HIV-uninfected Individuals Research Articles

Smokeless Tobacco Use and Oral Potentially Malignant Disorders Among People Living with HIV (PLHIV) in Pune, India: Implications for Oral Cancer Screening in PLHIV

Background: In India, smokeless tobacco (SLT) is a predominant form of tobacco used among people living with HIV (PLHIV). Despite SLT being a risk factor for oral potentially malignant disorders (OPMDs), no prior studies have quantified the association of OPMDs with SLT use among PLHIV. This limits the planning of preventive and control strategies for oral cancer among PLHIV, who are at higher risk for the disease. Methods: We enrolled 601 PLHIV and 633 HIV-uninfected individuals in an oral cancer screening study at BJ Government Medical College, Pune, India. Oral cavity images were collected using an m-Health application and reviewed by three clinicians. Participants with two clinician positive diagnoses were deemed to have suspected OPMDs. Prevalence ratios (PRs) were used to quantify the association between suspected OPMDs and SLT use among PLHIV. PRs for current SLT users, across HIV status and use duration were also estimated. Corrected PRs were obtained by modifying the maximum likelihood estimation. Models were adjusted for age, smoking, alcohol use and CD4 counts. Findings: Of those enrolled, 61% were men, median age was 36 years (IQR: 28-44), and 33% currently use SLT. Proportion of current SLT users was similar across PLHIV and HIV-uninfected groups but use duration for current SLT use was higher among PLHIV(p<0.05). Among PLHIV, current users had a 5-times (95% CI:3·1-7·0) higher prevalence of suspected OPMDs, compared to non-users. Relative to HIV uninfected individuals with the same SLT use duration, significant associations with suspected OPMDs were seen for PLHIV with<10 use years (PR: 3·5, 95% CI: 1·5 – 8·1) but not for PLHIV with≥10 use years (PR: 1·3, 95% CI: 0·9 – 1·8). Interpretation: PLHIV that are current SLT users are at high risk of OPMDs and potentially oral cancer. The development of strategies for screening, early detection, and management of OPMDs must be considered for this group. Funding: This work was supported by amfAR, The Foundation for AIDS Research, with support from the U.S. National Institutes of Health’s National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Cancer Institute, the National Institute of Mental Health, the National Institute on Drug Abuse, the National Heart, Lung, and Blood Institute, the National Institute on Alcohol Abuse and Alcoholism, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Fogarty International Center, as part of the International Epidemiology Databases to Evaluate AIDS (IeDEA; U01AI069907) and the NIH-funded Johns Hopkins Baltimore-Washington-India Clinical Trials Unit for NIAID Networks [UM1AI069465]. Declaration of Interest: The authors have no competing interests to declare. Ethical Approval: The Institutional Review Board of Johns Hopkins University (JHU) and Ethics Committee of BJGMC-JHU Clinical Research Site approved the project.

Increased risk for cerebral small vessel disease is associated with quantitative susceptibility mapping in HIV infected and uninfected individuals

The aim of this study was to assess, in the context of cerebral small vessel disease (CSVD), whether cardiovascular risk factors and white matter hyperintensities (WMHs) were associated with brain tissue susceptibility as measured by quantitative susceptibility mapping (QSM). Given that CSVD is diagnosed by the presence of lacunar strokes, periventricular and deep WMHs, increased perivascular spaces, and microbleeds, we expected that QSM could capture changes in brain tissue due to underlying CSVD pathology. We compared a cohort of 101 HIV-infected individuals (mean age ± SD = 53.2 ± 10.9 years) with mild to moderate cardiovascular risk scores, as measured by the Reynolds risk score, to 102 age-matched controls (mean age (SD) = 50.3 (15.7) years) with similar Reynolds scores. We performed brain MRI to assess CSVD burden by acquiring 3D T1-MPRAGE, 3D FLAIR, 2D T2-TSE, and mGRE for QSM. We found that signs of CSVD are significantly higher in individuals with HIV-infection compared to controls and that WMH volumes are significantly correlated with age and cardiovascular risk scores. Regional QSM was associated with cardiovascular risk factors, age, sex, and WMH volumes but not HIV status. These results suggest that QSM may be an early imaging marker reflective of alterations in brain microcirculation.

