In this study, we aim to explore the effects on lipids of integrase strand transfer inhibitors (INSTIs) in naïve and switch randomised controlled trials, and compare them with protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). We reviewed phase 3/4 randomised clinical trials in the Cochrane and PubMed databases that compare an INSTI with a boosted PI, an NNRTI, or another INSTI plus one or two nucleoside/nucleotide reverse transcriptase inhibitors (NtRTIs) in naïve patients and switching strategies in HIV-infected patients. We reported the baseline plasma concentration of total cholesterol (TC), low and high-density lipoprotein cholesterol (LDL-c, HDL-c), triglycerides (TG), and the TC/HDL-c ratio, as well as the change at weeks 48 and 96, when available. In naïve HIV-infected patients, raltegravir (RAL) and dolutegravir (DTG) have a more favourable lipid profile compared with NNRTI and boosted PI. Elvitegravir (EVG/c) has a superior lipid profile compared with efavirenz and is similar to that observed with ritonavir-boosted atazanavir except in TG, which increases less with EVG/c. In naïve patients, RAL, DTG, and bictegravir (BIC) produce a similar, slight increase in lipids. In switching trials, the regimen change based on a boosted PI or efavirenz to RAL, DTG, or BIC is associated with clinically significant decreases in lipids that are minor when the change is executed on EVG/c. No changes were observed in lipids by switching trials between INSTIs. In summary, RAL, DTG, and BIC have superior lipid profiles compared with boosted-PI, efavirenz, and EVG/c, in studies conducted in naïve participants, and they are associated with a clinically significant decrease in lipoproteins by switching studies.

Objectives Dyslipidaemic effects of antiretrovirals (ARVs) may contribute to increased cardiovascular risk (CR) in HIV‐1‐infected patients. The ARTEN (atazanavir/ritonavir on a background of tenofovir and emtricitabine vs. nevirapine on the same background, in naïve HIV‐1‐infected patients) study compared prospectively ritonavir‐boosted atazanavir (ATZ/r) 300 mg/100 mg once daily (qd) with immediate release nevirapine (NVP) 200 mg twice daily or 400 mg qd, each combined with fixed‐dose tenofovir 300 mg/emtricitabine 200 mg qd in 569 ARV‐naïve HIV‐1‐infected patients. Lipid profiles and CR from baseline to week 48 are reported. Methods Changes from baseline to week 48 in fasting plasma levels of total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐c), low‐density lipoprotein cholesterol (LDL‐c), TC:HDL‐c ratio, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and total triglycerides (TG) were determined. The Framingham algorithm was used to estimate CR. Analysis was by intention‐to‐treat (ITT) with last observation carried forward (LOCF) for missing data. Results At week 48, NVP treatment resulted in significantly greater mean increases from baseline in TC (24.4 vs. 19.6 mg/dL; P=0.038), HDL‐c (9.7 vs. 3.9 mg/dL; P<0.0001), LDL‐c (15.0 vs. 10.4 mg/dL; P=0.011) and ApoA1 (0.18 vs. 0.08 g/L; P<0.0001) but not ApoB (0.02 vs. 0.02 g/L) compared with ATZ/r treatment. ATZ/r use was associated with higher mean TG increases (27.80 vs. 0.02 mg/dL; P=0.0001). Significantly greater mean decreases in TC:HDL‐c and ApoB/ApoA ratios were observed with NVP vs. ATZ/r (P=0.0001 and P=0.008, respectively). Framingham CR scores were low and comparable between the arms, with only a slight mean increase from baseline to week 48 of 0.70 for NVP and 0.80 for ATZ/r [difference −0.069; 95% confidence interval (CI) −0.61 to 0.46; P=0.80]. Conclusions In ARV‐naïve patients with low CR at the outset, NVP showed a potentially less atherogenic lipid profile compared with ATZ/r.

