 exposed infants were registered from the reviewed sites, of whom 4,292 (88.3%) were screened for HIV infection. Overall proportion of tested infants in the three regions increased from 77.2% in 2009 to 97.8% in 2011. A total of 452 (10.5%) were found to be HIV infected (judged by the result of the first test). The prevalence of HIV infection among infants was higher in Mbeya when compared to Kilimanjaro region RR = 1.872 (95%CI = 1.408 - 2.543) p < 0.001. However sample turnaround time was significantly shorter in both Mbeya (2.7 weeks) and Tanga (5.0 weeks) as compared to Kilimanjaro (7.0 weeks), p=<0.001. A substantial of loss to follow-up (LTFU) was evident at all stages of EID services in the period of 2009 to 2011. Among the infants who were receiving treatment, 61% were found to be LFTU during the review period. The study showed an increase in testing of HIV exposed infants within the three years, there is large variations of HIV prevalence among the regions. Challenges like; sample turnaround time and LTFU must be overcome before this can translate into the intended goal of early initiation of lifelong lifesaving antiretroviral therapy for the infants

Expression of fibroblast growth factor-21 in muscle is associated with lipodystrophy, insulin resistance and lipid disturbances in patients with HIV

BACKGROUND: Fibroblast growth factor (FGF)-21 is a novel regulator of glucose and lipid metabolism. Recently, increased FGF-21 mRNA expression in muscle was found in patients with type 2 diabetes, but the role for FGF-21 in muscle is not well understood. Patients with HIV-infection and lipodystrophy are characterised by various degree of lipid-driven insulin resistance. We hypothesized that muscle FGF-21 mRNA would be altered in HIV patients with lipodystrophy. DESIGN: Twenty-five HIV-infected men with lipodystrophy (LD) and 15 age-matched healthy controls, received an oral glucose tolerance test and a euglycemic-hyperinsulinemic clamp (50 mU/m2/min) combined with 6,6-H2 glucose infusion. Muscle biopsies were obtained and FGF-21 mRNA and glycogen synthase (GS) activity were measured. RESULTS: Subjects with HIV were insulin resistant compared with non-HIV subjects. Compared to controls, HIV subjects demonstrated a twofold increase of plasma FGF-21 from 70.4±56.8 pg/ml vs 109.1±71.8 pg/ml, respectively (p = 0.04) and an eight-fold increase in muscular FGF-21 mRNA expression (p = 0.001). Muscle FGF-21 mRNA correlated inversely with the rate of disappearance of glucose during insulin clamp (r = -0.54, p = 0.0009), and the GS fractional velocity in muscle (r = -0.39, p = 0.03), and directly with fasting insulin (r = 0.50, p = 0.0022), HOMA-IR (r = 0.47, p = 0.004), triglycerides (r = 0.60. P = 0.0001), waist-to-hip ratio (r = 0.51, p = 0.0001) and limb fat mass (-0.46, p = 0.004), but not to plasma FGF-21. CONCLUSION: FGF-21 mRNA is increased in skeletal muscle in HIV patients and correlates to whole-body (primarily reflecting muscle) insulin resistance, but not to plasma FGF-21. Those findings add to the evidence that FGF-21 is a myokine and may suggest that muscle FGF-21 is working in a local manner

Head and neck cancer in HIV patients and their parents: a Danish cohort study

The mechanism for the increased risk of head and neck cancer (HNC) observed in HIV patients is controversial. We hypothesized that family-related risk factors increase the risk of HNC why we estimated the risk of this type of cancer in both HIV patients and their parents

A Highly Selective Cc Chemokine Receptor (Ccr)8 Antagonist Encoded by the Poxvirus Molluscum Contagiosum