Seroprevalence of SARS-CoV-2 after the Second Wave in South Africa in HIV-Infected and Uninfected Persons: A Cross-Sectional Household Survey, November 2020 – April 2021

Background: Seroprevalence studies are important for quantifying the burden of SARS-CoV-2 infections in resource-constrained countries.Methods: We conducted a cross-sectional household survey spanning the second pandemic wave (November 2020 – April 2021) in three communities. Blood was collected for SARS-CoV-2 antibody (two ELISA assays targeting spike and nucleocapsid) and HIV testing. An individual was considered seropositive if testing positive on ≥1 assay. Factors associated with infection, and the age-standardised infection to case detection rate (ICR), infection hospitalisation rate (IHR) and infection fatality rate (IFR) were calculated.Findings: Overall 7959 participants were enrolled, with a median age of 34 years and HIV prevalence of 22.7%. SARS-CoV-2 seroprevalence was 45.2% (95% confidence interval 43.7% - 46.7%), and increased from 26.9% among individuals enrolled in December 2020 to 47.1% among individuals in April 2021. On multivariable analysis, seropositivity was associated with age, sex, race, being overweight/obese, having respiratory symptoms, and low socioeconomic status. Persons living with HIV (PLWH) with high viral load were less likely to be seropositive compared to HIV-uninfected individuals. The site-specific ICR, IHR and IFR ranged across sites from 4.4% to 8.2%, 1.2% to 2.5% and 0.3% to 0.6%, respectively.Interpretation: South Africa has experienced a large burden of SARS-CoV-2 infections, with Funding Information: This study was supported by the South African MRC, Wellcome Trust and UK Foreign, Commonwealth and Development Office, and US CDC.Declaration of Interests: C. Cohen has received grant support from Sanofi Pasteur, Advanced Vaccine Initiative, and payment of travel costs from Parexel. NW and AvG have received grant support from Sanofi Pasteur. All other authors declare no conflict of interest.Ethics Approval Statement: This study was approved by the University of the Witwatersrand (M200861) and by the respective community and provincial research committees.

80. COVID-19 Testing, Characteristics, and Outcomes Among People Living with HIV in an Integrated Health System

BackgroundUnderstanding attributes of COVID-19 clinical severity among people living with HIV/AIDS (PLWH) is critical for risk stratification and treatment strategies, but data among this population are limited.MethodsWe conducted a retrospective study among health plan members at Kaiser Permanente Southern California. We identified PLWH aged ≥ 18 years with a positive SARS-CoV-2 molecular diagnostic test or COVID-19 diagnosis and compared COVID-19 outcomes to HIV-negative cases. Chart review was conducted to examine HIV viral suppression, most recent CD4+ counts, and antiretroviral regimens in the year prior to COVID-19 diagnosis, as well as COVID-19 clinical presentation and outcomes.ResultsBetween 3/1/20 and 5/31/20, 590 PLWH were tested for SARS-CoV-2, of which 47 (8.0%) were positive. An additional 14 patients had a clinical COVID-19 diagnosis, for a total of 61 cases identified among the population of 10,702 PLWH. Of these, 10 (16.4%) were hospitalized, 4 (6.6%) were admitted to ICU, 3 (6.4%) required invasive mechanical ventilation, and 1 (1.6%) died from COVID-19. In comparison, of the 12,921 HIV-negative individuals with COVID-19, 1975 (15.3%) were hospitalized, 494 (3.8%) were admitted to ICU, 444 (3.4%) required invasive mechanical ventilation, and 300 (2.3%) died from COVID-19. For 42 PLWH for whom chart review was complete (cases through 5/7/20), 52% were aged ≥ 50 years, and 98% were male. In the year prior to COVID-19 diagnosis, 98% were virally suppressed (HIV RNA < 40 copies/mL). Most recent mean CD4+ count was 600 cells/mm3, and 4.8% had CD4+ ≤ 200 cells/mm3. Median CD4 count was similar between hospitalized and non-hospitalized patients. Antiretroviral regimens included NRTIs (98% of patients), NNRTIs (31%), PIs (26%), INSTIs (57%), and CCR5 inhibitors (2.3%). The most common presenting symptoms were cough (76% of patients), fever (71%), and shortness of breath (48%).Table 1. SARS-CoV-2 testing, characteristics, and COVID-19 outcomes of HIV-infected and HIV-uninfected individuals at Kaiser Permanente Southern California, 3/1/20 to 5/31/20 ConclusionIn this population of patients with well-controlled HIV, risks of severe COVID-19 outcomes were similar to HIV-negative individuals, although sample sizes of PLWH with COVID-19 were small. Analyses adjusted for demographics and comorbidities are needed to assess risk of severe COVID-19 among PLWH and to determine clinical predictors in this population.DisclosuresKatia Bruxvoort, PhD, MPH, GlaxoSmithKlein (Research Grant or Support) Lie Hong Chen, DrPH, Merk (Research Grant or Support)