Background: The aim of this study was to assess the short-term and long-term consequences of stopping antiretroviral therapy (ART) in patients with preserved immune function. Methods: This was a randomized 144-week follow-up CD4 ⁺ T-cell-count-guided treatment-interruption trial. HIV-1-infected adults with plasma HIV-1 RNA500 cells/ml and nadir CD4 ⁺ T-cell count >100 cells/ml were randomized to continuous treatment (CT) or treatment interruption (TI) until CD4 ⁺ T-cell count decreased to <350 cells/ml. The primary end points were AIDS-defining illnesses, death, CD4 ⁺ T-cell count <200 cells/ml, or virological failure after restarting ART. Results: A total of 106 patients were included, 50 in the CT arm and 56 in the TI arm. A trend to a higher rate of primary end points was observed in the TI group (26.8% versus 14%, difference 12.8%, 95% CI -2.3, 27.8; P=0.105). In addition, 10 patients presented clinical events related with HIV rebound, including 8 cases of thrombocytopaenia. The CD4 ⁺ T-cell count significantly decreased in the TI group (even in patients with persistently high CD4 ⁺ T-cell counts and no clinical events) versus the CT group (median change -408 cells/ml versus -21.5 cells/ml; P<0.001), whereas a significant increase in CD8 ⁺ T-cell count was observed (256 cells/ml versus -59 cells/ml; P<0.001). The time to ART re-initiation was significantly associated with nadir and baseline CD4 ⁺ T-cell counts. Conclusions: Discontinuation of ART in patients with preserved immune function is followed by significant immunological impairment even in those with no clinical events, and may be associated with an increased risk of HIV-related complications. Hence, patients who stop ART voluntarily should be closely monitored, regardless of their CD4 ⁺ T-cell count.

To determine etravirine concentrations in CSF in HIV-infected patients. Twelve HIV-1 adult antiretroviral-experienced patients receiving an etravirine-containing regimen for at least 1 month were enrolled. Both CSF and blood samples were taken around 12 h after the last etravirine dose. Liquid chromatography-tandem mass spectrometry was used to determine etravirine concentrations, and HIV-1 viral load was determined by real-time PCR (limit of detection 40 copies/mL). Twelve blood and 12 CSF samples were collected. The median CD4 count was 333 (84–765) cells/mm³ and the median plasma HIV-1 viral load was <40 (range 40 copies/mL in one patient and plasma viral load was still detectable after 4 weeks of therapy. Etravirine achieves concentrations several times greater than the IC₅₀ range in CSF. All patients with undetectable plasma viral load were virologically suppressed in CSF while receiving an etravirine-containing regimen. Etravirine may help in controlling HIV-1 in CNS.

Background: The aim of this study was to assess changes in the size and cholesterol content of low-density lipo-proteins (LDL) and changes in lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in HIV-infected patients switching to tenofovir + emtricitabine (TDF+FTC) or abacavir + lamivudine (ABC+3TC). Methods: This was a substudy of a multicentre randomized trial comparing TDF+FTC with ABC+3TC-based regimens in patients with virological suppression. Fasting lipids and apolipoproteins (apo), LDL size and cholesterol content and Lp-PLA2 activity were measured at baseline and at week 48. Results: A total of 62 patients, naive for the compared drugs, were included. At baseline, groups were comparable except for total Lp-PLA2 activity ( P=0.047) and for a tendency towards the use of a major baseline thymidine analogue in the TDF+FTC arm (25 versus 18 patients; P=0.054). In the ABC+3TC arm a significant increase in total cholesterol (0.64 mmol/l; P=0.003), high-density lipoprotein cholesterol (HDL-c, 0.13 mmol/l; P=0.031), triglycerides (0.39 mmol/l; P=0.036), apo A-I (0.12 g/l; P=0.006), apo B (0.16 g/l; P=0.015) and non-HDL-c (0.50 mmol/l; P=0.009) concentrations was observed at week 48 compared with the TDF+FTC treatment arm. In addition, an increase in the cholesterol content of small, dense LDL subfractions (0.48 mmol/l; P=0.003) and a decrease in LDL size (-2.6 nm; P=0.011) was observed in the ABC arm without changes in the TDF patients. Total PLA2, LDL-PLA2 and HDL-PLA2 activity decreased in the TDF arm, but multivariate analysis showed baseline PLA2 values and previous use of thymidine analogues as the factors associated with these changes. Estimated cardiovascular risk did not change in either arm. Conclusions: A more atherogenic LDL profile, including a decrease in LDL size, was found in the ABC group and not in TDF patients.