Browsing by Subject "HIV"
Now showing 1 - 20 of 73
Results Per Page
Sort Options
Item Open Access A Foilized Polyethylene Pouch for the Prevention of Transmission of HIV from Mother to Child.(The open biomedical engineering journal, 2012-01) Malkin, Robert; Howard, CarolineMany children become HIV+ due to mother-to-child transmission, a risk that can be largely eliminated if infants ingest antiretroviral (ARV) medications immediately after birth. As most mothers in Africa deliver at home, the ARV must be provided at their last antenatal visit, sometimes months before birth. No current drug delivery system allows the mother to store the medication at home long enough to be effective. We propose a preserving, foilized, polyethylene pouch to be pre-dosed and sealed by a pharmacist for later delivery to the newborn.Pouches were filled with 0.6 ml of Nevirapine (NVP). Thirty-three pouches were immediately studied to measure the impact of medication handling (oxygen, light, filling and sealing the pouches). The remaining samples were stored for up to one year at three storage conditions (25°C/60%RH, 30°C/65%RH, and 40°C/75%RH). Every two months, moisture loss, preservative concentration, impurity concentrations and NVP concentration were measured. Flora and fauna challenges were conducted.THE POUCH NEARLY ELIMINATED MOISTURE LOSS: pouches lost less than 0.7% of their weight over twelve months. As expected, exposing the medication to light, oxygen, and handling significantly affected the sacrificial preservative concentrations (Propyl paraben dropped 38%, Methyl paraben dropped 12% at time point zero). However, after the initial time point, preservative levels were stable in the package over twelve months under all storage conditions (4.1% average concentration drop), leaving sufficient preservatives to protect the medication. The concentration of NVP changed an average of only 1.3% over all storage conditions and times points (maximum 1.4%).We conclude that the foilized polyethylene pouch can preserve NVP, and perhaps other ARV's, for up to one year.Item Open Access A randomized trial comparing the diagnostic accuracy of visual inspection with acetic acid to Visual Inspection with Lugol's Iodine for cervical cancer screening in HIV-infected women.(PLoS One, 2015) Huchko, Megan J; Sneden, Jennifer; Zakaras, Jennifer M; Smith-McCune, Karen; Sawaya, George; Maloba, May; Bukusi, Elizabeth Ann; Cohen, Craig RVisual inspection with Acetic Acid (VIA) and Visual Inspection with Lugol’s Iodine (VILI) are increasingly recommended in various cervical cancer screening protocols in low-resource settings. Although VIA is more widely used, VILI has been advocated as an easier and more specific screening test. VILI has not been well-validated as a stand-alone screening test, compared to VIA or validated for use in HIV-infected women. We carried out a randomized clinical trial to compare the diagnostic accuracy of VIA and VILI among HIV-infected women. Women attending the Family AIDS Care and Education Services (FACES) clinic in western Kenya were enrolled and randomized to undergo either VIA or VILI with colposcopy. Lesions suspicious for cervical intraepithelial neoplasia 2 or greater (CIN2+) were biopsied. Between October 2011 and June 2012, 654 were randomized to undergo VIA or VILI. The test positivity rates were 26.2% for VIA and 30.6% for VILI (p = 0.22). The rate of detection of CIN2+ was 7.7% in the VIA arm and 11.5% in the VILI arm (p = 0.10). There was no significant difference in the diagnostic performance of VIA and VILI for the detection of CIN2+. Sensitivity and specificity were 84.0% and 78.6%, respectively, for VIA and 84.2% and 76.4% for VILI. The positive and negative predictive values were 24.7% and 98.3% for VIA, and 31.7% and 97.4% for VILI. Among women with CD4+ count < 350, VILI had a significantly decreased specificity (66.2%) compared to VIA in the same group (83.9%, p = 0.02) and compared to VILI performed among women with CD4+ count ≥ 350 (79.7%, p = 0.02). VIA and VILI had similar diagnostic accuracy and rates of CIN2+ detection among HIV-infected women.Item Open Access A Smoking Cessation Mobile App for Persons Living With HIV: Preliminary Efficacy and Feasibility Study.(JMIR formative research, 2022-08) Schnall, Rebecca; Liu, Jianfang; Alvarez, Gabriella; Porras, Tiffany; Ganzhorn, Sarah; Boerner, Samantha; Huang, Ming-Chun; Trujillo, Paul; Cioe, PatriciaBackground
The prevalence of smoking in the United States general population has gradually declined to the lowest rate ever recorded; however, this has not been true for persons with HIV.Objective
We conducted a pilot test to assess the feasibility and efficacy of the Lumme Quit Smoking mobile app and smartwatch combination with sensing capabilities to improve smoking cessation in persons with HIV.Methods
A total of 40 participants were enrolled in the study and randomly assigned 1:1 to the control arm, which received an 8-week supply of nicotine replacement therapy, a 30-minute smoking cessation counseling session, and weekly check-in calls with study staff, or to the intervention arm, which additionally received the Lumme Quit Smoking app and smartwatch.Results
