Publications by authors named "David A Wohl"

117 Publications

Molnupiravir, an Oral Antiviral Treatment for COVID-19.

medRxiv 2021 Jun 17. Epub 2021 Jun 17.

Background: Easily distributed oral antivirals are urgently needed to treat coronavirus disease-2019 (COVID-19), prevent progression to severe illness, and block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the results of a Phase 2a trial evaluating the safety, tolerability, and antiviral efficacy of molnupiravir in the treatment of COVID-19 ( ClinicalTrials.gov NCT04405570 ).

Methods: Eligible participants included outpatients with confirmed SARS-CoV-2 infection and symptom onset within 7 days. Participants were randomized 1:1 to 200 mg molnupiravir or placebo, or 3:1 to molnupiravir (400 or 800 mg) or placebo, twice-daily for 5 days. Antiviral activity was assessed as time to undetectable levels of viral RNA by reverse transcriptase polymerase chain reaction and time to elimination of infectious virus isolation from nasopharyngeal swabs.

Results: Among 202 treated participants, virus isolation was significantly lower in participants receiving 800 mg molnupiravir (1.9%) versus placebo (16.7%) at Day 3 (p = 0.02). At Day 5, virus was not isolated from any participants receiving 400 or 800 mg molnupiravir, versus 11.1% of those receiving placebo (p = 0.03). Time to viral RNA clearance was decreased and a greater proportion overall achieved clearance in participants administered 800 mg molnupiravir versus placebo (p = 0.01). Molnupiravir was generally well tolerated, with similar numbers of adverse events across all groups.

Conclusions: Molnupiravir is the first oral, direct-acting antiviral shown to be highly effective at reducing nasopharyngeal SARS-CoV-2 infectious virus and viral RNA and has a favorable safety and tolerability profile.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/2021.06.17.21258639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219109PMC
June 2021

SARS-CoV-2 infectious virus, viral RNA in nasopharyngeal swabs, and serostatus of symptomatic COVID-19 outpatients in the United States.

medRxiv 2021 Jun 1. Epub 2021 Jun 1.

Gillings School of Global Public Health, University of North Carolina at Chapel Hill, NC (KRM, JJE, TJK, AJB, JJW, MGH, RSB, TPS); School of Medicine, University of North Carolina at Chapel Hill, NC (KRM, JJE, LP, AJL, DAW, WAF); Center for AIDS Research, University of North Carolina at Chapel Hill, NC (KRM, JJE, TJK, PLA, JK, MGH); Ridgeback Biotherapeutics LP, Miami, Florida (WP, LJS); Fred Hutchinson Cancer Research Center, Seattle, WA (ERD); Wake Forest School of Medicine, Winston-Salem, NC (CGM); Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA (EAG, EJDA, JAD, RWC); Duke University Medical Center, Durham, NC (CRW); Pharstat Inc., Raleigh, NC (LF); Division of Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, NC (WAF).

Background: SARS-CoV-2 infectious virus isolation in the upper airway of COVID-19 patients is associated with higher levels of viral RNA. However, comprehensive evaluation of the relationships between host and disease factors and infectious, replication competent virus is needed.

Methods: Symptomatic COVID-19 outpatients were enrolled from the United States. Clinical symptoms were recorded via patient diary. Nasopharyngeal swabs were collected to quantitate SARS-CoV-2 RNA by reverse transcriptase polymerase chain reaction and for infectious virus isolation in Vero E6-cells. SARS-CoV-2 antibodies were measured in serum using a validated ELISA assay.

Findings: Among 204 participants within one week of reported symptom onset (median=5, IQR 4-5 days), median age was 40 (min-max: 18-82 years), median nasopharyngeal viral RNA was 6.5 (IQR 4.7-7.6 log copies/mL), and 26% had detectable SARS-CoV-2 antibodies at baseline. Infectious virus was recovered in 7% of participants with antibodies compared to 58% of participants without antibodies (probability ratio (PR)=0.12, 95% CI: 0.04, 0.36; p=0.00016). Infectious virus isolation was also associated with higher levels of viral RNA (mean RNA difference +2.6 log , 95% CI: 2.2, 3.0; p<0.0001) and fewer days since symptom onset (PR=0.79, 95% CI: 0.71, 0.88 per day; p<0.0001).

Interpretation: The presence of SARS-CoV-2 antibodies is strongly associated with clearance of infectious virus isolation. Seropositivity and viral RNA are likely more reliable markers of infectious virus suppression than subjective measure of COVID-19 symptoms. Virus-targeted treatment and prevention strategies should be administered as early as possible and ideally before seroconversion.

Funding: Ridgeback Biotherapeutics, LP and NIH.

Clinicaltrialsgov Identifier: NCT04405570.

Research In Context: A deeper understanding of the viral and host factors associated with infectious virus detection is essential to accurately identify and quarantine contagious individuals. Several studies have reported associations between SARS-CoV-2 virus isolation and viral RNA levels or time from symptom onset. However, little is known about which host factors (i.e. demographics, comorbidities, SARS-CoV-2 seropositivity, symptomatology etc.) are associated with infectious virus detection. A search of PubMed on 12 April 2021 using keywords "COVID-19" or "SARS-CoV-2" and "infectious virus isolation" yielded 14 publications that evaluated virus isolation from respiratory samples of SARS-CoV-2 infected individuals. Five of these studies were case reports or case series that included up to 5 individuals. Seven studies included cohorts of both outpatients and hospitalized individuals and found strong associations between virus isolation and time from symptom onset and viral RNA level. Of these seven, only two studies evaluated the association between SARS-CoV-2-specific antibodies and virus isolation, but were limited by the late timing of collection (>10 days after symptom onset) or the small number of participants included. The remaining two articles compared virus isolation with antigen and molecular based diagnostics and reviewed prior literature respectively. Collectively, these studies suggest that infectious virus isolation from nasopharyngeal swab samples is possible up to 10 days from symptom onset in individuals with mild disease and for longer in those with severe illness or an underlying immune deficiency. No study has systematically evaluated host, disease, and viral factors associated with infectious virus isolation in the same cohort. To better understand the host, disease, and viral factors associated with virus isolation in ambulatory individuals with COVID-19, we analyzed demographic, symptom, virologic, and SARS-CoV-2-specific antibody data at baseline entry to outpatient care from 204 individuals enrolled in a randomized placebo-controlled study of a novel oral therapeutic. Host characteristics were self-reported and viral RNA quantitation, virus isolation, and SARS-2 specific antibody testing (IgG, IgM, IgA and total Ig) were performed at central laboratories. This represents the largest evaluation of virus isolation from symptomatic outpatients with COVID-19 reported to date, and affords an important opportunity to understand which host, virus, and disease factors are associated with the presence and clearance of infectious virus in the nasopharynx. Consistent with prior studies, we found that isolation of replication competent SARS-CoV-2 strongly correlated with both higher nasal viral qRT-PCR RNA levels and shorter time since symptom onset. Importantly, we also found that SARS-CoV-2 antibodies are strongly associated with the clearance of infectious virus, with virus isolation in 7% of seropositive individuals compared to 58% of seronegative individuals. Our findings provide a comprehensive analysis of key virus, host, and disease factors associated with infectious virus isolation and suggest that antibody detection appears to be a more reliable marker of infectious virus clearance than patient-reported symptom duration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/2021.05.28.21258011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183023PMC
June 2021

