Suspected Treatment Failure Research Articles

Neisseria gonorrhoeae treatment failure to the recommended antibiotic regimen-Québec, Canada, 2015-19.

To describe Neisseria gonorrhoeae treatment failure to the recommended antimicrobial regimens (azithromycin, cefixime and ceftriaxone). Our study was a longitudinal analysis of treatment failures from an observational open cohort of gonococcal infection cases collected in Québec, Canada (n = 2547) between September 2015 and December 2019. Epidemiological and clinical data were collected using a self-administered questionnaire, direct case interviews and chart reviews. Antimicrobial susceptibility testing was performed using the agar dilution method. To be retained as a treatment failure, cases must have had (i) a laboratory-confirmed gonococcal infection; (ii) a documented treatment; (iii) a positive test of cure (TOC) performed within a defined period and (iv) no sexual contact (vaginal, oral or anal), even protected with a condom, between the beginning of treatment and the positive TOC. A broader definition, including suspected cases, was also examined. Among 1593 cases where a TOC was performed, 83 had a positive TOC: 11 were retained as treatment failure, and 6 were considered suspected cases (overall = 17/1593; 1.1%). Possible explanations for retained or suspected treatment failure included resistance to the antibiotics used for treatment (n = 1), pharyngeal infection (n = 9, of which 5 had been treated with ceftriaxone and 4 with other regimens); and azithromycin monotherapy (n = 1). Some cases had more than one potential explanation. Treatment failure occurred in 1.1% of cases of Neisseria gonorrhoeae infection for which a TOC was performed, including some cases of pharyngeal infection treated with ceftriaxone.

Comparison of Microscopy, Culture and Molecular Methods for Diagnosing Gonorrhea

Gonorrhea, a sexually transmitted infection caused by Neisseria gonorrhoeae, continues to be a significant global public health concern. The timely and accurate diagnosis of this infectious disease is crucial for its effective management. Traditional methods, especially culture, were historically considered the gold standard for diagnosing gonorrhea. However, the introduction of nucleic acid amplification tests (NAATs), such as Real-Time PCR, has revolutionized diagnostic approaches. Currently, the Center for Disease Control and Prevention (CDC) recommends NAAT as the primary diagnostic method, with culture reserved for specific cases, particularly for testing antimicrobial susceptibility in instances of suspected treatment failure. The International Union against Sexually Transmitted Infections (IUSTI) provides guidelines for the use of NAAT or culture, depending on clinical scenarios. This study conducted a retrospective comparative analysis of various diagnostic methods at the Apex Regional STD Centre in New Delhi, India, spanning from January 1, 2022, to December 31, 2022. Culture, Real-Time PCR, and smear examination were compared for the diagnosis of gonorrhea. A total of 33 samples were included in the analysis, with the following percentages: culture (92.02%), PCR (100%), and smear examination (100%). An intriguing finding was that 7.98% of samples were culture-negative but PCR-positive, highlighting a significant disparity between the two methods. This observation underscores the limitations of relying solely on culture for gonorrhea diagnosis and the potential consequences, including treatment delays, disease transmission, and the development of antibiotic-resistant strains. In summary, this study underscores the critical need for accurate and reliable diagnostic methods for gonorrhea. It emphasizes the evolving diagnostic landscape, with NAATs emerging as essential tools. The findings from multiple studies stress the complementary roles of different diagnostic methods and the necessity of adapting to evolving diagnostic techniques. This research highlights the importance of collaborative approaches to enhance accuracy and address the evolving challenges of gonorrhea diagnosis. Ultimately, the significance of laboratory testing extends beyond individual patient care to broader public health goals and the prevention of sexually transmitted infections.

Treatment factors associated with viral suppression among adolescents on antiretroviral therapy in Kenya

Background: There are approximately 99,159 adolescents living with human immunodeficiency virus in Kenya, with a viral suppression rate of 67%, according to the Joint United Nations Program on HIV/AIDS in 2021 [1] . There are limited studies in Kenya on factors associated with viral load suppression among adolescents. The objectives of this study were to determine the treatment factors associated with viral suppression among adolescents on antiretroviral therapy. Methods: A retrospective cross-sectional analysis of 38,503 HIV-infected adolescents receiving antiretroviral therapy for at least 6 months with a documented viral load result. The data was from routinely collected HIV program data in Kenya that is submitted from comprehensive care centers with electronic medical records to the National Aids and STI Control Program (NASCOP) for the period of January 2018–December 2022. Results: The study population was 38503 HIV-infected adolescents (10–19 years) on antiretroviral therapy. The viral suppression was at 81.2%., higher than the 2021 UNAIDS estimate of 67%. low detectable levels were 88%, low level viremia was 12%, high-risk LLV was 38%, and suspected treatment failure as 62%. Virological suppression with integrase strand transfer inhibitors based regimens – Abacavir and Tenofovir was 81.6% and 86.4%, respectively. The suppression with protease inhibitors based regimens was 70% (highest) and 56.4% (Lowest) Conclusion: The viral suppression among adolescents on antiretroviral therapy was 81.2% lower than the UNAIDS 95/95/95 global target but higher than the 2021 UNAIDS estimate of 67%. There is a need to interrogate the viral suppression in adolescents on protease inhibitors.