Of the 40 participants enrolled, 37 completed the follow-up study assessments and 16 used the app every day during the 56-day period. During the 6-month recruitment and enrollment period, 122 people were screened for eligibility, with 67.2% (82/122) deemed ineligible. Smoking criteria and incompatible tech were the major reasons for ineligibility. There was no difference in the proportion of 7-day point prevalence abstinence by study arm and no significant decrease in exhaled carbon monoxide for the intervention and control arms separately. However, the average exhaled carbon monoxide decreased over time when analyzing both arms together (P=.02).Conclusions
Results suggest excellent feasibility and acceptability of using a smoking sensor app among this smoking population. The knowledge gained from this research will enable the scientific community, clinicians, and community stakeholders to improve tobacco cessation outcomes for persons with HIV.Trial registration
ClinicalTrials.gov NCT04808609; https://clinicaltrials.gov/ct2/show/NCT04808609.Item Open Access Adolescents' and caregivers' perceptions of caregiver-provided testing and HIV self-testing using oral mucosal transudate tests in Zimbabwe: a short report.(AIDS care, 2020-04-16) Rainer, Crissi; Chihota, Belinda; Dziva Chikwari, Chido; McHugh, Grace; Dauya, Ethel; Mujuru, Hilda; Ferrand, Rashida A; Stewart, Kearsley AUptake of HIV testing remains lower among children and adolescents compared to adults. This study explored adolescents' perceptions of HIV self-testing (HIVST) and caregivers' perceptions of testing their children using an oral mucosal transudate (OMT) rapid HIV test (caregiver-provided testing). We conducted 31 interviews with adolescents aged 16-18 years and caregivers of children aged 2-15 years who received an OMT test. Participants described barriers to HIV testing including lack of privacy and the potential for discrimination by community members towards children and adolescents who received an HIV test. Most participants felt caregiver-provided testing and HIVST could address these barriers through increased privacy. Some participants expressed worry about their ability to correctly perform the OMT and their anxious reactions to a positive result. Counseling and assistance from health care workers were viewed as ways to alleviate concerns. Concerns shaped participants' preferences for facility-based HIVST and caregiver-provided testing. Findings demonstrate HIVST performed by adolescents and caregiver-provided testing could increase the uptake of HIV testing. Concerns related to being able to test correctly and the availability of post-test counseling must be addressed in any future delivery mechanisms.Item Open Access Antiretroviral Effects on Host Lipoproteins Are Associated With Changes in Hepatitis C Virus (HCV) RNA Levels in Human Immunodeficiency Virus/HCV Coinfected Individuals.(Open forum infectious diseases, 2015-04) Naggie, Susanna; Patel, Keyur; Yang, Lan-Yan; Chow, Shein-Chung; Johnson, Victoria; Guyton, John R; Muir, Andrew J; Sulkowski, Mark; Hicks, CharlesWe evaluated the impact of antiretroviral-induced dyslipidemia on hepatitis C virus (HCV) biogenesis in human immunodeficiency virus (HIV)/HCV coinfected patients. This study used serum samples from antiretroviral-naive HIV/HCV patients initiating their first regimen as part of AIDS Clinical Trials Group study protocols (A5142, A5202). Initiation of antiretrovirals increased most lipoproteins and apolipoproteins. In the multivariable model, changes in apolipoproteins were associated with changes in log10 HCV RNA from baseline to week-24 of therapy. Off-target lipogenic changes need to be considered in the context of liver and other metabolic disease in HIV/HCV patients.Item Open Access Application of area scaling analysis to identify natural killer cell and monocyte involvement in the GranToxiLux antibody dependent cell-mediated cytotoxicity assay.(Cytometry. Part A : the journal of the International Society for Analytical Cytology, 2018-04) Pollara, Justin; Orlandi, Chiara; Beck, Charles; Edwards, R Whitney; Hu, Yi; Liu, Shuying; Wang, Shixia; Koup, Richard A; Denny, Thomas N; Lu, Shan; Tomaras, Georgia D; DeVico, Anthony; Lewis, George K; Ferrari, GuidoSeveral different assay methodologies have been described for the evaluation of HIV or SIV-specific antibody-dependent cell-mediated cytotoxicity (ADCC). Commonly used assays measure ADCC by evaluating effector cell functions, or by detecting elimination of target cells. Signaling through Fc receptors, cellular activation, cytotoxic granule exocytosis, or accumulation of cytolytic and immune signaling factors have been used to evaluate ADCC at the level of the effector cells. Alternatively, assays that measure killing or loss of target cells provide a direct assessment of the specific killing activity of antibodies capable of ADCC. Thus, each of these two distinct types of assays provides information on only one of the critical components of an ADCC event; either the effector cells involved, or the resulting effect on the target cell. We have developed a simple modification of our previously described high-throughput ADCC GranToxiLux (GTL) assay that uses area scaling analysis (ASA) to