1100. Outcomes of HIV-Associated Lymphoma Treatments: A Contemporary Single Center Cohort Study

BackgroundThere is a paucity of outcome studies on HIV-associated lymphoma treated with chemotherapy with or without autologous hematopoietic stem cell transplantation (autoHSCT) in comparison to HIV-uninfected individuals with similar histology.MethodsIn our retrospective matched cohort study, we enrolled adult HIV-positive patients with lymphoma treated with chemotherapy with (group 2) or without autoHSCT (group 1) between January 1, 2007 to December 31, 2018 at the University of Kansas Medical Center and followed until May 1, 2020. Group 1 were matched 1:1 to HIV-negative patients based on age, gender, lymphoma histology, stage at diagnosis, year of lymphoma diagnosis, and Group 2 were matched 1:2 to HIV-negative patients based on age at autoHSCT, gender, lymphoma histology, stage at diagnosis and year of transplantation. Overall survival (OS) and progression-free survival (PFS) at 2 years were calculated using Kaplan-Meier (KM) analysis, and adjustment for ECOG and IPI/IPS scores was done using multivariate Cox model.ResultsWe had 37 HIV+ patients with lymphoma in our cohort: 9 Hodgkin’s disease (HD), 28 Non Hodgkin’s Lymphoma (NHL). Eleven underwent autoHSCT (3 HD, 8 NHL). The majority were white (76.2%), non-hispanic (92.9%), males (90.5%) and mean age was 46 years. Median CD4 was 172.5, HIV viral load was < 50 copies/mL in 43..2%, and 76.2% were on antiretroviral therapy (ART) at diagnosis. ART was interrupted in 14.6% and adjusted in 40.5% of patients. After excluding rare histological types, 22 in group 1 and 9 in group 2 were included in the matched analysis. On KM survival at 2-years, group 1 had worse OS (75% vs 95%, p=0.02), and a trend for worse PFS (75% vs 90%, p=0.07) than the matched referent group, while group 2 had similar OS (100% vs 94%, p= 0.47) and better PFS (100% vs 70%, p=0.02) than the matched referent group. On Cox models adjusting for ECOG and IPI/IPS, HIV status was no longer independently associated with OS in group 1 or PFS in group 2.Group 1 HIV lymphoma cases and controls characteristics Group 2 HIV lymphoma with HSCT cases and controls characteristics ConclusionIn patients with HIV and lymphoma treated with chemotherapy with or without autoHSCT, the outcomes are comparable to those without HIV in our single center contempory cohort.Disclosures Wissam El Atrouni, MD, ViiV (Advisor or Review Panel member)

1648. CD4 T Lymphocyte and Monocyte Activation within One Year After Treatment Completion for Pulmonary Tuberculosis: A Pilot Study

BackgroundPersons with active tuberculosis (TB) have increased immune activation, which declines with TB treatment. Whether residual immune activation is present after completion of TB treatment is unknown. We conducted immunophenotyping of T cells and monocytes from individuals who had completed TB treatment, and compared them to controls without history of active TB.MethodsCross-sectional study of HIV-uninfected individuals 40 to 70 years old recruited in Lima, Peru. For this analysis, we included 6 individuals who had completed treatment for pulmonary TB within the past year, and 10 healthy controls without history of active TB (6 QuantiFERON®-TB positive; 4 QuantiFERON®-TB negative). Participants provided blood for T cell and monocyte immunophenotyping using multi-parameter flow cytometry, including expression of cell surface activation markers.ResultsThere were no significant differences in age, sex, or comorbidities between patients previously treated for TB and controls without history of active TB. Median time since TB treatment completion was 4 months (range, 2 – 9) for the previously treated group. Compared to controls, persons previously treated for TB had increased CD4+ to CD8+ ratio (2.4 vs. 1.3; p=0.03), increased proportion of CD4+ T cells co-expressing HLA-DR and CD38 activation markers (5.8% vs. 3.1%; p=0.02), increased CD4+ T cell ICAM-1 expression (56.3% vs. 33.2%; p=0.03), as well as increased density of HLA-DR in monocytes (HLA-DR MFI; 7572 vs. 3917; p=0.03).ConclusionIn this pilot study, individuals who recovered from pulmonary TB exhibited increased CD4+ T cell and monocyte activation phenotypes within one year of TB treatment completion. These results suggest residual immune activation after clinical TB cure.Disclosures Carl Fichtenbaum, MD, Amgen (Grant/Research Support, outside the submitted work)Clinical Care Options (Other Financial or Material Support, outside the submitted work)Cytodyn (Grant/Research Support, outside the submitted work)Gilead Sciences (Grant/Research Support, outside the submitted work)Janssen (Grant/Research Support, outside the submitted work)Merck (Grant/Research Support, outside the submitted work)ViiV Healthcare (Research Grant or Support, outside the submitted work)

