Course Of Human Immunodeficiency Virus Infection Research Articles

Adaptation to HLA-associated immune pressure over the course of HIV infection and in circulating HIV-1 strains.

Adaptation to human leukocyte antigen (HLA)-associated immune pressure represents a major driver of human immunodeficiency virus (HIV) evolution at both the individual and population level. To date, there has been limited exploration of the impact of the initial cellular immune response in driving viral adaptation, the dynamics of these changes during infection and their effect on circulating transmitting viruses at the population level. Capturing detailed virological and immunological data from acute and early HIV infection is challenging as this commonly precedes the diagnosis of HIV infection, potentially by many years. In addition, rapid initiation of antiretroviral treatment following a diagnosis is the standard of care, and central to global efforts towards HIV elimination. Yet, acute untreated infection is the critical period in which the diversity of proviral reservoirs is first established within individuals, and associated with greater risk of onward transmissions in a population. Characterizing the viral adaptations evident in the earliest phases of infection, coinciding with the initial cellular immune responses is therefore relevant to understanding which changes are of greatest impact to HIV evolution at the population level. In this study, we utilized three separate cohorts to examine the initial CD8+ T cell immune response to HIV (cross-sectional acute infection cohort), track HIV evolution in response to CD8+ T cell-mediated immunity over time (longitudinal chronic infection cohort) and translate the impact of HLA-driven HIV evolution to the population level (cross-sectional HIV sequence data spanning 30 years). Using next generation viral sequencing and enzyme-linked immunospot interferon-gamma recall responses to peptides representing HLA class I-specific HIV T cell targets, we observed that CD8+ T cell responses can select viral adaptations prior to full antibody seroconversion. Using the longitudinal cohort, we uncover that viral adaptations have the propensity to be retained over time in a non-selective immune environment, which reflects the increasing proportion of pre-adapted HIV strains within the Western Australian population over an approximate 30-year period.

Effect of Combined Antiretroviral Therapy on the Levels of Selected Parameters Reflecting Metabolic and Inflammatory Disturbances in HIV-Infected Patients.

Subjects infected with human immunodeficiency virus (HIV) treated with combined antiretroviral therapy (cART) show a greater predisposition to metabolic disturbances compared to the general population. The aim of the study was to assess the effect of cART on the level of selected parameters related to carbohydrate and lipid metabolism, cardiovascular diseases and inflammation in the plasma of HIV-infected patients against the uninfected. The levels of irisin (IRS), myostatin (MSTN), peptide YY (PYY), glucagon-like peptide-1 (GLP-1), dipeptidyl peptidase IV (DPP-4), fetuin A (FETU-A), pentraxin 3 (PTX 3), chemokine stromal cell-derived factor 1 (SDF-1), and regulated on activation normal T cell expressed and secreted (RANTES) in the plasma of HIV-infected patients and the control group were measured by immunoassay methods. HIV-infected patients were analyzed in terms of CD4+ T cells and CD8+ T cell count, HIV RNA viral load, and the type of therapeutic regimen containing either protease inhibitors (PIs) or integrase transfer inhibitors (INSTIs). The analysis of HIV-infected patients before and after cART against the control group showed statistically significant differences for the following parameters: IRS (p = 0.02), MSTN (p = 0.03), PYY (p = 0.03), GLP-1 (p = 0.03), PTX3 (p = 0.03), and RANTES (p = 0.02), but no significant differences were found for DPP-4, FETU-A, and SDF-1. Comparing the two applied therapeutic regimens, higher levels of all tested parameters were shown in HIV-infected patients treated with INSTIs compared to HIV-infected patients treated with PIs, but the differences were not statistically significant. The obtained results indicated significant changes in the expression of selected parameters in the course of HIV infection and cART. There is need for further research on the clinical usefulness of the selected parameters and for new information on the pathogenesis of HIV-related comorbidities to be provided. The obtained data may allow for better monitoring of the course of HIV infection and optimization of therapy in order to prevent the development of comorbidities as a result of long-term use of cART.

