163. High Prevalence of Urogenital and Rectal Mycoplasma genitalium in U.S. MSM with a History of STIs in the Last Year

Abstract Background M. genitalium (M. gen) is an under-recognized sexually transmitted bacterial pathogen that causes 15-25% of nongonococcal urethritis (NGU) in men. Asymptomatic M. gen may serve as a reservoir, lead to transmission to sexual contacts, and drive the development of drug resistance. M. gen may be associated with an increased risk of HIV acquisition, as seen in some studies. Data are limited on M. gen prevalence among U.S. men who have sex with men (MSM) living with HIV or HIV-uninfected and on pre-exposure prophylaxis (PrEP). Methods We analyzed baseline prevalence of urogenital and rectal M. gen using the Aptima Mycoplasma genitalium nucleic acid amplification test in participants enrolled in DoxyPEP, an ongoing randomized, open label trial of the effectiveness of doxycycline post-exposure prophylaxis (PEP) on incidence of gonorrhea, chlamydia, and early syphilis among MSM and transgender women living with HIV or on PrEP in San Francisco and Seattle (NCT03980223). Participants completing at least one follow up visit were also assessed for M. gen persistence, clearance, and incidence. Testing was at regular intervals and not symptom driven. Results This analysis included 122 men; 34% with HIV and 66% on PrEP. In the prior 12 months, 18.9% had a diagnosis of syphilis, 58.2% chlamydia, and 63.9% gonorrhea. At baseline, M. gen was present in at least one site in 24%; 9% in the urine and 16% in the rectum, with 1 testing positive at both sites. M. gen presence was not associated with age, ethnicity, race, HIV status, number of partners in the past 3 months, or bacterial STI in the past 3 months. 65 participants had follow up tests a median of 9.1 months after baseline (IQR 7.8-9.8); among 7 participants with urogenital M. gen at baseline, M. gen cleared in 6 and persisted in 1. Among 11 participants with rectal M. gen at baseline, M. gen cleared in 4 cleared and persisted in 7. At follow up, M. gen was detected in 2 urine and 9 rectal specimens in those previously negative at these sites. Figure 1. Baseline prevalence of urogenital and rectal M. genitalium in MSM at high risk for STIs enrolled in DoxyPEP Figure 2. Detection of urogenital and rectal M. genitalium among participants with baseline and follow up testing Conclusion In this cohort of MSM with a recent diagnosis of a bacterial STI, routine testing identified urogenital or rectal M. gen in 24% of participants at baseline and 31% at either baseline or follow-up. The association of persistent M. gen with the risk for subsequent symptomatic infection and drug resistance merits further investigation. Disclosures Emma D. Bainbridge, MD, MPH, Hologic (Grant/Research Support) Olusegun O. Soge, PhD, Hologic Inc. (Grant/Research Support)SpeeDx Inc. (Grant/Research Support) Annie Luetkemeyer, MD, Cepheid (Grant/Research Support)Hologic (Grant/Research Support)Mayne Pharma (Grant/Research Support)

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Prevalence of Asymptomatic Cryptococcal Antigenemia and Association with Follow-up risk of Cryptococcal Meningitis and Mortality among HIV Infected Patients in North West India – A Prospective Cohort Study

Current HIV Research ◽

10.2174/1570162x18666200827113816 ◽

2020 ◽

Vol 18 ◽

Author(s):

Rajendra Bhati ◽

Pramendra Sirohi ◽

Bharat Sejoo ◽

Deepak Kumar ◽

Gopal K Bohra ◽

...

