scholarly journals Bictegravir-based antiretroviral therapy associated accelerated hyperglycemia and diabetes mellitus

2021 ◽  
Author(s):  
Nathanial S Nolan ◽  
Samantha Adamson ◽  
Dominic Reeds ◽  
Jane A O’Halloran
Keyword(s):  
Diabetes Mellitus ◽  
Antiretroviral Therapy ◽  
Metabolic Effects ◽  
Strand Transfer ◽  
First Line ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor

Abstract Integrase strand transfer inhibitor (INSTI) based antiretroviral therapy (ART) is first line for treatment of people with HIV (PWH). Emerging data suggests the possibility of adverse metabolic effects of these medications. We describe three cases in which PWH developed hyperglycemia and ketoacidosis within months of being switched to bictegravir-based ART.

Transmission of integrase strand-transfer inhibitor multidrug-resistant HIV-1: case report and response to raltegravir-containing antiretroviral therapy

2011 ◽  
Vol 16 (2) ◽  
pp. 253-256 ◽  
Author(s):  
Benjamin Young ◽  
Signe Fransen ◽  
Kenneth S Greenberg ◽  
Amy Thomas ◽  
Sharon Martens ◽  
...  
Keyword(s):  
Case Report ◽  
Antiretroviral Therapy ◽  
Multidrug Resistant ◽  
Strand Transfer ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor ◽  
Hiv 1

Weight gain in antiretroviral therapy-naive HIV-1-infected patients starting a regimen including an integrase strand transfer inhibitor or darunavir/ritonavir

Infection ◽  
2019 ◽  
Vol 48 (2) ◽  
pp. 213-221 ◽  
Author(s):  
Leonardo Calza ◽  
Vincenzo Colangeli ◽  
Marco Borderi ◽  
Isabella Bon ◽  
Aurora Borioni ◽  
...  
Keyword(s):  
Weight Gain ◽  
Antiretroviral Therapy ◽  
Strand Transfer ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor ◽  
Hiv 1

scholarly journals 334. Weight Change Associated with Antiretroviral Therapy Switch to Integrase Strand Transfer Inhibitor-Based Regimens

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S177-S177 ◽  
Author(s):  
Saghar Saber ◽  
Andrew B Bernstein ◽  
Andrew D Sparks ◽  
Marc O Siegel
Keyword(s):  
Weight Gain ◽  
Antiretroviral Therapy ◽  
Weight Change ◽  
Statistical Significance ◽  
Inverse Correlation ◽  
Cd4 Count ◽  
Strand Transfer ◽  
Significant Difference ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor

Abstract Background An association between switching antiretroviral therapy (ART) to integrase strand transfer inhibitor (INSTI)-based ART and weight gain has been previously reported. However, insufficient data exists on risk factors associated with such weight gain. Methods We reviewed charts of 119 virally-suppressed HIV-positive patients switched from nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI)-based ART to INSTI-based ART and compared their weight change over 17 months to 56 virally-suppressed patients who were maintained on NNRTI-based regimens over the same period.We looked at variables associated with weight gain including age, weight, body mass index (BMI), gender, CD4 count, starting ART, and final INSTI-based ART. Results The 119 patients switched to INSTI-based ART gained an average of 6.9 lbs compared with an average 1 lbs weight gain in the 56 patients who were maintained on NNRTI-based ART (P = 0.002). There was also a statistically significant difference in the percentage % weight change between the two groups (4.2% vs. 0.7%, P < 0.001).There was an average 1.2 lbs weight loss in 92 of the 119 patients with weights recorded 17 months before switching ART, compared with an average 6.7 lbs weight gain after the switch (P < 0.001).There was no association between gender, CD4 count at the time of switch, starting ART, or final INSTI-based ART with weight gain. However, patients weighing < 150 lbs at the time of switch had a greater % weight gain than patients weighing >200 lbs (6.9% vs. 2.7%, P = 0.02) and a trend to greater % weight gain than those weighing ≥150 to ≤ 200 lbs (6.9% vs. 3.8%, P = 0.06). There was marginal statistical significance when comparing those with BMIs < 25 to those with BMIs ≥25 to ≤ 30 (8.2 vs. 6.5 lbs, P = 0.069) and those with BMIs >30 (8.2 vs. 5.0 lbs, P = 0.057). There was an inverse correlation between age and weight gain, indicating that less weight was gained when switching to INSTI-based ART as the age of the patient increased (ρ = -0.211, P = 0.021). Conclusion Our study showed a statistically significant weight gain in patients switched from NNRTI- or PI- to INSTI-based ART compared with patients maintained on NNRTI-based ART.Baseline variables associated with greater weight gain included weight <150 lbs, BMI <25 and younger age. Disclosures All authors: No reported disclosures.

