Significant improvement in triglyceride levels after switching from ritonavir to cobicistat in suppressed HIV-1-infected subjects with dyslipidaemia.

OBJECTIVES: Cobicistat seems to have a low rate of adverse events compared with ritonavir. METHODS: This restrospective observational study to evaluated changes in lipid parameters and the percentage of subjects with dyslipidemia in virologically suppressed HIV-infected patients who were receiving a regimen containing darunavir/ritonavir and were then switched from ritonavir to cobicistat, carried out from December 2015 to May 2016, included 299 HIV-1-infected patients who were on stable antiretroviral treatment including darunavir/ritonavir (monotherapy, bitherapy or triple therapy for at least 6 months) and were then switched from ritonavir to cobicistat. Lipid parameters, as well as plasma HIV-1 RNA and CD4 cell counts, were recorded at baseline just before the switch, and 24 weeks after the switch. Patients were stratified according to the presence of hypercholesterolaemia [baseline total cholesterol > 200 mg/dL and/or low-density lipoprotein (LDL) cholesterol > 130 mg/dL] or hypertriglyceridaemia (baseline triglyceride levels > 200 mg/dL). RESULTS: Two hundred and ninety-nine patients were enrolled in the study. Fifty-two per cent of the total study population showed dyslipidaemia at baseline. All patients maintained HIV-1 RNA ≤ 50 HIV-1 RNA copies/mL at week 24. No statistically significant changes were seen in CD4 T-cell count from baseline to week 24 [654 (298) to 643 (313) cells/µL; P = 0.173]. When patients were stratified according to the presence of hypercholesterolaemia at baseline (n = 124), significant changes were observed in total cholesterol (P < 0.001), LDL cholesterol (P = 0.047), high-density lipoprotein (HDL) cholesterol (P = 0.002) and triglyceride levels (P = 0.025), and when they were stratified according to the presence of hypertriglyceridaemia at baseline (n = 64), changes from baseline to week 24 in triglyceride level were statistically significant [median (interquartile range) 352 (223, 389) mg/dL at baseline and 229 (131, 279) mg/dL at week 24; P < 0.001]. CONCLUSIONS: Cobicistat as a booster of darunavir in HIV-infected subjects had a beneficial effect on the lipid profile in patients with hypercholesterolaemia or hypertrigliceridaemia at baseline.

Variable endothelial cell function restoration after initiation of two antiretroviral regimens in HIV-infected individuals.

Background: The effect of ART on endothelial cell function is incompletely characterized. Methods: We performed a 24 week prospective, case-control and comparative pilot study of ART-naive HIV-infected patients who started a darunavir- or rilpivirine-based regimen, matched with non-HIV-infected volunteers, to compare changes at week 24 from baseline in levels of circulating endothelial cells (CECs), endothelial progenitor cells (EPCs) and circulating angiogenic cells, as well as changes in immune-activation markers. Results: The study population comprised 24 HIV-infected patients and 24 non-infected volunteers. Both HIV groups completely suppressed viraemia. HIV-infected patients had higher levels of activation markers than the control group in CD8 T cells at baseline; these decreased after 24 weeks of treatment, but without reaching the levels of the control group. No statistical differences in immune activation were seen between the darunavir and rilpivirine groups. Levels of CECs were higher and levels of EPCs and circulating angiogenic cells were lower in HIV-infected patients than in the control group, although these parameters were similar between the darunavir group and the control group, but not the rilpivirine group, at week 24. An unfavourable association was observed between rilpivirine, age and increased number of CECs. Conclusions: Restoration of circulating levels of EPCs and CECs in darunavir-treated patients was greater than in those treated with rilpivirine, suggesting ongoing endothelial repair mechanisms.

Impact of protease inhibitors on the evolution of urinary markers: Subanalyses from an observational cross-sectional study.

