Lipid changes and tolerability in a cohort of adult HIV-infected patients who switched to rilpivirine/emtricitabine/tenofovir due to intolerance to previous combination ART: the PRO-STR study.

Objectives: To analyse lipid changes and tolerability in a cohort of HIV-infected patients who switched their antiretroviral regimens to rilpivirine/emtricitabine/tenofovir (RPV/FTC/TDF) in a real-world setting. Methods: PRO-STR is a 48 week prospective observational post-authorization study in 25 hospitals. Patients with a viral load <1000 copies/mL, receiving at least 12 months of combination ART (cART), with constant posology for at least the prior 3 months, were categorized according to previous treatment [NNRTI or ritonavir-boosted PI (PI/r)]. Analytical tests were performed at the baseline visit, between week 16 and week 32, and at week 48. Results: A total of 303 patients were included (mean age 46.6 years; male 74.0%; previous treatment 74.7% NNRTI and 25.3% PI/r). Both groups exhibited significantly reduced lipid profiles, except for HDL cholesterol, for which a non-significant increase was observed. [NNRTI patients: total cholesterol (baseline: 195.5 ±âŸ38.4 mg/dL; week 48: 171.0 ±âŸ35.5 mg/dL), total cholesterol/HDL ratio (baseline: 4.2 ±âŸ1.2; week 48: 4.0 ±âŸ1.2), HDL (baseline: 49.1 ±âŸ12.0 mg/dL; week 48: 49.2 ±âŸ45.8 mg/dL), LDL (baseline: 119.2 ±âŸ30.2 mg/dL; week 48: 114.2 ±âŸ110.7 mg/dL), and triglycerides (baseline: 136.6 ±âŸ86.8 mg/dL; week 48: 113.4 ±âŸ67.8 mg/dL); PI/r patients: total cholesterol (baseline: 203.2 ±âŸ48.8 mg/dL; week 48: 173.4 ±âŸ36.9 mg/dL), total cholesterol/HDL ratio (baseline: 4.7 ±âŸ1.6; week 48: 4.0 ±âŸ1.2), HDL (baseline: 46.4 ±âŸ12.5 mg/dL; week 48: 52.1 ±âŸ54.4 mg/dL), LDL (baseline: 127.0 ±âŸ36.3 mg/dL; week 48: 111.4 ±âŸ35.8 mg/dL), and triglycerides (baseline: 167.6 ±âŸ107.7 mg/dL; week 48: 122.7 ±âŸ72.1 mg/dL)]. The most common intolerances were neuropsychiatric in the NNRTI patients and gastrointestinal and metabolic in the PI/r patients, and these intolerances were significantly reduced in both groups at week 48 [NNRTI: neuropsychiatric (baseline: 81.3%; week 48: 0.0%); PI/r: gastrointestinal (baseline: 48.7%; week 48: 0.0%) and metabolic (baseline: 42.1%; week 48: 0.0%)]. Conclusions: RPV/FTC/TDF improved the lipid profiles and reduced the intolerances after switching from NNRTI or PI-based regimens, in a cohort of HIV-infected patients.

Elvitegravir concentrations in seminal plasma in HIV-1-infected men.

OBJECTIVES: The aim of the study was to quantify elvitegravir (EVG) concentrations in the semen of HIV-1-infected men receiving antiretroviral therapy (ART) consisting of an elvitegravir/cobicistat/emtricitabine/tenofovir (EVG/COBI/FTC/TDF) single-tablet regimen. METHODS: A phase IV, cross-sectional study was carried out including HIV-1-infected male adults with suppressed plasma HIV-1 RNA who switched ART to EVG/COBI/FTC/TDF. Total EVG concentrations at the end of the dosing interval (C24 h ) and HIV-1 RNA were measured in paired seminal plasma (SP) and blood plasma (BP) samples 4 weeks after switching to EVG/COBI/FTC/TDF. Validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to quantify EVG concentrations, and HIV-1 RNA was determined by real-time polymerase chain reaction (PCR). RESULTS: Ten men were included. Their median age was 40 years (range 24-47 years), the median time on ART was 50 months (range 10-186 months), the median time with plasma HIV-1 RNA < 40 copies/mL was 37 months (range 7-113 months), and the median CD4 count was 737 cells/µL (range 190-1122 cells/µL). Four weeks after switching to EVG/COBI/FTC/TDF, all subjects had HIV-1 RNA < 40 copies/mL in both BP and SP. Median EVG C24 h was 277 ng/mL (range 64.8-1790 ng/mL) in BP and 169 ng/mL (range 12.8-792 ng/mL) in SP. A significant correlation was observed between BP and SP EVG concentrations (Spearman rho 0.952; P < 0.001). The median SP:BP EVG concentration ratio was 0.39 (range 0.20-0.92). EVG C24 h in SP was at least 23-fold the in vitro protein-unbound 50% effective response (EC50 ) of HIV-1 clinical isolates (0.04-0.55 ng/mL). In all but one individual, EVG C24 h in SP was also higher than the blood plasma protein binding-adjusted 95% inhibitory concentration (IC95 ) of wild-type HIV-1 (45 ng/mL). CONCLUSIONS: Seminal EVG concentrations in HIV-infected men treated with EVG/COBI/FTC/TDF sufficed to contribute to maintaining HIV-1 RNA suppression in this compartment.