facilitate simultaneous quantification of ADCC activity at the target cell level, and assessment of the contribution of natural killer cells and monocytes to the total observed ADCC activity when whole human peripheral blood mononuclear cells are used as a source of effector cells. The modified analysis method requires no additional reagents and can, therefore, be easily included in prospective studies. Moreover, ASA can also often be applied to pre-existing ADCC-GTL datasets. Thus, incorporation of ASA to the ADCC-GTL assay provides an ancillary assessment of the ability of natural and vaccine-induced antibodies to recruit natural killer cells as well as monocytes against HIV or SIV; or to any other field of research for which this assay is applied. © 2018 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of ISAC.Item Open Access Assessing Neurocognitive Impairment in HIV-positive Patients: The Sensitivity and Specificity of the CogState Brief Battery(2012) Yechoor, NirupamaObjective: The prevalence of cognitive impairment in HIV-positive patients is estimated to be 39% in Uganda [1]. Despite the high prevalence of impairment, routine HIV management in Uganda does not include neuropsychological assessment. The objective of this study was to compare performance on the gold standard neuropsychological exam and on the CogState computerized exam. We hypothesized that there would be a high degree of correlation between performance on the two exams.
Methods: This cross-sectional survey was conducted from August to October 2011. Each participant completed the standard neuropsychological exam, which consisted of 10 tasks across 7 cognitive ability domains. Patients also completed CogState, which consisted of 4 tasks using playing cards. Performance for each exam was standardized using normative data from HIV seronegative controls to produce z-scores. The primary outcome measures were average z-scores of performance for each exam.
Results: Out of 181 patients tested, 130 (72%) were classified as impaired on the gold standard neuropsychological exam, while 104 (57%) were classified as impaired on CogState. The sensitivity of CogState compared to the gold standard was 65% (95% CI = 56% - 73%) and the specificity was 63% (95% CI = 48% - 73%). The Pearson's correlation of cumulative performance between the exams is 0.552, which is significant at the 0.01 level. Finally, those patients with normal cognition performed the best on CogState, while those with the most severe impairment performed the worst.
Conclusions: Our findings suggest that CogState is a feasible and useful tool to screen for and monitor impairment in HIV-positive patients, especially in resource-limited settings. Future studies are needed to examine how individual performance on CogState changes over time.
Item Open Access Associations of Adverse Childhood Experiences With Key Health Outcomes and Viral Suppression Maintenance Among Tanzanian Youth Living With HIV(2022) Brtek, Veronica RaquelBackground: Despite improved access to HIV testing and medication, AIDS remains a leading cause of death among youth living with HIV (YLWH) in Tanzania. YLWH are prone to worse HIV outcomes than other age groups, which may be caused or mediated by mental health, social determinants of health (SDH), and adverse childhood experiences (ACEs). In this study, the investigators sought to determine if ACEs were correlated with key health variables in hopes of better understanding the factors associated with negative HIV and mental health outcomes among Tanzanian youth. Additionally, the investigators aimed to observe longitudinal trends in virologic suppression to understand the extent to which undetectable = untransmittable or “U=U” messaging applies to the more volatile youth demographic. Finally, the investigators sought to identify patterns and predictors that could aid in understanding risk of virologic failure in this population. Methods: The investigators incorporated and merged secondary data from participants who were enrolled in both of two distinct studies to create a longitudinal database spanning from 2013 to 2020. Participant ACE scores were derived from trauma exposure questionnaires and were compared with data about mental health, stigma, SDH, sexual experiences, self-reported adherence and HIV RNA (viral load). Associations of ACEs and other key variables were performed using linear regression. Results: ACEs were common among YLWH, especially loss of a parent and physical abuse. ACEs were also correlated with both mental health outcomes and virologic failure. Of the 48 participants who were virologically suppressed at the beginning of the study, one third had subsequent virologic failure, which was often associated with changes in ACEs, medication regimen, and SDH. Conclusion: Understanding common ACEs in this vulnerable population has direct relevance for the design of targeted interventions to prevent and treat repercussions of childhood trauma and improve mental health and HIV outcomes. ACEs, experiences with suicide risk, and low social support are important correlates of virologic failure and should be an alert when considering repeat HIV RNA testing and eligibility for supportive services.