Keyword(s):

Cryptococcal Meningitis ◽

Morbidity And Mortality ◽

People Living With Hiv ◽

Cryptococcal Antigen ◽

North West ◽

Cryptococcal Disease ◽

Increased Risk ◽

Living With Hiv ◽

Inflammatory Syndrome

Objective: Cryptococcal meningitis is an important cause of morbidity and mortality in HIV infected individuals. In the era of universal antiretroviral therapy incidence of immune reconstitution inflammatory syndrome (IRIS) related cryptococcal meningitis has increased. Detection of serum cryptococcal antigen in asymptomatic PLHIV (People Living With HIV) and pre-emptive treatment with fluconazole can decrease the burden of cryptococcal disease. We conducted this study to find the prevalence of asymptomatic cryptococcal antigenemia in India and its correlation with mortality in PLHIV. Method and material: This was a prospective observational study. HIV infected ART naïve patients with age of ≥ 18 years who had CD4 counts ≤ 100 /µL were included and serum cryptococcal antigen test was done. These patients were followed for six months to look for the development of Cryptococcal meningitis and mortality. Results: A total of 116 patients were analysed. Asymptomatic cryptococcal antigenemia was detected in 5.17% patients and it correlated with increased risk of cryptococcal meningitis and mortality on follow-up in PLHIV. Conclusion: Serum cryptococcal positivity is correlated with increased risk of Cryptococcal meningitis and mortality in PLHIV. We recommend the screening of asymptomatic PLHIV with CD4 ≤ 100/µL for serum cryptococcal antigen, so that pre-emptive treatment can be initiated to reduce morbidity and mortality.

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O06 Baseline predictors of methotrexate-related adverse events in methotrexate-naïve patients with RA

Rheumatology ◽

10.1093/rheumatology/keab246.005 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Ahmad A Sherbini ◽

James M Gwinnutt ◽

Kimme L Hyrich ◽

Suzanne M M Verstappen ◽

Keyword(s):

Rheumatoid Arthritis ◽

Adverse Events ◽

Health Assessment ◽

Prevalence Rates ◽

Clinical Predictors ◽

Research Support ◽

Related Data ◽

Increased Risk ◽

One Year

Abstract Background/Aims Methotrexate (MTX) is the most common treatment for rheumatoid arthritis (RA). The prevalence of adverse events (AEs) associated with MTX treatment for RA have been studied extensively, but there are limited data on the predictors of these AEs. This study aims to summarise the prevalence rates of MTX AEs, including gastrointestinal (GI), neurological, mucocutaneous, and elevated alanine transaminase (ALT) enzyme, and to identify baseline demographic and clinical predictors of these AEs. Methods The Rheumatoid Arthritis Medication Study (RAMS) is a UK multi-centre prospective cohort study of patients with RA starting MTX for the first time. Relevant demographic, medication, clinical and disease related data were collected at baseline. AEs were reported at six and twelve months follow-ups. The prevalence rates of AEs were calculated based on the proportions of patients who reported having had an AE within one year of follow-up. The associations between candidate baseline predictors and AEs were assessed using multivariable logistic regression. Results A total of 2,089 patients were included with a mean age of 58.4 (standard deviation: 13.5) years, 1390 (66.5%) were women. 1,814 and 1,579 patients completed the 6 and 12 months follow-up visits, respectively. The prevalence rates of the AEs within one year of follow-up were: GI = 777 (40.6%), mucocutaneous = 441 (23.1%), neurological = 487 (25.5%), elevated ALT (> upper limit of normal [ULN]) = 286 (15.5%). Younger age and being a woman were associated with increased risk of GI AEs, (age: OR 0.97 per year increase in age, 95% CI 0.98, 1.00; male sex: OR 0.58 vs female, 95% CI 0.46, 0.74) (Table 1). Higher baseline Health Assessment Questionnaire (HAQ) score was an independent predictor of GI, mucocutaneous, and neurological AEs. Furthermore, having ALT >1xULN at baseline or history of diabetes was associated with increased risk of subsequent ALT elevation during the study follow-up. Conclusion In patients with RA starting MTX, GI AEs were the most commonly reported AEs during the first year of follow-up. The identified predictors of AEs may facilitate discussions between clinicians and patients prior to commencing MTX, and may lead to increased adherence and consequently improved effectiveness. Disclosure A.A. Sherbini: None. J.M. Gwinnutt: Grants/research support; BMS. K.L. Hyrich: Member of speakers’ bureau; Abbvie. Grants/research support; Pfizer, UCB, BMS. S.M.M. Verstappen: Consultancies; Celltrion. Member of speakers’ bureau; Pfizer. Grants/research support; BMS.

