Safety and tolerability of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil fumarate in a real life setting: Data from surveillance cohort long-term toxicity antiretrovirals/antivirals (SCOLTA) project

Abstract

ObjectivesThe study aim was to evaluate the impact on Liver and Kidney toxicity of the single tablet regimen Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate (EVG/COBI/FTC/TDF) on Antiretroviral Therapy (ART) experienced or naïve patients.MethodsPatients initiating EVG/COBI/FTC/TDF were enrolled in the SCOLTA project, a multicenter observational study reporting grade 3–4 Adverse Events in subjects beginning new antiretroviral drug regimens. In this analysis, patients were evaluated at T0 (baseline), T1 (six months) and at T2 (twelve months).ResultsA total of 329 patients were enrolled, and 280 (85.1%) of these had at least one follow-up visit. Median observation time was 11 months (IQR 7.0–15.5). Two hundred and two patients (72.1%) were ART experienced and 78 (27.9%) ART naive. Prevalence of HCV-co-infection was 21.4%. At T1, we observed a significant decline in estimated glomerular filtration rate (eGFR), both in experienced and naive patients (mean change from T0–7.5 ± 12.8 ml/min, -15.5 ± 17.8 ml/min, respectively, p = 0.0005), which was confirmed at T2 (mean change from T0–8.2 ± 15.8 ml/min, -17.6 ± 19.4 ml/min, respectively, p = 0.001). Regarding aspartate aminotransferase (AST) and alanine transaminase (ALT) grade 1–2 modifications, no significant differences were observed between experienced and naïve subjects, but an increased prevalence of abnormal liver function test was observed in patients with chronic HCV infection (p<0.001).ConclusionsA significant decline in eGFR was observed in patients initiating EVG/COBI/FTC/TDF in the first 6 months, with no significant worsening occurring at 12 months vs. 6 months of therapy. Patients with chronic HCV infection were at higher risk to develop abnormal liver tests.

Tenofovir disoproxil fumarate initiation and changes in urinary biomarker concentrations among HIV-infected men and women

“…The observed kinetics of biomarker changes and kidney function decline within the first year following TDF initiation are also concordant with reported TDF-associated eGFR SCr declines that subsequently plateau at 6 months to 1 year. [45,46] In another study using this cohort of new TDF users, we have demonstrated that 6 of these 14 biomarkers, including β2M, KIM-1, clusterin, UMOD, cystatin C, and IL-18, were independently associated with eGFR decline during follow-up. [47] The recent introduction of tenofovir alafenamide fumarate (TAF), a less nephrotoxic alternative to TDF, has eased some concerns regarding tenofovir-associated nephrotoxicity.…”

Antiretroviral therapy and liver disorders in the OPERA® cohort

“…26 Over 6–12 months of follow-up in the SCOLTA cohort, only 1% of ART-naïve and 1% of ART-experienced PLWH using EVG experienced a severe LCE. 15 Finally, in a 3-year study in Spain of RAL users, only 1% of PLWH developed a grade 3 or 4 hepatotoxicity which were attributed to HCV co-infection. The cumulative incidence of any hepatotoxicity (i.e.…”

Investigational drugs in HIV: Pros and cons of entry and fusion inhibitors (Review)

“…Furthermore, many patients are diagnosed at late stage with a low immune recovery (23). Second, since it is a chronic disease that needs life-long treatment, HIV is burdened with a lot of co-morbidities due to the virus and treatment thereof (17). The safe profile showed by entry inhibitors could represent advancement in terms of drug-related toxicities in comparison with actual HAART.…”

“…The mean maximum reduction in HIV-1 RNA observed for the 324 mg weekly dose was 1,65 log. Individual viral nadirs were typically observed on day 22 (range, day [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29].…”