Reaching Viral Suppression Among People With HIV With Suspected Treatment Failure who Received Enhanced Adherence Counseling in Southern Nigeria: A Retrospective Analysis.

This study assessed viral load (VL) testing and viral suppression following enhanced adherence counseling (EAC) among people with HIV (PWH) with suspected treatment failure and identified factors associated with persistent viremia. We conducted a retrospective review of electronic medical records of PWH aged 15 years or older who had received antiretroviral therapy (ART) for at least 6 months as of December 2020 and had a high viral load (HVL; ≥1000 copies/mL) across 22 comprehensive HIV treatment facilities in Akwa Ibom State, Nigeria. Patients with HVL were expected to receive 3 EAC sessions delivered in person or virtually and repeat VL testing upon completion of EAC and after documented good adherence. At 6 months post-EAC enrollment, we reviewed the data to determine client uptake of 1 or more EAC sessions, completion of 3 EAC sessions, a repeat viral load (VL) test conducted post-EAC, and persistent viremia with a VL of ≥1000 copies/mL. Selected sociodemographic and clinical variables were analyzed to identify factors associated with persistent viremia using SPSS, version 26. Of the 3257 unsuppressed PWH, EAC uptake was 94.8% (n = 3088), EAC completion was 81.5% (2517/3088), post-EAC VL testing uptake was 75.9% (2344/3088), and viral resuppression was 73.8% (2280/3088). In multivariable analysis, those on ART for <12 months (P ≤ .001) and those who completed EAC within 3 months (P = .045) were less likely to have persistent viremia. An HVL resuppression rate of 74% was achieved, but EAC completion was low. Identification of the challenges faced by PWH with a higher risk of persistent viremia is recommended to optimize the potential benefit of EAC.

Standardized enhanced adherence counseling for improved HIV viral suppression among children and adolescents in Homa Bay and Turkana Counties, Kenya.

Viral suppression is suboptimal among children and adolescents on antiretroviral therapy (ART) in Kenya. We implemented and evaluated a standardized enhanced adherence counseling (SEAC) package to improve viral suppression in children and adolescents with suspected treatment failure in Homa Bay and Turkana. The SEAC package, implemented from February 2019 to September 2020, included: standard procedures operationalizing the enhanced adherence counseling (EAC) process; provider training on psychosocial support and communication skills for children living with HIV and their caregivers; mentorship to providers and peer educators on EAC processes; and individualized case management. We enrolled children and adolescents aged 0 to 19 years with suspected treatment failure (viral load [VL] >1000 copies/mL) who received EAC before standardization as well as those who received SEAC in a pre-post evaluation of the SEAC package conducted in 6 high-volume facilities. Pre-post standardization comparisons were performed using Wilcoxon-Mann-Whitney and Pearson’s chi-square tests at a 5% level of significance. Multivariate logistic regression was performed to identify factors associated with viral resuppression. The study enrolled 741 participants, 595 pre- and 146 post-SEAC implementation. All post-SEAC participants attended at least 1 EAC session, while 17% (n = 98) of pre-SEAC clients had no record of EAC attendance. Time to EAC following the detection of high VL was reduced by a median of 8 days, from 49 (interquartile range [IQR]: 23.0–102.5) to 41 (IQR: 20.0–67.0) days pre- versus post-SEAC (P = .006). Time to completion of at least 3 sessions was reduced by a median of 12 days, from 59.0 (IQR: 36.0–91.0) to 47.5 (IQR: 33.0–63.0) days pre- versus post-SEAC (P = .002). A greater percentage of clients completed the recommended minimum 3 EAC sessions at post-SEAC, 88.4% (n = 129) versus 61.1% (n = 363) pre-SEAC, P < .001. Among participants with a repeat VL within 3 months following the high VL, SEAC increased viral suppression from 34.6% (n = 76) to 52.5% (n = 45), P = .004. Implementation of the SEAC package significantly reduced the time to initiate EAC and time to completion of at least 3 EAC sessions, and was significantly associated with viral suppression in children and adolescents with suspected treatment failure.

Diagnostics to support the eradication of yaws-Development of two target product profiles.