Outpatient Treatment of SARS-CoV-2 Infection to Prevent COVID-19 Progression.

Clin Infect Dis 2021 May 28. Epub 2021 May 28.

University of North Carolina School of Medicine, Chapel Hill, NC, United States.

As of March 2021, COVID-19 has caused more than 123 million infections, and almost 3 million deaths worldwide. Dramatic advances have been made in vaccine development and non-pharmaceutical interventions to stop the spread of infection. But treatments to stop the progression of disease are limited. A wide variety of "repurposed" drugs explored for treatment of COVID-19 have had little or no benefit. More recently, intravenous monoclonal antibody (mAb) combinations have been authorized by the US FDA for emergency use (EUA) for outpatients with mild to moderate COVID-19 including some active against emerging SARS-COV-2 variants of concern (VOC). Easier to administer therapeutics including intramuscular and subcutaneous mAbs and oral antivirals are in clinical trials. Reliable, safe, effective COVID-19 treatment for early infection in the outpatient setting is of urgent and critical importance. Availability of such treatment should lead to reduced progression of COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciab494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194682PMC
May 2021

Racial, ethnic, and gender disparities in hospitalizations among persons with HIV in the United States and Canada, 2005-2015.

AIDS 2021 07;35(8):1229-1239

School of Medicine, Johns Hopkins University, Baltimore, MD, USA.

Objective: To examine recent trends and differences in all-cause and cause-specific hospitalization rates by race, ethnicity, and gender among persons with HIV (PWH) in the United States and Canada.

Design: HIV clinical cohort consortium.

Methods: We followed PWH at least 18 years old in care 2005-2015 in six clinical cohorts. We used modified Clinical Classifications Software to categorize hospital discharge diagnoses. Incidence rate ratios (IRR) were estimated using Poisson regression with robust variances to compare racial and ethnic groups, stratified by gender, adjusted for cohort, calendar year, injection drug use history, and annually updated age, CD4+, and HIV viral load.

Results: Among 27 085 patients (122 566 person-years), 80% were cisgender men, 1% transgender, 43% White, 33% Black, 17% Hispanic of any race, and 1% Indigenous. Unadjusted all-cause hospitalization rates were higher for Black [IRR 1.46, 95% confidence interval (CI) 1.32-1.61] and Indigenous (1.99, 1.44-2.74) versus White cisgender men, and for Indigenous versus White cisgender women (2.55, 1.68-3.89). Unadjusted AIDS-related hospitalization rates were also higher for Black, Hispanic, and Indigenous versus White cisgender men (all P < 0.05). Transgender patients had 1.50 times (1.05-2.14) and cisgender women 1.37 times (1.26-1.48) the unadjusted hospitalization rate of cisgender men. In adjusted analyses, among both cisgender men and women, Black patients had higher rates of cardiovascular and renal/genitourinary hospitalizations compared to Whites (all P < 0.05).

Conclusion: Black, Hispanic, Indigenous, women, and transgender PWH in the United States and Canada experienced substantially higher hospitalization rates than White patients and cisgender men, respectively. Disparities likely have several causes, including differences in virologic suppression and chronic conditions such as diabetes and renal disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAD.0000000000002876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172437PMC
July 2021

Current and Past Immunodeficiency are Associated with Higher Hospitalization Rates among Persons on Virologically Suppressive Antiretroviral Therapy for up to Eleven Years.

J Infect Dis 2020 Dec 26. Epub 2020 Dec 26.

School of Medicine, Johns Hopkins University, Baltimore, MD, USA.

Background: Persons with HIV (PWH) with persistently low CD4 counts despite efficacious antiretroviral therapy could have higher hospitalization risk.

Methods: In six US and Canadian clinical cohorts, PWH with virologic suppression for ≥1 year in 2005-2015 were followed until virologic failure, loss to follow-up, death, or study end. Stratified by early (Years 2-5) and long-term (Years 6-11) suppression and lowest pre-suppression CD4 count <200 and ≥200 cells/µL, Poisson regression models estimated hospitalization incidence rate ratios (aIRR) comparing patients by time-updated CD4 count category, adjusted for cohort, age, gender, calendar year, suppression duration, and lowest pre-suppression CD4 count.

Results: The 6997 included patients (19 980 person-years) were 81% cisgender men and 40% White. Among patients with lowest pre-suppression CD4 <200 cells/μL (44%), patients with current CD4 200-350 versus >500 cells/μL had an aIRR of 1.44 during early suppression (95% CI 1.01-2.06), and 1.67 (1.03-2.72) during long-term suppression. Among patients with lowest pre-suppression CD4 ≥200 (56%), patients with current CD4 351-500 versus >500 cells/μL had an aIRR of 1.22 (0.93-1.60) during early suppression and 2.09 (1.18-3.70) during long-term suppression.

Conclusions: Virologically suppressed patients with lower CD4 counts experienced higher hospitalization rates, and could potentially benefit from targeted clinical management strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jiaa786DOI Listing
December 2020

Guidance for Restarting Inflammatory Bowel Disease Therapy in Patients Who Withheld Immunosuppressant Medications During COVID-19.

J Crohns Colitis 2020 Oct;14(14 Suppl 3):S769-S773

Department of Gastroenterology, Evaggelismos-Ophthalmiatreion Athinon-Polykliniki GHA, Athens, Greece.