Viral and inflammatory markers in cerebrospinal fluid of patients with HIV-1-associated neurocognitive impairment during antiretroviral treatment switch.

OBJECTIVES: The aim of the study was to evaluate HIV-1 viral load (VL) and inflammatory markers in cerebrospinal fluid (CSF) and neurocognitive performance in patients with neurocognitive impairment (NCI) while they were receiving tenofovir (TDF)/ emtricitabine (FTC)/efavirenz (EFV) and after switching to a regimen with enhanced central nervous system (CNS) penetrability. METHODS: This was a prospective, single-arm pilot study. HIV-1-infected patients with plasma viral suppression and HIV-associated NCI on a regimen including TDF/FTC/EFV were switched to abacavir (ABC)/lamivudine (3TC)/maraviroc (MVC). The Global Deficit Score (GDS) was used to score cognitive function at baseline and 48 weeks after treatment switch. Both CSF and blood samples were taken at baseline and between weeks 24 and 36 after switching. HIV-1 RNA in plasma and CSF was determined by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Inflammatory biomarkers in CSF were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 71 patients receiving TDF/FTC/EFV were screened. Twelve of them (17%) had documented NCI, lacked the human leucocyte antigen (HLA)-B*57:01 haplotype and harboured Chemokine Receptor Type-5 (CCR5)-tropic virus. Eight patients had detectable HIV-1 RNA (between 2.7 and 41.6 HIV-1 RNA copies/mL) in CSF at baseline. All participants had elevated levels of neopterin and Monocyte Chemoattractant Protein 1 (MCP-1) in CSF at baseline. Eight out of 12 patients completed their follow-up assessment after treatment switch. The GDS decreased from 0.55 to 0.4 (P = 0.085). Median HIV-1 RNA in CSF decreased from 3.49 to 2.20 (P = 0.23). Among the inflammation markers in CSF, tumour necrosis factor (TNF)-α decreased significantly from median 0.51 to 0.35 pg/mL (P = 0.027), showing a correlation with the changes in neopterin, interferon (IFN)-γ and interleukin (IL)-6. CONCLUSIONS: Most patients with NCI receiving TDF/FTC/EFV had low-level viraemia and/or increased inflammatory markers in CSF. Treatment switching to an MVC-containing regimen with better CNS penetration resulted in a trend towards improvement in neurocognitive status and reduced TNF-α concentrations in CSF.

Abacavir/lamivudine plus darunavir/ritonavir in routine clinical practice: a multicentre experience in antiretroviral therapy-naive and -experienced patients.

OBJECTIVES: To present clinical experience with a regimen including abacavir/lamivudine + darunavir/ritonavir in a cohort of HIV-1-infected patients. METHODS: A retrospective, multicentre cohort study, including all consecutive adult HIV-1-infected patients who started abacavir/lamivudine + darunavir/ritonavir from April 2008 to December 2010 and had at least one follow-up visit. The primary endpoint was HIV-1 viral load (VL) <40 copies/mL at week 48. RESULTS: One hundred and eighty-three patients (42 naive and 141 experienced) from 19 hospitals in Spain were studied. The median follow-up was 26.7 (0.5-58.6) months, 79.8% were men, the median age was 47.1 (21.4-80.5) years, 26.2% had AIDS and 38.8% were positive for hepatitis C virus. At baseline, the median CD4 count was 246 cells/mm(3) in naive patients and 393 cells/mm(3) in experienced patients and the median VL was 4.80 and <1.59 log copies/mL, respectively. At week 48, 81.8% of naive patients and 84.2% of experienced patients receiving the regimen reached a VL <40 copies/mL, whereas at 96 weeks this occurred in 90.5% and 92.8%, respectively. CD4 cell count increases at 48 and 96 weeks were +176.5 and +283.5 cells/mm(3) in naive patients and +74.9 and +93 cells/mm(3) in experienced patients, respectively. Overall, 86 (47%) patients discontinued the study regimen, in many cases possibly related to non-medical reasons, such as drug switches to reduce cost or changes in address due to economic constraints. Three patients died of causes unrelated to therapy and 19 (10.4%) discontinued the regimen due to adverse events. CONCLUSIONS: In our cohort, abacavir/lamivudine + darunavir/ritonavir was safe, well tolerated and achieved high rates of virological suppression. In a proportion of patients, discontinuation of this effective regimen was possibly due to non-medical reasons.