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Improved PrEP Awareness and Use among Trans Women in San Francisco, California

AIDS and Behavior ◽

10.1007/s10461-021-03417-3 ◽

2021 ◽

Author(s):

Erin C. Wilson ◽

Christopher J. Hernandez ◽

Susan Scheer ◽

Dillon Trujillo ◽

Sean Arayasirikul ◽

...

Keyword(s):

San Francisco ◽

Anal Intercourse ◽

Receptive Anal Intercourse ◽

The Past ◽

National Hiv Behavioral Surveillance ◽

Trans Women ◽

Gender Based ◽

Prep Awareness ◽

Almost All ◽

Exposure Prophylaxis

AbstractTransgender women face a serious risk of HIV infection. Despite this, there is limited knowledge and use of Pre-exposure prophylaxis (PrEP). We measured the continuity of prevention across services in the PrEP cascade and correlates of PrEP use among trans women in San Francisco enrolled in the 2019/20 National HIV Behavioral Surveillance Study. Knowledge and use of PrEP among trans women in San Francisco increased in recent years; almost all (94.0%) had heard about PrEP, 64.7% had discussed PrEP with a healthcare provider, and 44.8% had taken PrEP in the past 12 months. PrEP use was associated with participation in a PrEP demonstration project (aOR = 31.44, p = 0.001) and condomless receptive anal intercourse (aOR = 3.63, p = 0.024). Injection drug use was negatively associated (aOR = 0.19, p = 0.014). Efforts are needed to combat the gender-based stigma and discrimination faced by trans women, which can result in avoidance and mistrust of the medical system.

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834. Characterization of Heavily Treatment Experienced HIV-1 Infected Clinical Trial Participants Infected with SARS-CoV-2 COVID 19: Fostemsavir BRIGHTE Phase 3 Clinical Trial

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1030 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S509-S509

Author(s):

Shiven Chabria ◽

Stephane De Wit ◽

Amy Pierce ◽

Bronagh M Shepherd ◽

Michael Warwick-Sanders ◽

...

Keyword(s):

