Costs of integrating cervical cancer screening at an HIV clinic in Kenya.

OBJECTIVE: To estimate the societal-level costs of integrating cervical cancer screening into HIV clinics in Nairobi, Kenya. METHODS: A cross-sectional micro-costing study was performed at Coptic Hope Center for Infectious Diseases and Kenyatta National Hospital, Kenya, between July 1 and October 31, 2014. To estimate direct medical, non-medical, and indirect costs associated with screening, a time-and-motion study was performed, and semi-structured interviews were conducted with women aged at least 18 years attending the clinic for screening during the study period and with clinic staff who had experience relevant to cervical cancer screening. RESULTS: There were 148 patients and 23 clinic staff who participated in interviews. Visual inspection with acetic acid was associated with the lowest estimated marginal per-screening costs ($3.30), followed by careHPV ($18.28), Papanicolaou ($24.59), and Hybrid Capture 2 screening ($31.15). Laboratory expenses were the main cost drivers for Papanicolaou and Hybrid Capture 2 testing ($11.61 and $16.41, respectively). Overhead and patient transportation affected the costs of all methods. Indirect costs were cheaper for single-visit screening methods ($0.43 per screening) than two-visit screening methods ($2.88 per screening). CONCLUSIONS: Integrating cervical cancer screening into HIV clinics would be cost-saving from a societal perspective compared with non-integrated screening. These findings could be used in cost-effectiveness analyses to assess incremental costs per clinical outcome in an integrated setting.

Misclassification of Antiretroviral Treatment Failure Using WHO 2006 and 2010/2013 Immunologic Criteria in HIV-Infected Children and Adolescents in Western Kenya.

We evaluated treatment failure misclassification in human immunodeficiency virus-infected Kenyan children whose targeted viral loads were determined after suspected immunologic/clinical failure according to 2006 and 2010/2013 World Health Organization guidelines. The misclassification rate was 21% for the 2006 guidelines and 46% for the 2010/2013 guidelines, which supports current recommendations for routine viral load monitoring but not necessarily the proposed CD4 thresholds.

Active Surveillance versus Spontaneous Reporting for First-Line Antiretroviral Medicines in Namibia: A Cost-Utility Analysis.

INTRODUCTION: Active surveillance pharmacovigilance is a systematic approach to medicine safety assessment and health systems strengthening, but has not been widely implemented in low- and middle-income countries. This study aimed to assess the cost effectiveness of a national active surveillance pharmacovigilance system for highly active antiretroviral therapy (HAART) compared with the existing spontaneous reporting system in Namibia. METHODS: A cost-utility analysis from a governmental perspective compared active surveillance pharmacovigilance to spontaneous reporting. Data from a sentinel site active surveillance program in Namibia from August 2012 to April 2013 was projected to all HIV-infected adults initiating HAART in Namibia. Costs (pharmacovigilance program, HAART, adverse event [AE] treatment), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs, dollars/QALY) were evaluated. Analysis was completed for (i) cohort analysis: a single cohort beginning HAART in 1 year in Namibia followed over their remaining lifetime, and (ii) population analysis: patients continued to enter and leave care and treatment over 10 years. RESULTS: For the cohort analysis, totals were US$21,267,902 (2015 US dollars) and 116,224 QALYs for care and treatment under active surveillance pharmacovigilance versus US$15,257,381 and 116,122 QALYs for care and treatment under spontaneous reporting pharmacovigilance, resulting in an ICER of US$58,867/QALY for active surveillance compared with spontaneous reporting pharmacovigilance. The population analysis ICER was US$4989/QALY. Results were sensitive to quality of life associated with AEs. CONCLUSION: Active surveillance pharmacovigilance was projected to be highly cost effective to improve treatment for HIV in Namibia. Active surveillance pharmacovigilance may be valuable to improve lives of HIV patients and more efficiently allocate health resources in Namibia.

Sentinel site active surveillance of safety of first-line antiretroviral medicines in Namibia.