The MC148 CC chemokine from the human poxvirus molluscum contagiosum (MCV) was probed in parallel with viral macrophage inflammatory protein (vMIP)-II encoded by human herpesvirus 8 (HHV8) in 16 classified human chemokine receptors. In competition binding using radiolabeled endogenous chemokines as well as radiolabeled MC148, MC148 bound with high affinity only to CCR8. In calcium mobilization assays, MC148 had no effect on its own on any of the chemokine receptors, but in a dose-dependent manner blocked the stimulatory effect of the endogenous I-309 chemokine on CCR8 without affecting chemokine-induced signaling of any other receptor. In contrast, vMIP-II acted as an antagonist on 10 of the 16 chemokine receptors, covering all four classes: XCR, CCR, CXCR, and CX3CR. In chemotaxis assays, MC148 specifically blocked the I-309–induced response but, for example, not stromal cell–derived factor 1α, monocyte chemoattractant protein 1, or interleukin 8–induced chemotaxis. We thus concluded that the two viruses choose two different ways to block the chemokine system: HHV8 encodes the broad-spectrum chemokine antagonist vMIP-II, whereas MCV encodes a highly selective CCR8 antagonist, MC148, conceivably to interfere with monocyte invasion and dendritic cell function. Because of its pharmacological selectivity, the MC148 protein could be a useful tool in the delineation of the role played by CCR8 and its endogenous ligand, I-309

The Prevalence of Human Immunodeficiency Virus Coinfection Among Patients Newly Diagnosed With Chronic Hepatitis B or C in Denmark:A Nationwide Cohort Study

Background: Early identification of patients with chronic viral hepatitis coinfected with human immunodeficiency virus (HIV) is essential for optimal care. The objectives of this study were to estimate the prevalence of HIV coinfection among patients newly diagnosed with chronic viral hepatitis, HIV testing prevalence, and identify factors associated with coinfection.Methods: Patients with chronic viral hepatitis newly enrolled in The Danish Database for Hepatitis B and C between 2002 and 2015 were identified. The HIV coinfection prevalence was calculated, and risk factors associated with HIV coinfection were estimated by logistic regression.Results: In total, 8490 patients were included: 3091 had chronic hepatitis B (CHB), 5305 had chronic hepatitis C (CHC), and 94 had CHB and CHC. The prevalence of HIV coinfection was 4.4% (95% confidence interval [CI], 4.0-4.9) and was higher among CHC and CHB-CHC patients than CHB patients with a prevalence of 5.3% (95% CI, 4.7-5.9), 6.4% (95% CI, 2.4-13.4), and 2.9 (95% CI, 2.3-3.5), respectively (P &lt; .0001). The HIV testing prevalence increased from 65% to 88% between 2002 and 2014 concurrently with a decrease in the HIV coinfection prevalence from 7.8% (95% CI, 5.5-10.7) to 1.6% (95% CI, 0.7-3.2). Age 35-50 years, male sex, and sexual route of viral hepatitis transmission were associated with HIV coinfection with odds ratios of 4.42 (95% CI, 1.40-13.94), 2.21 (95% CI, 1.74-2.81), and 8.81 (95% CI, 6.30-12.33), respectively.Conclusions: The prevalence of HIV coinfection among patients with newly diagnosed chronic viral hepatitis decreased concurrently with an increase in HIV testing prevalence.</p

Cytomegalovirus-specific T-cells are associated with immune senescence, but not with systemic inflammation, in people living with HIV

Abstract In people living with HIV (PLWHIV), coinfection with cytomegalovirus (CMV) has been associated with inflammation, immunological ageing, and increased risk of severe non-AIDS related comorbidity. The effect of CMV-specific immune responses on systemic inflammation, immune activation and T-cell senescence was evaluated in 53 PLWHIV treated with combination antiretroviral therapy (cART). Activated-, terminally differentiated-, naïve-, and senescent T-cells were assessed by flow cytometry, and plasma levels of CMV IgG, interleukin-6, tumor necrosis factor-α, high-sensitivity C-reactive protein and soluble-CD14 were measured. In PLWHIV, expression of interleukin-2, tumor necrosis factor-α and interferon-γ was measured by intracellular-cytokine-staining after stimulation of T-cells with CMV-pp65, CMV-IE1, and CMV-gB. Increased CMV-specific T-cell responses were associated with a higher ratio of terminally differentiated/naïve CD8+ T-cells and with increased proportions of senescent CD8+ T-cells, but not with systemic inflammation or sCD14. Increased CMV-specific CD4+ T-cell responses were associated with increased proportions of activated CD8+ T-cells. In PLWHIV with expansion of CMV-specific T-cells or increased T-cell senescence, CMV-specific polyfunctionality was maintained. That the magnitude of the CMV-specific T-cell response was associated with a senescent immune phenotype, suggests that a dysregulated immune response against CMV may contribute to the immunological ageing often described in PLWHIV despite stable cART