Patients with inflammatory bowel diseases [IBD] are frequently treated with immunosuppressant medications. During the coronavirus disease 2019 [COVID-19] pandemic, recommendations for IBD management have included that patients should stay on their immunosuppressant medications if they are not infected with the severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], but to temporarily hold these medications if symptomatic with COVID-19 or asymptomatic but have tested positive for SARS-CoV-2. As more IBD patients are infected globally, it is important to also understand how to manage IBD medications during convalescence while an individual with IBD is recovering from COVID-19. In this review, we address the differences between a test-based versus a symptoms-based strategy as related to COVID-19, and offer recommendations on when it is appropriate to consider restarting IBD therapy in patients testing positive for SARS-CoV-2 or with clinical symptoms consistent with COVID-19. In general, we recommend a symptoms-based approach, due to the current lack of confidence in the accuracy of available testing and the clinical significance of prolonged detection of virus via molecular testing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ecco-jcc/jjaa135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665410PMC
October 2020

Hospitalization Rates and Causes Among Persons With HIV in the United States and Canada, 2005-2015.

J Infect Dis 2021 Jun;223(12):2113-2123

School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

Background: To assess the possible impact of antiretroviral therapy improvements, aging, and comorbidities, we examined trends in all-cause and cause-specific hospitalization rates among persons with HIV (PWH) from 2005 to 2015.

Methods: In 6 clinical cohorts, we followed PWH in care (≥1 outpatient CD4 count or HIV load [VL] every 12 months) and categorized ICD codes of primary discharge diagnoses using modified Clinical Classifications Software. Poisson regression estimated hospitalization rate ratios for calendar time trends, adjusted for demographics, HIV risk factor, and annually updated age, CD4, and VL.

Results: Among 28 057 patients (125 724 person-years), from 2005 to 2015, the median CD4 increased from 389 to 580 cells/µL and virologic suppression from 55% to 85% of patients. Unadjusted all-cause hospitalization rates decreased from 22.3 per 100 person-years in 2005 (95% confidence interval [CI], 20.6-24.1) to 13.0 in 2015 (95% CI, 12.2-14.0). Unadjusted rates decreased for almost all diagnostic categories. Adjusted rates decreased for all-cause, cardiovascular, and AIDS-defining conditions, increased for non-AIDS-defining infection, and were stable for most other categories.

Conclusions: Among PWH with increasing CD4 counts and viral suppression, unadjusted hospitalization rates decreased for all-cause and most cause-specific hospitalizations, despite the potential effects of aging, comorbidities, and cumulative exposure to HIV and antiretrovirals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jiaa661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205637PMC
June 2021

"My Death Will Not [Be] in Vain": Testimonials from Last Gift Rapid Research Autopsy Study Participants Living with HIV at the End of Life.

AIDS Res Hum Retroviruses 2020 12 24;36(12):1071-1082. Epub 2020 Jun 24.

Department of Medicine, University of California San Diego School of Medicine, AntiViral Research Center, University of California San Diego, San Diego, California, USA.

End-of-life (EOL) HIV cure-related research provides a novel approach to studying HIV reservoirs. The Last Gift is a rapid autopsy research study at the University of California San Diego that enrolls terminally ill people living with HIV (PLWHIV) with a desire to contribute to HIV cure-related research. We conducted in-depth baseline and follow-up interviews with Last Gift study participants. We analyzed interview data applying conventional content analysis. Since summer 2017, 13 participants have been enrolled ( = 11 males and 2 females; aged 45-89 years) and 8 participants interviewed. Terminal illnesses included cancers, heart diseases, and neurodegenerative illnesses. Our analysis revealed five key themes: (1) The Last Gift study has tremendous meaning for participants at the end of their life. (2) HIV-specific altruism was a primary motivator to join the Last Gift study, nested within the context of community, scientific advancement, and moral obligation. (3) Participants did not expect physical benefits yet they perceived emotional/psychological, financial, and societal/scientific benefits. (4) There were minimal participant-perceived risks and concerns. (5) Last Gift participants expressed immense gratitude toward study staff. The Last Gift study provides a framework for ethical HIV cure-related research at EOL and highlighted participants' perspectives, motivations, and experiences. Knowing how PLWHIV understand and experience such studies will remain critical to designing ethical, fully informed HIV cure research protocols that are acceptable to PLWHIV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/AID.2020.0020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703253PMC
December 2020

Participant Perspectives in an HIV Cure-Related Trial Conducted Exclusively in Women in the United States: Results from AIDS Clinical Trials Group 5366.

AIDS Res Hum Retroviruses 2020 04;36(4):268-282

John Hopkins University School of Medicine, Baltimore, Maryland.

Women remain underrepresented in HIV research. The AIDS Clinical Trials Group (ACTG) 5366 study was the first HIV cure-related trial conducted exclusively in women. Our multidisciplinary team integrated participant-centered reports into the ACTG 5366 protocol to elicit their perspectives. We nested mixed-methods surveys at the enrollment and final study visits to assess ACTG 5366 participants' perceptions and experiences. Of 31 participants enrolled in the ACTG 5366, 29 study agreed to complete the entry questionnaire and 27 completed the exit survey. The majority of study participants were nonwhite. We identified societal and personal motivators for participation, understanding of risks and benefits, and minor misconceptions among some trial participants. Stigma was pervasive for several women who joined the study, and served as a motivator for study participation. Reimbursements to defray costs of study participation were reported to facilitate involvement in the trial by about one-third of participants. Almost all respondents reported positive experiences participating in the ACTG 5366 trial. The ACTG 5366 study showed that it is possible to recruit and retain women in HIV cure-related research and to embed participant-centered outcomes at strategic time points during the study. The findings could help in the design, implementation, recruitment, and retention of women in HIV cure-related research and highlight the value of assessing psychosocial factors in HIV cure-related research participation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/AID.2019.0284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185351PMC
April 2020

Burden of respiratory viral infection in persons with human immunodeficiency virus.

Influenza Other Respir Viruses 2020 07 9;14(4):465-469. Epub 2020 Mar 9.