Kidney injury (defined as the presence of albuminuria, proteinuria, glycosuria [without hyperglycemia], hematuria, and/or renal hypophosphatemia) is an emerging problem in human immunodeficiency virus (HIV)-infected patients, although few data are available on the role of protease inhibitors (PIs) in this condition.To determine the time to kidney injury in a cohort of HIV-infected patients receiving a PI-containing regimen.We report the results of a subanalysis of a published cross-sectional study. The subanalysis included only patients receiving PI-containing regimens for more than 6 months (377 of the overall 970 patients). We determined associated factors and constructed receiver operating characteristic curves to estimate time to kidney injury depending on the PI used.The percentage of patients with kidney injury was 27.7% for darunavir, 27.9% for lopinavir, and 30% for atazanavir. Time to kidney injury was as follows: 229 days for atazanavir/ritonavir (area under the curve [AUC], 0.639; sensitivity, 0.89; specificity, 0.41); 332 days for atazanavir/ritonavir plus tenofovir (AUC, 0.603; sensitivity, 0.75; and specificity, 0.29); 318 days for nonboosted atazanavir (AUC, 0.581; sensitivity, 0.89; and specificity, 0.29); 478 days for lopinavir/ritonavir (AUC, 0.566; sensitivity, 0.864; and specificity, 0.44); 1339 days for lopinavir/ritonavir plus tenofovir (AUC, 0.667; sensitivity, 0.86; and specificity, 0.77); 283 days for darunavir/ritonavir (AUC, 0.523; sensitivity, 0.80; and specificity, 0.261); and 286 days for darunavir/ritonavir plus tenofovir (AUC, 0.446; sensitivity, 0.789; and specificity, 0.245). The use of lopinavir/ritonavir without tenofovir was a protective factor (odds ratio = 1.772; 95%CI, 1.070-2.93; P = 0.026).For all PIs, the percentage of patients with kidney injury exceeded 27%, irrespective of tenofovir use. The longest time to kidney injury was recorded with lopinavir/ritonavir. These results demonstrate the need for renal monitoring, including urine samples, in patients receiving a PI-based regimen, even when tenofovir is not used concomitantly.

Comparison of two different strategies of treatment with zoledronate in HIV-infected patients with low bone mineral density: single dose versus two doses in 2 years.

OBJECTIVES: Given the need for easily managed treatment of osteoporosis in HIV-infected patients, we evaluated the efficacy and tolerability of two doses of zoledronate, by comparing three groups of patients: those with annual administration, those with biennial administration (one dose in 2 years) and a control group with no administration of zoledronate. METHODS: We randomized (2:1) 31 patients on antiretroviral therapy with low bone mineral density (BMD) to zoledronate (5 mg administered intravenously; 21 patients) plus diet counselling and to a control group (diet counselling; 10 patients). At week 48, patients treated with zoledronate were randomized again to receive a second dose (two-dose group; n = 12) or to continue with diet counselling only (single-dose group; n = 9). Changes in lumbar spine and hip BMD and bone turnover markers were compared. RESULTS: The median percentage change from baseline to week 96 in L1-L4 BMD was -1.74% [interquartile range (IQR) -2.56, 3.60%], 7.90% (IQR 4.20, 16.57%) and 5.22% (IQR 2.02, 7.28%) in the control, two-dose and single-dose groups, respectively (P < 0.01, control vs. two doses; P = 0.02, control vs. single dose; P = 0.18, two doses vs. single dose). Hip BMD changed by a median of 2.12% (IQR -0.12, 3.08%), 5.16% (IQR 3.06, 6.74%) and 4.47% (IQR 1, 5.58%), respectively (P = 0.04, control vs. two doses; P = 0.34, two doses vs. single dose). No differences between the two-dose and single-dose groups were detected in bone markers at week 96. CONCLUSIONS: The benefits for BMD of a single dose of zoledronate in 2 years may be comparable to those obtained with two doses of the drug after 96 weeks, although this study is insufficiently powered to exclude a real difference. Future studies should explore whether biennial administration of zoledronate is a useful alternative in the treatment of osteoporosis in HIV-infected patients.

Switching from zidovudine/lamivudine to tenofovir/emtricitabine improves fat distribution as measured by fat mass ratio.

OBJECTIVES: Fat mass ratio (FMR) has been suggested as an objective indicator of abnormal body fat distribution in HIV infection. Although it could provide more comprehensive information on body fat changes than limb fat mass, FMR has scarcely been used in clinical trials examining body fat distribution in HIV-infected patients. METHODS: A subanalysis of a controlled, randomized clinical trial in virologically suppressed HIV-1-infected men switching from zidovudine (ZDV)/lamivudine (3TC) to emtricitabine (FTC)/tenofovir (TDF) versus continuing on ZDV/3TC was carried out. FMR was assessed by dual X-ray absorptiometry (DEXA) for a period of 72 weeks. Lipoatrophy was defined as FMR ≥ 1.5. Multivariate linear regression models for the change in FMR from baseline were fitted. RESULTS: Sixty-five men were randomized and treated (28 in the FTC/TDF arm and 37 in the ZDV/3TC arm), and 57 completed the study (25 and 32 in each arm, respectively). In the FTC/TDF arm, adjusted mean FMR decreased by 0.52 at week 72 (P = 0.014), and in the ZDV/3TC arm it increased by 0.13 (P = 0.491; P between arms = 0.023). Among subjects with lipoatrophy (baseline FMR ≥ 1.5), adjusted FMR decreased by 0.76 (P = 0.003) in the FTC/TDF arm and increased by 0.21 (P = 0.411; P between arms = 0.009) in the ZDV/3TC arm. Baseline FMR and treatment group were significant predictors (P < 0.05) of post-baseline changes in FMR. CONCLUSIONS: Switching from ZDV/3TC to FTC/TDF led to an improvement in FMR, compared with progressive worsening of FMR in subjects receiving ZDV/3TC, showing that fat mass not only increased but was also distributed in a healthier way after the switch.

