Efficacy and Safety of Atazanavir-Ritonavir Plus Abacavir-Lamivudine or Tenofovir-Emtricitabine in Patients with Hyperlipidaemia Switched from a Stable Protease Inhibitor-Based Regimen Including One Thymidine Analogue

Abstract

Randomized, open-label, prospective clinical trial assessing efficacy and safety on hyperlipidemia of a switching from a regimen including one protease inhibitor and one thymidine analogue to atazanavir/ritonavir plus abacavir/lamivudine or tenofovir/emtricitabine. Adult HIV-infected patients on their first antiretroviral therapy (of at least 48-week duration), including one protease inhibitor and zidovudine or stavudine, with stable immunovirologic features, and having diagnosis of persisting hyperlipidemia, were randomized to replace current treatment with atazanavir/ritonavir plus abacavir/lamivudine (arm A) or tenofovir/emtricitabine (arm B), and were followed for 48 weeks. Eighty-nine patients were enrolled: 42 patients were randomized to arm A, and 47 to arm B. At the end of the 48-week follow-up, incidence of virologic failure was comparable in both arms, and associated with a poor drug compliance. Increase in CD4 lymphocyte count was significantly higher in arm A after a 24-week study period (62.5 versus 39.2 x 10(6) cells/L; p < 0.05), while immunologic responses were comparable at the end of 48-week follow-up (91.5 versus 83.6; p > 0.05). A statistically significant reduction (-15.4%) in mean triglyceridaemia versus respective baseline values was reported in both groups (p < 0.05), without statistically significant difference between arm A and B. Similar results were reported for total cholesterol and low-density lipoprotein (LDL) cholesterol levels. Safety and tolerability profiles were comparable in both groups. Switching from a protease inhibitor- and thymidine analogue-based antiretroviral regimen to atazanavir/ritonavir plus abacavir/lamivudine or tenofovir/emtricitabine proved effective in the management of hyperlipidemia, without significant differences in lipid-lowering effect, virologic efficacy, and safety profile between these regimens.

Virological responses to lamivudine or emtricitabine when combined with tenofovir and a protease inhibitor in treatment‐naïve HIV‐1‐infected patients in the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort

“…Therefore, FTC/TDF was always compared with 3TC co‐formulated with abacavir or zidovudine in boosted PI‐based regimens (), in NNRTI‐based regimens or in INI‐based regimens . Several trials found comparable efficacies of FTC and 3TC, but randomized patients when they had already become HIV RNA suppressed on previous cART . The use of 3TC in combination with TDF in an NRTI backbone was only evaluated in three small studies in NNRTI‐based regimens, including two pilot trials without an FTC‐containing comparator arm , and one unpublished underpowered open‐label randomized trial .…”

Atazanavir/Ritonavir-Based Combination Antiretroviral Therapy for Treatment of HIV-1 Infection in Adults

“…In the ACTG 5202 study, at 96 weeks, patients treated with atazanavir/r had significantly lower increases in fasting total cholesterol, LDL and HDL compared with efavirenz, regardless of the NRTI backbone used [76]. Several other studies have switched patients with suppressed HIV RNA from other PI-based cART regimens to atazanavir/r, with subsequent improvements observed in lipids (Table 5) [102–107]. Using this strategy, the total cholesterol decreased from 12 to 25 mg/dl, LDL decreased from 4 to 6 mg/dl and triglycerides decreased from 38 to 182 mg/dl, depending on the population studied.…”

Abacavir/lamivudine fixed-dose combination antiretroviral therapy for the treatment of HIV

“…53,60–62 In fact, early in its development and use, abacavir was often prescribed to patients thought to be at risk for CHD. This predisposition was shown in the D:A:D study where 27% of patients starting abacavir had moderate or high predicted 10-year risk of CHD compared to 19% of those starting other NRTIs such as zidovudine or stavudine.…”