Yaws is targeted for eradication by 2030, using a strategy based on mass drug administration (MDA) with azithromycin. New diagnostics are needed to aid eradication. Serology is currently the mainstay for yaws diagnosis; however, inaccuracies associated with current serological tests makes it difficult to fully assess the need for and impact of eradication campaigns using these tools. Under the recommendation of the WHO Diagnostic Technical Advisory Group (DTAG) for Neglected Tropical Diseases(NTDs), a working group was assembled and tasked with agreeing on priority use cases for developing target product profiles (TPPs) for new diagnostics tools. The working group convened three times and established two use cases: identifying a single case of yaws and detecting azithromycin resistance. One subgroup assessed the current diagnostic landscape for yaws and a second subgroup determined the test requirements for both use cases. Draft TPPs were sent out for input from stakeholders and experts. Both TPPs considered the following parameters: product use, design, performance, configuration, cost, access and equity. To identify a single case of yaws, the test should be able to detect an analyte which confirms an active infection with at least 95% sensitivity and 99.9% specificity. The high specificity was deemed important to avoid a high false positive rate which could result in unnecessary continuation or initiation of MDA campaigns. If used in settings where the number of suspected cases is low, further testing could be considered to compensate for imperfect sensitivity and to improve specificity. The test to detect azithromycin resistance should be able to detect known genetic resistance mutations with a minimum sensitivity and specificity of 95%, with the caveat that all patients with suspected treatment failure should be treated as having resistant yaws and offered alternative treatment. The TPPs developed will provide test developers with guidance to ensure that novel diagnostic tests meet identified public health needs.

Adherence challenges and opportunities for optimizing care through enhanced adherence counseling for adolescents with suspected HIV treatment failure in Kenya

BackgroundAdolescents living with HIV (ALHIV) experience higher mortality and are more likely to have poor antiretroviral therapy (ART) adherence and unsuppressed viral load (VL) compared to adults. Enhanced adherence counseling (EAC) is a client-centered counseling strategy that aims to identify and address barriers to optimal ART use and can be tailored to the unique needs of adolescents. This study aimed to better understand adherence barriers among ALHIV with suspected treatment failure and their experience with EAC to inform future programming.MethodsA qualitative study was conducted in Homa Bay and Turkana counties, Kenya in 2019 with adolescents and caregivers of children and adolescents living with HIV with suspected treatment failure after ≥6 months on ART and who had received ≥1 EAC sessions. Sixteen focus group discussions (FGDs) were conducted; five FGDs each were held with adolescents 12–14 years (n = 48) and 15–19 years (n = 36). Caregivers (n = 52) participated in six FGDs. Additionally, 17 healthcare workers providing pediatric/adolescent HIV services participated in in-depth interviews. Audio recordings were transcribed and translated from Kiswahili or Dholuo into English and coded using MAXQDA software. Data were thematically analyzed by participant group.ResultsParticipants identified adolescents’ fear of being stigmatized due to their HIV status and their relationship with and level of support provided by caregivers. This underpinned and often undermined adolescents’ ART-taking behavior and progress towards more independent medication management. Adolescents were generally satisfied with EAC and perceived it to be important in improving adherence and reducing VL. However, problems were noted with facility-based, individual EAC counseling, including judgmental attitudes of providers and difficulties traveling to and keeping EAC clinic appointments. Participant-suggested improvements to EAC included peer support groups in addition to individual counseling, allowing for greater flexibility in the timing and location of sessions and greater caregiver involvement.ConclusionsThe findings provide opportunities to better tailor EAC interventions to promote improved ALHIV adherence and caregiver-supported disease management. Multi-prong EAC interventions that include peer-led and community approaches and target adolescent and caregiver treatment literacy may improve EAC delivery, address issues contributing to poor adherence, and position adolescents to achieve viral suppression.Trial registrationClinicalTrials.gov: NCT04915469.

Subjective Outcome after Discontinuation of Botulinum Toxin-A Detrusor Injection for Lower Urinary Tract Disorders: The Majority Suffers!