The Effect of Antiretroviral Therapy on SIRT1, SIRT3 and SIRT6 Expression in HIV-Infected Patients

Human Immunodeficiency Virus (HIV) infection and the chronic use of combined antiretroviral therapy (cART) may affect the occurrence of certain disturbances in the body. There is growing interest in sirtuins–enzymes involved in the regulation of many metabolic processes in the organism and in the pathogenesis of many diseases which also exhibit potential antiviral activity. The aim of the study was to investigate the connection of cART to the expression of Sirtuin 1 (SIRT1), Sirtuin 3 (SIRT3) and Sirtuin 6 (SIRT6) in HIV-infected men. The plasma levels of sirtuins were measured before and one year after cART, and related to HIV viral load, lymphocytes T CD4+ and CD8+ count as well as the applied cART. The levels of sirtuins in plasma were measured in HIV-infected patients (n = 53) and the control group (n = 35) by immunoassay methods. There were statistically significant (p < 0.05) differences between SIRT6 in the HIV-infected patients before therapy and in the subgroups, depending on the count of lymphocytes T CD8+. There were significant differences in the levels of SIRT1 depending on the applied treatment regimen. The obtained results indicate the most significant changes in the expression of SIRT6 in the course of HIV infection and suggest an influence of the type of cART on the level of SIRT1, which indicates its important role in the course of HIV.

Anatomical Distribution of Myeloid-Derived Suppressor Cells During HIV Infection.

In recent years, expansion of myeloid-derived suppressor cells (MDSCs) has been reported to play a detrimental role in the pathogenesis of human immunodeficiency virus (HIV) infection. Much effort has been focused to comprehend the mechanisms and factors that regulate the expansion of such unwanted immune cell populations. Of particular interest has been the mechanisms by which MDSCs could contribute to the pathogenesis of HIV infection. So far, the studies have been restricted to MDSCs in the circulatory system of HIV patients, but not in other tissue compartments. In fact, lymphatic tissues/organs are the primary sites where HIV replication and immune depletion/dysfunction occur during the course of HIV infection. Therefore, investigating the anatomical distribution of MDSCs in such compartments is essential to understand the role that they play in the pathogenesis of HIV infection. Hence, we aim to shed light on the available literature about the anatomical distribution of MDSCs during HIV infection and compare it with the distribution of MDSCs in other pathological conditions, mainly cancer.

Mucocutaneous Manifestations in HIV/AIDS Patients

Background: The main target of human immunodeficiency virus (HIV) is cluster of differentiation 4 (CD4) T lymphocytes and several other immune cells that have CD4 receptors. They are also present in skin and mucosa, such as Langerhans cells (LC). Mucocutaneous lesions are one of the first clinical presentations of immunosuppression in HIV seropositive patients that manifest at different stages of the infection and require early diagnosis and prompt treatment. Purpose: To determine the clinical characteristics and the pattern of various mucocutaneous manifestations in Human immunodeficiency virus/Acquired immune deficiency syndrome (HIV/AIDS) patients at Intermediate Care and Infectious Diseases Dr. Soetomo General Academic Hospital Surabaya. Methods: This is a descriptive retrospective study with a cross-sectional design. The study subject was classified as all HIV-AIDS patients with mucocutaneous manifestations treated in Intermediate Care and Infectious Diseases Dr. Soetomo General Academic Hospital Surabaya in 2019. Result: Out of the 614 patients who participated in the study, 72.1% were males. The majority of patients were in the age group 25–49 years (75.4%). The most common risk factor was heterosexuality (41.7%). Based on the distribution of mucocutaneous manifestations, the most common mucocutaneous manifestation was candidiasis mucocutan 387 patients (49.4%) followed by the pruritic papular eruption (PPE) 118 patients (15.1%) and human papillomavirus infection 57 patients (7.3%). Conclusion: Mucocutaneous manifestations occur throughout the course of HIV infection, and they can be considered as good clinical indicators for the progression of the disease and underlying immune status in resource-poor settings.

Identification of HIV-1-specific cascaded microRNA-mRNA regulatory relationships by parallel mRNA and microRNA expression profiling with AIDS patients after antiviral treatment.