Differential subcutaneous adipose tissue gene expression patterns in a randomized clinical trial of efavirenz or lopinavir-ritonavir in antiretroviral-naive patients.

Gene expression studies of subcutaneous adipose tissue may help to better understand the mechanisms behind body fat changes in HIV-infected patients who initiate antiretroviral therapy (ART). Here, we evaluated early changes in adipose tissue gene expression and their relationship to fat changes in ART-naive HIV-infected patients randomly assigned to initiate therapy with emtricitabine/tenofovir plus efavirenz (EFV) or ritonavir-boosted lopinavir (LPV/r). Patients had abdominal subcutaneous adipose tissue biopsies at baseline and week 16 and dual-energy-X-ray absorptiometry at baseline and weeks 16 and 48. mRNA changes of 11 genes involved in adipogenesis, lipid and glucose metabolism, mitochondrial energy, and inflammation were assessed through reverse transcription-quantitative PCR (RT-qPCR). Additionally, correlations between gene expression changes and fat changes were evaluated. Fat increased preferentially in the trunk with EFV and in the limbs with LPV/r (P < 0.05). After 16 weeks of exposure to the drug regimen, transcripts of CEBP/A, ADIPOQ, GLUT4, LPL, and COXIV were significantly down-regulated in the EFV arm compared to the LPV/r arm (P < 0.05). Significant correlations were observed between LPL expression change and trunk fat change at week 16 in both arms and between CEBP/A or COXIV change and trunk fat change at the same time point only in the EFV arm and not in the LPV/r arm. When combined with emtricitabine/tenofovir as standard backbone therapy, EFV and LPV/r induced differential early expression of genes involved in adipogenesis and energy metabolism. Moreover, these mRNA expression changes correlated with trunk fat change in the EFV arm. (This was a substudy of a randomized clinical trial [LIPOTAR study] registered at ClinicalTrials.gov under identifier NCT00759070.).

Consensus statement: recommendations for the management of metabolic bone disease in human immunodeficiency virus patients / Documento de consenso: Recomendaciones para el manejo de la enfermedad ósea metabólica en pacientes con virus de la inmunodeficiencia humana

"OBJECTIVE: To provide practical recommendations for the evaluation and treatment of metabolic bone disease in human immunodeficiency virus (HIV) patients. PARTICIPANTS: Members of scientific societies related to bone metabolism and HIV: Grupo de Estudio de Sida (GeSIDA), Sociedad Española de Endocrinología y Nutrición (SEEN), Sociedad Española de Investigación Ósea y del Metabolismo Mineral (SEIOMM), and Sociedad Española de Fractura Osteoporótica (SEFRAOS). METHODS: A systematic search was carried out in PubMed, and papers in English and Spanish with a publication date before 28 May 2013 were included. Recommendations were formulated according to GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) setting both their strength and the quality of supporting evidence. Working groups were established for each major part, and the final resulting document was later discussed in a face-to-face meeting. All the authors reviewed the final written document and agreed with its content. CONCLUSIONS: The document provides evidence-based practical recommendations on the detection and treatment of bone disease in HIV-infected patients"

"Objetivo Proporcionar unas recomendaciones prácticas para el manejo de la enfermedad metabólica ósea en pacientes con virus de la inmunodeficiencia humana (VIH). Participantes Miembros de diferentes sociedades científicas relacionadas con el metabolismo óseo y con la enfermedad VIH: Grupo de Estudio de Sida (GeSIDA), Sociedad Española de Endocrinología y Nutrición (SEEN), Sociedad Española de Investigación Ósea y del Metabolismo Mineral (SEIOMM) y Sociedad Española de Fractura Osteoporótica (SEFRAOS). Métodos Se realizó una búsqueda sistemática en PubMed de la evidencia disponible para cada aspecto, y se revisaron artículos escritos en inglés y en castellano con fecha de inclusión hasta 28 de mayo de 2013. Las recomendaciones se formularon según el sistema GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) para establecer tanto la fuerza de las recomendaciones como el grado de evidencia. Los autores trabajaron por grupos en la formulación de cada apartado de las recomendaciones y posteriormente el documento global se discutió en una reunión conjunta. Todos los autores revisaron el documento escrito final y lo consensuaron. Conclusiones El documento establece unas recomendaciones prácticas basadas en la evidencia acerca de la evaluación y el tratamiento de la enfermedad metabólica ósea en pacientes con VIH"

Early lipid changes with atazanavir/ritonavir or darunavir/ritonavir.