Clinical Trial ◽

Supplemental Oxygen ◽

Multidrug Resistant ◽

Cd4 Count ◽

People Living With Hiv ◽

Research Support ◽

Increased Risk ◽

Living With Hiv ◽

Hiv 1

Abstract Background BRIGHTE is an ongoing global study evaluating the gp120 attachment inhibitor fostemsavir (FTR) in heavily treatment-experienced (HTE) adults with multidrug resistant (MDR) HIV-1 unable to form a viable antiretroviral (ARV) regimen. An estimated 2 million people living with HIV-1 have been infected with SARS-CoV-2. Those with HIV viremia and/or low CD4+ counts are at increased risk of serious adverse outcome. We describe the reported COVID cases in a clinical trial population of people living with MDR HIV and immune suppression. Methods At the start of the COVID pandemic, all ongoing BRIGHTE subjects had achieved ≥ 192 weeks on FTR and optimized background ARVs; results through Week 96 were presented previously. Investigators used WHO guidelines for COVID diagnosis and reported exposure, testing results and symptom presence. Figure 1. BRIGHTE Study Design Results 371 subjects [272 Randomized Cohort (RC), 99 Non-Randomized Cohort (NC)] were enrolled; 44% were ≥ 50 years of age and 86% had an AIDS history. Median CD4+ count at study start of was 80 cells/mm3 (IQR 11–202); 30% with ≤ 20 cells/mm3. 250 subjects remained in BRIGHTE at pandemic start. By April 2021, 17 subjects (14 RC, 3 NC) had confirmed COVID infection (positive PCR test). Severity was Grade 1-3, all cases resolved with no deaths. Six subjects were hospitalized (Table 1); most recent CD4+ count prior to COVID were 293-1641 cells/mm3 and 5/6 subjects were virologically suppressed. Treatments often included prophylactic anticoagulants and supplemental oxygen; no cART changes were made. The remaining 11/17 confirmed cases were managed outpatient. Five more subjects had suspect COVID not confirmed by PCR and 2 subjects had negative PCR tests. Table 1. Characterization of Participants with Serious AEs of Confirmed COVID-19 Infections – All Hospitalizations Conclusion A total of 22/250 COVID-19 cases (17 confirmed, 5 unconfirmed) have been reported in BRIGHTE. Outcomes were reassuring with no deaths or known persistent sequelae, despite having advanced HIV and comorbid diseases at baseline associated with poorer COVID outcomes. Outcomes may have benefitted from immunologic improvement during the trial. Disclosures Shiven Chabria, MD, Viiv Healthcare (Employee) Stephane De Wit, MD, Gilead (Grant/Research Support)Janssen (Grant/Research Support)Merck Sharpe & Dohme (Grant/Research Support)ViiV Healthcare (Grant/Research Support) Amy Pierce, BS, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Bronagh M. Shepherd, PhD, GlaxoSmithKline (Employee, Shareholder) Michael Warwick-Sanders, BM BSc DPM MFPM, GSK (Employee) Marcia Wang, PhD, GlaxoSmithKline (Employee, Shareholder) Andrew Clark, MD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Peter Ackerman, MD, GSK/ViiV Healthcare (Employee, Shareholder)

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Abstract MP86: The Joint Effect of Outdoor Recreational Activity and 25-Hydroxyvitamin D on Cardiovascular Mortality in THE NHANES III Population

Circulation ◽

10.1161/circ.127.suppl_12.amp86 ◽

2013 ◽

Vol 127 (suppl_12) ◽

Author(s):

Macarius Donneyong ◽

Carlton A Hornung

Keyword(s):

Elevated Risk ◽

Physical Activities ◽

Mortality Data ◽

Nhanes Iii ◽

Additive Interaction ◽

Joint Effects ◽

The Past ◽

Increased Risk ◽

Cvd Mortality

Purpose Recreational physical activity (PA) reduces the risk of cardiovascular disease (CVD) morbidity and mortality. Outdoor-based recreational physical activities (ORA) have been reported to be associated with elevated 25(OH)D levels. We investigate the joint effects of frequent ORA and 25(OH)D levels on the risk of CVD mortality and the modifying effects of 25(OH)D. Methods Our sample consisted of 13,031 nationally representative adults (20 - 90 years old) free from CVD and cancer at baseline in the NHANES III (1988 - 1994) linked mortality dataset with follow-up mortality data through 2006. CVD mortality was based on reported deaths with corresponding ICD-10 codes for CVD as underlying cause of death. ORA was defined as self-reported participation in recreational physical activities considered to have occurred outdoors in the past month. Time to CVD mortality was estimated from multivariable adjusted Cox proportional hazards (CPH) models. A joint effects model was used in estimating multiplicative and additive interaction between ORA and 25(OH)D. Results A crude unweighted CVD mortality rate of 7.4% (964/13,031) occurred during a median follow-up of 14.33 years. Frequency of ORA <5 in the past month (HR=1.38, 95%CI:1.09 - 1.75) and 25(OH)D <30 ng/mL (HR=1.28, 95%CI:1.01 - 1.60) were associated with increased risk of CVD mortality compared to ORA ≥5 and 25(OH)D ≥30 ng/mL respectively, in a multivariable adjusted CPH model. In the joint effects model, frequency of ORA <5 and 25(OH)D <30 ng/mL (HR=1.81, 95%CI:1.05 - 3.10) and frequency of ORA <5 and 25(OH)D ≥30 ng/mL (HR=1.33, 95%CI:1.02 - 1.73) were associated with elevated risk of CVD mortality compared to the joint effects of ORA ≥5 and 25(OH)D ≥30 ng/mL. The joint effects model indicated the presence of multiplicative interaction. The synergy index, 1.52 (95%CI:0.31 - 7.41) suggested presence of additive interaction even though not statistically significant. Conclusion Lower frequency of ORA and serum 25(OH)D levels were jointly associated with elevated risk of CVD mortality. Serum 25(OH)D modified the risk of CVD mortality associated with lower frequency of outdoor-based recreational activities.