Introduction: According to the EAU guidelines, botulinum toxin type A (BoNT-A) detrusor injections are one of the last options in the management of overactive bladder before opting for invasive surgery. So far, there have been no studies dedicated exclusively to such patients who have undergone this treatment and in whom this treatment has presumably failed. From the patient’s point of view, there are questions regarding what reasons led to discontinuation, how patients perceive their BoNT-A treatment in hindsight, what further treatment do these patients receive, and how satisfied such patients are with their current situation. Methods: A database of clinical and inpatient records was searched, and 695 records from 406 patients were identified in a 6-year period, who had received BoNT-A detrusor injections. There were 255 cases that were treated with BoNT-A injections into the detrusor muscle where the therapy was not repeated for at least 12 months (= suspected treatment failures). Interviews with these patients were conducted by mail and phone, and 115 questionnaires could be included in the analysis. Results: From the subjective and prospective points of view of the patients, the most common reason for stopping the therapy was a lack of efficacy of BoNT-A injections (39.1%). For 26.1% of all patients, side effects were a reason for dissatisfaction but never a reason for discontinuation. For 10.4%, the reason for stopping the therapy was spontaneous improvement. 35.6% of the respondents had no follow-up therapy. Those with a follow-up therapy mostly returned to anticholinergic treatment (33%). Operations were carried out on 13%, of which about half were highly invasive. For 71.3% of those patients, who were under any current therapy, this therapy led to no improvement or only some improvement of the symptoms. Surprisingly, 50.4% of the respondents would choose to undergo BoNT-A injection therapy again. Discussion/Conclusion: The majority of patients who did not continue BoNT-A therapy are still suffering from lower urinary tract symptoms. The lack of efficacy was the reason for stopping the BoNT-A injection therapy for less than half of the patients. From the patient’s point of view, reasons other than the effectiveness also seem to be relevant in the choice of the treatment. When changing therapy, most returned to drug treatment. However, for the majority of patients with any follow-up therapy, this therapy could not improve the symptoms.

Enhancing U.S. Local, State, and Federal Preparedness Through Simulated Interactive Tabletop Exercises of a Mock Antibiotic-Resistant Gonorrhea Outbreak, 2018-2019.

Responding effectively to outbreaks of antibiotic-resistant gonorrhea (ARGC) in the future will likely prove challenging. Tabletop exercises (TTXs) may assist local, state, and federal public health officials evaluate existing ARGC outbreak response plans, strengthen preparedness and response effectiveness, and identify critical gaps to address before an outbreak. In 2018 to 2019, Centers for Disease Control and Prevention (CDC) collaborated with state partners to develop and implement TTXs to simulate a public health emergency involving an ARGC outbreak. Before the TTXs, 2 state-local health department pairs developed ARGC outbreak response plans. During each 1-day exercise (in Indiana and Illinois), participants discussed roles, clinical management, public health response, and communication based on predeveloped response plans. Observers identified outbreak response strengths and gaps, and participants completed feedback forms. Forty-one (Illinois) and 48 people (Indiana) participated in each TTX, including sexually transmitted disease clinical staff, laboratorians, public health infectious disease program staff, and CDC observers. Strengths and gaps varied by jurisdiction, but identified gaps included: (1) local access to gonorrhea culture and timely antimicrobial susceptibility testing, (2) protocols for clinical management of suspected treatment failures, (3) communication plans, and (4) clarity regarding state and local responsibilities. The CDC observers identified opportunities to provide national-level technical assistance, foster local antimicrobial susceptibility testing, and develop further response guidance. Tabletop exercises summary reports were used to guide modifications to local response plans to address gaps. The TTXs allowed participants to practice responding to a simulated public health emergency and may have enhanced local response capacity. Centers for Disease Control and Prevention made TTX implementation materials publicly available.

High failure rates of protease inhibitor-based antiretroviral treatment in rural Tanzania - A prospective cohort study.

BackgroundPoor adherence to antiretroviral drugs and viral resistance are the main drivers of treatment failure in HIV-infected patients. In sub-Saharan Africa, avoidance of treatment failure on second-line protease inhibitor therapy is critical as treatment options are limited.MethodsIn the prospective observational study of the Kilombero & Ulanga Antiretroviral Cohort in rural Tanzania, we assessed virologic failure (viral load ≥1,000 copies/mL) and drug resistance mutations in bio-banked plasma samples 6–12 months after initiation of a protease inhibitor-based treatment regimen. Additionally, viral load was measured before start of protease inhibitor, a second time between 1–5 years after start, and at suspected treatment failure in patients with available bio-banked samples. We performed resistance testing if viral load was ≥1000 copies/ml. Risk factors for virologic failure were analyzed using logistic regression.ResultsIn total, 252 patients were included; of those 56% were female and 21% children. Virologic failure occurred 6–12 months after the start of a protease inhibitor in 26/199 (13.1%) of adults and 7/53 of children (13.2%). The prevalence of virologic failure did not change over time. Nucleoside reverse transcriptase inhibitors drug resistance mutation testing performed at 6–12 months showed a positive signal in only 9/16 adults. No cases of resistance mutations for protease inhibitors were seen at this time. In samples taken between 1–5 years protease inhibitor resistance was demonstrated in 2/7 adults. In adult samples before protease inhibitor start, resistance to nucleoside reverse transcriptase inhibitors was detected in 30/41, and to non-nucleoside reverse-transcriptase inhibitors in 35/41 patients. In 15/16 pediatric samples, resistance to both drug classes but not for protease inhibitors was present.ConclusionOur study confirms high early failure rates in adults and children treated with protease inhibitors, even in the absence of protease inhibitors resistance mutations, suggesting an urgent need for adherence support in this setting.