Ritonavir- or cobicistat-boosted antiretroviral therapy and direct oral anticoagulants: A case for apixaban

2019 ◽  
Vol 30 (7) ◽  
pp. 718-722 ◽  
Author(s):  
Sarah A Nisly ◽  
Brooke N Stevens
Keyword(s):  
Antiretroviral Therapy ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Case Series ◽  
Strand Transfer ◽  
Reduced Dose ◽  
Immunodeficiency Virus ◽  
Transfer Inhibitor ◽  
Cyp Inhibition ◽  
Integrase Strand Transfer Inhibitor

Summary The potential for drug–drug interactions (DDIs) between direct oral anticoagulants and antiretroviral therapy (ART) is vast. Ritonavir and cobicistat are used as pharmacokinetic enhancers with either concurrent protease inhibitors or the integrase strand transfer inhibitor, elvitegravir, to optimize therapeutic concentrations by cytochrome P450 (CYP) inhibition. To date, only rivaroxaban and dabigatran have reported cases of use with ritonavir-boosted ART. Apixaban is metabolized similarly to rivaroxaban, but offers a dose reduction in the case of major DDIs. We report the successful use of reduced-dose apixaban to treat and prevent thromboembolic complications in six persons living with human immunodeficiency virus (HIV) on ritonavir- or cobicistat-boosted ART. This case series and available literature support the use of apixaban or dabigatran, depending on the boosted ART regimen.

scholarly journals Impact of first-line antiretroviral therapy regimens on the restoration of the CD4/CD8 ratio in the CNICS cohort

2020 ◽  
Vol 75 (6) ◽  
pp. 1604-1610 ◽  
Author(s):  
Sabina Herrera ◽  
Borja M Fernandez-Felix ◽  
Peter W Hunt ◽  
Steven G Deeks ◽  
Talía Sainz ◽  
...  
Keyword(s):  
Baseline Viral Load ◽  
Strand Transfer ◽  
First Line ◽  
Hiv Rna ◽  
Art Initiation ◽  
Primary Endpoints ◽  
Secondary Endpoints ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor

Abstract Background The CD4/CD8 ratio is an indicator of immunosenescence and a predictor of all-cause mortality in HIV-infected patients. The effects of different ART regimens on CD4/CD8 ratio recovery remain unclear. Methods Clinical cohort study of ART-treated patients from the CFAR Network of Integrated Clinical Systems (CNICS). We included ART-naive adults with HIV infection who achieved undetectable HIV RNA during the first 48 weeks of treatment and had additional follow-up 48 weeks after virological suppression (VS). Primary endpoints included increase in CD4/CD8 ratio at both timepoints and secondary endpoints were CD4/CD8 ratio recovery at cut-offs of ≥0.5 or ≥1.0. Results Of 3971 subjects who met the study criteria, 1876 started ART with an NNRTI, 1804 with a PI and 291 with an integrase strand transfer inhibitor (INSTI). After adjusting for age, sex, race, year of entry, risk group, HCV serostatus, baseline viral load and baseline CD4/CD8 ratio, subjects on an NNRTI showed a significantly greater CD4/CD8 ratio gain compared with those on a PI, either 48 weeks after ART initiation or after 48 weeks of HIV RNA VS. The greater CD4/CD8 ratio improvement in the NNRTI arm was driven by a higher decline in CD8 counts. The INSTI group showed increased rates of CD4/CD8 ratio normalization at the ≥1.0 cut-off compared with the PI group. Conclusions NNRTI therapy was associated with a greater increase in the CD4/CD8 ratio compared with PIs. NNRTI- and INSTI-based first-line ART were associated with higher rates of CD4/CD8 ratio normalization at a cut-off of 1.0 than a PI-based regimen, which might have clinical implications.