OBJECTIVES: Ritonavir-boosted atazanavir and darunavir are protease inhibitors that are recommended for initial treatment of HIV infection because each has shown better lipid effects and overall tolerability than ritonavir-boosted lopinavir. The extent to which lipid effects and overall tolerability differ between treatments with atazanavir and darunavir and whether atazanavir-induced hyperbilirubinaemia may result in more favourable metabolic effects are issues that remain to be resolved. METHODS: A 96-week randomized clinical trial was carried out. The primary endpoint was change in total cholesterol at 24 weeks. Secondary endpoints were changes in lipids other than total cholesterol, insulin sensitivity, total bilirubin, estimated glomerular filtration rate, and CD4 and CD8 cell counts, and the proportion of patients with plasma HIV RNA < 50 HIV-1 RNA copies/mL and study drug discontinuation because of adverse effects at 24 weeks. Analyses were intent-to-treat. RESULTS: One hundred and seventy-eight patients received once-daily treatment with either atazanavir/ritonavir (n = 90) or darunavir/ritonavir (n = 88) plus tenofovir/emtricitabine. At 24 weeks, mean total cholesterol had increased by 7.26 and 11.47 mg/dL in the atazanavir/ritonavir and darunavir/ritonavir arms, respectively [estimated difference -4.21 mg/dL; 95% confidence interval (CI) -12.11 to +3.69 mg/dL; P = 0.75]. However, the ratio of total to high-density lipoprotein (HDL) cholesterol tended to show a greater decrease with atazanavir/ritonavir compared with darunavir/ritonavir (estimated difference -1.02; 95% CI -2.35 to +0.13; P = 0.07). Total bilirubin significantly increased with atazanavir/ritonavir (estimated difference +1.87 mg/dL; 95% CI +1.58 to +2.16 mg/dL; P < 0.01), but bilirubin changes were not associated with lipid changes. Secondary endpoints other than total bilirubin were not significantly different between arms. CONCLUSIONS: Atazanavir/ritonavir and darunavir/ritonavir plus tenofovir/emtricitabine did not show significant differences in total cholesterol change or overall tolerability at 24 weeks. However, there was a trend towards a lower total to HDL cholesterol ratio with atazanavir/ritonavir and this effect was unrelated to bilirubin.

Documento de consenso sobre el manejo de la patología renal en pacientes con infección por VIH / Consensus document on the management of renal disease in HIV-infected patients

OBJETIVO: Actualizar las recomendaciones sobre la evaluación y el manejo de la afectación renal en pacientes con infección por el virus de la inmunodeficiencia humana (VIH). MÉTODOS: Este documento ha sido consensuado por un panel de expertos del Grupo de Estudio de Sida (GESIDA) de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC), de la Sociedad Española de Nefrología (S.E.N.) y de la Sociedad Española de Química Clínica y Patología Molecular (SEQC). Para la valoración de la calidad de la evidencia y la graduación de las recomendaciones se ha utilizado el sistema Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTADOS: La evaluación renal debe incluir la medida de la concentración sérica de creatinina, la estimación del filtrado glomerular (ecuación chronic kidney disease epidemiological collaboration [CKD-EPI]), la medida del cociente proteína/creatinina en orina y un sedimento urinario. El estudio básico de la función tubular ha de incluir la concentración sérica de fosfato y la tira reactiva de orina (glucosuria). En ausencia de alteraciones, el cribado será anual. En pacientes tratados con tenofovir o con factores de riesgo para el desarrollo de enfermedad renal crónica (ERC), se recomienda una evaluación más frecuente. Se debe evitar el uso de antirretrovirales potencialmente nefrotóxicos en pacientes con ERC o factores de riesgo para evitar su progresión. En este documento se revisan las indicaciones de derivación del paciente a Nefrología y las de la biopsia renal, así como las indicaciones y la evaluación y el manejo del paciente en diálisis o del trasplante renal. CONCLUSIONES: La función renal debe monitorizarse en todos los pacientes con infección por el VIH y este documento pretende optimizar la evaluación y el manejo de la afectación renal.(AU)

