Marita Mann

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.

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.

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

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

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

2700. Estimated mean revascularization costs were lower by US

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

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

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

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.

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

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

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

3500, on average, or

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

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