Plasma lipidome abnormalities in people with HIV initiating antiretroviral therapy

BackgroundDyslipidemia often accompanies human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART). Lipid abnormalities likely contribute to increased cardiometabolic disease among people with HIV (PWH). Here, we expand our previous findings on changes in the lipidome following ART initiation, and associations among lipid species, including ceramides (CER), diacylglycerols (DAG), and triacylglycerols (TAG), with immune activation.MethodsConcentrations and fatty acid composition of plasma lipids (~ 1300 species) were measured by differential mobility spectroscopy in samples from 35 treatment-naïve PWH pre- and post-initiation of ART (raltegravir (RAL)/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)); lipidomes were compared to those found in demographically similar HIV-uninfected individuals (n = 13).ResultsCompared to people without HIV, 37.1% of all lipid species measured were altered in PWH at baseline, and 31.8% of lipid species were altered following 48 weeks of ART. Concentrations of lipid classes were also altered in PWH; diacylglycerols (DAGs) and triacylglycerols (TAGs) were increased at baseline, and DAGs remained increased after 48 weeks of ART. Lipids previously linked to cardiovascular disease (CVD) and diabetes were enriched in PWH pre- and post ART, and were related to immune activation and insulin resistance scores. Polyunsaturated fatty acid (PUFA)-containing lipids were lower in PWH compared to levels in controls, and were inversely related to levels of inflammatory biomarkers.ConclusionsHIV infection and ART initiation both induce cardiometabolic changes to the composition of the plasma lipidome. These alterations are associated with inflammatory biomarkers, and may directly contribute to elevated CVD risk and diabetes.Trial registrationThis study is registered with Clinicaltrials.gov (NCT00660972). Registered April 16, 2008.

Monocyte activation in persons living with HIV and tuberculosis coinfection.

To characterize monocyte subsets and activation in persons living with HIV (PLWH) with tuberculosis coinfection. Cross-sectional study within a cohort of PLWH and HIV-uninfected participants at the Joint Clinical Research Centre in Kampala, Uganda. Participants were at least 45 years old with at least one cardiovascular risk factor. PLWH had an HIV viral load 1000 copies/ml or less on stable antiretroviral therapy prior to cohort entry. QuantiFERON-TB testing was performed to define latent tuberculosis infection (LTBI). Prior active TB was defined by self-report and verified by medical records. Blood was stained with monocyte subset markers (CD14+, CD16), CD62p, CD69, CX3CR1, HLA-DR, and tissue factor, and examined with flow cytometry. One hundred and twenty-five participants (83 PLWH and 42 without HIV) were included. Median CD4+ count was 582 cells/μl in PLWH. PLWH had a higher frequency of total monocytes (4.3% vs. 3.2%; P < 0.001) and inflammatory monocyte subset (15.5% vs. 11.7%; P = 0.016) compared with HIV-uninfected individuals. No differences in the frequency of monocyte subsets were observed by TB status. Among PLWH, prior active TB was associated with increased frequency of total monocytes compared with LTBI (5.1% vs. 3.7%; P = 0.013). HLA-DR density on monocytes was three-fold higher in PLWH with LTBI or prior TB compared with PLWH without LTBI (P = 0.002). In multivariate analysis, a higher monocyte HLA-DR density remained associated with LTBI or prior TB in PLWH (log-MFI; b = 1.17; P < 0.001). Our findings indicate enhanced monocyte activation in PLWH with LTBI or prior active TB, which may contribute to the pathogenesis of noncommunicable diseases in HIV.

The DARC-null trait is associated with moderate modulation of NK cell profiles and unaltered cytolytic T cell profiles in black South Africans.

The Duffy Antigen Receptor for Chemokines (DARC)-null trait, common among persons of African descent and associated with lower absolute neutrophil counts (ANCs), may be linked to increased risk to certain infections including HIV-1 but the underlying causes are poorly understood. We hypothesized that DARC-null-linked neutropenia may negatively impact neutrophil immunoregulatory modulation of other immune cells such as natural killer (NK) and CD8+ T cells leading to altered phenotype, functionality and homeostatic activity of these immune cells. HIV-1 uninfected (n = 20) and HIV-1 chronically infected (n = 19) participants were assessed using multi-parametric flow cytometry to determine NK and CD8+ T cell counts, phenotypic profiles, and cytokine production and degranulation. Annexin V and carboxyfluorescein succinimidyl ester (CFSE) staining were used to examine NK cell survival and NK cell and CD8+ T cell proliferation respectively. Participants were genotyped for the DARC-null polymorphism using allelic discrimination assays and ANCs were measured by full blood count. In HIV uninfected individuals, a reduction of total NK cell counts was noted in the absence of DARC and this correlated with lower ANCs. HIV uninfected DARC-null subjects displayed a less mature NK cell phenotype. However, this did not translate to differences in NK cell activation or effector functionality by DARC state. Whilst HIV-1 infected subjects displayed NK cell profiling that is typical of HIV infection, no differences were noted upon DARC stratification. Similarly, CD8+ T cells from HIV infected individuals displayed phenotypic and functional modulation that is characteristic of HIV infection, but profiling was unaffected by the DARC-null variant irrespective of HIV status. Overall, the data suggests that the DARC-null polymorphism and lower ANCs does not impede downstream cytolytic cell priming and functionality.