795P - A prospective observational study on the optimal maintenance strategy in HER2-positive advanced gastric cancer treated with trastuzumab based therapy

BackgroundTrastuzumab plus chemotherapy is an effective therapy in HER2 positive advanced gastric cancer (AGC). However, the optimal maintenance treatment in patients benefited from the initial therapy remains unclear. MethodsThis was a prospective observational study in patients with untreated HER2 positive AGC. After 6 cycles of trastuzumab combined with chemotherapy, patients who had not progression disease were divided into two arms: trastuzumab monotherapy (arm A) and trastuzumab plus single chemo-agent derived from the initial chemotherapy (arm B). Patients received CT/MRI for response evaluation every 8 weeks or anytime suspected treatment failure. Adverse effects and costs were recorded every cycles. The primary end point was overall survival (OS), secondary end points included progression free survival (PFS), cost-effectiveness ratio per progression-free life-year saved (PF-LYS) and safety. ResultsIn total, 115 HER2 positive AGC treated with trastuzumab based first line chemotherapy were registered. After 6 cycles, 78 patients (6 CR, 46 PR, 26 SD) were eligible: 30 patients were in arm A accepted trastuzumab monotherapy as their maintenance therapy, 48 were in arm B. The clinicalpathological characteristics of two arms were well balanced. There was no significant differences of median OS (16.5 vs 20.0 months, P=0.169) or PFS (7.9 vs 11.0, P=0.892) between two arms. Adverse effects were also similar including cardiac safety. Subgroup analysis showed chemotherapy additional to trastuzumab benefited on OS in patients who had stable disease (SD) of response (HR: 0.084, P=0.004), without liver metastasis (HR:0.271, P=0.008) or less than 2 organs of distance metastatic (HR: 0.263, P=0.005). The average cost per patients in arm A was 153,137 RMB and 165,195 RMB in arm B. While, PF-LYS in arm A was 1.29 times higher than arm B (19,384 vs 15,018 RMB). ConclusionsBoth maintenance therapy strategies are optional for patients who benefit from the initial 6 cycles of therapy. However, there is an advantage on PF-LYS in patients treated with trastuaumab plus single chemotherapy agent. Furthermore, continual single-chemotherapy agent was beneficial in Patients with certain characterisitic. Legal entity responsible for the studyZhongshan Hospital, Fudan University. FundingShanghai Science and Technology Funds 1741195400. DisclosureAll authors have declared no conflicts of interest.

Drug Use Evaluation (DUE) of Ceftriaxone in Mubende Regional Referral Hospital, Uganda: A Cross-Sectional Survey

Introduction: Ceftriaxone is a third generation cephalosporin recommended as first line treatment option for a number of diseases in Uganda. However, the National Drug Authority has in the recent past received complaints of suspected treatment failure from clinicians who use different brands of ceftriaxone in Uganda. The main aim of the study was to document the treatment outcome following use of ceftriaxone and evaluating the use of ceftriaxone against the current treatment guidelines in Uganda.

Treatment Failure in Patients Receiving Direct Oral Anticoagulants: Clinical Management and Outcomes from a Single-Center Review of 59 Consecutive Patients