Integrase strand transfer inhibitor-associated diabetes mellitus: A case report

2016 ◽  
Vol 28 (6) ◽  
pp. 626-628 ◽  
Author(s):  
Peter S Fong ◽  
Devon M Flynn ◽  
Christopher D Evans ◽  
P Todd Korthuis
Keyword(s):  
Diabetes Mellitus ◽  
Case Report ◽  
Hemoglobin A1c ◽  
Hemophilia A ◽  
Strand Transfer ◽  
Exogenous Insulin ◽  
Integrase Strand Transfer Inhibitors ◽  
History Of ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor

Integrase strand transfer inhibitors (INSTIs) have become integral antiretroviral therapy (ART) agents for treating HIV infection. We report the case of a 44-year-old male with a history of hemophilia A who developed diabetes mellitus four months after switching from abacavir, lamivudine, and efavirenz to abacavir, lamivudine, and raltegravir. Hemoglobin A1C normalized without further need for exogenous insulin after raltegravir was switched back to efavirenz. In this case report, we will review a possible mechanism for INSTI-induced hyperglycemia and/or diabetes mellitus.

scholarly journals Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting

2020 ◽  
Vol 28 ◽  
pp. 204020662092790
Author(s):  
Wassim Chehadeh ◽  
Osama Albaksami ◽  
Shaikhah Al-Shammari
Keyword(s):  
Salvage Therapy ◽  
Virologic Failure ◽  
Strand Transfer ◽  
Adherence To Treatment ◽  
First Line ◽  
Transfer Inhibitor ◽  
High Level ◽  
Integrase Strand Transfer Inhibitor ◽  
Hiv 1 ◽  
Level Resistance

Background With the advent of next generation integrase strand transfer inhibitors, the rates of virologic failure in treated subjects are expected to decrease. In this study, we analyzed the mutation patterns leading to virologic failure before and after starting integrase strand transfer inhibitor-based regimen as first-line or salvage therapy. Methods Between 2016 and 2019, blood samples were received from 258 patients with HIV-1 infection. Plasma HIV-1 RNA concentrations, and pol gene sequences were determined at baseline, and 16–48 weeks of treatment with integrase strand transfer inhibitor-based regimen. Only patients who did not achieve viral suppression at 48 weeks of integrase strand transfer inhibitor-based treatment were eligible for the current study. Results Virologic failure was observed in seven patients on raltegravir-based regimen. All patients with virologic failure but one were infected with CRF01_AE virus subtype. Raltegravir based-regimen was offered as first-line therapy for four patients, and as salvage therapy for three patients. M184V mutation associated with high level resistance to lamivudine and emtricitabine was detected in six out of seven patients. Primary mutations (Y143C, N155H, T66I, G118R, E138K) conferring high level resistance to raltegravir were detected in only three patients. Pre-existing polymorphic integrase mutation (T97A) was detected in two patients. Furthermore, two patients reported low adherence to treatment. Conclusions Emergence of primary mutations in the integrase gene can account for virologic failure in less than half of patients on raltegravir-based regimen. Low adherence to treatment, pre-existing accessory mutations, and resistance to reverse transcriptase inhibitors may have some role in virologic outcome.

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