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Abstract 092: No Change in Peripartum Cardiomyopathy Outcomes or Risk Factors Over the Past Decade

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.10.suppl_3.092 ◽

2017 ◽

Vol 10 (suppl_3) ◽

Author(s):

Nivedita Basu ◽

Madeline Mahowald ◽

Kris Kawamoto ◽

Melinda Davis

Keyword(s):

Risk Factors ◽

Maternal Age ◽

Care Center ◽

Tertiary Care ◽

Temporal Trends ◽

Peripartum Cardiomyopathy ◽

Icd Implantation ◽

The Past ◽

Increased Risk

Background: Few studies have evaluated temporal trends in outcomes and risk factors for peripartum cardiomyopathy (PPCM). Prior research using administrative data could only assess short-term in-hospital adverse events. It has also been hypothesized that the incidence of PPCM is rising due to advancing maternal age and increased risk factors. Therefore, we examined long-term outcomes and prognostic factors to determine if there has been any change over the past decade. Methods: Patients seen at a tertiary care center between 2000 and 2011 with a diagnosis of PPCM were identified by ICD9 code 674.5x and confirmed by manual chart review. Year of diagnosis, clinical and demographic variables, echocardiographic data, and outcomes including myocardial recovery (defined as EF>=55%), ICD placement, LVAD, transplant, and death were reviewed for follow-up through November 2016. Results: Of 60 patients, 31 (52%) were diagnosed recently (2006-2011) and 29 (48%) were diagnosed prior to 2006 (1996-2005). There were no significant differences in the recent group compared to the past group in initial EF (19% vs 22%), final EF (39% vs 39%), and final recovery status (52% vs 48%). Similarly, there were no differences in rates of ICD implantation, LVAD/transplant, mortality, and years of survival. There were no differences in age at diagnosis or in rates of hypertension, smoking, or diabetes. Few patients in either category underwent a subsequent pregnancy. Mean years of follow-up (through 2016) were longer for those diagnosed prior to 2006 (8.3 years vs 3.4 years, p<0.001). Conclusions: There has been no improvement in outcomes for patients diagnosed with PPCM in the past decade. Maternal age and risk factors do not appear to be increasing. Despite advances in heart failure treatment and increased awareness of PPCM, more research about the management and follow-up of young mothers with PPCM is needed.

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Early Adopters of Event-driven Human Immunodeficiency Virus Pre-exposure Prophylaxis in a Large Healthcare System in San Francisco

Clinical Infectious Diseases ◽

10.1093/cid/ciaa474 ◽

2020 ◽

Vol 71 (10) ◽

pp. 2710-2712 ◽

Cited By ~ 1

Author(s):

J Carlo Hojilla ◽

Julia L Marcus ◽

Michael J Silverberg ◽

C Bradley Hare ◽

Rachel Herbers ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Side Effects ◽

Healthcare System ◽

San Francisco ◽

Hiv Infections ◽

Early Adopters ◽

Immunodeficiency Virus ◽

Event Driven ◽

Exposure Prophylaxis

Abstract Among 279 patients within a large healthcare system in San Francisco, event-driven HIV pre-exposure prophylaxis using a 2–1–1 regimen was a desirable alternative to daily dosing. Problems with adherence, planning sex in advance, or side effects were infrequent (13.9%). We found no new HIV infections over 136 person-years of follow-up.