Several direct oral anticoagulants (DOACs) have been developed that dose-dependently inhibit thrombin or activated factor X and offer potential advantages over vitamin K antagonists (VKAs), such as rapid onset and offset of action, absence of an effect of dietary vitamin K intake on their activity, and fewer drug interactions. DOACs have gained in popularity for the treatment and prevention of recurrence of venous thromboembolism (VTE), and the prevention of stroke/systemic embolism in patients with non-valvular atrial fibrillation (AF). However, the lack of routine monitoring means that their pharmacodynamic effect is rarely determined, leaving patients at potential risk of under- or over-anticoagulation. If adequately anticoagulated, the occurrence of thromboembolism (whether primary or recurrent) constitutes treatment failure; this has been reported in approximately 2% of patients in large DOAC clinical trials. The optimal management of such an event occurring with a DOAC remains unclear.In this study, we sought to characterise DOAC treatment failures in our institution, and to rationalise the subsequent anticoagulation strategies in this setting. All VTE patients starting a DOAC at our centre are followed in a consultant-led clinic. Cases of suspected treatment failure are also referred from other specialities and primary care. Between September 2014 and May 2018, we identified 59 consecutive patients (male/female: 34/25) in whom a DOAC treatment failure was diagnosed, including non-resolution of the presenting complaint, and recurrence of or a new thrombotic event. Patient mean age at DOAC initiation was 56 (23-89) years. The median time from DOAC initiation to failure detection was 42 (3-1055) days. 36/59 (61%) patients were receiving a DOAC for treatment of acute VTE, while 19/59 (32%) patients were treated for the prevention of recurrent VTE and 4/59 (7%) patients were on a DOAC for atrial fibrillation. 4 (7%) patients had a thrombophilia background while 5 patients (8%) had an active cancer diagnosis.On recognition of DOAC failure, 34 patients were on apixaban 5mg bd; 7 were on apixaban 2.5mg bd; 15 failed on rivaroxaban 20mg od; and 1 patient failed on each of rivaroxaban 10mg od, dabigatran 110 mg bd and edoxaban 30 mg od. All patients were compliant with their medication. For apixaban 5mg, the median time to failure was 29 (3-551) days; for apixaban 2.5mg it was 140 (26-441) days; for rivaroxaban it was 82 (20-1055) days. Two thirds of patients (39/59) were switched over to therapeutic low-molecular-weight heparin (LMWH), 6/59 patients (10%) were initiated to warfarin with appropriate LMWH bridging, and 11/59 patients (19%) were switched to an alternative DOAC. 3 patients (5%) continued their existing anticoagulant. Most patients (33/39, 85%) initially switched to LMWH following a median time on parenteral anticoagulation of 57 (14-472) days were subsequently switched to oral anticoagulants: 18% to warfarin, 82% to a DOAC. By the end of follow-up, 37/59 patients (63%) were taking a DOAC, including 8 patients who had been switched back to the anticoagulation regimen that failed at the outset, and a further 4 patients returned to the same drug at a higher dose. Of the remainder, 8 patients (14%) were taking a VKA, 8 patients (14%) remained on LMWH, 1 patient was on aspirin and 5 patients (8%) had stopped their anticoagulation treatment. A diagnosis of post-thrombotic leg was made in 15/36 (42%) patients with acute lower limb VTE who failed their DOAC.There is currently a lack of guidance on how to manage patients who fail initial treatment with a DOAC. To the best of our knowledge our study is the first to record the clinical experience in this challenging patient group. Based on our findings, a common strategy is to switch to therapeutic LMWH. After a successful period of parenteral therapy, most patients were switched back to oral treatment, typically another DOAC. Still this did not seem to prevent post-thrombotic syndrome in 42% of patients who were initially diagnosed with acute lower limb thrombosis.Treatment failure is a recognised risk of nearly all medical therapies including DOACs. It is therefore not surprising to encounter such patients in day-to-day practice. The growth in the number of anticoagulant choices has made it more difficult to know how to respond when one fails. As the use of DOACs continues to expand, this problem - and the need for an evidence-based solution - is likely to grow. DisclosuresSmith:BMS: Honoraria, Speakers Bureau. Beale:Daiichi Sankyo: Speakers Bureau. Kartsios:Bayer: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Speakers Bureau; Boehringer Inglelheim: Consultancy, Honoraria, Speakers Bureau.

Factors Associated with Virological Non-suppression among HIV-Positive Patients on Antiretroviral Therapy in Uganda, August 2014\u2013July 2015

BackgroundDespite the growing number of people on antiretroviral therapy (ART), there is limited information about virological non-suppression and its determinants among HIV-positive (HIV+) individuals enrolled in HIV care in many resource-limited settings. We estimated the proportion of virologically non-suppressed patients, and identified the factors associated with virological non-suppression.MethodsWe conducted a descriptive cross-sectional study using routinely collected program data from viral load (VL) samples collected across the country for testing at the Central Public Health Laboratories (CPHL) in Uganda. Data were generated between August 2014 and July 2015. We extracted data on socio-demographic, clinical and VL testing results. We defined virological non-suppression as having ≥1000 copies of viral RNA/ml of blood for plasma or ≥5000 copies of viral RNA/ml of blood for dry blood spots. We used logistic regression to identify factors associated with virological non-suppression.ResultsThe study was composed of 100,678 patients; of these, 94,766(94%) were for routine monitoring, 3492(4%) were suspected treatment failures while 1436(1%) were repeat testers after suspected failure. The overall proportion of non-suppression was 11%. Patients on routine monitoring registered the lowest (10%) proportion of non-suppressed patients. Virological non-suppression was higher among suspected treatment failures (29%) and repeat testers after suspected failure (50%). Repeat testers after suspected failure were six times more likely to have virological non-suppression (ORadj = 6.3, 95%CI = 5.5–7.2) when compared with suspected treatment failures (ORadj = 3.3, 95%CI = 3.0–3.6). The odds of virological non-suppression decreased with increasing age, with children aged 0–4 years (ORadj = 5.3, 95%CI = 4.6–6.1) and young adolescents (ORadj = 4.1, 95%CI = 3.7–4.6) registering the highest odds. Poor adherence (ORadj = 3.4, 95%CI = 2.9–3.9) and having active TB (ORadj = 1.9, 95%CI = 1.6–2.4) increased the odds of virological non-suppression. However, being on second/third line regimens (ORadj = 0.86, 95%CI = 0.78–0.95) protected patients against virological non-suppression.ConclusionYoung age, poor adherence and having active TB increased the odds of virological non-suppression while second/third line ART regimens were protective against non-suppression. We recommend close follow up and intensified targeted adherence support for repeat testers after suspected failure, children and adolescents.