Schistosoma mansoni Infection Is Associated With a Higher Probability of Tuberculosis Disease in HIV-Infected Adults in Kenya.

Helminth infections can modulate immunity to Mycobacterium tuberculosis (Mtb). However, the effect of helminths, including Schistosoma mansoni (SM), on Mtb infection outcomes is less clear. Furthermore, HIV is a known risk factor for tuberculosis (TB) disease and has been implicated in SM pathogenesis. Therefore, it is important to evaluate whether HIV modifies the association between SM and Mtb infection. HIV-infected and HIV-uninfected adults were enrolled in Kisumu County, Kenya, between 2014 and 2017 and categorized into 3 groups based on Mtb infection status: Mtb-uninfected healthy controls, latent TB infection (LTBI), and active TB disease. Participants were subsequently evaluated for infection with SM. We used targeted minimum loss estimation and super learning to estimate a covariate-adjusted association between SM and Mtb infection outcomes, defined as the probability of being Mtb-uninfected healthy controls, LTBI, or TB. HIV status was evaluated as an effect modifier of this association. SM was not associated with differences in baseline demographic or clinical features of participants in this study, nor with additional parasitic infections. Covariate-adjusted analyses indicated that infection with SM was associated with a 4% higher estimated proportion of active TB cases in HIV-uninfected individuals and a 14% higher estimated proportion of active TB cases in HIV-infected individuals. There were no differences in estimated proportions of LTBI cases. We provide evidence that SM infection is associated with a higher probability of active TB disease, particularly in HIV-infected individuals.

Activation-Induced Marker Expression Identifies Mycobacterium tuberculosis-Specific CD4 T Cells in a Cytokine-Independent Manner in HIV-Infected Individuals with Latent Tuberculosis.

HIV infection is a significant risk factor for reactivation of latent Mycobacterium tuberculosis infection (LTBI) and progression to active tuberculosis disease, yet the mechanisms whereby HIV impairs T cell immunity to M. tuberculosis have not been fully defined. Evaluation of M. tuberculosis–specific CD4 T cells is commonly based on IFN-γ production, yet increasing evidence indicates the immune response to M. tuberculosis is heterogeneous and encompasses IFN-γ–independent responses. We hypothesized that upregulation of surface activation-induced markers (AIM) would facilitate detection of human M. tuberculosis–specific CD4 T cells in a cytokine-independent manner in HIV-infected and HIV-uninfected individuals with LTBI. PBMCs from HIV-infected and HIV-uninfected adults in Kenya were stimulated with CFP-10 and ESAT-6 peptides and evaluated by flow cytometry for upregulation of the activation markers CD25, OX40, CD69, and CD40L. Although M. tuberculosis–specific IFN-γ and IL-2 production was dampened in HIV-infected individuals, M. tuberculosis–specific CD25+OX40+ and CD69+CD40L+ CD4 T cells were detectable in the AIM assay in both HIV-uninfected and HIV-infected individuals with LTBI. Importantly, the frequency of M. tuberculosis–specific AIM+ CD4 T cells was not directly impacted by HIV viral load or CD4 count, thus demonstrating the feasibility of AIM assays for analysis of M. tuberculosis–specific CD4 T cells across a spectrum of HIV infection states. These data indicate that AIM assays enable identification of M. tuberculosis–specific CD4 T cells in a cytokine-independent manner in HIV-uninfected and HIV-infected individuals with LTBI in a high-tuberculosis burden setting, thus facilitating studies to define novel T cell correlates of protection to M. tuberculosis and elucidate mechanisms of HIV-associated dysregulation of antimycobacterial immunity.