Background:The pathogenesis of human immunodeficiency virus 1 (HIV-1) infection is so complex that have not been clearly defined, despite intensive efforts have been made by many researchers. MicroRNA (miRNA) as regulation factor in various human diseases may influence the course of HIV-1 infection by targeting mRNAs. Thus, studies combining transcription of posttranscriptional miRNA regulation are required.Methods:With the purpose of identifying cascaded miRNA-mRNA regulatory relationships related to HIV infection in gene level, the parallel miRNA, and mRNA expression profiles were analyzed to select differential expressed miRNAs and mRNAs. Then, miRNA-mRNA interactions were predicted using 3 data sources and Pearson correlation coefficient was calculated based on the gene expression level for accuracy improvement. Furthermore, the calculation of the regulatory impact factors was conducted to reveal crucial regulators in HIV-1 infection. To give further insight into these transcription factor (TF) regulators, the differentially co-expression analysis was conducted to identify differentially co-expressed links and differential co-expressed genes and the co-expression gene modules were identified using a threshold-based hierarchical clustering method, then modules were combined into a miRNA-TF-mRNA network.Results:A total of 69,126 differentially co-expressed links and 626 differential co-expressed genes were identified. Functional enrichment analysis indicated that these co-expressed genes were significantly involved in immune response and apoptosis. Moreover, according to regulatory impact factors, 5 most influential TFs and miRNA in HIV-1 infection were identified and miRNA-TF-mRNA regulatory networks were built during the computing process.Conclusions:In our study, a set of integrated methods was generated to identify important regulators and miRNA-TF-mRNA interactions. Parallel profiling analysis of the miRNAs and mRNAs expression of HIV/acquired immunodeficiency syndrome (AIDS) patients after antiretroviral therapy indicated that some regulators have wide impact on gene regulation and that these regulatory elements may bear significant implications on the underlying molecular mechanism and pathogenesis of AIDS occurrence.

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.

Disruption of brain network organization in patients with human immunodeficiency virus (HIV) infection.

In 2019, approximately 38 million people were living with human immunodeficiency virus (HIV). Combined antiretroviral therapy (cART) has determined a change in the course of HIV infection, transforming it into a chronic condition which results in cumulative exposure to antiretroviral drugs, inflammatory effects and aging. Relatedly, at least one quarter of HIV-infected patients suffer from cognitive, motor and behavioral disorder, globally known as HIV-associated neurocognitive disorders (HAND). In this context, objective, neuroimaging-based biomarkers are therefore highly desirable in order to detect, quantify and monitor HAND in all disease stages. In this study, we employed functional MRI in conjunction with graph-theoretical analysis as well as a newly developed functional brain network disruption index to assess a putative functional reorganization in HIV positive patients. We found that brain function of HIV patients is deeply reorganized as compared to normal controls. Interestingly, the regions in which we found reorganized hubs are integrated into neuronal networks involved in working memory, motor and executive functions often altered in patients with HAND. Overall, our study demonstrates that rs-fMRI combined with advanced graph theoretical analysis and disruption indices is able to detect early, subtle functional changes of brain networks in HIV patients before structural changes become evident.

Enhanced Human Immunodeficiency Virus-1 Replication in CD4+ T Cells Derived From Individuals With Latent Mycobacterium tuberculosis Infection.

Mycobacterium tuberculosis (Mtb) and human immunodeficiency virus (HIV) coinfection increases mortality, accelerates progression to acquired immune deficiency syndrome, and exacerbates tuberculosis disease. However, the impact of pre-existing Mtb infection on subsequent HIV infection has not been fully explored. We hypothesized that Mtb infection creates an immunological environment that influences the course of HIV infection, and we investigated whether pre-existing Mtb infection impacts the susceptibility of CD4+ T cells to HIV-1 infection. Plasma and blood CD4+ T cells isolated from HIV-negative individuals across the Mtb infection spectrum and non-Mtb-infected control individuals were analyzed for inflammation markers and T-cell phenotypes. CD4+ T cells were infected with HIV-1 in vitro and were monitored for viral replication. We observed differences in proinflammatory cytokines and the relative proportion of memory T-cell subsets depending on Mtb infection status. CD4+ T cells derived from individuals with latent Mtb infection supported more efficient HIV-1 transcription, release, and replication. Enhanced HIV-1 replication correlated with higher percentages of CD4+ TEM and TTD cells. Pre-existing Mtb infection creates an immunological environment that reflects Mtb infection status and influences the susceptibility of CD4+ T cells to HIV-1 replication. These findings provide cellular and molecular insights into how pre-existing Mtb infection influences HIV-1 pathogenesis.

Gender differences in innate responses and gene expression profiles in memory CD4 T cells are apparent very early during acute simian immunodeficiency virus infection.