Item Open Access Canary in the Coal Mine? Transmitted Mutations Conferring Resistance to All Integrase Strand Transfer Inhibitors in a Treatment-Naive Patient.(Open forum infectious diseases, 2018-11-08) McGee, Kara S; Okeke, Nwora Lance; Hurt, Christopher B; McKellar, Mehri STransmitted drug resistance to the integrase strand transfer inhibitor (INSTI) class of antiretrovirals is very rare. We present a case of a treatment-naive female patient with human immunodeficiency virus harboring resistance to all INSTIs, including bictegravir and dolutegravir.Item Open Access Cardiovascular Disease Risk Management in Persons With HIV: Does Clinician Specialty Matter?(Open forum infectious diseases, 2020-09) Okeke, Nwora Lance; Schafer, Katherine R; Meissner, Eric G; Ostermann, Jan; Shah, Ansal D; Ostasiewski, Brian; Phelps, Evan; Kieler, Curtis A; Oladele, Eniola; Garg, Keva; Naggie, Susanna; Bloomfield, Gerald S; Bosworth, Hayden BBackground
The impact of clinician specialty on cardiovascular disease risk factor outcomes among persons with HIV (PWH) is unclear.Methods
PWH receiving care at 3 Southeastern US academic HIV clinics between January 2014 and December 2016 were retrospectively stratified into 5 groups based on the specialty of the clinician managing their hypertension or hyperlipidemia. Patients were followed until first atherosclerotic cardiovascular disease event, death, or end of study. Outcomes of interest were meeting 8th Joint National Commission (JNC-8) blood pressure (BP) goals and National Lipid Association (NLA) non-high-density lipoprotein (HDL) goals for hypertension and hyperlipidemia, respectively. Point estimates for associated risk factors were generated using modified Poisson regression with robust error variance.Results
Of 1667 PWH in the analysis, 965 had hypertension, 205 had hyperlipidemia, and 497 had both diagnoses. At study start, the median patient age was 52 years, 66% were Black, and 65% identified as male. Among persons with hypertension, 24% were managed by an infectious diseases (ID) clinician alone, and 5% were co-managed by an ID clinician and a primary care clinician (PCC). Persons managed by an ID clinician were less likely to meet JNC-8 hypertension targets at the end of observation than the rest of the cohort (relative risk [RR], 0.84; 95% CI, 0.75-0.95), but when mean study blood pressure was considered, there was no difference between persons managed by ID and the rest of the cohort (RR, 0.96; 95% CI, 0.88-1.05). There was no significant association between the ID clinician managing hyperlipidemia and meeting NLA non-HDL goals (RR, 0.89; 95% CI, 0.68-1.15).Conclusions
Clinician specialty may play a role in suboptimal hypertension outcomes in persons with HIV.Item Open Access Chlamydia trachomatis Infection of Endocervical Epithelial Cells Enhances Early HIV Transmission Events.(PloS one, 2016-01) Buckner, Lyndsey R; Amedee, Angela M; Albritton, Hannah L; Kozlowski, Pamela A; Lacour, Nedra; McGowin, Chris L; Schust, Danny J; Quayle, Alison JChlamydia trachomatis causes a predominantly asymptomatic, but generally inflammatory, genital infection that is associated with an increased risk for HIV acquisition. Endocervical epithelial cells provide the major niche for this obligate intracellular bacterium in women, and the endocervix is also a tissue in which HIV transmission can occur. The mechanism by which CT infection enhances HIV susceptibility at this site, however, is not well understood. Utilizing the A2EN immortalized endocervical epithelial cell line grown on cell culture inserts, we evaluated the direct role that CT-infected epithelial cells play in facilitating HIV transmission events. We determined that CT infection significantly enhanced the apical-to-basolateral migration of cell-associated, but not cell-free, HIVBaL, a CCR5-tropic strain of virus, across the endocervical epithelial barrier. We also established that basolateral supernatants from CT-infected A2EN cells significantly enhanced HIV replication in peripheral mononuclear cells and a CCR5+ T cell line. These results suggest that CT infection of endocervical epithelial cells could facilitate both HIV crossing the mucosal barrier and subsequent infection or replication in underlying target cells. Our studies provide a mechanism by which this common STI could potentially promote the establishment of founder virus populations and the maintenance of local HIV reservoirs in the endocervix. Development of an HIV/STI co-infection model also provides a tool to further explore the role of other sexually transmitted infections in enhancing HIV acquisition.Item Open Access Clinical epidemiology and outcome of HIV-associated talaromycosis in Guangdong, China, during 2011-2017.(HIV medicine, 2020-12) Ying, RS; Le, T; Cai, WP; Li, YR; Luo, CB; Cao, Y; Wen, CY; Wang, SG; Ou, X; Chen, WS; Chen, SZ; Guo, PL; Chen, M; Guo, Y; Tang, XP; Li, LHObjectives