PURPOSE: Active surveillance pharmacovigilance systems better estimate the burden of adverse events (AEs) and can generate useful information on risk factors of AEs for more effective medicine use, especially in conjunction with introduction of new medicines and/or changes in treatment guidelines. This project aimed to implement an active surveillance pilot program for first-line antiretroviral therapy (ART) at sentinel sites in Namibia. METHODS: Sentinel sites were outpatient ART clinics at the Windhoek Central Hospital and Katutura Intermediate Hospital. An active surveillance data collection form was developed and placed into patient charts. HIV+ adults naïve to ART were enrolled. Physicians recorded ART and health information during each follow-up visit, including presence or absence of AEs. RESULTS: A total of 413 patients were included from August 2012 to April 2013. Average age was 37 years; 51% of patients were at WHO clinical stage 1; and mean baseline CD4 count was 216. The most common ART regimen was tenofovir/lamivudine/nevirapine. Presence or absence of AEs was recorded in active surveillance forms for 94% of first follow-up visits. In total, 66 patients experienced 119 AEs of any severity. Incidence of experiencing at least one AE was 33/100 person-years. Most common AEs were rash and abdominal pain. On active surveillance forms, demographic variables were missing in 14% of patients, and follow-up visits were recorded for 82% of patients. CONCLUSIONS: Completeness of AE recording on active surveillance forms was high. With improved logistical considerations, such as incorporation of active surveillance forms into medical records, long-term active surveillance programs could be successful. Copyright © 2016 John Wiley & Sons, Ltd.

The potential cost-effectiveness of the Diamondback 360® Coronary Orbital Atherectomy System for treating de novo, severely calcified coronary lesions: an economic modeling approach.

BACKGROUND: Patients who undergo percutaneous coronary intervention (PCI) for severely calcified coronary lesions have long been known to have worse clinical and economic outcomes than patients with no or mildly calcified lesions. We sought to assess the likely cost-effectiveness of using the Diamondback 360(®) Orbital Atherectomy System (OAS) in the treatment of de novo, severely calcified lesions from a health-system perspective. METHODS AND RESULTS: In the absence of a head-to-head trial and long-term follow up, cost-effectiveness was based on a modeled synthesis of clinical and economic data. A cost-effectiveness model was used to project the likely economic impact. To estimate the net cost impact, the cost of using the OAS technology in elderly (⩾ 65 years) Medicare patients with de novo severely calcified lesions was compared with cost offsets. Elderly OAS patients from the ORBIT II trial (Evaluate the Safety and Efficacy of OAS in Treating Severely Calcified Coronary Lesions) [ClinicalTrials.gov identifier: NCT01092426] were indirectly compared with similar patients using observational data. For the index procedure, the comparison was with Medicare data, and for both revascularization and cardiac death in the following year, the comparison was with a pooled analysis of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI)/Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trials. After adjusting for differences in age, gender, and comorbidities, the ORBIT II mean index procedure costs were 17% (p < 0.001) lower, approximately US$2700. Estimated mean revascularization costs were lower by US$1240 in the base case. These cost offsets in the first year, on average, fully cover the cost of the device with an additional 1.2% cost savings. Even in the low-value scenario, the use of the OAS is cost-effective with a cost per life-year gained of US$11,895. CONCLUSIONS: Based on economic modeling, the recently approved coronary OAS device is projected to be highly cost-effective for patients who undergo PCI for severely calcified lesions.

The clinical and cost burden of coronary calcification in a Medicare cohort: An economic model to address under-reporting and misclassification.