Factors Associated with Virologic Failure Amongst Adults on Antiretroviral Therapy in Nyanza Region, Kenya.

Background: Access to Antiretroviral Therapy (ART) to patients living with HIV (PLHIV) has markedly improved especially in Sub-Saharan Africa. The goal of ART is to ensure viral suppression and prevention of treatment failure which may be clinical, immunological or virologic. Viral suppression is important to better outcomes of treatment. This study aimed at determining the factors associated with virologic failure amongst patients with clinical and/or immunologic failure. Methodology: This was a cross sectional study based on a retrospective review of viral load test electronic data of patients with immunologic and/or clinical treatment failure. A total of 320 randomly selected records of patients tested for viral load were included in the analysis. Statistical Package for Social Sciences (SPSS) was used to analyze the data. Descriptive statistics such as frequency and median was used to describe demographic and clinical characteristics of patients. Univariate, bivariate and multivariate analysis was done to determine the factors associated with virologic failure. Odd ratio was calculated. Results: Among patients with suspected ART treatment failure and viral load test requested to confirm failure, the median age was 39 years; 186 (58.1%) were female; 173 (54.1%) were aged ≤ 40; only 6 (1.9%) had missed ARVs for a period of more than 2 weeks; 31 (9.7%) had missed ARVs due to missing clinic visits; majority (30.6%) of the patients had been on ARVs for more than 4 years; (96.9%) of the patients were on first line ART regimen; 208 (65.2%) had baseline CD4 less than 100 cells/mm 3 ; baseline median CD4 of 152 cells/mm 3 , peak median was 336 cells/mm 3 and median CD4 at the time of viral load request was 170 cells/mm 3 . Age younger than 40 years was associated with virologic failure (AOR 2.33, p value 0.0011). Other patient characteristics were not associated with virologic failure. Conclusion: Key factor associated with virologic failure amongst patients with suspected treatment failure is age lower than 40 years. Recommendation:Focus on patients younger than 40 years should be prioritized and comprehensive and focused services friendly to the young need to be strengthened at the health facility level.

Retention in care among HIV-positive patients initiating second-line antiretroviral therapy: a retrospective study from an Ethiopian public hospital clinic

BackgroundAccess to second-line antiretroviral therapy (ART) for HIV-positive patients remains limited in sub-Saharan Africa. Furthermore, outcomes of second-line ART may be compromised by mortality and loss to follow-up (LTFU).ObjectiveTo determine retention in care among patients receiving second-line ART in a public hospital in Ethiopia, and to investigate factors associated with LTFU among adults and adolescents.DesignHIV-positive persons with documented change of first-line ART to a second-line regimen were retrospectively identified from hospital registers, and data were collected at the time of treatment change and subsequent clinic visits. Baseline variables for adults and adolescents were analyzed using multivariate Cox proportional hazards models comparing subjects remaining in care and those LTFU (defined as a missed appointment of ≥90 days).ResultsA total of 383 persons had started second-line ART (330 adults/adolescents; 53 children) and were followed for a median of 22.2 months (the total follow-up time was 906 person years). At the end of study follow-up, 80.5% of patients remained in care (adults and adolescents 79.8%; children 85.7%). In multivariate analysis, LTFU among adults and adolescents was associated with a baseline CD4 cell count <100 cells/mm3 and a first-line regimen failure that was not confirmed by HIV RNA testing.ConclusionsAlthough retention in care during second-line ART in this cohort was satisfactory, and similar to that reported from first-line ART programs in Ethiopia, our findings suggest the benefit of earlier recognition of patients with first-line ART failure and confirmation of suspected treatment failure by viral load testing.

Management of Gonorrhea in Adolescents and Adults in the United States.