OBJECTIVE: To update the 2010 recommendations on the evaluation and management of renal disease in HIV-infected patients. METHODS: This document was approved by a panel of experts from the AIDS Working Group (GESIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Nephrology (S.E.N.), and the Spanish Society of Clinical Chemistry and Molecular Pathology (SEQC). The quality of evidence and the level of recommendation were evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: The basic renal work-up should include measurements of serum creatinine, estimated glomerular filtration rate by CKD-EPI, Urine protein-to-creatinine ratio, and urinary sediment. Tubular function tests should include determination of serum phosphate levels and urine dipstick for glucosuria. In the absence of abnormal values, renal screening should be performed annually. In patients treated with tenofovir or with risk factors for chronic kidney disease (CKD), more frequent renal screening is recommended. In order to prevent disease progression, potentially nephrotoxic antiretroviral drugs are not recommended in patients with CKD or risk factors for CKD. The document advises on the optimal time for referral of a patient to the nephrologist and provides indications for renal biopsy. The indications for and evaluation and management of dialysis and renal transplantation are also addressed. CONCLUSIONS: Renal function should be monitored in all HIV-infected patients. The information provided in this document should enable clinicians to optimize the evaluation and management of HIV-infected patients with renal disease.(AU)

Impact of switching from zidovudine/lamivudine to tenofovir/emtricitabine on lipoatrophy: the RECOMB study.

OBJECTIVES: Lipoatrophy is a long-term adverse effect of some antiretrovirals that affects quality of life, compromises adherence and may limit the clinical impact of HIV treatments. This paper explores the effect of tenofovir/emtricitabine (TDF/FTC) on the amount of limb fat in patients with virological suppression. METHODS: A randomized, prospective clinical trial was performed to compare continuation on a zidovudine/lamivudine (ZDV/3TC)-based regimen with switching to a TDF/FTC-based regimen in terms of the effect on limb fat mass as assessed by DEXA over a 72-week period. RESULTS: Eighty patients were included (39 in the TDF/FTC arm and 41 in the ZDV/3TC arm) and 73 completed the study (37 and 36, respectively). In the switch arm, limb fat increased by a median of 540 g from baseline (P = 0.022), while in the ZDV/3TC arm it decreased by a median of 379 g (P = 0.112; p between groups = 0.007). Subjects with baseline limb fat ≤ 7200 g, previous time on ZDV > 5 years or a body mass index > 25 kg/m(2) experienced higher limb fat gains than other subjects, and these differences were statistically significant. Haemoglobin increased by a median of 1.0 g/dL in the TDF/FTC arm (P < 0.001) and remained unchanged in the ZDV/3TC arm (p between groups = 0.0002). There were no significant differences between groups in other secondary endpoints (body weight, total body and trunk fat content, total body bone mineral density, laboratory parameters, CD4 cell count and viral load). CONCLUSIONS: Switching from a ZDV/3TC-based to a TDF/FTC-based regimen led to a statistically significant improvement in limb fat, in contrast to the progressive loss of limb fat in subjects continuing ZDV/3TC.

Similar antiviral efficacy and tolerability between efavirenz and lopinavir/ritonavir, administered with abacavir/lamivudine (Kivexa), in antiretroviral-naïve patients: a 48-week, multicentre, randomized study (Lake Study).

BACKGROUND: Although efavirenz and lopinavir/ritonavir(r) are both recommended antiretroviral agents in antiretroviral-naïve HIV-infected patients, there are few randomized comparisons of their efficacy and tolerability. METHODS: A multicenter and randomized study was performed including 126 antiretroviral-naïve patients, randomly assigned to efavirenz+Kivexa (n=63) or lopinavir/r+Kivexa (n=63). Efficacy endpoints were the percentage of patients with HIV-RNA < or =50 copies/mL at week 48 and CD4 recovery. Safety was assessed by comparing toxicity and discontinuations. Statistical analyses were performed on an intention-to-treat (ITT) basis (Missing=Failure). RESULTS: At week 48, 56.7% of patients in the efavirenz and 63.2% in the lopinavir/r groups showed HIV-1 RNA <50 copies/mL (P=0.770) (intention-to-treat analysis; Missing=Failure). Only 1 (1.53%) patient from each group experienced virological failure. CD4 values increased in both groups (298 cells in the efavirenz group, P=0.001; 249 cells in the lopinavir/r group, P=0.002; P=0.126 between groups). HDL-cholesterol only increased in the efavirenz group (from 39+/-12 mg/dL to 49+/-11; P=0.001). Discontinuations were more frequent in the lopinavir/r group (36.5% versus 28.5%; P=0.193), but more patients with efavirenz interrupted due to toxicity (11.1% versus 6.3%); most of them were attributed to hypersensitivity reaction. CONCLUSIONS: Similar virological efficacy was observed for efavirenz and lopinavir/r, when administered with Kivexa in antiretroviral-naïve patients, while immunological improvement was slightly superior for efavirenz. The higher rate of discontinuation due to toxicity in the efavirenz group was related to a higher incidence of hypersensitivity reaction. Nowadays, the use of the new formulation of lopinavir/r and the HLA-B*5701 genotype test before starting abacavir should improve the safety profiles of these regimens.