BACKGROUND: Coronary artery calcification (CAC) is a well-established risk factor for the occurrence of adverse ischemic events. However, the economic impact of the presence of CAC is unknown. OBJECTIVES: Through an economic model analysis, we sought to estimate the incremental impact of CAC on medical care costs and patient mortality for de novo percutaneous coronary intervention (PCI) patients in the 2012 cohort of the Medicare elderly (≥65) population. METHODS: This aggregate burden-of-illness study is incidence-based, focusing on cost and survival outcomes for an annual Medicare cohort based on the recently introduced ICD9 code for CAC. The cost analysis uses a one-year horizon, and the survival analysis considers lost life years and their economic value. RESULTS: For calendar year 2012, an estimated 200,945 index (de novo) PCI procedures were performed in this cohort. An estimated 16,000 Medicare beneficiaries (7.9%) were projected to have had severe CAC, generating an additional cost in the first year following their PCI of $3500, on average, or $56 million in total. In terms of mortality, the model projects that an additional 397 deaths would be attributable to severe CAC in 2012, resulting in 3770 lost life years, representing an estimated loss of about $377 million, when valuing lost life years at $100,000 each. CONCLUSIONS: These model-based CAC estimates, considering both moderate and severe CAC patients, suggest an annual burden of illness approaching $1.3 billion in this PCI cohort. The potential clinical and cost consequences of CAC warrant additional clinical and economic attention not only on PCI strategies for particular patients but also on reporting and coding to achieve better evidence-based decision-making.

HIV-1 RNA levels and antiretroviral drug resistance in blood and non-blood compartments from HIV-1-infected men and women enrolled in AIDS clinical trials group study A5077.

BACKGROUND: Detectable HIV-1 in body compartments can lead to transmission and antiretroviral resistance. Although sex differences in viral shedding have been demonstrated, mechanisms and magnitude are unclear. We compared RNA levels in blood, genital-secretions and saliva; and drug resistance in plasma and genital-secretions of men and women starting/changing antiretroviral therapy (ART) in the AIDS Clinical Trials Group (ACTG) 5077 study. METHODS: Blood, saliva and genital-secretions (compartment fluids) were collected from HIV-infected adults (≥ 13 years) at 14 United-States sites, who were initiating or changing ART with plasma viral load (VL) ≥ 2,000 copies/mL. VL testing was performed on all compartment fluids and HIV resistance genotyping on plasma and genital-secretions. Spearman rank correlations were used to evaluate concordance and Fisher's and McNemar's exact tests to compare VL between sexes and among compartments. RESULTS: Samples were available for 143 subjects; 36% treated (23 men, 29 women) and 64% 'untreated' (40 men, 51 women). RNA detection was significantly more frequent in plasma (100%) than genital-secretions (57%) and saliva (64%) (P<0.001). A higher proportion of men had genital shedding versus women (78% versus 41%), and RNA detection was more frequent in saliva versus genital-secretions in women when adjusted for censoring at the limit of assay detection. Inter-compartment fluid VL concordance was low in both sexes. In 22 (13 men, 9 women) paired plasma-genital-secretion genotypes from treated subjects, most had detectable resistance in both plasma (77%) and genital-secretions (68%). Resistance discordance was observed between compartments in 14% of subjects. CONCLUSIONS: HIV shedding and drug resistance detection prior to initiation/change of ART in ACTG 5077 subjects differed among tissues and between sexes, making the gold standard blood-plasma compartment assessment not fully representative of HIV at other tissue sites. Mechanisms of potential sex-dependent tissue compartmentalization should be further characterized to aid in optimizing treatment and prevention of HIV transmission. TRIAL REGISTRATION: ClinicalTrials.gov NCT00007488.

Antiretroviral treatment interruptions induced by the Kenyan postelection crisis are associated with virological failure.

BACKGROUND: Antiretroviral treatment interruptions (TIs) cause suboptimal clinical outcomes. Data on TIs during social disruption are limited. METHODS: We determined effects of unplanned TIs after the 2007-2008 Kenyan postelection violence on virological failure, comparing viral load (VL) outcomes in HIV-infected adults with and without conflict-induced TI. RESULTS: Two hundred and one patients were enrolled, median 2.2 years after conflict and 4.3 years on treatment. Eighty-eight patients experienced conflict-related TIs and 113 received continuous treatment. After adjusting for preconflict CD4, patients with TIs were more likely to have detectable VL, VL >5,000 and VL >10,000. CONCLUSIONS: Unplanned conflict-related TIs are associated with increased likelihood of virological failure.