Gender differences in Human immunodeficiency virus (HIV) disease progression and comorbidities have been extensively reported. Using the simian immunodeficiency virus (SIV) infected rhesus macaque model, we show that these differences are apparent very early during the course of infection. Though there were no major changes in the proportions of CD4 T cells or its subsets, central memory CD4 T cells from female macaques were found to differentially regulate a significantly larger number of genes at day 4 post-infection (PI) as compared to males. Pathway analysis revealed divergence of both canonical and biological pathways that persisted at day 10 PI. Changes in gene expression profiles were accompanied by a significant increase in plasma levels of pro-inflammatory mediators such as MCP-1/CCL2, I-TAC/CXCL11, and MIF. Though plasma levels of IFNα did not differ between male and female macaques, the expression levels of IFNα subtype-14, 16, IFNβ, and IFNω were significantly upregulated in the lymph nodes of female macaques at day 10 PI as compared to male macaques. Our results suggest that the pathogenic sequelae seen during chronic infection may be shaped by gender differences in immune responses induced very early during the course of HIV infection.

Pleiotropic Roles of Cytokines in HIV-1 Pathogenesis and Control: A Literature Review

Introduction: Human Immunodeficiency Virus (HIV) is a retrovirus that infects human immune cells, primarily CD4+ T cells and macrophages. During HIV disease progression, infected individuals have declining CD4+ T cell counts and increasing HIV RNA, indicative of virus replication. Numerous studies have identified important roles for cytokines in immune responses during the course of HIV infection. Cytokines are small molecular weight proteins that communicate signals between a broad range of cells in the immune system. This review aims to highlight a key subset of cytokines that bear potential as targets for the prevention and treatment of HIV infection. Methods: We conducted a literature review categorizing pertinent cytokines on the basis of four criteria: correlations with HIV replication, impact on host innate immune cells, characteristic expression in elite controllers, and therapeutic applications. Results: We identified several cytokines in the interleukin (IL) family and the C-C and C-X-C chemokine families with important roles in HIV-1 control. Indeed, the expression of many cytokines was correlated with reduced HIV-1 replication (e.g. IL-21, IL-32, IL-27). Several cytokines directly impact cells of the innate immune system in their HIV-1 control mechanisms. Among many, IL-7 and IL-15 are able to enhance natural killer cell function, while IL-27 enhances macrophage resistance to HIV infection. Elite controllers, individuals who have suppressed HIV-1 replication and preserved CD4+ T cell levels without exogenous antiviral drug treatment, express a uniquely characteristic array of chemokines. Namely, CCL14, CCL27, CCL21, XCL1 and CXCL12 are upregulated in elite controllers compared to non-controllers. Finally, considering the diversity and pleiotropic roles of cytokines during HIV-1 infection, many bear potential for inclusion in therapeutic designs. Conclusion: Herein, we have highlighted the antiviral roles of several cytokines, demonstrating that many cytokines are key regulators of HIV replication. This work provides a focus for future research aiming to better understand HIV pathogenesis and informs novel preventative and therapeutic designs.

Haematological profile of human immunodeficiency virus infected patients

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; In India, approximately 6 million populations are affected by human immunodeficiency virus (HIV). Anemia and leukopenia, especially thrombocytopenia is seen commonly in HIV infections. Low CD4+ count and increased viral load are some of the factors associated with increased risk of thrombocytopenia. The aim of the study was to study the hematological changes that occur in HIV infected patients who attend the Institute of Venereology, before starting HAART.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This cross-sectional study was conducted in the Institute of Venereology, Madras Medical College/Rajiv Gandhi Government General Hospital, Chennai in 100 treatment-naive HIV infected patients. Detailed history and clinical examination was done. Blood samples were collected. Complete blood count, CD4 count, prothrombin time, activated plasma thromboplastin time, peripheral smear etc., were done. Results were collected and analysed.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Out of 100 patients, 56% were males and 43% females and one transgender. Anaemia was detected in 72%patients. 73.5% males and 76.2% females with CD4 count &amp;lt;350/μl were anemic. The commonest anaemia was normochromic normocytic, seen in 65% patients. 7 male and 7 female patients had leukopenia. 81.25%patients with lymphocytopenia had CD4 count &amp;lt;350/μl. 12% males and 4% females had neutropenia. 17% had neutrophilia. Patients in WHO stage I did not have neutropenia. 23% patients had thrombocytopenia. 47% patients with thrombocytopenia were in stage IV. Maximum number of patients with normal platelet count was in stage I.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Haematological abnormalities are a common occurrence during the course of HIV infection. Identifying and treating the haematological changes have great impact on both the morbidity and mortality of HIV infected patients.&lt;/p&gt;