Etravirine concentrations in seminal plasma in HIV-infected patients.

OBJECTIVES: To determine etravirine concentrations and the HIV-1 viral load (VL) in blood plasma (BP) and seminal plasma (SP) of HIV-infected patients. METHODS: Ten adult antiretroviral-experienced HIV-1 patients receiving an etravirine-containing regimen for at least 1 month were enrolled. Semen and blood samples were collected ~12 or 24 h after the last etravirine dose, depending on twice-daily or once-daily dosing, respectively. Liquid chromatography tandem mass spectrometry was used to determine etravirine concentrations and HIV-1 VL was determined by real-time PCR (detection limit 40 copies/mL). Results are presented as the median (range) unless otherwise indicated. RESULTS: Ten blood and 20 semen samples were collected. The CD4 count was 502 (252-817) cells/mm(3) and the BP VL was <40 (<40-362) copies/mL. The time on etravirine was 52 (12-124) weeks. The BP etravirine concentration was 452.5 (258-751) ng/mL. The SP etravirine concentration was 62.9 (31.2-166.0) ng/mL and values were above the IC(50) range (0.39-2.4 ng/mL) in all cases. The median etravirine SP:BP ratio was 0.16 (0.07-0.26). The SP VL was <40 copies/mL in all patients, whereas the BP VL was detectable in one patient with poor adherence to treatment. CONCLUSIONS: Etravirine concentrations in male genital secretions are modest, reaching only 16% of the BP concentration. Nevertheless, they are more than 10 times greater than the wild-type IC(50) range (not adjusted for protein binding).

Real World Patient-reported Outcomes in HIV-infected Adults Switching to EVIPLERA®, Because of a Previous Intolerance to cART. PRO-STR Study.

BACKGROUND: To investigate the impact of switching from stable Combined Antiretroviral Therapy (cART) to single-tablet regimen (RPV/FTC/TDF=EVIPLERA® /COMPLERA®) on patient- reported outcomes in HIV-infected adults who cannot tolerate previous cART, in a real-world setting. METHODS: PRO-STR is a 48-week observational, prospective, multicenter study. Presence and magnitude of symptoms (main endpoint), health-related quality-of-life (HRQoL), adherence, satisfaction with treatment and patient preferences were assessed. RESULTS: Three hundred patients with 48-week follow-up, who switched to EVIPLERA® (mean age: 46.6 years; male: 74.0%; 74.7% switched from a non-nucleoside reverse-transcriptase-inhibitor, 25.3% from a protease inhibitor + ritonavir) were included. There was no statistical difference in median CD4+ cell count (baseline: 678.5 cells/mm3; 48-week: 683.0 cells/mm3) neither in virological suppression (≤50 copies/mL) (baseline: 98.3%; 48-week: 95.3%). The most frequent reasons for switching were neuropsychiatric (62.3%), gastrointestinal (19.3%) and biochemical/metabolic (19.3%) events. Only 7.7% of patients permanently discontinued therapy. At 48-week, all outcomes showed an improvement compared to baseline. Overall, there was a significant decrease (pvalue≤ 0.05) in number and magnitude of symptoms, while HRQoL, satisfaction and adherence improved significantly. Most patients prefered EVIPLERA® than previous cART. According to the type of intolerance, HRQoL was improved, but only significantly in patients with neuropsychiatric and gastrointestinal symptoms. Adherence improved significantly in patients with metabolic disturbances and satisfaction with EVIPLERA® was higher in the three groups. CONCLUSION: Switching to EVIPLERA® from non-nucleoside reverse-transcriptase-inhibitor or protease inhibitor-based regimens due to toxicity, improved the presence/magnitude of symptoms, HRQoL, and preference with treatment. EVIPLERA® maintained a virological response, CD4+ cell count and maintained or improved adherence.