Capacity building and predictors of success for HIV-1 drug resistance testing in the Asia-Pacific region and Africa.

BACKGROUND: The TREAT Asia Quality Assessment Scheme (TAQAS) was developed as a quality assessment programme through expert education and training, for laboratories in the Asia-Pacific and Africa that perform HIV drug-resistance (HIVDR) genotyping. We evaluated the programme performance and factors associated with high-quality HIVDR genotyping. METHODS: Laboratories used their standard protocols to test panels of human immunodeficiency virus (HIV)-positive plasma samples or electropherograms. Protocols were documented and performance was evaluated according to a newly developed scoring system, agreement with panel-specific consensus sequence, and detection of drug-resistance mutations (DRMs) and mixtures of wild-type and resistant virus (mixtures). High-quality performance was defined as detection of ≥95% DRMs. RESULTS: Over 4.5 years, 23 participating laboratories in 13 countries tested 45 samples (30 HIV-1 subtype B; 15 non-B subtypes) in nine panels. Median detection of DRMs was 88-98% in plasma panels and 90-97% in electropherogram panels. Laboratories were supported to amend and improve their test outcomes as appropriate. Three laboratories that detected <80% DRMs in early panels demonstrated subsequent improvement. Sample complexity factors - number of DRMs (p<0.001) and number of DRMs as mixtures (p<0.001); and laboratory performance factors - detection of mixtures (p<0.001) and agreement with consensus sequence (p<0.001), were associated with high performance; sample format (plasma or electropherogram), subtype and genotyping protocol were not. CONCLUSION: High-quality HIVDR genotyping was achieved in the TAQAS collaborative laboratory network. Sample complexity and detection of mixtures were associated with performance quality. Laboratories conducting HIVDR genotyping are encouraged to participate in quality assessment programmes.

How does use of a prescription monitoring program change pharmacy practice?

OBJECTIVES: To assess differences in prescription monitoring program (PMP) use between two states with different PMP accessibility (Connecticut [CT] and Rhode Island [RI]), to explore use of PMPs in pharmacy practice, and to examine associations between PMP use and pharmacists' responses to suspected diversion or "doctor shopping." DESIGN: Descriptive nonexperimental study. SETTING: CT and RI from March through August 2011. PARTICIPANTS: Licensed pharmacists in CT and RI. INTERVENTION: Anonymous surveys e-mailed to pharmacists MAIN OUTCOME MEASURES: PMP use, use of patient reports in pharmacy practice, and responses to suspected doctor shopping or diversion. RESULTS: Responses from 294 pharmacists were received (CT: 198; RI: 96). PMP users were more likely to use the PMP to detect drug abuse (CT: 79%; RI: 21.9%; P < 0.01) and doctor shopping (67%; 7%; P < 0.01). When faced with suspicious medication use behavior, PMP users were less likely than nonusers to discuss their concerns with the patient (adjusted odds ratio 0.48 [95% CI 0.25-0.92]) but as likely to contact the provider (0.86 [0.21-3.47]), refer the patient back to the prescriber (1.50 [0.79-2.86]), and refuse to fill the prescription (0.63 [0.30-1.30]). PMP users were less likely to state they were out of stock of the drug (0.27 [0.12-0.60]) compared with nonusers. Pharmacists reported high interest in attending continuing education on safe dispensing (72.8%). CONCLUSION: Pharmacists are important participants in the effort to address prescription drug misuse and abuse. Current PMP use with prevailing systems had limited influence on pharmacy practice. Findings point to future research and needed practice and education innovations to improve patient safety and safer opioid dispensing for pharmacists.

Effects of political conflict-induced treatment interruptions on HIV drug resistance.