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An analysis of tumor-related potential spinal column instability (Spine Instability Neoplastic Scores 7–12) eventually requiring surgery with a 1-year follow-up

Neurosurgical FOCUS ◽

10.3171/2021.2.focus201098 ◽

2021 ◽

Vol 50 (5) ◽

pp. E6

Author(s):

Enrique Vargas ◽

Dennis T. Lockney ◽

Praveen V. Mummaneni ◽

Alexander F. Haddad ◽

Joshua Rivera ◽

...

Keyword(s):

Logistic Regression ◽

San Francisco ◽

Surgical Intervention ◽

Nonoperative Management ◽

Multivariable Analysis ◽

Spinal Instability ◽

Karnofsky Performance Scale ◽

Surgery Group ◽

Increased Risk

OBJECTIVE Within the Spine Instability Neoplastic Score (SINS) classification, tumor-related potential spinal instability (SINS 7–12) may not have a clear treatment approach. The authors aimed to examine the proportion of patients in this indeterminate zone who later required surgical stabilization after initial nonoperative management. By studying this patient population, they sought to determine if a clear SINS cutoff existed whereby the spine is potentially unstable due to a lesion and would be more likely to require stabilization. METHODS Records from patients treated at the University of California, San Francisco, for metastatic spine disease from 2005 to 2019 were retrospectively reviewed. Seventy-five patients with tumor-related potential spinal instability (SINS 7–12) who were initially treated nonoperatively were included. All patients had at least a 1-year follow-up with complete medical records. A univariate chi-square test and Student t-test were used to compare categorical and continuous outcomes, respectively, between patients who ultimately underwent surgery and those who did not. A backward likelihood multivariate binary logistic regression model was used to investigate the relationship between clinical characteristics and surgical intervention. Recursive partitioning analysis (RPA) and single-variable logistic regression were performed as a function of SINS. RESULTS Seventy-five patients with a total of 292 spinal metastatic sites were included in this study; 26 (34.7%) patients underwent surgical intervention, and 49 (65.3%) did not. There was no difference in age, sex, comorbidities, or lesion location between the groups. However, there were more patients with a SINS of 12 in the surgery group (55.2%) than in the no surgery group (44.8%) (p = 0.003). On multivariate analysis, SINS > 11 (OR 8.09, CI 1.96–33.4, p = 0.004) and Karnofsky Performance Scale (KPS) score < 60 (OR 0.94, CI 0.89–0.98, p = 0.008) were associated with an increased risk of surgery. KPS score was not correlated with SINS (p = 0.4). RPA by each spinal lesion identified an optimal cutoff value of SINS > 10, which were associated with an increased risk of surgical intervention. Patients with a surgical intervention had a higher incidence of complications on multivariable analysis (OR 2.96, CI 1.01–8.71, p = 0.048). CONCLUSIONS Patients with a mean SINS of 11 or greater may be at increased risk of mechanical instability requiring surgery after initial nonoperative management. RPA showed that patients with a KPS score of 60 or lower and a SINS of greater than 10 had increased surgery rates.

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LB5. PROVENT: Phase 3 Study of Efficacy and Safety of AZD7442 (Tixagevimab/Cilgavimab) for Pre-exposure Prophylaxis of COVID-19 in Adults

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1646 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S810-S810

Author(s):

Myron J Levin ◽

Andrew Ustianowski ◽

Stéphane De Wit ◽

Odile Launay ◽

Miles Avila ◽

...

Keyword(s):