Talaromycosis is an invasive mycosis endemic to Southeast Asia. This study aimed to investigate the epidemiology, clinical features and prognostic factors of HIV-associated talaromycosis in Guangdong, China.Methods
We retrospectively evaluated HIV patients hospitalized with histopathology- or culture-confirmed talaromycosis between 2011 and 2017. Factors associated with poor prognosis were identified using logistic regression.Results
Overall, 1079 patients with HIV-associated talaromycosis were evaluated. Both the number and prevalence of talaromycosis among HIV admissions increased from 125 and 15.7% in 2011 to 253 and 18.8% in 2017, respectively, reflecting the increase in HIV admissions. Annual admissions peaked during the rainy season between March and August. Common clinical manifestations included fever (85.6%), peripheral lymphadenopathy (72.3%), respiratory symptoms (60.8%), weight loss (49.8%), skin lesions (44.5%) and gastrointestinal symptoms (44.3%). Common laboratory abnormalities were hypoalbuminaemia (98.6%), anaemia (95.6%), elevated aspartate aminotransferase level (AST) (76.9%), elevated alkaline phosphatase level (55.8%) and thrombocytopenia (53.7%). The median CD4 count was 9 cells/μL. Talaromyces marneffei was isolated from blood and bone marrow cultures of 66.6% and 74.5% of patients, respectively. The rate increased to 86.6% when both cultures were performed concurrently. At discharge, 14% of patients showed worsening conditions or died. Leucocytosis, thrombocytopenia, elevated AST, total bilirubin, creatinine and azole monotherapy independently predicted poor prognosis.Conclusions
The incidence of HIV-associated talaromycosis has increased in Guangdong with the high HIV burden in China. Skin lesions were seen in less than half of patients. Induction therapy with azole alone is associated with higher mortality. Findings from this study should help to improve treatment of the disease.Item Open Access Comparison of Detection Limits of Fourth- and Fifth-Generation Combination HIV Antigen-Antibody, p24 Antigen, and Viral Load Assays on Diverse HIV Isolates.(Journal of clinical microbiology, 2018-08) Stone, Mars; Bainbridge, John; Sanchez, Ana M; Keating, Sheila M; Pappas, Andrea; Rountree, Wes; Todd, Chris; Bakkour, Sonia; Manak, Mark; Peel, Sheila A; Coombs, Robert W; Ramos, Eric M; Shriver, M Kathleen; Contestable, Paul; Nair, Sangeetha Vijaysri; Wilson, David H; Stengelin, Martin; Murphy, Gary; Hewlett, Indira; Denny, Thomas N; Busch, Michael PDetection of acute HIV infection is critical for HIV public health and diagnostics. Clinical fourth-generation antigen (Ag)/antibody (Ab) combination (combo) and p24 Ag immunoassays have enhanced detection of acute infection compared to Ab-alone assays but require ongoing evaluation with currently circulating diverse subtypes. Genetically and geographically diverse HIV clinical isolates were used to assess clinical HIV diagnostic, blood screening, and next-generation assays. Three-hundred-member panels of 20 serially diluted well-characterized antibody-negative HIV isolates for which the researchers were blind to the results (blind panels) were distributed to manufacturers and end-user labs to assess the relative analytic sensitivity of currently approved and preapproved clinical HIV fourth-generation Ag/Ab combo or p24 Ag-alone immunoassays for the detection of diverse subtypes. The limits of detection (LODs) of virus were estimated for different subtypes relative to confirmed viral loads. Analysis of immunoassay sensitivity was benchmarked against confirmed viral load measurements on the blind panel. On the basis of the proportion of positive results on 300 observations, all Ag/Ab combo and standard sensitivity p24 Ag assays performed similarly and within half-log LODs, illustrating the similar breadth of reactivity and diagnostic utility. Ultrasensitive p24 Ag assays achieved dramatically increased sensitivities, while the rapid combo assays performed poorly. The similar performance of the different commercially available fourth-generation assays on diverse subtypes supports their use in broad geographic settings with locally circulating HIV clades and recombinant strains. Next-generation preclinical ultrasensitive p24 Ag assays achieved dramatically improved sensitivity, while rapid fourth-generation assays performed poorly for p24 Ag detection.Item Open Access Correlates of HIV testing among abused women in South Africa.