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Tenofovir disoproxil fumarate is associated with renal and bone toxicity. In a single-arm, open-label study of 242 virologically suppressed, HIV-infected participants with creatinine clearance 30–69 mL/min who switched to elvitegravir/cobicistat/ emtricitabine/tenofovir alafenamide, participants had stable creatinine clearance, significant and durable improvements in proteinuria, albuminuria, and tubular proteinuria (P < 0.001), and significant increases in hip and spine bone mineral density through 96 weeks (P < 0.001). Eighty-eight percent maintained HIV-1 RNA <50 c/mL at week 96. These longer-term results support the use of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in HIV-infected individuals with mild-moderately impaired renal function. [ABSTRACT FROM AUTHOR]

Background: HIV-infected, treatment-experienced adults with a history of prior resistance and regimen failure can be virologically suppressed but may require multitablet regimens associated with lower adherence and potential resistance development. Methods: We enrolled HIV-infected, virologically suppressed adults with 2-class to 3-class drug resistance and at least 2 prior regimen failures into this phase 3, open-label, randomized study. The primary endpoint was the percentage of participants with HIV-1 RNA <50 copies per milliliter at week 24 [Food and Drug Administration (FDA) snapshot algorithm]. Results: For 135 participants [elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) plus darunavir (DRV), n = 89; baseline regimen, n = 46], most of whom were taking a median of 5 tablets/d, simplification to E/C/F/TAF plus DRV was noninferior to continuation of baseline regimens at week 24 (plasma HIV-1 RNA <50 copies per milliliter: 96.6% vs. 91.3%, difference 5.3%, 95.001% CI: 23.4% to 17.4%). E/C/F/TAF plus DRV met prespecified criteria for noninferiority and superiority at week 48 for the same outcome. E/C/F/TAF plus DRV was well tolerated and had an improved renal safety profile compared with baseline regimens, with statistically significant differences between groups in quantitative total proteinuria and markers of proximal tubular proteinuria. Compared with baseline regimens, participants who switched to E/C/F/TAF plus DRV reported higher mean treatment satisfaction scale total scores and fewer days with missed doses. Conclusions: This study demonstrated that regimen simplification from a 5-tablet regimen to the 2-tablet, once-daily combination of E/C/F/TAF plus DRV has durable maintenance of virologic suppression and improvements in specific markers of renal safety. Such a strategy may lead to greater adherence and improved quality of life. [ABSTRACT FROM AUTHOR]

The contribution of current antiretroviral treatment regimens to the long-term survival of HIV-infected individuals is accompanied by increased risk of glucose metabolism abnormalities in this patient population. The risk of insulin resistance and diabetes in HIV-infected patients receiving antiretroviral treatment stems from 2 sources: exposure to the same environmental factors that have led to an increased incidence of these conditions in the general population and the negative effects on glucose metabolism inherent to components of antiretroviral treatment regimens. This article reviews the pathogenesis and diagnosis of insulin resistance and diabetes and the contribution of components of antiretroviral therapy regimens to increased risk for these conditions. Optimization of antiretroviral treatment regimens for HIV-infected patients with or at increased risk for development of abnormalities in glucose metabolism is discussed. [ABSTRACT FROM AUTHOR]

The article examines the influence of kidney disease and hemodialysis on the pharmacokinetics of enfuvirtide. It was found that enfuvirtide area under the curve and maximum observed plasma concentration for patients with normal kidney function, respectively. The enfurvitide exposure in patients with end-stage renal disease requiring dialysis or chronic kidney disease was slightly higher than in patients with normal kidney function.

The article shows that switching to a protease inhibitor-containing, nucleoside-sparing regimen increases limb fat but raises serum lipid levels. It evaluates the effects of nucleoside-sparing and protease inhibitor-sparing regimens on fat distribution, bone mineral density, and metabolic parameters in 62 subjects.

Focuses on a study which investigated whether insulin resistance or insulin deficiency and an elevated body mass index contribute to HIV protease inhibitor (PI) diabetes. Cross-sectional evaluation of five groups of HIV-infected subjects from the Washington University Medical School; Results and implications of the research.

CCR5 is an important co-receptor for HIV entry and zinc finger nuclease (ZFN)-mediated modification of this receptor in CD4 T cells may render a survival advantage in HIV infection.We conducted a Phase 1 clinical trial at the University of Pennsylvania evaluating the use of genetically modified CD4 T cells with SB-728-T (a CCR5 directed ZFN).6 immunologic responders (IR) with CD4≥450 were infused with 1010 genetically modified cells. At week 4, all participants underwent a 12-week HAART treatment interruption (TI). In addition 6 immunological non responders (NIR) were also infused. The mean CD4 and SB-728-T count increased by 1533/µL (range 216 to 3025) and 83/µL, respectively, on D7. Increases in CD4 over time correlated with SB-728-T engraftment (= 0.78, p <0.0001). SB-728-T was detected in the gut mucosa of all subjects biopsied (median 6%). During TI, HIV-RNA dropped ∼0.8 to 2.1 log from their peak levels in 3 subjects. In one CCR5 32 heterozygous subject with a viral set point of 165K copies/mL, viral load peaked at 6247 during week 6 of TI and was undetectable by week 12. HIV proviral DNA was evaluated using a new Digital Droplet qPCR method. The levels of HIV proviral DNA returned quickly to baseline levels after the resumption of ART. SB-728-T infusions were well tolerated with only mild reversible infusion-related adverse events. SB-728-T infusion increases CD4 counts that persist over time both in IR and NIR. SB-728-T expands rapidly and home to the gut. In one subject with the highest level of CCR5 modification, viral load was controlled for 12 weeks.These data suggest that in addition to the previously documented increases in CD4 cell, SB-728-T may also suppress HIV replication. [ABSTRACT FROM AUTHOR]