Safety Analysis ◽

Controlled Study ◽

Primary Study ◽

Inadequate Response ◽

Efficacy And Safety ◽

Research Support ◽

Phase 3 ◽

Increased Risk ◽

Study Results ◽

Exposure Prophylaxis

Abstract Background Vaccines effectively prevent COVID-19, but some individuals have medical comorbidities or receive therapies that impair their immune response to vaccination, or are ineligible for vaccination. For such individuals who remain at risk of COVID-19, monoclonal antibodies may provide additional rapid protection. AZD7442 comprises 2 fully human extended half-life SARS-CoV-2–neutralizing antibodies that bind distinct epitopes of the viral spike protein receptor binding domain. AZD7442 is in development for the prevention and treatment of COVID-19. Here, we report primary Phase 3 study results of AZD7442 for pre-exposure prophylaxis of symptomatic COVID-19. Methods PROVENT (NCT04625725) is a Phase 3, 2:1 randomized, double-blind, placebo-controlled study of a single 300-mg AZD7442 dose (2 intramuscular injections; 150 mg each of tixagevimab and cilgavimab) for symptomatic COVID-19 prevention. Participants were unvaccinated adults (≥ 18 years old) without prior SARS-CoV-2 infection, who may benefit from immunoprophylaxis with antibodies due to an increased risk of either inadequate response to vaccination or SARS-CoV-2 exposure. The primary study endpoints were first case of SARS-CoV-2 RT-PCR-positive symptomatic illness post dose and prior to Day 183 (efficacy), and safety of AZD7442. Results In total, 5197 participants (mean age 53.5 years, 46% female) were randomized and dosed (safety analysis set): AZD7442 n=3460; placebo n=1737. In the primary efficacy analysis (full pre-exposure analysis set, n=5172), AZD7442 reduced the risk of developing symptomatic COVID-19 by 77% (95% confidence interval 46.0, 90.0) vs placebo (P< 0.001) (Table). Adverse events occurred in 35% and 34% of participants administered AZD7442 and placebo, respectively, and injection site reactions occurred in 2.4% and 2.1% of participants, respectively (safety analysis set). There was 1 case of severe/critical COVID-19 and 2 COVID-19–related deaths in the placebo arm. Conclusion The primary study endpoints were met: a one-time dose of AZD7442 demonstrated statistically significant protection against symptomatic COVID-19 and was well tolerated. AZD7442 is the first long-acting monoclonal antibody combination that represents a potential new option to augment COVID-19 prevention. PROVENT funding statement image Disclosures Myron J. Levin, MD, GSK group of companies (Employee, Research Grant or Support) Andrew Ustianowski, MBBS, Vir/GlaxoSmithKline (Advisor or Review Panel member) Stéphane De Wit, MD, Gilead (Grant/Research Support)Janssen (Grant/Research Support)Merck Sharpe & Dohme (Grant/Research Support)ViiV Healthcare (Grant/Research Support) Odile Launay, MD, PhD, AstraZeneca (Grant/Research Support)GlaxoSmithKline (Consultant, Grant/Research Support, Other Financial or Material Support, Data safety monitoring board)Johnson & Johnson (Consultant, Grant/Research Support)Moderna (Consultant)Pfizer (Consultant, Grant/Research Support)Sanofi Pasteur (Consultant, Grant/Research Support) Miles Avila, MPH, GStat, AstraZeneca (Employee, Shareholder) Seth Seegobin, PhD, AstraZeneca (Employee, Shareholder) Alison Templeton, PhD, AstraZeneca (Employee, Shareholder) Yuan Yuan, PhD, AstraZeneca (Employee, Shareholder) Philip Ambery, FRCP, AstraZeneca (Employee, Shareholder) Rosalinda H. Arends, PhD, AstraZeneca (Employee, Shareholder) Rohini Beavon, PhD, AstraZeneca (Employee, Shareholder) Karen A. Near, MD, AstraZeneca (Employee, Shareholder) Kelly W. Padilla, PharmD, AstraZeneca (Employee, Shareholder) Konstantina Psachoulia, PhD, AstraZeneca (Employee, Shareholder) Audrey Sharbaugh, PhD, AstraZeneca (Employee, Shareholder) Katie Streicher, PhD, AstraZeneca (Employee, Shareholder) Menelas N. Pangalos, PhD, AstraZeneca (Employee, Shareholder) Mark T. Esser, PhD, AstraZeneca (Employee, Shareholder) Robert A. Gasser, Jr., MD, AstraZeneca (Employee, Shareholder)

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Predictors of first-line antiretroviral therapy failure among adults and adolescents living with HIV/AIDS in a large prevention and treatment program in Nigeria

AIDS Research and Therapy ◽

10.1186/s12981-020-00317-9 ◽

2020 ◽

Vol 17 (1) ◽

Author(s):

Nicaise Ndembi ◽

Fati Murtala-Ibrahim ◽

Monday Tola ◽

Jibreel Jumare ◽

Ahmad Aliyu ◽

...

