Current use of statins reduces risk of HIV rebound on suppressive HAART

<div><p>Background</p><p>Despite compelling evidence for activity against HIV-1 <i>in vitro</i>, a virologic effect of statins has not been shown in clinical studies. Given their short plasma half-lives, such an effect may be transient and only apparent during ongoing exposure.</p><p>Methods</p><p>We studied all HIV infected US-Veterans who started HAART 1995–2011, had a documented HIV viral load (VL) >1000 copies/mL, reached an undetectable VL on HAART, and had ≥1 follow-up VL within 13 months. We defined virologic failure (VF) as the first VL >1,000 copies/mL or the first of 2 consecutive VL >200 copies/mL. We built a time-updated drug exposure model for antiretrovirals (ARVs), statins, and other cardiovascular drugs (CVMs), investigating current use (yes/no), recent use (proportion of days used), and categorical use (ever/never). We used both multiply adjusted and inverse-probability-weighted (IPW) Cox models to explore the association between statin and CVM use and VF.</p><p>Results</p><p>19,324 veterans met inclusion criteria. Median follow-up was 13 months (IQR: 5–32 months); 63% experienced VF after a median time of 9 months (IQR 4–21 months). Almost 1/3 patients ever used statins but exposure comprised only 41% of follow-up time covered after initial prescription. Unadjusted, current statin use was associated with a hazard ratio (HR) for VF of 0.60 (CI: 0.56–0.65). This remained statistically significant after multivariate adjustment (MVA) for demographics, HIV and HAART parameters [HR 0.81 (CI: 0.75–0.88), p<0.001] and IPW (truncation <1%/>99%) HR: 0.83 (CI: 0.75–0.92), p<0.001]. No independent association was observed for other CVMs. The association between categorical-statin use and VF after MVA was much weaker: HR 0.94 (CI: 0.88–1.00, p = 0.04).</p><p>Conclusion</p><p>Current statin exposure was associated with reduced risk of VF in univariate, multivariate, and inverse-probability-weighted models. Our results highlight the importance of time-updated medication exposure models for observational studies.</p></div

Baseline Characteristics <i>at the time of First VL Suppression</i>.

<p>Baseline Characteristics <i>at the time of First VL Suppression</i>.</p

Proportion of patients with virological failure by overall HAART adherence since suppression (rows), and time period (columns).

<p>Solid line: not on statins or CVMs, broken line: other CVMs, dotted line: on statins. Statin use was associated with a decreased probability of virological failure.</p

Proportion of patients experiencing virological failure by likelihood of statin exposure based on propensity score.

<p>Solid line: not on statins or CVMs, dotted line: on statins. Statin use was associated with a decreased probability of failure.</p

Cross-sectional Selection of Time-Updated Characteristics by Statin and CVM Use (all patients under observation).

<p>Cross-sectional Selection of Time-Updated Characteristics by Statin and CVM Use (all patients under observation).</p

Main Analysis.

<p>Hazard Ratio (95% CI) of first VF (n = 19,324 / 10, 534 failures).</p

Sensitivity Analysis.

<p>Hazard Ratio (95% CI) for first VF after sustained viral suppression >6 months (n = 14,389 / 6,295 failures).</p

Tenofovir-Associated Bone Adverse Outcomes among a US National Historical Cohort of HIV-Infected Veterans: Risk Modification by Concomitant Antiretrovirals

<p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here </p> <p><a href="https://link.springer.com/article/10.1007/s40121-018-0194-1">https://link.springer.com/article/10.1007/s40121-018-0194-1</a></p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact [email protected].</p> <p> </p> <p><br></p><p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p> <p> </p

The RADAR Study: Week 48 Safety and Efficacy of RAltegravir Combined with Boosted DARunavir Compared to Tenofovir/Emtricitabine Combined with Boosted Darunavir in Antiretroviral-Naive Patients. Impact on Bone Health

<div><p>Background</p><p>NRTI-sparing regimens may avoid long-term mitochondrial, bone and renal toxicities and maintain viral suppression.</p><p>Methods</p><p>In the RADAR study, 85 antiretroviral-naïve HIV-infected patients were randomized to receive either raltegravir (RAL) (n = 42) or tenofovir/emtricitabine (TDF/FTC) (n = 43), each with ritonavir-boosted darunavir (DRV/r). Virologic efficacy was assessed at weeks 24 and 48. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry (DXA) scan at baseline and week 48, and bone turnover markers (BTM) assessed at weeks 0, 16 and 48.</p><p>Results</p><p>Using an intention-to-treat analysis, 62.5% of RAL subjects and 83.7% of TDF/FTC subjects were responders (VL<48 copies/mL) at week 48 (p = 0.045; chi-square test). The proportions of patients achieving VL<200 copies/mL were similar: 72.5% and 86.0% (p = 0.175). Premature treatment discontinuation was the main cause for failure. No treatment-emergent resistance was observed. Changes from baseline in RAL vs. TDF/FTC for CD4⁺ (+199 vs. +216 cells/µL, p = 0.63), total cholesterol/HDL (−0.25 vs. −0.71 mg/dL (p = 0.270), and eGFR (−4.4 vs. −7.9 ml/min, p = 0.44) were comparable between groups. Changes in subtotal BMD to week 48 were: +9.2 with RAL vs. −7 g/cm² with TDF/FTC (p = 0.002). Mean CTX changes were +0.04 vs. +0.24 ng/mL (p = 0.001), and mean P1NP changes were +3.59 vs. +30.09 ng/mL (p = 0.023). BTM changes at week 16 predicted change in BMD by week 48 (R = −0.394, p = 0.003 for CTX; and R = −0.477, p<0.001 for P1NP).</p><p>Conclusion</p><p>The NRTI-sparing regimen RAL+DRV/r did not achieve similar week 48 virologic efficacy compared with TDF/FTC+DRV/r, but was better with regard to markers of bone health.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00677300?term=RADAR&rank=5" target="_blank">NCT 00677300</a></p></div

Proportion of subjects with plasma HIV-1 RNA<48 copies/mL and <200 copies/mL using the Intention-to-Treat Analysis (top) and the On-Treatment-Analysis (bottom, with number of patients indicated).

<p>Proportion of subjects with plasma HIV-1 RNA<48 copies/mL and <200 copies/mL using the Intention-to-Treat Analysis (top) and the On-Treatment-Analysis (bottom, with number of patients indicated).</p