Pulmonary tuberculosis masquerading as coronavirus disease 2019 in an HIV-infected individual with advanced immune suppression

Pulmonary tuberculosis masquerading as coronavirus disease 2019 in an HIV-infected individual with advanced immune suppression

Quantifying the burden of cardiovascular diseases among people living with HIV in sub-Saharan Africa: findings from a modeling study for Uganda

Background The burden of non-communicable diseases (NCDs) is rapidly increasing in low- and middle-income countries, but remains largely unknown among people living with HIV (PLWH) in most sub-Saharan African countries. Methods We estimated the proportion of PLWH in Uganda with raised blood pressure and high total cholesterol, and used a modified cardiovascular disease (CVD) risk prediction model (Globorisk) to assess the 10-year risk of atherosclerotic cardiovascular disease using individual-level data on cardiometabolic risk factors, population-level data on HIV prevalence and ART coverage, and the impact of HIV on blood pressure and cholesterol. Results Among PLWH aged 30 to 69 years, the prevalence of raised blood pressure was 30% (95% uncertainty range, UR=27-33%) in women and 26% in men (95% UR=23-29%). The predicted mean 10-year CVD risk was 5% for HIV-infected women, and 6% for HIV-infected men. Five percent (n=41,000) of PLWH may experience a CVD event from 2016 to 2025 with an estimated 38% of these events being fatal. Full ART coverage would have little effect on the predicted number of CVD cases. Conclusions Despite having a high prevalence of raised blood pressure, the burden of atherosclerotic CVD among PLWH in Uganda remains low. ART programs should prioritize routine screening and treatment of raised blood pressure. An approach of using HIV treatment delivery platforms to deliver care for NCDs may miss the larger burden of disease among HIV-uninfected individuals that are not routinely seen at health facilities.

Management Issues in Myasthenia Gravis Patients Living With HIV: A Case Series and Literature Review.

South Africa is home to more than seven million people living with human immunodeficiency virus (HIV) and a high prevalence of tuberculosis. Human immunodeficiency virus–infected individuals may develop myasthenia gravis (MG), which raises questions regarding their management. An MG database, with 24 years of observational data, was audited for HIV-infected persons. Case reports of MG in HIV-infected persons were reviewed. We identified 17 persons with MG and HIV infection. All had generalized MG with a mean age at onset of 37.8 years. Eleven had acetylcholine receptor antibody–positive MG; one had antibodies against muscle-specific kinase. Six developed MG prior to HIV infection (mean CD4+ 361 cells/mm3); four worsened <6 months of starting antiretrovirals. Eleven developed MG while HIV-infected (mean CD4+ 423 cells/mm3); five presented with mild MG; three in MG crisis requiring rescue therapies (intravenous immune globulin or plasma exchange and/or intravenous cyclophosphamide). Two were diagnosed with HIV infection and MG at the same time. Fifteen required maintenance steroid-sparing immune therapies, predominantly azathioprine, or methotrexate. Plasma HIV viral loads remained below detectable levels on antiretrovirals during immunosuppressant treatment. Over the average follow-up of 6 years, 10 achieved minimal manifestation status, and the remainder improved to mild symptoms. Three cases had tuberculosis before MG, but none developed tuberculosis reactivation on immunosuppressive therapy; one used isoniazid prophylaxis. Herpes zoster reactivation during treatment occurred in one. Conclusions include the following: MG in HIV-infected patients should be managed similarly to individuals without HIV infection; half develop moderate–severe MG; MG symptoms may worsen within 6 months of antiretroviral initiation; safety monitoring must include plasma HIV viral load estimation. Isoniazid prophylaxis may not be indicated in all cases.

Increased IL-8 levels in HIV-infected individuals who initiated ART with CD4+ T cell counts

The identification of inflammatory markers in HIV+ individuals on ART is fundamental since chronic ART-controlled HIV infection is linked to an increased inflammatory state. In this context, we assessed plasma levels of pro-inflammatory cytokines (IL-1β, IL-8, and IL-12p70) of HIV+ individuals who initiated ART after immunosuppression (CD4+ T cell counts <350 cells/mm3). HIV+ individuals were stratified according to two extreme phenotypes: Slow Progressors (SPs; individuals with at least 8 years of infection before ART initiation) and Rapid Progressors (RPs; individuals who needed to initiate ART within 1–4 years after infection). A control group was composed of HIV-uninfected individuals. We found increased IL-8 levels (median: 5.13 pg/mL; SPs and RPs together) in HIV-infected individuals on ART as compared to controls (median: 3.2 pg/mL; p = 0.04), although no association with the progression profile (slow or rapid progressors) or CD4+ T cell counts at sampling was observed. This result indicates that IL-8 is a general marker of chronic inflammation in HIV+ individuals on ART, independently of CD4+ T cell counts at the beginning of the treatment or of the potential progression profile of the patient. In this sense, IL-8 may be considered a possible target for novel therapies focused on reducing inflammation in chronic HIV infection.

