Dynamics of Lipid Profile in Antiretroviral-Naïve HIV-Infected Patients, Treated with TAF-Based Regimens: A Multicenter Observational Study.

Background: The introduction of tenofovir alafenamide (TAF) in antiretroviral therapy has deeply modified the choice of the backbone for different treatment regimens, allowing the prevention of the bone and renal toxicity that was related to the previous formulation of tenofovir disoproxil fumarate (TDF). At the same time, literature data show an onset of dyslipidemia after a switch from TDF to TAF. To better understand the possible role of TAF in dyslipidemia, antiretroviral-naïve HIV-infected patients were evaluated, comparing those treated with TAF/emtricitabine with those with abacavir/lamivudine. Methods: We enrolled 270 antiretroviral-naïve HIV-infected patients in an observational, retrospective, longitudinal, multicenter study; they started treatment from 2017 to 2019 and were followed up for at least 72 weeks. We divided patients into two groups, one treated with a TAF-based backbone in their antiretroviral regimens (TAF group) and one without TAF (NO TAF group), to evaluate possible differences in the dynamics of lipid profiles from baseline(T0) to week 24 (T24), 48 (T48) and 72 (T72). Results: No significant differences were observed at baseline between the 2 groups. In the TAF group we observed a significant development of hypercholesterolemia throughout the follow-up (p < 0.0001), not evident in the NO TAF group, that instead showed a significant increase in high-density lipoprotein (HDL). There were no significant differences between the two groups regarding triglycerides, low-density lipoprotein (LDL) and cardiovascular risk index (CRI). A cholesterol-lowering treatment with statin, finally, was prescribed in 6 patients in both groups during the study. At binary logistic regression analysis, no factor was independently associated with hypercholesterolemia, except for higher age at T0. Conclusions: This real-life study shows that in HIV-naïve patients, TAF was associated with hypercholesterolemia throughout the follow-up. The clinical significance of this hypercholesterolemia will have to be clarified in further studies.

Durability and tolerability of first-line regimens including two nucleoside reverse transcriptase inhibitors and raltegravir or ritonavir boosted-atazanavir or -darunavir: data from the ICONA Cohort.

Background We aimed to mimic the ACTG 5257 trial, comparing raltegravir (RAL), ritonavir-boosted atazavavir (ATV/r) and ritonavir-boosted darunavir (DRV/r) in the observational setting. Methods All the ICONA patients starting a first cART with 2NRTI + ATV/r, DRV/r or RAL were included. Primary end-point was treatment failure, i.e. virological failure (confirmed HIV-RNA > 200copies/mL > 6 months therapy) or discontinuation for any reason of the third drug. Secondary end-points: virological failure50 (50 copies/mL threshold), and discontinuation of the third drug due to intolerance/toxicity. Cox regression analyses were run to compare the risk of outcomes between the three regimens. Results 2249 patients were included, 985 (44%) initiated ATV/r, 1023 (45%) DRV/r and 241 (11%) RAL; median follow-up of 3.6 years (IQR: 2.3-5.2). After controlling for baseline confounding factors, patients given ATV/r showed a 26% higher risk of treatment failure (TF) vs. DRV/r (AHR 1.26, 95%CI 1.11-1.43); patients on RAL had a lower risk of TF vs. ATV/r (AHR 0.81, 95%CI 0.66-0.99). The probability of virological failure50 was significantly lower for people initiating RAL vs. DRV/r (AHR 0.46, 95%CI 0.24-0.87) or ATV/r (AHR 0.52, 95%CI 0.27-0.99). In addition, RAL was associated to a lower risk of discontinuation for toxicity vs. both DRV/r (AHR: 0.37, 95%CI: 0.19-0.72) and ATV/r (AHR: 0.18, 95%CI: 0.09-0.34). ATV/r was associated with a higher risk of discontinuing due to toxicity (AHR 2.09, 95%CI 1.63-2.67) vs. DRV/r. Conclusions In our observational study, we confirmed higher risk of treatment failure and lower tolerability of ATV/r-based regimens as compared to those including DRV/r or RAL.

Efficacy and Tolerability of Integrase Inhibitors in Antiretroviral-Naive Patients.

Integrase strand transfer inhibitors are a new class of antiretroviral agents recently licensed for the treatment of both naive and experienced HIV-infected patients. They inhibit the catalytic activity of the HIV-encoded enzyme integrase and prevent the integration of the HIV genome into the host cell genome, so slowing the propagation of the infection. Integrase strand transfer inhibitors cause a rapid drop in viral load, exhibit very low drug interactions (except elvitegravir/cobicistat), and have low pill burden and convenient dosing frequency. Drugs in this class have been compared to others in antiretroviral-naive patients with efavirenz and with protease inhibitors. Final results of the STARTMRK trial highlighted the better virologic and immunologic performance of raltegravir over efavirenz/emtricitabine/tenofovir disoproxil co-formulation. Raltegravir was also superior to atazanavir/ritonavir and darunavir/ritonavir in the ACTG 5257 study for the combined virologic/tolerability endpoint. Elvitegravir/cobicistat/emtricitabine/tenofovir was non-inferior to efavirenz/emtricitabine/tenofovir and to atazanavir/ritonavir plus emtricitabine/tenofovir in terms of confirmed virologic response in the GS-US-236-0102 and GS-US-236-0103 studies, respectively. Finally, dolutegravir showed non-inferiority compared to raltegravir in the SPRING-2 study and was superior to efavirenz and darunavir/ritonavir in the SINGLE and FLAMINGO trials, respectively. The aim of this review is to analyze the data on efficacy and safety of integrase strand transfer inhibitors in antiretroviral-naive HIV patients and discuss the strengths and weaknesses of drugs within this class.

Safety of fosamprenavir in a cohort of HIV-1-infected patients with co-morbidities.

BACKGROUND: The hypothesis that fosamprenavir-including highly active antiretroviral therapy (HAART) regimens would be associated with few metabolic and hepatic side-effects was investigated. PATIENTS AND METHODS: An observational single-arm retrospective study was set up on a cohort of 139 human immunodeficiency virus (HIV)-infected patients, followed up at A.O.R.N. Cotugno Hospital, Naples, Italy, treated with antiretroviral regimens including fosamprenavir, in order to evaluate the safety of these regimens in relationship to hepatic and metabolic side-effects, also considering co-morbidities and other risk factors. RESULTS: Only seven patients met the criteria to reach the primary end-point (grade ≥ 3 adverse event) and none of them discontinued HAART therapy during the follow-up period. Eighty percent of the patients reached viral load <50 cp/µl at 48 weeks of observation. At the end of follow-up, no patient with fasting serum total cholesterol and/or fasting serum triglycerides above grade 3 was found, while 1 out of 114 (0.88%) cases presented aspartate transaminase and alanine transaminase ≥ grade 3 and 1 out of 114 (0.88%) cases had fasting serum glucose ≥ grade 3. One out of 137 patients developed a malignant neoplasm (0.73%) and 4 (2.92%) displayed newly diagnosed hypertension. CONCLUSION: Fosamprenavir-based regimens caused a low number of serious metabolic adverse events during a 48 week follow-up period, with a low incidence of co-morbidities and satisfying results in terms of viro-immunological response including for patients with already existing co-morbidities requiring other therapies.