Division of Pulmonary and Critical Care Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

This study was conducted to determine the prevalence of respiratory viral infections (RVI) in persons living with HIV (PLH) admitted with a respiratory complaint using real-time reverse transcription polymerase chain reaction and primer-independent next-generation sequencing (NGS). Of 82 subjects, respiratory viruses were the most common pathogen identified in 27 (33%), followed by fungus and bacteria in 8 (10%) and 4 (5%) subjects, respectively. Among subjects with RVI, 11 (41%) required ICU admission and 16 (59%) required mechanical ventilation. The proportion of respiratory viruses identified, and the associated complicated hospital course highlights the significant role that RVIs play in the lung health of PLH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/irv.12734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298306PMC
July 2020

Long-term Complications of Ebola Virus Disease: Prevalence and Predictors of Major Symptoms and the Role of Inflammation.

Clin Infect Dis 2020 10;71(7):1749-1755

Eternal Love Winning Africa Hospital, Paynesville, Liberia.

Background: Cohort studies have reported a high prevalence of musculoskeletal, neurologic, auditory, and visual complications among Ebola virus disease (EVD) survivors. However, little is known about the host- and disease-related predictors of these symptoms and their etiological mechanisms.

Methods: The presence and patterns of 8 cardinal symptoms that are most commonly reported following EVD survival were assessed in the 326 EVD survivors who participated in the ongoing longitudinal Liberian EVD Survivor Study. At quarterly study visits, symptoms that developed since acute EVD were recorded and blood was collected for biomarkers of inflammation and immune activation.

Results: At baseline (mean 408 days from acute EVD), 75.5% of survivors reported at least 1 new cardinal symptom since surviving EVD, which in 85.8% was rated as highly interfering with life. Two or more incident symptoms were reported by 61.0% of survivors, with pairings of joint pain, headache, or fatigue the most frequent. Women were significantly more likely than men to report headache, while older age was significantly associated with musculoskeletal and visual symptoms. In analyses adjusted for multiple comparisons, no statistically significant association was found between any symptom and 26 markers of inflammation and immune activation. Symptom frequency remained largely unchanged during study follow-up.

Conclusions: Post-EVD complications occur in a majority of survivors and remain present more than 4 years after acute infection. An association between markers of inflammation and immune activation and individual symptoms was not found, suggesting an alternative etiology for persistent post-EVD symptomatology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciz1062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755089PMC
October 2020

Hospitalization Rates and Outcomes Among Persons Living With Human Immunodeficiency Virus in the Southeastern United States, 1996-2016.

Clin Infect Dis 2020 10;71(7):1616-1623

Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Background: Antiretroviral therapy (ART) advances, aging, and comorbidities impact hospitalizations in human immunodeficiency virus (HIV)-positive populations. We examined temporal trends and patient characteristics associated with hospitalization rates and outcomes.

Methods: Among patients in the University of North Carolina Center for AIDS Research HIV Clinical Cohort receiving care during 1996-2016, we estimated annual hospitalization rates, time to inpatient mortality or live discharge, and 30-day readmission risk using bivariable Poisson, Fine-Gray, and log-binomial regression models.

Results: The 4323 included patients (29% women, 60% African American) contributed 30 007 person-years. Overall, the hospitalization rate per 100 person-years was 34.3 (95% confidence interval [CI], 32.4-36.4) with a mean annual change of -3% (95% CI, -4% to -2%). Patients who were black (vs white), older, had HIV RNA >400 copies/mL, or had CD4 count <200 cells/μL had higher hospitalization rates (all P < .05). Thirty-day readmission risk was 18.9% (95% CI, 17.7%-20.2%), stable over time (P > .05 for both 2010-2016 and 2003-2009 vs 1996-2002), and higher among black patients, those with detectable HIV RNA, and those with lower CD4 cell counts (all P < .05). Higher inpatient mortality was associated with older age and lower CD4 cell count (both P < .05).

Conclusions: Hospitalization rates decreased from 1996 to 2016, but high readmissions persisted. Older patients, those of minority race/ethnicity, and those with uncontrolled HIV experienced higher rates and worse hospitalization outcomes. These findings underscore the importance of early ART and care engagement, particularly at hospital discharge.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciz1043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755093PMC
October 2020

The Dose Response: Perceptions of People Living with HIV in the United States on Alternatives to Oral Daily Antiretroviral Therapy.

AIDS Res Hum Retroviruses 2020 04 4;36(4):324-348. Epub 2019 Dec 4.

Institute of Global Health and Infectious Diseases (IGHID), University of North Carolina, Chapel Hill, North Carolina.

There are two concurrent and novel major research pathways toward strategies for HIV control: (1) long-acting antiretroviral therapy (ART) formulations and (2) research aimed at conferring sustained ART-free HIV remission, considered a step toward an HIV cure. The importance of perspectives from people living with HIV on the development of new modalities is high, but data are lacking. We administered an online survey in which respondents selected their likelihood of participation or nonparticipation in HIV cure/remission research based on potential risks and perceived benefits of these new modalities. We also tested the correlation between perceptions of potential risks and benefits with preferences of virologic control strategies and/or responses to scenario choices, while controlling for respondent characteristics. Of the 282 eligible respondents, 42% would be willing to switch from oral daily ART to long-acting ART injectables or implantables taken at 6-month intervals, and 24% to a hypothetical ART-free remission strategy. We found statistically significant gender differences in perceptions of risk and preferences of HIV control strategies, and possible psychosocial factors that could mediate willingness to switch to novel HIV treatment or remission options. Our study yielded data on possible desirable product characteristics for future HIV treatment and remission options. Findings also revealed differences in motivations and preferences across gender and other sociodemographic characteristics that may be actionable as part of research recruitment efforts. The diversity of participant perspectives reveals the need to provide a variety of therapeutic options to people living with HIV and to acknowledge their diverse experiential expertise when developing novel HIV therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/AID.2019.0175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185332PMC
April 2020

Reproductive health sequelae among women who survived Ebola virus disease in Liberia.

Int J Gynaecol Obstet 2019 Aug 14;146(2):212-217. Epub 2019 Jun 14.

Eternal Love Winning Africa Hospital, Monrovia, Liberia.

Objective: To estimate the incidence of failed pregnancy and menstrual irregularities among Liberian women who had survived Ebola virus disease (EVD) and to identify host-specific and disease-specific factors associated with these outcomes.

Methods: A cross-sectional questionnaire-based study was conducted between August 10, 2016, and February 7, 2017. The study population comprised 111 women aged 18-45 years who had survived EVD and were enrolled in the Longitudinal Liberian Ebola Survivor study based at the Eternal Love Winning Africa Hospital, Monrovia, Liberia. Self-reported data on outcomes related to pregnancy and menstrual changes since recovery from EVD were collected.