Human T-lymphotropic Virus-1/2 detected in drug abused men who have sex with men infected with HIV in Surakarta, Indonesia

Human T-lymphotropic virus types 1 and 2 (HTLV-1/2) share similar routes of transmission with human immunodeficiency virus (HIV), and the HTLV-1/2 co-infection may affect the clinical course of HIV infection. The HIV/HTLV-1/2 co-infection risk higher if the patient performing the high-risk activities. This study evaluated the presentation of HTLV-1 and 2 in HIV-infected men who have sex with men with drug abused history in Surakarta Indonesia. Blood samples collected from HIV-infected men who have sex with men with drug abused history in Surakarta were tested using HTLV-1/2 enzyme-linked immunosorbent assays and confirmed by RT-PCR nested addressed the part of HTLV-1 LTR and HTLV-2 LTR region, respectively. The specificity of the molecular assays was confirmed by sequencing the amplicons. The anti HTLV-1/2 positive rate was 17.4% (8/46). All positive serological samples were confirmed by nested RT-PCR. Of these, three was HTLV-1 positive and five was HTLV-2 positive. Molecular analysis of positive PCR products revealed that all HTLV-1 isolates had a close relationship with HTLV-1 isolated in Japan while all HTLV-2 isolates with that of isolated in the USA. HTLV-1 and HTLV-2 were detected in drug abused men who have sex with men infected with HIV in Surakarta.

A20 upregulation during treated HIV disease is associated with intestinal epithelial cell recovery and function.

Untreated Human Immunodeficiency Virus (HIV) infection is characterized by intestinal epithelial barrier dysfunction and chronic inflammation, related features that are attenuated to variable degrees by suppressive antiretroviral therapy (ART). Specific mediators of intestinal epithelial cell (IEC) dysfunction and restoration during HIV disease and treatment have yet to be identified. We studied IECs isolated from intestinal biopsies by RNAseq and found that mRNA levels for the ubiquitin-modifying enzyme, A20, are upregulated in ART-treated individuals and are positively correlated with markers of epithelial function (e.g., CTNNB, CLDN4, and TJP1). In a murine intestinal organoid model, A20 expression was suppressed by interferon-alpha (IFNα), which is highly expressed during HIV viremia and induces IFN-mediated signaling. Notably, A20 deletion rendered intestinal organoids more susceptible to cell death and inhibition of barrier-related genes mediated by interferon-gamma (IFNγ), a cytokine also present at elevated levels during untreated infection. Furthermore, A20 specifically restricted expression of IL-17A-induced inflammatory genes in organoids. Finally, ART-suppressed chronically infected individuals treated with pegylated IFNα2a for five weeks demonstrated reduced expression of A20 in peripheral blood mononuclear cells. Our results are thus consistent with a model in which enhanced type I interferons suppress A20 levels, leading to IFNγ-mediated dysfunction. As such, variation in A20 expression during the course of HIV infection could underlie both the development of epithelial dysfunction before the initiation of ART and the recovery of intestinal epithelial integrity thereafter.Trial registrationClinicalTrials.gov Clinical Trial NCT00594880

Interferon-α Subtypes As an Adjunct Therapeutic Approach for Human Immunodeficiency Virus Functional Cure.

Human immunodeficiency virus (HIV) establishes life-long latency in infected individuals. Although highly active antiretroviral therapy (HAART) has had a significant impact on the course of HIV infection leading to a better long-term outcome, the pool of latent reservoir remains substantial even under HAART. Numerous approaches have been under development with the goal of eradicating the latent HIV reservoir though with limited success. Approaches that combine immune-mediated control of HIV to activate both the innate and the adaptive immune system under suppressive therapy along with “shock and kill” drugs may lead to a better control of the reactivated virus. Interferon-α (IFN-α) is an innate cytokine that has been shown to activate intracellular defenses capable of restricting and controlling HIV. IFN-α, however, harbors numerous functional subtypes that have been reported to display different binding affinities and potency. Recent studies have suggested that certain subtypes such as IFN-α8 and IFN-α14 have potent anti-HIV activity with little or no immune activation, whereas other subtypes such as IFN-α4, IFN-α5, and IFN-α14 activate NK cells. Could these subtypes be used in combination with other strategies to reduce the latent viral reservoir? Here, we review the role of IFN-α subtypes in HIV infection and discuss the possibility that certain subtypes could be potential adjuncts to a “shock and kill” or therapeutic vaccination strategy leading to better control of the latent reservoir and subsequent functional cure.