Thirty-four million people worldwide were living with the HIV by the end of 2010. Despite significant advances in antiretroviral therapy, drug resistance remains a major deterrent to successful, enduring treatment. Unplanned interruptions in antiretroviral therapy have negative effects on HIV treatment outcomes, including increased morbidity and mortality, as well as development of drug resistance. Treatment interruptions due to political conflicts, not infrequent in resource-limited settings, result in disruptions in health care, infrastructure, or treatment facilities and patient displacement. Such circumstances are ideal bases for antiretroviral therapy resistance development, but there is limited awareness of and data available on the association between political conflict and the development of HIV drug resistance. In this review we identify and discuss this association and review how varying antiretroviral therapy half-lives, genetic barriers, different HIV subtypes, and archived resistance can lead to lack of medication effectiveness upon post-conflict resumption of care. Optimized antiretroviral therapy stopping strategies as well as infrastructural concerns and stable HIV treatment systems to ensure continuity of care and rapid resumption of care must be addressed in order to mitigate risks of HIV drug resistance development during and after political conflicts. Increased awareness of such associations by clinicians as well as politicians and stakeholders is essential.

How does use of a prescription monitoring program change medical practice?

OBJECTIVES: The objectives of this study were to test for differences in prescription monitoring program (PMP) use between two states, Connecticut (CT) and Rhode Island (RI), with a different PMP accessibility; to explore use of PMP reports in clinical practice; and to examine associations between PMP use and clinician's responses to suspected diversion or "doctor shopping" (i.e., multiple prescriptions from multiple providers). DESIGN, SETTING, SUBJECTS: From March to August 2011, anonymous surveys were emailed to providers licensed to prescribe Schedule II medications in CT (N = 16,924) and RI (N = 5,567). OUTCOME MEASURES: PMP use, use of patient reports in clinical practice, responses to suspected doctor shopping, or diversion. RESULTS: Responses from 1,385 prescribers were received: 998 in CT and 375 in RI. PMP use was greater in CT, where an electronic PMP is available (43.9% vs 16.3%, χ(2) = 85.2, P < 0.0001). PMP patient reports were used to screen for drug abuse (36.2% CT vs 10.0% RI, χ(2) = 60.9, P < 0.0001) and detect doctor shopping (43.9% CT vs 18.5% RI, χ(2) = 68.3, P < 0.0001). Adjusting for potential confounders, responses by PMP users to suspicious medication use behavior were more likely to entail clinical response (i.e., refer to another provider odds ratio, OR, 1.75 [95% confidence interval, CI, 1.10, 2.80]; screen for drug abuse OR 1.93 [1.39, 2.68]; revisit pain/treatment agreement OR 1.97 [1.45, 2.67]; conduct urine screen OR 1.82 [1.29, 2.57]; refer to substance abuse treatment OR 1.30 [0.96, 1.75]) rather than legal intervention (OR 0.45 [0.21, 0.94]) or inaction (OR 0.09 [0.01, 0.70]). CONCLUSIONS: Prescribers' use of an electronic PMP may influence medical practice, especially opioid abuse detection, and is associated with clinical responses to suspected doctor shopping or diversion.

Life after the ban: an assessment of US syringe exchange programs' attitudes about and early experiences with federal funding.

OBJECTIVES: We aimed to determine whether syringe exchange programs (SEPs) currently receive or anticipate pursuing federal funding and barriers to funding applications following the recent removal of the long-standing ban on using federal funds for SEPs. METHODS: We conducted a telephone-administered cross-sectional survey of US SEPs. Descriptive statistics summarized responses; bivariate analyses examined differences in pursuing funding and experiencing barriers by program characteristics. RESULTS: Of the 187 SEPs (92.1%) that responded, 90.9% were legally authorized. Three received federal funds and 116 intended to pursue federal funding. Perceived federal funding barriers were common and included availability and accessibility of funds, legal requirements such as written police support, resource capacity to apply and comply with funding regulations, local political and structural organization, and concern around altering program culture. Programs without legal authorization, health department affiliation, large distribution, or comprehensive planning reported more federal funding barriers. CONCLUSIONS: Policy implementation gaps appear to render federal support primarily symbolic. In practice, funding opportunities may not be available to all SEPs. Increased technical assistance and legal reform could improve access to federal funds, especially for SEPs with smaller capacity and tenuous local support.