Results: In all, 29 (26.1%) of the participants had become pregnant since surviving EVD. Of the 23 women whose pregnancies continued to term, 10 (43.4%) reported live birth, 11 (47.8%) reported spontaneous abortion, and two (8.7%) reported stillbirth. Of the 105 women who reported having regular menstruation before EVD, 27 (29.0%) reported experiencing irregular menstruation for unknown reasons after EVD. In bivariate logistic models, no associations were found between failed pregnancy or irregular menstruation and any of the factors of interest.

Conclusions: Adverse pregnancy outcomes and irregular menstruation were frequently reported among EVD survivors in Liberia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijgo.12858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675397PMC
August 2019

Bictegravir combined with emtricitabine and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial.

Lancet HIV 2019 06 5;6(6):e355-e363. Epub 2019 May 5.

Department of HIV Clinical Research, Gilead Sciences Inc, Foster City, CA, USA.

Background: Bictegravir co-formulated with emtricitabine and tenofovir alafenamide as a fixed-dose combination is recommended for treatment of HIV-1-infection and might be better tolerated than other integrase inhibitor-based single-tablet regimens, but long-term outcomes data are not available. We assessed the efficacy, safety and tolerability of bictegravir, emtricitabine, and tenofovir alafenamide compared with co-formulated dolutegravir, abacavir, and lamivudine at week 96.

Methods: This ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial was done at 122 outpatient centres in nine countries. We enrolled adults (aged ≥18 years) living with HIV who were treatment naive and HLA-B*5701 negative, did not have hepatitis B virus infection, and had an estimated glomerular filtration rate of at least 50 mL/min. We randomly assigned participants (1:1) to receive co-formulated bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg (the bictegravir group) or co-formulated dolutegravir 50 mg, abacavir 600 mg, and lamivudine 300 mg (the dolutegravir group), each with matching placebo, once daily for 144 weeks. Treatment allocation was masked to all participants and investigators. All participants who received at least one dose of study drug were included in primary efficacy and safety analyses. We previously reported the primary endpoint. Here, we report the week 96 secondary outcome of proportion of participants with plasma HIV-1 RNA less than 50 copies per mL at week 96 by US Food and Drug Administration snapshot algorithm, with a prespecified non-inferiority margin of -12%. This study was registered with ClinicalTrials.gov, number NCT02607930.

Findings: Between Nov 13, 2015, and July 14, 2016, we screened 739 participants, of whom 108 were excluded and 631 enrolled and randomly assigned to bictegravir, emtricitabine, and tenofovir alafenamide (n=316) or dolutegravir, abacavir, and lamivudine (n=315). Two participants in the bictegravir group did not receive at least one dose of their assigned drug and were excluded from analyses. At week 96, bictegravir, emtricitabine, and tenofovir alafenamide was non-inferior to dolutegravir, abacavir, and lamivudine, with 276 (88%) of 314 participants in the bictegravir group versus 283 (90%) of 315 participants in the dolutegravir group achieving HIV-1 RNA less than 50 copies per mL (difference -1·9%; 95% CI -6·9 to 3·1). The most common adverse events were nausea (36 [11%] of 314 for the bictegravir group vs 76 [24%] of 315 for the dolutegravir group), diarrhoea (48 [15%] vs 50 [16%]), and headache (41 [13%] vs 51 [16%]). 36 (11%) participants in the bictegravir group versus 39 (12%) participants in the dolutegravir group had a serious adverse event. Two individuals died in the bictegravir group (recreational drug overdose and suicide, neither of which was treatment related) and none died in the dolutegravir group. No participants discontinued because of adverse events in the bictegravir group compared with five (2%) of 315 in the dolutegravir group. Study drug-related adverse events were reported for 89 (28%) participants in the bictegravir group and 127 (40%) in the dolutegravir group.

Interpretation: These week 96 data support bictegravir, emtricitabine, and tenofovir alafenamide as a safe, well tolerated, and durable treatment for people living with HIV-1 with no emergent resistance.

Funding: Gilead Sciences, Inc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2352-3018(19)30077-3DOI Listing
June 2019

Estimated Impact of Targeted Pre-Exposure Prophylaxis: Strategies for Men Who Have Sex with Men in the United States.

Int J Environ Res Public Health 2019 05 7;16(9). Epub 2019 May 7.

Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06510, USA.

Pre-exposure prophylaxis (PrEP) effectively reduces human immunodeficiency virus (HIV) transmission. We aimed to estimate the impact of different PrEP prioritization strategies among Black and Latino men who have sex with men (MSM) in the United States, populations most disproportionately affected by HIV. We developed an agent-based simulation to model the HIV epidemic among MSM. Individuals were assigned an HIV incidence risk index (HIRI-MSM) based on their sexual behavior. Prioritization strategies included PrEP use for individuals with HIRI-MSM ≥10 among all MSM, all Black MSM, young (≤25 years) Black MSM, Latino MSM, and young Latino MSM. We estimated the number needed to treat (NNT) to prevent one HIV infection, reductions in prevalence and incidence, and subsequent infections in non-PrEP users avoided under these strategies over 5 years (2016-2020). Young Black MSM eligible for PrEP had the lowest NNT (NNT = 10) followed by all Black MSM (NNT = 33) and young Latino MSM (NNT = 35). All Latino MSM and all MSM had NNT values of 63 and 70, respectively. Secondary infection reduction with PrEP was the highest among young Latino MSM (53.2%) followed by young Black MSM (37.8%). Targeting all MSM had the greatest reduction in prevalence (14.7% versus 2.9%-3.9% in other strategies) and incidence (49.4% versus 9.4%-13.9% in other groups). Using data representative of the United States MSM population, we found that a strategy of universal PrEP use by MSM was most effective in reducing HIV prevalence and incidence of MSM. Targeted use of PrEP by Black and Latino MSM, however, especially those ≤25 years, had the greatest impact on HIV prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph16091592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539923PMC
May 2019

Best practices for identifying men who have sex with men for corrections-based pre-exposure prophylaxis provision.

Health Justice 2019 Apr 13;7(1). Epub 2019 Apr 13.

Division of Infectious Diseases, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Purpose: Men who have sex with men (MSM) who are incarcerated are at increased risk for HIV acquisition, yet there are challenges associated with disclosing sexual identity/orientation among people who are incarcerated.