Analysis of the CCR2-64I (rs1799864) genetic polymorphism distribution and its effect on the risk of HIV-1 infection and immunovirological outcomes in Moroccan ART-treated individuals

BackgroundSeveral studies have reported that the CCR2-64I genetic polymorphism influences the rate of markers of HIV-1 disease progression (HIV-1 viral loads and CD4+ T cell counts). However, the association between this mutation and HIV-1 infection among antiretroviral therapy (ART)-treated HIV-1 seropositive patients is controversial. In Morocco, no data is available regarding this polymorphism. ObjectivesIn the present case-control study, we aimed to investigate the frequency of the CCR2-64I genetic polymorphism and to evaluate the association of this mutant allele with susceptibility to HIV-1 infection and immunovirological outcomes in Morocco. MethodsWe recruited 100 HIV-1 seropositive patients (cases) undergoing antiretroviral therapy (ART) and 200 HIV-1 seronegative individuals from Mohammed V Military Training Hospital in Rabat. Genotyping of the CCR2-64I polymorphism was performed using Polymerase Chain Reaction (PCR) assay and automated DNA sequencing. The comparison between variables was performed using χ2-test, Fisher's exact test, or Mann–Whitney U test, as appropriate. Factors associated with immunovirological outcomes were assessed using logistic regression analysis. ResultsThe frequencies of CCR2-64V/CCR2-64V, CCR2-64V/CCR2-64I and CCR2-64I/CCR2-64I genotypes were 67, 30 and 3%, respectively among HIV-1 infected patients (cases), compared to 73, 24.50, and 2.50%, respectively, among HIV-1 uninfected individuals (controls). We didn't observe any statistically significant difference in the genotype distribution between cases and control groups. Additionally, the multivariate logistic regression analysis didn't reveal a significant association between the CCR2-64I polymorphism and the immunovirological outcomes after one year of ART (p> 0.05). ConclusionWe are the first to report the frequency of CCR2-64I polymorphism and its association with HIV-1 infection in Moroccan individuals. Our findings suggest that the CCR2-64I allele may not influence the susceptibility to HIV-1 infection, as was previously reported in other populations. Besides, we hypothesize that this mutation, independently of classical risk factors, may not impact the virological outcomes and immunological recovery among HIV-1 infected patients under treatment. Nevertheless, this result required confirmation by further large scale and extended follow-up studies, considering the low frequency of the CCR2-64I/CCR2-64I homozygous genotype in our population.

Functional anomaly of CD8 T cells at earlier differentiation stages during HIV infection as established by analysis of synaptic interface and degranulation pattern

Abstract It is thought that HIV infection could lead to a global defect in CD8+ T cell function. However, the effect of the infection on CD8+ T cells at various stages of differentiation has not been well studied. To evaluate the functional activity of CD8+ T cells from HIV infected people at various differentiation stages, we assessed their ability to form synaptic interfaces using planar lipid bilayers containing anti-CD3 antibody and soluble ICAM-1 ligand. We analyzed the dynamics of the T cell/bilayer interface formation, size of adhesion area, and kinetics of T-cell degranulation, parameters that are linked to the efficiency of CD8+ T cell functional activity. Unexpectedly, we observed that purified naïve CD8+ T cells (TN) and transitional memory (TTM) from HIV-infected individuals developed mature synapses whereas the same subsets from HIV uninfected individuals did not. While the kinetics of degranulation of naïve T cells was slower, both TN and TTM cells reached a similar extent of degranulation. The fraction and kinetics of CD27-CD45RO+ T cell degranulation were similar to that observed for TTM cells. Treatment with ART led to increase in the fraction of degranulating CD27-CD45RO+ T cells. As opposed to memory cells from healthy donors, a sizable fraction of CD27-CD45RO+ T cells from infected individuals develop lamellopodia and a larger adhesion area after synapse formation. These data suggest that less differentiated CD8+ T cells from HIV-infected people revealed functional anomaly that is likely mediated by aberrant functions of integrins and cytoskeleton causing changes in T-cell plasticity as a result of continuous inflammation during chronic HIV infection.

Escherichia coli Antimicrobial Susceptibility Reduction amongst HIV-Infected Individuals at the University Teaching Hospital, Lusaka, Zambia.

