Lifetime benefits of early detection and treatment of diabetic kidney disease.

OBJECTIVES: Diabetic kidney disease (DKD) is a frequent complication of diabetes with potentially devastating consequences that may be prevented or delayed. This study aimed to estimate the health and economic benefit of earlier diagnosis and treatment of DKD. METHODS: Life expectancy and medical spending for people with diabetes were modeled using The Health Economics Medical Innovation Simulation (THEMIS). THEMIS uses data from the Health and Retirement Study to model cohorts of individuals over age 50 to project population-level lifetime health and economic outcomes. DKD status was imputed based on diagnoses and laboratory values in the National Health and Nutrition Examination Survey. We simulated the implementation of a new biomarker identifying people with diabetes at an elevated risk of DKD and DKD patients at risk of rapid progression. RESULTS: Compared to baseline, the prevalence of DKD declined 5.1% with a novel prognostic biomarker test, while the prevalence of diabetes with stage 5 chronic kidney disease declined 3.0%. Consequently, people with diabetes gained 0.2 years in life expectancy, while per-capita annual medical spending fell by 0.3%. The estimated cost was $12,796 per life-year gained and $25,842 per quality-adjusted life-year. CONCLUSIONS: A biomarker test that allows earlier treatment reduces DKD prevalence and slows DKD progression, thereby increasing life expectancy among people with diabetes while raising healthcare spending by less than one percent.

HIV Drug Resistance Profiles and Clinical Outcomes in Patients with Viremia Maintained at Very Low Levels.

We describe an observational study of clinical, virologic and drug resistance profiles in HIV-positive antiretroviral adherent subjects with stable low level viremia (LLV) 50-1,000 copies/mL for more than 12 months. Subjects were followed from time of first detectable viral load (VL). In total, 102 episodes of LLV were detected among 80 individuals. The median (mean, range) HIV copy number at genotyping was 250 (486, <50-3900) copies/mL after 14 (17.9, 0-58) months of LLV. Few patients maintained LLV for the entire 9 year period of observation, with half (52%) experiencing viremic progression following a stable period of LLV either spontaneously or after treatment interruption or failed regimen intensification. In the setting of prolonged periods of sustained LLV, mean duration 22 (range 8 - 106) months, drug resistance (DR) was almost universal. Resistance to ≥1 on-treatment drugs was defined in 97% of specimens and DR to all drugs in the treatment regimen in over half of all patients. Evolution of DR mutations during the period of LLV was observed in 20/28 (71%) subjects with specimens available for follow-up testing. This evolution was associated with viremic progression to levels >1000 copies/mL (p=0.03). Our data suggest that DR present in patients with LLV is likely to impact long term clinical outcomes, highlighting the importance of optimizing techniques to detect the presence of drug resistant HIV in the setting of LLV and the need for larger prospective studies to assess the emergence of DR in the setting of sustained LLV and the impact of this DR on treatment outcomes.

Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity.

Mutations in the connection domain (CD) of reverse transcriptase have been implicated in reverse transcriptase inhibitor (RTI) resistance, but this is controversial and little is known in non-B subtype HIV-1. We determined CD mutations prevalence in a population infected predominantly with CRF02_AG and investigated associations with phenotypic RTI resistance. Detected CD mutations were G335D (82.3%), A371V (69.8%), E399D (9.4%), N348I (5.2%), V365I (4.2), Y318F (2.1%), G333E (2.1%), and A360V (2.1%). Mutations were largely polymorphic and did not confer RTI resistance. The observed trend toward reduced likelihood of etravirine or nevirapine resistance in the presence of G335D should be investigated further.