Methods: The current study used semi-structured, qualitative interviews to explore attitudes and awareness of pre-exposure prophylaxis (PrEP) among 26 MSM who were incarcerated at the Rhode Island Department of Corrections.

Results: Participants noted variable levels of willingness to disclose sexual identity/orientation.

Conclusions: CJ institutions should consider involving medical staff and outside agencies when using the CDC PrEP guidelines or consider a WHO-based, rather than behavior-based, approach to determining candidacy for PrEP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40352-019-0088-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717965PMC
April 2019

Shifting the Paradigm - Applying Universal Standards of Care to Ebola Virus Disease.

N Engl J Med 2019 Apr;380(15):1389-1391

From the Divisions of Pulmonary and Critical Care Medicine (W.A.F.) and Infectious Diseases (D.A.W.), University of North Carolina at Chapel Hill, Chapel Hill; Integrated Research Facility, Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD (I.C.); the UK Public Health Rapid Support Team, Public Health England, and the London School of Hygiene and Tropical Medicine, London (D.G.B.), and the Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool (S.T.J.) - all in the United Kingdom; Institut National de Recherche Biomédicale and Département de Microbiologie, Faculté de Médecine, Université de Kinshasa - both in Kinshasa, Democratic Republic of Congo (J.-J.M., S.M.); the Clinical Management Team, Health Emergencies Program, World Health Organization, Geneva (J.V.D.); and the Alliance for International Medical Action (ALIMA), Dakar, Senegal (R.K.).

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMp1817070DOI Listing
April 2019

Antiretroviral Adherence Following Prison Release in a Randomized Trial of the imPACT Intervention to Maintain Suppression of HIV Viremia.

AIDS Behav 2019 Sep;23(9):2386-2395

The Institute for Global Health and Infectious Diseases, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Many people living with HIV (PLWH) pass through correctional facilities each year, a large proportion of whom do not maintain viral suppression following release. We examined the effects of imPACT, an intervention designed to promote post-release viral suppression, on antiretroviral therapy (ART) adherence. PLWH awaiting release from prisons in two southern states were randomized to imPACT (consisting of motivational interviewing, care linkage coordination, and text message medication reminders) versus standard care (SC). ART adherence, measured by unannounced monthly telephone pill counts, was compared between study arms over 6 months post-release. Of 381 participants eligible for post-release follow-up, 302 (79%) completed ≥ 1 of 6 possible pill counts (median: 4; IQR 1-6). Average adherence over follow-up was 80.3% (95% CI 77.5, 83.1) and 81.0% (78.3, 83.6) of expected doses taken in the imPACT and SC arms, respectively. There was no difference between arms when accounting for missing data using multiple imputation (mean difference = - 0.2 percentage points [- 3.7, 3.3]), controlling for study site and week of follow-up. Of the 936 (40.9%) pill counts that were missed, 212 (22.7%) were due to re-incarceration. Those who missed pill counts for any reason were more likely to be unsuppressed, suggesting that they had lower adherence. However, missingness was balanced between arms. Among PLWH released from prison, ART adherence averaged > 80% in both study arms over 6 months-a level higher than seen with most other chronic diseases. However, missing data may have led to an overestimate of adherence. Factors independent of the intervention influence ART adherence in this population and should be identified to inform future targeted interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10461-019-02488-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822683PMC
September 2019

Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate: a pooled analysis of 26 clinical trials.

AIDS 2019 07;33(9):1455-1465

Departments of Biometrics and HIV & Emerging Viral Infections Clinical Research, Gilead Sciences, Inc., Foster City, California, USA.

Objective: Compared with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has been associated with improvement in markers of renal dysfunction in individual randomized trials; however, the comparative incidence of clinically significant renal events remains unclear.

Design: We used a pooled data approach to increase the person-years of drug exposure analysed, maximizing our ability to detect differences in clinically significant outcomes.

Methods: We pooled clinical renal safety data across 26 treatment-naive and antiretroviral switch studies to compare the incidence of proximal renal tubulopathy and discontinuation due to renal adverse events between participants taking TAF-containing regimens vs. those taking TDF-containing regimens. We performed secondary analyses from seven large randomized studies (two treatment-naive and five switch studies) to compare incidence of renal adverse events, treatment-emergent proteinuria, changes in serum creatinine, creatinine clearance, and urinary biomarkers (albumin, beta-2-microglobulin, and retinol binding protein-to-creatinine ratios).

Results: Our integrated analysis included 9322 adults and children with HIV (n = 6360 TAF, n = 2962 TDF) with exposure of 12 519 person-years to TAF and 5947 to TDF. There were no cases of proximal renal tubulopathy in participants receiving TAF vs. 10 cases in those receiving TDF (P < 0.001), and fewer individuals on TAF (3/6360) vs. TDF (14/2962) (P < 0.001) discontinued due to a renal adverse event. Participants initiating TAF-based vs. TDF-based regimens had more favourable changes in renal biomarkers through 96 weeks of therapy.

Conclusion: These pooled data from 26 studies, with over 12 500 person-years of follow-up in children and adults, support the comparative renal safety of TAF over TDF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAD.0000000000002223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635043PMC
July 2019

Effectiveness of integrase strand transfer inhibitors among treatment-experienced patients in a clinical setting.

AIDS 2019 06;33(7):1187-1195

Department of Medicine.

Objective: Characterize virologic and immunologic outcomes of INSTI-based antiretroviral therapy (ART) in experienced patients with and without virologic failure.

Design: Prospective clinical cohort.

Methods: ART-experienced, INSTI-naive participants in the University of North Carolina Center for AIDS Research HIV Clinical Cohort (UCHCC) initiating an INSTI-containing regimen 2007-2016 were followed from INSTI initiation (baseline) to the earliest of: outcome of interest, loss to follow-up (LTFU, 1 year without clinical visit), or death. Outcomes of interest were virologic failure (first of two consecutive viral loads at least 200 copies/ml more than 2 weeks apart, or one viral load ≥200 before LTFU) and immune recovery (first CD4 ≥500 cells/μl). Patients with baseline viral load at least 50 copies/ml were given 24 weeks before meeting virologic failure criteria. Kaplan-Meier curves and Cox proportional hazards models compared INSTI regimens and patient characteristics.