Sustained antiretroviral treatment adherence in survivors of the pre-HAART era: attitudes and beliefs.

The objective of this study was to assess adherence of HIV-1-infected patients who started treatment in the pre-HAART era and to determine variables associated with better adherence, including relevant attitudes and beliefs. This is a cross-sectional study enrolling patients who had received antiretroviral therapy for >or=10 years. Adherence was evaluated through self-reporting and plasma drug concentrations. Treatment variables, attitudes and beliefs were collected during structured interviews. The results show that for 87 patients the median (interquartile range) time on therapy was 13 (10-19) years; 80 were on therapy at the time of analysis. Adherence was >or=95% in 54 patients (67.5%), 90-94% in 22 (27.5%) and <90% in 4 (5%). Drug concentrations were below the lower limit of detection in five patients. Younger age (p=0.014), female gender (p=0.005), current substance abuse (p=0.004) and hepatitis C virus co-infection (p<0.001) were related to lower adherence. Adherence did not differ in relation to different drug families or once- or twice-daily regimens. Patients with adherence <95% were more likely to have interrupted treatment without doctor's recommendation (p=0.009). Adherent patients exhibited a higher perception of risk of developing the illness and of benefits of therapy, higher self-efficacy and intention to adhere and were more influenced by events that motivate medication intake. To conclude, adherence was >90% in most patients on antiretroviral therapy for >or=10 years. Adherence was more related to beliefs about health and illness than to the characteristics of medication or level of knowledge about treatment. Care adherence interventions should include assessment of health beliefs.

Targeting only reverse transcriptase with zidovudine/lamivudine/abacavir plus tenofovir in HIV-1-infected patients with multidrug-resistant virus: a multicentre pilot study.

OBJECTIVES: To evaluate the safety, immunological outcome and HIV-1 evolution in the reverse transcriptase (RT) in patients with multidrug resistance receiving zidovudine/lamivudine/abacavir (TZV) plus tenofovir (TDF). METHODS: Pilot analysis of highly experienced patients (n=28), with > or =1 thymidine-associated mutation (TAM) and the M184V mutation. RESULTS: Median of 8.5 treatment regimens, 58% Centers for Disease Control stage C. Baseline (nadir) CD4 count 363 (112) cells/microL. There was a sustained 24-week drop in viral load (VL) of 0.71 HIV-1 RNA copies/mL (P<0.001), with 35.7% (10/28) achieving a VL of <50 copies/mL. The median 24-week decrease in CD4 was -53 cells/microL and only-17 cells/microL when baseline CD4 was <350 cells/microL. There was no evolution in RT mutations, TAMs, accessory mutations or K65R. No clinical progression and one out of 28 suspected abacavir Hypersensitivity Reaction (HSR). Lower probability of achieving VL<400 copies/mL was associated with D67N (P=0.007), D67N/M41L (P=0.01), > or =3 TAMs (P=0.07) and VL>10 000 copies/mL (P=0.01). Mutations conferring zidovudine hypersusceptibility (Y181C, K65R and L74V) did not improve virological or immunological outcomes. Better CD4 outcomes were seen in patients without M41L (P=0.04) or with baseline VL<10,000 copies/mL (P=0.01). CONCLUSIONS: A bridging regimen with TZV+TDF prevents significant immunological decline and may forestall viral evolution in HIV-1 RT despite persistent viral replication.

Hepatotoxicity of nevirapine in virologically suppressed patients according to gender and CD4 cell counts.