Keyword(s):

Drug Resistance ◽

Virologic Failure ◽

Resistance Mutations ◽

First Line ◽

Drug Resistance Mutations ◽

Entry Points ◽

The Mean ◽

Living With Hiv ◽

Hiv 1

Abstract Background A substantial number of persons living with HIV (PLWH) in Nigeria do not experience durable viral suppression on first-line antiretroviral therapy (ART). Understanding risk factors for first-line treatment failure informs patient monitoring practices and distribution of limited resources for second-line regimens. We determined predictors of immunologic and virologic failures in a large ART delivery program in Abuja, Nigeria. Methods A retrospective cohort study was conducted at the University of Abuja Teaching Hospital, a tertiary health care facility, using data from February 2005 to December 2014 in Abuja, Nigeria. All PLWH aged ≥ 15 years who initiated ART with at least 6-month follow-up and one CD4 measurement were included. Immunologic failure was defined as a CD4 decrease to or below pre-ART level or persistent CD4 < 100 cells per mm3 after 6 months on ART. Virologic failure (VF) was defined as two consecutive HIV-1 RNA levels > 1000 copies/mL after at least 6 months of ART and enhanced adherence counselling. HIV drug resistance (Sanger sequences) was analyzed using the Stanford HIV database algorithm and scored for resistance to common nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Univariate and multivariate log binomial regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Results Of 12,452 patients followed, a total of 5928 initiated ART with at least 6 months of follow-up and one CD4 measurement. The entry point for 3924 (66.2%) was through the program’s own voluntary counseling and testing (VCT) center, while 1310 (22.1%) were referred from an outside clinic/program, 332 (5.6%) in-patients, and 373 (6.3%) through other entry points including prevention of mother to child transmission (PMTCT) and transferred from other programs. The mean CD4 at enrollment in care was 268 ± 23.7 cells per mm3, and the mean HIV-1 RNA was 3.3 ± 1.3.log10 copies/mL. A total of 3468 (80.5%) received nevirapine (NVP) and 2260 (19.5%) received efavirenz (EFV)—based regimens. A total of 2140 (36.1%) received tenofovir (TDF); 2662 (44.9%) zidovudine (AZT); and 1126 (19.0%) stavudine (d4T). Among those receiving TDF, 45.0% also received emtricitabine (FTC). In a multivariate model, immunologic failure was more common among PLWH with female gender as compared to male [RR (95% CI) 1.22 (1.07–1.40)] and less common among those who entered care at the program’s VCT center as compared to other entry points [0.79 (0.64–0.91)], WHO stage 3/4 as compared to 1/2 [0.19 (0.16–0.22)], or CD4 200 + cells per mm3 as compared to lower [0.19 (0.16–0.22)]. Virologic failure was more common among PLWH who entered care at the program’s VCT center as compared to other entry points [RR (95% CI) 1.45 (1.11–1.91) and those with CD4 < 200 cells per mm3 at entry into care as compared to higher [1.71 (1.36–2.16)]. Of 198 patient-derived samples sequenced during virologic failure, 42 (21%) were wild-type; 145 (73%) carried NNRTI drug resistance mutations; 151 (76.3%) M184I/V; 29 (14.6%) had ≥ 3 TAMs, and 37 (18.7%) had K65R, of whom all were on TDF-containing first-line regimens. Conclusions In this cohort of Nigerian PLWH followed for a period of 9 years, immunologic criteria poorly predicted virologic failure. Furthermore, a subset of samples showed that patients failing ART for extended periods of time had HIV-1 strains harboring drug resistance mutations.

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