(Violence Against Women, 2011-08) Adams, Julie L; Hansen, Nathan B; Fox, Ashley M; Taylor, Baishakhi B; van Rensburg, Madri Jansen; Mohlahlane, Rakgadi; Sikkema, Kathleen JGender-based violence increases a woman's risk for HIV but little is known about her decision to get tested. We interviewed 97 women seeking abuse-related services from a nongovernmental organization (NGO) in Johannesburg, South Africa. Forty-six women (47%) had been tested for HIV. Caring for children (odds ratio [OR] = 0.27, 95% confidence interval [CI] = [0.07, 1.00]) and conversing with partner about HIV (OR = 0.13, 95% CI = [0.02, 0.85]) decreased odds of testing. Stronger risk-reduction intentions (OR = 1.27, 95% CI = [1.01, 1.60]) and seeking help from police (OR = 5.51, 95% CI = [1.18, 25.76]) increased odds of testing. Providing safe access to integrated services and testing may increase testing in this population. Infection with HIV is highly prevalent in South Africa where an estimated 16.2% of adults between the ages of 15 and 49 have the virus. The necessary first step to stemming the spread of HIV and receiving life-saving treatment is learning one's HIV serostatus through testing. Many factors may contribute to someone's risk of HIV infection and many barriers may prevent testing. One factor that does both is gender-based violence.Item Open Access Correlation Between Tenofovir Drug Levels and the Renal Biomarkers RBP-4 and ß2M in the ION-4 Study Cohort.(Open forum infectious diseases, 2019-01) Chan, Austin; Park, Lawrence; Collins, Lauren F; Cooper, Curtis; Saag, Michael; Dieterich, Douglas; Sulkowski, Mark; Naggie, SusannaBackground
Concomitant dosing of ledipasvir (LDV) and tenofovir disoproxil fumarate (TDF) results in an increased tenofovir (TFV) area under the curve (AUC). The aim of this study was to examine whether there was a correlation between the renal biomarkers retinol binding protein-4 (RBP-4) and β2 microglobulin (β2M) and tenofovir AUC.Methods
The ION-4 trial enrolled HIV/hepatitis C virus-coinfected patients on nonpharmacologically boosted antiretroviral regimens with TDF-containing backbones. We assessed for a correlation between tenofovir AUC and urinary biomarkers and also for changes in serologic biomarkers with respect to clinically relevant changes in renal function (creatinine clearance decrease >25%, change in creatinine >0.2 mg/dL, change in proteinuria from negative/trace to ≥1+).Results
Three hundred thirty-five patients were enrolled in the ION-4 study; their demographic characteristics have been previously described. Both RBP-4 and β2M exhibited positive correlations with tenofovir AUC. Baseline and study levels of RBP-4 and β2M were higher for patients with increases in urine proteinuria and an absolute creatinine increase.Conclusions
TFV exposure is associated with increased proximal tubule urine biomarkers in participants on ledipasvir/sofosbuvir and nonpharmacologically boosted TDF-based antiretroviral regimens. Baseline proximal tubule biomarkers may predict nephrotoxicity risk if events are prevalent. Further studies assessing the predictive role of these urine biomarkers may help guide medical decision-making and risk/benefit assessments in patients with risk factors for renal dysfunction.Item Open Access Cost-Effectiveness of Amphotericin B Deoxycholate Versus Itraconazole for Induction Therapy of Talaromycosis in Human Immunodeficiency Virus-Infected Adults in Vietnam.(Open forum infectious diseases, 2021-07-05) Buchanan, James; Altunkaya, James; Van Kinh, Nguyen; Van Vinh Chau, Nguyen; Trieu Ly, Vo; Thi Thanh Thuy, Pham; Hai Vinh, Vu; Thi Hong Hanh, Doan; Thuy Hang, Nguyen; Phuong Thuy, Tran; van Doorn, Rogier; Thwaites, Guy; Gray, Alastair; Le, ThuyBackground
Talaromycosis (penicilliosis) is an invasive fungal infection and a major cause of human immunodeficiency virus (HIV)-related deaths in Southeast Asia. Guidelines recommend induction therapy with amphotericin B deoxycholate; however, treatment with itraconazole has fewer toxic effects, is easier to administer, and is less expensive. Our recent randomized controlled trial in Vietnam found that amphotericin B was superior to itraconazole with respect to 6-month mortality. We undertook an economic evaluation alongside this trial to determine whether the more effective treatment is cost-effective.Methods