Results: Of 773 patients, 32% were women, 59% African-American, and 42% had a viral load at least 50 copies/ml at INSTI initiation. After 2 years, 5% of patients with baseline viral load less than 50 copies/ml experienced virologic failure, compared with 35% of patients with baseline viral load at least 50 copies/ml (P < 0.01). Among patients with baseline viral load less than 50 copies/ml, dolutegravir/NRTIs was associated with longer time to virologic failure [adjusted hazard ratio (aHR) 0.11, 95% confidence interval (CI) 0.01-0.80], whereas among patients with baseline viral load at least 50 copies/ml, raltegravir/NRTIs was associated with longer time to virologic failure (aHR 0.35, 95% CI 0.18-0.68), both compared with elvitegravir/NRTIs. After 5 years suppressed, irrespective of baseline viral load, 61% of patients experienced immune recovery.

Conclusion: In this cohort, INSTI-containing regimens led to low virologic failure rates in patients switching ART while suppressed. Viremic patients initiating INSTIs were at high risk of virologic failure during follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAD.0000000000002194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6608711PMC
June 2019

Underutilization of HIV Testing Among Men with Incarceration Histories.

AIDS Behav 2019 Apr;23(4):883-892

Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, 130 Mason Farm Road, CB# 7030, Chapel Hill, NC, 27599, USA.

Annual HIV testing is recommended for individuals at high risk of infection, specifically incarcerated populations. Incarcerated men carry a higher lifetime risk of acquiring HIV than the general population, yet little is known about their HIV testing behaviors. We collected Audio Computer Assisted Self Interview data for 819 men entering a state prison in North Carolina. We assessed correlates of previous HIV testing, including stigmatizing attitudes and beliefs, and explored two outcomes: (1) ever HIV tested before current incarceration, and (2) recency of last HIV test. Eighty percent had been HIV tested before; of those, 36% reported testing within the last year. Being African American, having education beyond high school, prior incarceration, and higher HIV knowledge increased odds of ever having tested. Results of this study highlight the need to expand HIV testing and education specific to incarcerated populations. Additionally, efforts should be made to monitor and encourage repeat screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10461-018-02381-9DOI Listing
April 2019

Dissolution of Committed Partnerships during Incarceration and STI/HIV-Related Sexual Risk Behavior after Prison Release among African American Men.

J Urban Health 2018 08;95(4):479-487

Division of Infectious Disease, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Incarceration is strongly associated with post-release STI/HIV risk. One pathway linking incarceration and STI/HIV risk may be incarceration-related dissolution of protective network ties. Among African American men released from prison who were in committed partnerships with women at the time of incarceration (N = 207), we measured the association between committed partnership dissolution during incarceration and STI/HIV risk in the 4 weeks after release. Over one-quarter (28%) experienced incarceration-related partnership dissolution. In adjusted analyses, incarceration-related partnership dissolution was strongly associated with post-release binge drinking (adjusted odds ratio (AOR) 4.2, 95% confidence interval (CI); 1.4-15.5). Those who experienced incarceration-related partnership dissolution were much more likely to engage in multiple/concurrent partnerships or sex trade defined as buying or selling sex (64%) than those who returned to the partner (12%; AOR 20.1, 95% CI 3.4-175.6). Policies that promote maintenance of relationships during incarceration may be important for protecting health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11524-018-0274-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095753PMC
August 2018

Depression, Executive Dysfunction, and Prior Economic and Social Vulnerability Associations in Incarcerated African American Men.

J Correct Health Care 2018 07 1;24(3):295-308. Epub 2018 Jul 1.

1 Division of Comparative Effectiveness and Decision Science, Department of Population Health, NYU School of Medicine, New York, NY, USA.

Low executive function (EF) and depression are each determinants of health. This study examined the synergy between deficits in EF (impaired cognitive flexibility; >75th percentile on the Wisconsin Card Sorting Test perseverative error score) and depressive symptoms (modified Centers for Epidemiologic Studies-Depression) and preincarceration well-being among incarcerated African American men ( N = 189). In adjusted analyses, having impaired EF and depression was strongly associated with pre-incarceration food insecurity (odds ratio [ OR] = 3.81, 95% confidence interval [CI] = [1.35, 10.77]), homelessness ( OR = 3.00, 95% CI [1.02, 8.80]), concern about bills ( OR = 3.76, 95% CI [1.42, 9.95]), low significant other support ( OR = 4.63, 95% CI [1.62, 13.24]), low friend support ( OR = 3.47, 95% CI [1.30, 9.26]), relationship difficulties ( OR = 2.86, 95% CI [1.05, 7.80]), and binge drinking ( OR = 3.62, 95% CI [1.22, 10.80]). Prison-based programs to treat depression and improve problem-solving may improve postrelease success.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1078345818782440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040589PMC
July 2018

Medicaid Enrollment among Prison Inmates in a Non-expansion State: Exploring Predisposing, Enabling, and Need Factors Related to Enrollment Pre-incarceration and Post-Release.

J Urban Health 2018 08;95(4):454-466

University of North at Chapel Hill School of Medicine, Chapel Hill, NC, USA.

Prison inmates suffer from a heavy burden of physical and mental health problems and have considerable need for healthcare and coverage after prison release. The Affordable Care Act may have increased Medicaid access for some of those who need coverage in Medicaid expansion states, but inmates in non-expansion states still have high need for Medicaid coverage and face unique barriers to enrollment. We sought to explore barriers and facilitators to Medicaid enrollment among prison inmates in a non-expansion state. We conducted qualitative interviews with 20 recently hospitalized male prison inmates who had been approached by a prison social worker due to probable Medicaid eligibility, as determined by the inmates' financial status, health, and past Medicaid enrollment. Interviews were transcribed verbatim and analyzed using a codebook with both thematic and interpretive codes. Coded interview text was then analyzed to identify predisposing, enabling, and need factors related to participants' Medicaid enrollment prior to prison and intentions to enroll after release. Study participants' median age, years incarcerated at the time of the interview, and projected remaining sentence length were 50, 4, and 2 years, respectively. Participants were categorized into three sub-groups based on their self-reported experience with Medicaid: (1) those who never applied for Medicaid before prison (n = 6); (2) those who unsuccessfully attempted to enroll in Medicaid before prison (n = 3); and (3) those who enrolled in Medicaid before prison (n = 11). The six participants who had never applied to Medicaid before their incarceration did not hold strong attitudes about Medicaid and mostly had little need for Medicaid due to being generally healthy or having coverage available from other sources such as the Veteran's Administration. However, one inmate who had never applied for Medicaid struggled considerably to access mental healthcare due to lapses in employer-based health coverage and attributed his incarceration to this unmet need for treatment. Three inmates with high medical need had their Medicaid applications rejected at least once pre-incarceration, resulting in periods without health coverage that led to worsening health and financial hardship for two of them. Eleven inmates with high medical need enrolled in Medicaid without difficulty prior to their incarceration, largely due to enabling factors in the form of assistance with the application by their local Department of Social Services or Social Security Administration, their mothers, medical providers, or prison personnel during a prior incarceration. Nearly all inmates acknowledged that they would need health coverage after release from prison, and more than half reported that they would need to enroll in Medicaid to gain healthcare coverage following their release. Although more population-based assessments are necessary, our findings suggest that greater assistance with Medicaid enrollment may be a key factor so that people in the criminal justice system who qualify for Medicaid-and other social safety net programs-may gain their rightful access to these benefits. Such access may benefit not only the individuals themselves but also the communities to which they return.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11524-018-0275-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095764PMC
August 2018