Mucocutaneous manifestations in human immunodeficiency virus (HIV)-infected patients in Nouakchott, Mauritania.

Mucocutaneous manifestations are one of the first clinical signs in patients infected with human immunodeficiency virus (HIV). To the best of our knowledge, there has been no previous study describing dermatologic manifestations in Mauritanians infected with HIV. The aim of the present study was to determine the profiles of mucocutaneous manifestations in relation to CD4 T cell count in HIV-positive Mauritanian patients. A total of 86 adult patients aged > 18 years old attending the Ambulatory Treatment Center of the National Hospital of Nouakchott, Mauritania, with newly diagnosed HIV and who were not under antiretroviral treatment were included in the study in 2015. Dermatologic manifestations were documented before initiating antiretroviral treatment. Most of the included patients were in clinical stage 3 of the World Health Organization classification at initial diagnosis, with the mean CD4 T cell count (± SD) of 514 ± 319 cells/mm3 (range, 2-1328 cells/mm3 ), and 19 of 86 (22.1%) patients had CD4 T cell counts below 200 cells/mm3 . More than half (64%) of newly diagnosed HIV-infected patients had dermatoses, including the following: pruritic papular eruption (44.2%), seborrheic dermatitis (4.7%), Kaposi's sarcoma (3.5%), extensive xerosis cutis (2.3%), drug-induced skin reactions (1.2%), and various infectious dermatoses (dermatophyte infections [16.3%], oral candidiasis [11.6%], herpes zoster [8.1%], and scabies [2.3%]). A low CD4 T cell count (< 200 cells/mm3 ) was significantly correlated (P < 0.05) with the presence of following dermatoses: dermatophytosis, oral candidiasis, Kaposi's sarcoma, seborrheic dermatitis, and extensive xerosis cutis. Mucocutaneous lesions occur throughout the course of HIV infection, and dermatologic findings in Mauritanian HIV-positive patients are similar to those of patients in other countries. Early detection of skin disorders in some patients may help establish the diagnosis of HIV and management of HIV-associated diseases, limiting the cost of care in low-resource countries.

Patterns of Transmitted Drug Resistance and Virological Response to First-line Antiretroviral Treatment Among Human Immunodeficiency Virus-Infected People Who Use Illicit Drugs in a Canadian Setting.

Transmitted drug resistance (TDR) may compromise response to antiretroviral therapy (ART). However, there are limited data on TDR patterns and impacts among people who use illicit drugs (PWUD). Data were drawn from 2 prospective cohorts of PWUD in Vancouver, Canada. We characterized patterns of TDR among human immunodeficiency virus (HIV)-infected PWUD, and assessed its impacts on first-line ART virological outcomes. Between 1996 and 2015, among 573 ART-naive PWUD (18% with recent HIV infection), the overall TDR prevalence was 9.8% (95% confidence interval [CI], 7.3%-12.2%), with an increasing trend over time, from 8.5% in 1996-1999 to 21.1% in 2010-2015 (P = .003), mainly driven by resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs). TDR-associated mutations were more common for NNRTIs (5.4%), followed by nucleoside reverse transcriptase inhibitors (3.0%) and protease inhibitors (1.9%). TDR prevalence was lower among recently infected PWUD (adjusted odds ratio, 0.39 [95% CI, .15-.87]). Participants with TDR had higher risk of virological failure than those without TDR (log-rank P = .037) in the first year of ART. Between 1996 and 2015, TDR prevalence increased significantly among PWUD in Vancouver. Higher risk of virological failure among PWUD with TDR may be explained by some inappropriate ART prescribing, as well as undetected minority resistant variants in participants with chronic HIV infection. Our findings support baseline resistance testing early in the course of HIV infection to guide ART selection among PWUD in our setting.

Longitudinal study of surrogate aging measures during human immunodeficiency virus seroconversion.