Resource use, direct and indirect costs, and health and quality-of-life outcomes (measured using quality-adjusted life-years [QALYs]) were evaluated for 405 trial participants from 2012 to 2016. Both a Vietnamese health service and a broader societal costing perspective were considered. Mean costs and QALYs were combined to calculate the within-trial cost-effectiveness of amphotericin vs itraconazole from both perspectives.Results
From a Vietnamese health service perspective, amphotericin increases costs but improves health outcomes compared to itraconazole, at a cost of $3013/QALY gained. The probability that amphotericin is cost-effective at a conventional (World Health Organization CHOICE) threshold of value for money is 46%. From a societal perspective, amphotericin is cost-reducing and improves outcomes compared to itraconazole, and is likely to be a cost-effective strategy at any value for money threshold greater than $0.Conclusions
Our analysis indicates that induction therapy with amphotericin is a cost-effective treatment strategy for HIV-infected adults diagnosed with talaromycosis in Vietnam. These results provide the evidence base for health care providers and policy makers to improve access to and use of amphotericin.Item Open Access Country of residence is associated with distinct inflammatory biomarker signatures in HIV-infected patients.(J Virus Erad, 2017-01-01) Manion, Maura; Andrade, Bruno B; DerSimonian, Rebecca; Gu, Wenjuan; Rupert, Adam; Musselwhite, Laura W; Sierra-Madero, Juan G; Belaunzaran-Zamudio, Pablo F; Sanne, Ian; Lederman, Michael M; Sereti, IriniBACKGROUND: Inflammation and coagulation biomarkers are independent predictors of morbidity and mortality in HIV-infected patients. The impact of country of residence on these biomarkers is unknown and was investigated in persons at similar stages of HIV infection. METHODS: Cryopreserved plasma specimens were analysed from 267 ART-naive patients with CD4 cell counts <100 cells/μl from Mexico (n=124) and South Africa (n=143). Biomarkers were compared and dimension reduction analyses were performed to highlight biosignatures according to nationality, gender and tuberculosis co-infection. RESULTS: Mexican patients were significantly different from South Africans with regard to age, gender, CD4 cell count, haemoglobin, presence of AIDS-defining illness and prevalence of active tuberculosis. After adjusting for baseline characteristics, patients from Mexico had higher levels of IFN-γ, IL-8, and CXCL-10 whereas patients from South Africa had higher levels of fibrinogen, LTB4, P-selectin, protein S, and sCD40 ligand. The effect of country on the profile of biomarker expression was stronger than gender differences and tuberculosis co-infection. CONCLUSION: Inflammation and coagulation biomarkers vary significantly by country. Further studies are needed to evaluate how these differences may contribute to HIV pathogenesis and prognosis in diverse populations and how they can be accounted for in studies using biomarkers as surrogate end points.Item Open Access Determinants of protection among HIV‐exposed seronegative persons: an overview.(J Infect Dis, 2010-11-01) Lederman, Michael M; Alter, Galit; Daskalakis, Demetre C; Rodriguez, Benigno; Sieg, Scott F; Hardy, Gareth; Cho, Michael; Anthony, Donald; Harding, Clifford; Weinberg, Aaron; Silverman, Robert H; Douek, Daniel C; Margolis, Leonid; Goldstein, David B; Carrington, Mary; Goedert, James JBoth clinical experience and a growing medical literature indicate that some persons who have been exposed to human immunodeficiency virus (HIV) infection remain uninfected. Although in some instances this may represent good fortune, cohorts of uninfected persons have been reported who are considered at high risk for infection. In these cohorts a variety of characteristics have been proposed as mediating protection, but to date only the 32–base pair deletion in the chemokine (C‐C motif) receptor 5 gene, which results in complete failure of cell surface expression of this coreceptor, has been associated with high‐level protection from HIV infection. With this in mind, there are probably many other factors that may individually or in combination provide some level of protection from acquisition of HIV infection. Because some of these factors are probably incompletely protective or inconsistently active, identifying them with confidence will be difficult. Nonetheless, clarifying the determinants of protection against HIV infection is a high priority that will require careful selection of high‐risk uninfected cohorts, who should undergo targeted studies of plausible mediators and broad screening for unexpected determinants of protection.Item Open Access Development of a contemporary globally diverse HIV viral panel by the EQAPOL program.