Increased antimicrobial resistance among Human Immunodeficiency Virus (HIV)-infected individuals to commonly used antibiotics in the treatment of gastroenteritis is a public health concern, especially in resource-limited settings. We set out to compare the antimicrobial susceptibility pattern of Escherichia coli (E. coli) isolates from HIV-infected and HIV-uninfected individuals at a tertiary hospital in Lusaka, Zambia. An analytical cross-sectional study was conducted at the University Teaching Hospital from May 2019 to August 2019. Stool samples were screened, and 79 HIV-infected individuals matched by age and sex with 84 HIV-uninfected individuals that presented with E. coli associated gastroenteritis were studied. Demographics were collected from the Laboratory Information System (LIS) and stool samples were collected in a sterile leak-proof container. Samples were cultured and only those where E. coli was isolated were included in the study and tested for antimicrobial susceptibility by the Kirby–Bauer disk diffusion technique. HIV-positive individuals were 3 times (adjusted odds ratio (AOR) = 3.17; 95% CI (1.51, 6.66); p < 0.001) more likely to be resistant to quinolones compared with their HIV-negative counterparts. Similarly, HIV-positive individuals were almost 4 times (AOR = 3.97, 95% CI (1.37, 11.46); p = 0.011) more likely to have multidrug-resistant E. coli compared with those who were HIV-negative. HIV infection was associated with reduced E. coli susceptibility to commonly used antibiotics, and most cases showed resistance.

Bone mineral density changes among people living with HIV who have started with TDF-containing regimen: A five-year prospective study.

There are limited data regarding long-term BMD changes over time among treatment-naïve people living with HIV (PLHIV) after initiating combined antiretroviral therapy (cART) in Asia. We aimed to study bone mineral density (BMD) changes among treatment-naïve PLHIV started treatment with tenofovir disoproxil fumarate (TDF)- or non-TDF-containing regimen and HIV-uninfected controls in an Asian setting. The study was a five-year prospective study. BMD at lumbar spine (LS) (L1 to L4), total hip (TH), and femoral neck (FN) were measured by dual energy X-ray absorptiometry (DEXA) scans at baseline, months 12, 24 and 60. Multivariate logistic regression models were used to explore factors associated with mean BMD ≥5% reduction after 5 years of cART. A total of 106 PLHIV (75 and 31 started TDF- and non-TDF-containing regimen, respectively) and 66 HIV-uninfected individuals were enrolled. The mean percent changes of BMD were significantly different longitudinally between TDF and non-TDF users (p<0.001 for LS, p = 0.006 for TH and p = 0.02 for FN). HIV-positive status and on TDF-containing regimen was independently associated with BMD loss ≥5% at month 60 (adjusted odds ratio [aOR] 7.0, 95% confidence interval [95%CI] 2.3–21.0, P = 0.001 for LS; aOR 4.9, 95%CI 1.7–14.3, P = 0.003 for TH and aOR 4.3, 95%CI 1.6–11.2, P = 0.003 for FN) compared to HIV-uninfected individuals. In a multivariate model for PLHIV only, TDF use (vs. non-TDF, P = 0.005) and pre-treatment CD4+ count <350 cells/mm3 (vs. ≥350 cells/mm3, P = 0.02) were independently associated with ≥5% BMD loss in TH at month 60. Treatment-naïve PLHIV initiating treatment with TDF-containing regimen have higher BMD loss in a Thai cohort. TDF use and low pre-treatment CD4 count were independently associated with BMD loss at month 60 at TH. Earlier treatment initiation and interventions to prevent bone loss could improve skeletal health among PLHIV.Clinicaltrials.gov: NCT01634607

Post-exposure prophylaxis in the era of pre-exposure prophylaxis: a study of post-exposure prophylaxis use in South-East Queensland since the Pharmaceutical Benefits Scheme listing of pre-exposure prophylaxis.

Both post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP) involve the use of antiretroviral drugs taken by HIV-uninfected individuals to reduce HIV acquisition risk. While PEP has been available in Australia for many years, PrEP became widely accessible in 2018 after listing on the Pharmaceutical Benefits Scheme (PBS). Studies have reported on the impact of PrEP on condom use. The impact of PrEP on the use of PEP in Australia has not been reported. This project examined PEP use across three public sexual health services in South-East Queensland, Australia, comparing rates in 2016 (prePBS-listed PrEP) and 2019 (postPBS-listed PrEP), to determine if PEP prescribing, and the characteristics of people accessing PEP, have changed. Results showed that PEP prescribing made up 2.85% of all clients seen in 2016, dropping to 2.33% in 2019, reflecting a decrease of 0.5% (p = 0.048). There was a significant increase in Medicare-ineligible clients accessing PEP (9% in 2016; 21% in 2019; p = 0.002) and a significant increase in PrEP-experienced clients accessing PEP between the two study periods (4% in 2016; 14% in 2019; p ≤ 0.001). The marginal decrease in PEP prescribing highlights that PEP remains an important option especially for those with barriers to accessing and adhering to daily PrEP.