Anti-Ebola Virus Antibody Levels in Convalescent Plasma and Viral Load After Plasma Infusion in Patients With Ebola Virus Disease.

J Infect Dis 2018 07;218(4):555-562

Clinical Research Management, Inc, Hinckley, Ohio.

Background: Ebola virus (EBOV) neutralizing antibody in plasma may reduce viral load following administration of plasma to patients with Ebola virus disease (EVD), but measurement of these antibodies is complex.

Methods: Anti-EBOV antibody was measured by 2 neutralization and 2 enzyme-linked immunosorbent assays (ELISAs) in convalescent plasma (ECP) from 100 EVD survivor donors in Liberia. Viral load was assessed repetitively in patients with EVD participating in a clinical trial of enhanced standard of care plus ECP.

Results: All 4 anti-EBOV assays were highly concordant for detection of EBOV antibody. Antibodies were not detected in plasma specimens obtained from 15 of 100 donors, including 7 with documented EBOV-positive reverse-transcription polymerase chain reaction during EVD. Viral load was reduced following each dose in the 2 clinical trial participants who received ECP with higher antibody levels but not in the 2 who received ECP with lower antibody levels.

Conclusions: Recovery from EVD can occur with absence of detectable anti-EBOV antibody several months after disease onset. ELISAs may be useful to select ECP donors or identify ECP units that contain neutralizing antibody. ECP with higher anti-EBOV antibody levels may have greater effect on EBOV load-an observation that requires further investigation.

Clinical Trials Registration: NCT02333578.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jiy199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927845PMC
July 2018

Underutilization of Statins When Indicated in HIV-Seropositive and Seronegative Women.

AIDS Patient Care STDS 2017 Nov;31(11):447-454

1 Institute for Global Health and Infectious Diseases, University of North Carolina , Chapel Hill, North Carolina.

Increased life expectancy of persons living with HIV infection receiving antiretroviral therapy heightens the importance of preventing and treating chronic comorbidities such as cardiovascular disease. While guidelines have increasingly advocated more aggressive use of statins for low-density lipoprotein (LDL) cholesterol reduction, it is unclear whether people with HIV, especially women, are receiving statins when indicated, and whether their HIV disease is a factor in access. We assessed the cumulative incidence of statin use after an indication in the Women's Interagency HIV Study (WIHS), from 2000 to 2014. Additionally, we used weighted proportional hazards regression to estimate the effect of HIV serostatus on the time to initiation of a statin after an indication. Cumulative incidence of statin use 5 years after an indication was low: 38% in HIV-seropositive women and 30% in HIV-seronegative women. Compared to HIV-seronegative women, the weighted hazard ratio for initiation of a statin for HIV-seropositive women over 5 years was 0.94 [95% confidence interval (CI) 0.62, 1.43]. Applying the American College of Cardiology and the American Heart Association (ACC/AHA) guidelines increased the proportion of HIV-seropositive women with a statin indication from 16% to 45%. Clinicians treating HIV-seropositive women should consider more aggressive management of the dyslipidemia often found in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/apc.2017.0145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5665094PMC
November 2017

Financial Barriers and Lapses in Treatment and Care of HIV-Infected Adults in a Southern State in the United States.

AIDS Patient Care STDS 2017 Nov 17;31(11):463-469. Epub 2017 Oct 17.

1 University of North Carolina at Chapel Hill School of Medicine , Division of Infectious Diseases, Chapel Hill, North Carolina.

Antiretroviral (ARV) adherence has largely been considered from the perspective of an individual's behavior with less attention given to potential structural causes for lapses in treatment, such as the cost of medications and care. HIV medication expense is typically covered by third party payers. However, private insurance premiums and deductibles may rise, or policies terminated such as with a change in employment. Likewise, a patient's eligibility for publicly funded coverage like state AIDS Drug Assistance Programs (ADAP) or Medicaid can also be lost. We conducted a one-time survey of a sample of 300 patients receiving HIV care at a single large academic center in the south of United States to examine lapses in HIV therapy due to financial reasons. We found that during the prior year, financial issues including medication cost or coverage led to a lapse in ARVs in 10% (n = 31) of participants. However, of the 42% (n = 125) participants who had been enrolled in ADAP at any time during the prior year, 21% (n = 26) reported an ARV lapse due to problems with ADAP or medication cost. Respondents cited ADAP's required semi-annual renewal process and other administrative issues as the cause of ARV lapses. The median duration of missed ARVs was 2 weeks (range of <1-23 weeks). Non-HIV medication and transportation to and from clinic costs were also identified as financial burdens to care by respondents. In conclusion, although conducted at a single medical center and one state, this study suggests that a significant minority of HIV-infected patients encounter financial barriers to ARV access, and this is paradoxically more common among those enrolled in the state ADAP. Streamlining, supporting, and simplifying ADAP renewal procedures will likely reduce lapses in ARV adherence and persistence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/apc.2017.0125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5665096PMC
November 2017

Moving Lassa Fever Research and Care Into the 21st Century.

J Infect Dis 2017 06;215(12):1779-1781

Infectious Diseases, University of North Carolina atChapel Hill.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jix206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853919PMC
June 2017
-->