OBJECTIVES: A warning advising a higher risk of hepatotoxicity in antiretroviral-naive patients starting a nevirapine-containing combination antiretroviral therapy (NcART) has been issued by health authorities. It is unclear whether this higher risk also applies to stable virologically suppressed patients starting NcART. METHODS: We performed a meta-analysis of published randomized studies including virologically suppressed patients who switched to NcART with a follow-up >or=3 months. CD4 cell cell counts were classified as high (HCD4) (400 cells/microL for males and 250 cells/microL for females) or low (LCD4). The main endpoint was hepatotoxicity within the first 3 months. RESULTS: Four studies with a pooled total of 410 patients were included. The risk of hepatotoxicity within the first 3 months was 2% and 4% in the LCD4 and HCD4 groups, respectively, with a combined odds ratio of 1.46 [95% confidence interval (CI) 0.43-4.98; P=0.54]. The risk of hepatotoxicity at any point during the study was similar in both groups, with a combined hazard ratio of 0.8 (95% CI 0.3-2.5; P=0.80). CONCLUSIONS: In our study, virologically suppressed patients switching to nevirapine did not have a significantly higher risk of hepatotoxicity or rash when stratified by gender and CD4 cell count, although small differences may have gone undetected because of the sample size limitation.

Transient treatment exclusively containing nucleoside analogue reverse transcriptase inhibitors in highly antiretroviral-experienced patients preserves viral benefit when a fully active therapy was initiated.

BACKGROUND: We determined whether coformulated zidovudine/lamivudine/abacavir plus tenofovir could maintain immune status in comparison with a genotype-guided salvage regimen in highly pretreated patients. METHOD: This was a randomized pilot control-arm study. The primary endpoint was the proportion of patients who maintained their CD4+ T-cell count at Week 48. RESULTS: Thirteen patients were randomized to the study arm and 10 to the control arm. At 48 weeks, 8 (64%) patients in the study arm and 10 (100%) in the control arm maintained their immune status (p = .09). No new AIDS-defining events occurred. Three patients (27%) in the study arm and 5 (50%) in the control arm achieved an undetectable viral load (p = .39). When a fully suppressive regimen was initiated, 69% of patients in the study arm (9 patients) and 60% (6 patients) in the control arm reached <50 copies at 96 weeks (p = .98). CONCLUSION: Although no statistically significant differences in immunological course were observed between the arms, the control group achieved better results after 48 weeks. This transient therapy could be reserved for specific patients in whom the risk of incomplete adherence or toxicity compromises efficacy while they are awaiting a fully active drug, without jeopardizing viral efficacy when a fully suppressive regimen is initiated.

[Varicella pneumonia in the adult. Study of 9 cases]. / Neumonía varicelosa en el adulto. Estudio de nueve casos.

BACKGROUND: In the adult, the primary infection by the varicella-zoster virus acquires an unusual severity due to several complications, the most frequent of them being pneumonia. We study the main characteristics of nine patients diagnosed of pneumonia varicellosa. METHODS: Clinical, therapeutic and evolutive features of 9 adult patients, both immunocompetents and immunodepressed, diagnosed of pneumonia varicellosa are retrospectively reviewed, in the last ten years, at Hospital de Sant Pau, Barcelona. Diagnosis of varicella was established on the basis of the typical rash in the context of a feverish illness. The antecedents of smoking habit, pregnancy and underlying disease, evaluating especially arterial blood and platelet count at entrance, are assessed. RESULTS: Nine patients (4 males and 5 women; mean age 38 years) were included in the study. Seventy-eight percent of patients were smokers of more than 20 cigarettes a day; one met criteria of simple chronic bronchitis, another suffered ankylosing spondylitis and three were known carriers of human immunodeficiency virus. None of the female patients was pregnant. Respiratory symptoms began from the third and fifth day after the skin rash, and the most common symptoms were cough (89%), dyspnea (67%) and hemoptysis (22%). Arterial blood gas determination showed hypoxemia in four patients (45%). Chest X-ray revealed an interstitial pattern predominantly at both bases, with a case of right pleural effusion. Intravenous acyclovir was started in 6 patients, foscarnet in one and symptomatic therapy in two patients. All patients had a favourable clinical course, none of them requiring entrance to the Intensive Care Unit. CONCLUSIONS: Adult patients with varicella pneumonia that suffer respiratory insufficiency, thrombocytopenia or are carriers of base illnesses must be early treated with intravenous acyclovir. However, despite clinical, biological and radiological recovery is earlier with such treatment, the evolution seems equally favourable if it is only conducted, for instance, symptomatic therapy with antithermic and antihistaminic compounds.

Antiretroviral treatment simplification with nevirapine in protease inhibitor-experienced patients with hiv-associated lipodystrophy: 1-year prospective follow-up of a multicenter, randomized, controlled study.