(J Immunol Methods, 2014-07) Sanchez, Ana M; DeMarco, C Todd; Hora, Bhavna; Keinonen, Sarah; Chen, Yue; Brinkley, Christie; Stone, Mars; Tobler, Leslie; Keating, Sheila; Schito, Marco; Busch, Michael P; Gao, Feng; Denny, Thomas NThe significant diversity among HIV-1 variants poses serious challenges for vaccine development and for developing sensitive assays for screening, surveillance, diagnosis, and clinical management. Recognizing a need to develop a panel of HIV representing the current genetic and geographic diversity NIH/NIAID contracted the External Quality Assurance Program Oversight Laboratory (EQAPOL) to isolate, characterize and establish panels of HIV-1 strains representing global diverse subtypes and circulating recombinant forms (CRFs), and to make them available to the research community. HIV-positive plasma specimens and previously established isolates were collected through a variety of collaborations with a preference for samples from acutely/recently infected persons. Source specimens were cultured to high-titer/high-volume using well-characterized cryopreserved PBMCs from National y donors. Panel samples were stored as neat culture supernatant or diluted into defibrinated plasma. Characterization for the final expanded virus stocks included viral load, p24 antigen, infectivity (TCID), sterility, coreceptor usage, and near full-length genome sequencing. Viruses are made available to approved, interested laboratories using an online ordering application. The current EQAPOL Viral Diversity panel includes 100 viral specimens representing 6 subtypes (A, B, C, D, F, and G), 2 sub-subtypes (F1 and F2), 7 CRFs (01, 02, 04, 14, 22, 24, and 47), 19 URFs and 3 group O viruses from 22 countries. The EQAPOL Viral Diversity panel is an invaluable collection of well-characterized reagents that are available to the scientific community, including researchers, epidemiologists, and commercial manufacturers of diagnostics and pharmaceuticals to support HIV research, as well as diagnostic and vaccine development.Item Open Access Does Antiretroviral Therapy Packaging Matter? Perceptions and Preferences of Antiretroviral Therapy Packaging for People Living with HIV in Northern Tanzania.(Patient preference and adherence, 2020-01-23) Muiruri, Charles; Jazowski, Shelley A; Semvua, Seleman K; Karia, Francis P; Knettel, Brandon A; Zullig, Leah L; Ramadhani, Habib O; Mmbaga, Blandina T; Bartlett, John A; Bosworth, Hayden BIntroduction
Despite improvements in treatment (eg, reduction in pill intake), antiretroviral therapy (ART) is dispensed in socially inefficient and uneconomical packaging. To make pills less conspicuous and decrease the risk of being stigmatized, people living with HIV (PLWH) often engage in self-repackaging - the practice of transferring ART from original packaging to alternative containers. This behavior has been associated with ART nonadherence and failure to achieve viral load suppression. While much of the literature on ART packaging has centered around medication adherence, patients stated preferences for ART packaging and packaging attributes that influence the observed ART nonadherence are understudied.Methods
We conducted a qualitative study to elucidate perceptions of ART packaging among PLWH at two large referral hospitals in Northern Tanzania. Interviews were conducted until thematic saturation was reached. Interviews were audio-recorded, transcribed and coded.Results
Of the 16 participants whose data were used in the final analysis, a majority were between 36 and 55 years of age (Mean 45.5 years SD: 11.1), had primary-level education (n=11, 68.8%), were self-employed (n=9, 56.3%), reported that they had self-repacked ART (n=14, 88%), and were taking ART for more than 6 years (n=11, 68.8%). Participants identified three attributes of ART packaging that increased anticipated HIV stigma and prompted self-repackaging, including visual identification, bulkiness, and the rattling noise produced by ART pill bottles.Conclusion
Given the drastic reduction in the number of pills required for HIV treatment, there is an opportunity to not only assess the cost-effectiveness of innovative ART packaging but also evaluate the acceptability of such packaging among PLWH in order to address stigma and improve ART adherence.