Persons living with human immunodeficiency virus (HIV) harbor an increased risk of age-related conditions. We measured changes in telomere length and DNA methylation in the peripheral blood of 31 intravenous drug users, who were followed longitudinally with blood samples pre-HIV (T1), immediately post-HIV (T2; 1.9±1 year from T1), and at a later follow-up time (T3; 2.2±1 year from T2). Absolute telomere length measurements were performed using polymerase chain reaction methods. Methylation profiles were obtained using the Illumina Human Methylation450 platform. Methylation aging was assessed using the Horvath method. Telomere length significantly decreased between T1 and T2 (227±46 at T1 vs. 201±48 kbp/genome at T2, p=0.045), while no differences were observed between T2 and T3 (201±48 at T2 vs. 186±27 kbp/genome at T3, p=0.244). Methylation aging as measured by the age acceleration residual increased over the time course of HIV infection (p=0.035). CpG sites corresponding to PCBP2 and CSRNP1 were differentially methylated between T1 and T2 at a q-value <0.05. Telomere shortening and methylation changes can therefore be observed in the short-term period immediately following HIV seroconversion. Further studies to confirm these results in larger sample sizes and to compare these results to non-HIV and non-injection drug users are warranted.

MHC Class II Tetramer Labeling of Human Primary CD4+ T Cells from HIV Infected Patients.

Major Histocompatibility Complex (MHC) tetramers have been used for two decades to detect, isolate and characterize T cells specific for various pathogens and tumor antigens. In the context of Human Immunodeficiency Virus (HIV) infection, antigen-specific CD8+ T cells have been extensively studied ex vivo, as they can be readily detected by HIV peptide-loaded MHC class I tetramers. In contrast, the detection of HIV-specific CD4+ T cells has proven more challenging, due to the intrinsically lower clonal expansion rates of CD4+ T cells, and to the preferential depletion of HIV-specific CD4+ T cells in the course of HIV infection. In the following protocol, we describe a simple method that facilitates the identification of CD4+ T cells specific for an HIV-1 capsid epitope using peptide-loaded MHC class II tetramers. Tetramer labeled CD4+ T cells can be analyzed for their cell surface phenotype and/or FACS-sorted for further downstream applications. A key point for successful detection of specific CD4+ T cells ex vivo is the choice of a peptide/MHC II combination that results in high-affinity T Cell Receptor (TCR) binding ( Benati et al., 2016 ). A second key point for reliable detection of MHC II tetramer-positive cells is the systematic use of a control tetramer loaded with an irrelevant peptide, with the sample and control tubes being processed in identical conditions.

Association between CD4+ Lymphocyte Count and Left Ventricular Diastolic Function and Geometry in Newly Diagnosed Highly Active Antiretroviral Therapy (HAART) Naive HIV/AIDS Patients Seen at University of Port Harcourt Teaching Hospital, Port Harcourt, Rivers State, Nigeria

Background: Human Immunodeficiency Virus (HIV) infection is one of the leading causes of acquired heart diseases and specifically of symptomatic heart failure and pulmonary arterial hypertension. In the clinical course of HIV infection, CD4 + count decreases with disease progression and it has been considered to be correlated with LV dysfunction in the disease process. Method: This was a cross-sectional case-control study. One hundred newly diagnosed HAART naive HIV/ AIDS individuals seen in the retroviral clinic were evaluated clinically. One hundred age and sex matched HIV negative controls were recruited. Those with other cardiovascular risk factors were excluded. Blood samples were screened and confirmed for HIV1 and 2 infections using double ELISA. CD4 + count was estimated using the flow cytometry method. Left ventricular diastolic function and geometry were assessed using transthoracic echocardiography. Results: The mean age of cases with HIV/AIDS was 35.7 ± 10.13 years. Females were more than males in a ratio of 2.3:1. Diastolic dysfunction assessed by E/A ratio, deceleration time and isovolumic relaxation time (IVRT) occurred more in the cases compared to the controls (40% versus 6%) and this was statistically significant (x2=38.15, p=0.001). Abnormal geometry assessed using LVMI and RWT was commoner in the cases than in the control group and this was statistically significant (x2=25.49, p=0.01). There was an insignificant negative correlation between CD4 + count and IVRT (R=- 0.0086, P=0.393). Subjects with CD4 + count <200 cells/μL were more likely to have diastolic dysfunction (OR=1.680, P=0.2112). Lastly, there was an insignificant negative correlation between CD4 + count and LVMI (R=- 0.303, P=0.816). Subjects with CD4 + count<200 cells/μL were more likely to have abnormal geometry (OR=1.182, P=0.6312). Conclusion: Left ventricular diastolic dysfunction and abnormal geometry were shown in this study to be more common in people with HIV/AIDS than in the control group and there was association between degree of immunosuppression and diastolic dysfunction as well as abnormal geometry, although these were statistically not significant.