BACKGROUND: Simpler and less toxic antiretroviral strategies are needed to maximize treatment compliance without sacrificing potency, at least for drug-experienced HIV-infected patients currently on regimens containing protease inhibitors (PIs). Small nonrandomized studies have suggested a beneficial role of PI-sparing regimens on lipodystrophy. OBJECTIVES: To assess the virologic, immunologic, and clinical benefit of switching the PI to nevirapine in patients with HIV-associated lipodystrophy and sustained viral suppression before entry in the study. DESIGN: Open-labeled, prospective, randomized, multicenter study. SETTING: Seven reference inpatient centers for HIV/AIDS in Spain. PATIENTS: One hundred six HIV-infected adults with clinically evident lipodystrophy who sustained HIV-RNA suppression for at least 6 months with PI-containing antiretroviral combinations. INTERVENTION: Replacement of the PI with nevirapine during 48 weeks (Group A) versus continuing the prior PI (Group B). MEASUREMENTS: Several virologic and immunologic analyses, standard and specific biochemical tests, and anthropometric and dual X-ray absorptiometry measurements. RESULTS: At week 48, an HIV-1 RNA level <400 copies/ml was maintained in 79% and 77% of patients in Groups A and B, respectively, whereas 74% and 72% of patients had viral load levels <50 copies/ml. Absolute CD4+ counts significantly increased in both groups compared with baseline values, and a significant decrease in CD38+CD8+ cells was observed in Group A (p <.01) but not in group B. Overall, no significant changes in anthropometric or body shape measurements were found after 48 weeks. Fasting total cholesterol and triglyceride levels decreased in Group A (but not in Group B) compared with baseline values (p <.05), although no significant differences were seen between groups at the end of the study. Subjects in Group A reported a better quality of life (QOL) index than controls (p <.001), with the main reason reported being the greater simplicity of the new drug regimen. CONCLUSIONS: Protease inhibitor-sparing regimens, including nevirapine, seem to be an effective alternative for PI-experienced patients. Nevirapine-based triple therapies allow maintained control of HIV-1 RNA levels and improve the immunologic response at 48 weeks of follow-up in patients with prior sustained virologic suppression. The switch to nevirapine significantly improved the lipidic profile in Group A, although there were no differences between groups at the end of the study. Additionally, no significant changes were seen in terms of lipodystrophy-related body shape changes 1 year after the PI substitution. Finally, nevirapine-containing regimens have a simpler dosing schedule, and this facilitates high adherence and improves QOL.

Prospective randomized two-Arm controlled study to determine the efficacy of a specific intervention to improve long-term adherence to highly active antiretroviral therapy.

BACKGROUND: Nearly perfect compliance seems to be indispensable to obtain the maximum benefit from highly active antiretroviral therapy (HAART). Interventions to ensure a high level of adherence during a relatively long-term period of therapy are necessary. METHODS: This is a prospective, randomized, two-arm controlled study including patients starting their first-or second-line HAART who were randomized to receive psychoeducative intervention to implement adherence (experimental group [EG]) or a usual medical follow-up (control group [CG]). We aimed to study the efficacy of a psychoeducative intervention to ensure long-term adherence to HAART, its relation with the virologic efficacy of treatment, and to determine the variables related to long-term adherence. Visits were made at weeks 0, 4, 24, and 48 for data collection. Self-reported adherence was registered at each visit and its veracity was tested by randomized blood analyses performed without previous warning to 40% of patients. Appropriate adherence was defined as the consumption of >/=95% of medication prescribed. Statistical analyses were performed both by the as treated (AT) and the intention to treat missing = failure (ITT) methods. RESULTS: In all, 116 patients were included. At week 48, 94% of patients in the EG versus 69% controls achieved adherence >/=95% (p =.008); 89% of patients in the EG versus 66% controls had HIV-1 RNA levels <400 copies/ml (p =.026). Overall, 85% of patients with adherence >/=95% but only 45% of those with adherence <95% had viral load (VL) <400 copies/ml (p =. 008). In multivariate analysis, variables significantly related to adherence were having received a psychoeducative intervention (odds ratio [OR], 6.58; p =.04), poor effort to take medication (OR, 5.38; p =.03), and high self-perceived capacity to follow the regimen (OR, 13.76; p =.04). Self-reported adherence and drug plasma levels coincided in 93% of cases. However, differences in adherence did not reach statistical significance in the ITT analysis although a clear tendency toward benefit was observed in EG. CONCLUSIONS: Specific and maintained psychoeducative interventions based on excellence on clinical practice are useful to keep high levels of adherence as well as high levels of viral suppression. There is a clear relation between high adherence levels and virologic success. Assessment of certain specific variables related to adherence may be helpful to monitor patient's compliance in the clinical setting.