Gonorrhea is the second most commonly reported notifiable disease in the United States and is associated with serious health sequelae, including pelvic inflammatory disease, infertility, and ectopic pregnancy. Treatment for gonorrhea has been complicated by antimicrobial resistance. Neisseria gonorrhoeae has developed resistance to each of the antimicrobials that were previously recommended as first-line treatment regimens, and current treatment options are severely limited. This article summarizes the key questions and data that were discussed at the Sexually Transmitted Diseases (STD) Treatment Guidelines Expert Consultation meeting in April 2013, and the rationale for the 2015 Centers for Disease Control and Prevention STD treatment guidelines for gonococcal infections in adolescents and adults. Key issues addressed include whether to change the dosage of ceftriaxone and azithromycin used in the recommended dual treatment regimen, whether to continue to list dual treatment with cefixime and azithromycin as an alternative treatment regimen, and management of gonococcal infections in persons with severe cephalosporin allergy or suspected treatment failure.

Characterization of HIV drug resistance mutations among patients failing first-line antiretroviral therapy from a tertiary referral center in Lusaka, Zambia.

In settings of resource constraint, an understanding of HIV drug resistance can guide antiretroviral therapy (ART) at switch to second-line therapy. To determine the prevalence of such HIV drug resistance mutations (HIV DRM), we used an in-house sequencing assay in the pol gene (protease and partial reverse transcriptase) in a cohort of patients suspected of failing a first-line regimen, which in Zambia comprises two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI). Our analysis cohort (n = 68) was referred to the University Teaching Hospital in Lusaka from November 2009 to October 2012. Median duration on first-line ART to suspected treatment failure was 3.2 years (IQR 1.7-4.7 years). The majority of patients (95%) harbored HIV-1 subtype C virus. Analysis of reverse transcriptase revealed M184V (88%), K103N/S (32%), and Y181C/I/V (41%) DRMs, with the latter conferring reduced susceptibility to the salvage therapy candidates etravirine and rilpivirine. Three patients (5%) had major protease inhibitor (PI) resistance mutations: all three had the V82A mutation, and one patient (Clade J virus) had a concurrent M46I, Q58E, and L76V DRM. HIV-1 genotyping revealed major and minor DRMs as well as high levels of polymorphisms in subtype C isolates from patients failing first-line antiretroviral therapy. Closer monitoring of DRM mutations at first-line failure can inform clinicians about future options for salvage therapy.

Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel.

New data and antiretroviral regimens expand treatment choices in resource-rich settings and warrant an update of recommendations to treat adults infected with human immunodeficiency virus (HIV). To provide updated treatment recommendations for adults with HIV, emphasizing when to start treatment; what treatment to start; the use of laboratory monitoring tools; and managing treatment failure, switches, and simplification. An International Antiviral Society-USA panel of experts in HIV research and patient care considered previous data and reviewed new data since the 2012 update with literature searches in PubMed and EMBASE through June 2014. Recommendations and ratings were based on the quality of evidence and consensus. Antiretroviral therapy is recommended for all adults with HIV infection. Evidence for benefits of treatment and quality of available data increase at lower CD4 cell counts. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (NRTIs; abacavir/lamivudine or tenofovir disoproxil fumarate/emtricitabine) and a third single or boosted drug, which should be an integrase strand transfer inhibitor (dolutegravir, elvitegravir, or raltegravir), a nonnucleoside reverse transcriptase inhibitor (efavirenz or rilpivirine) or a boosted protease inhibitor (darunavir or atazanavir). Alternative regimens are available. Boosted protease inhibitor monotherapy is generally not recommended, but NRTI-sparing approaches may be considered. New guidance for optimal timing of monitoring of laboratory parameters is provided. Suspected treatment failure warrants rapid confirmation, performance of resistance testing while the patient is receiving the failing regimen, and evaluation of reasons for failure before consideration of switching therapy. Regimen switches for adverse effects, convenience, or to reduce costs should not jeopardize antiretroviral potency. After confirmed diagnosis of HIV infection, antiretroviral therapy should be initiated in all individuals who are willing and ready to start treatment. Regimens should be selected or changed based on resistance test results with consideration of dosing frequency, pill burden, adverse toxic effect profiles, comorbidities, and drug interactions.

Effectiveness of targeted viral load strategy in a public health HIV/AIDS programme

Methods Data of patients referred to School of Tropical Medicine, Kolkata for suspected treatment failure (TF) was analyzed for the period of December2008 to November2013 to ascertain the positive predictive value (PPV) of immunologic and/or clinical parameter for confirming virologic failure (VF) and to observe the short term outcome of secondline treatment. Paired ttest was used for data analysis.