Effectiveness and safety of dual therapy with rilpivirine and boosted darunavir in treatment-experienced patients with advanced HIV infection: a preliminary 24 week analysis (RIDAR study).

BACKGROUND: The objective was to analyze the effectiveness and safety of dual therapy with rilpivirine plus boosted-darunavir (RPV + bDRV) in real-life patients. METHODS: Observational, retrospective, multi-center study in HIV+ patients who had received RPV + bDRV for 24 weeks to optimize/simplify their previous antiretroviral treatment. We determined the percentage of patients without virologic failure (2 consecutive viral loads > 50 copies/mL) at 24 weeks of treatment. RESULTS: The study included 161 patients from 15 hospitals with median age of 49 years; 29.3% had previous AIDS stage and median CD4+ lymphocyte nadir of 170 cells/uL. They had been diagnosed with HIV for a median of 17 years and had received 14 years of ART, with five previous treatment combinations, and 36.6% had a history of virological failure. The reasons for the switch were simplification/optimization (49.7%), toxicity/intolerance (17.4%), or inadequate effectiveness of previous ART (10.6%). Baseline VL of 50-1000 copies/mL was recorded in 25.5% of the patients. In the"intention-to-treat" analysis at 24 weeks, 87.6% of 161 patients continued the study treatment without virologic failure criteria. In the "on treatment" analysis (excluding patients who discontinued treatment with dual therapy for any reason other than virologic failure) the efficacy was 94.6% (141/149 patients). CONCLUSIONS: Dual therapy with RPV + DRVb proved to be effective and safe in patients with advanced HIV infection, long exposure to ART, low CD4 nadir, previous virologic failure, and/or history of ineffective ART.

Executive summary: Prevention and treatment of opportunistic infections and other coinfections in HIV-infected patients: May 2015.

Opportunistic infections continue to be a cause of morbidity and mortality in HIV-infected patients. They often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an opportunistic infection. The present article is an executive summary of the document that updates the previous recommendations on the prevention and treatment of opportunistic infections in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome. This document is intended for all professionals who work in clinical practice in the field of HIV infection.

Prevention and treatment of opportunistic infections and other coinfections in HIV-infected patients: May 2015.

Despite the huge advance that antiretroviral therapy represents for the prognosis of infection by the human immunodeficiency virus (HIV), opportunistic infections (OIs) continue to be a cause of morbidity and mortality in HIV-infected patients. OIs often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an OI. The present article updates our previous guidelines on the prevention and treatment of various OIs in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome.

Renal safety of coformulated tenofovir/emtricitabine vs other nucleoside analogues in combination therapy in antiretroviral-naive patients aged 50 years or older in Spain: The TRIP study.

OBJECTIVES: Our aim is to describe the impact of emtricitabine (FTC)/tenofovir (TDF) versus other nucleoside reverse transcriptase inhibitor (NRTIs)-based regimens on renal function of human immunodeficiency virus (HIV) naïve patients >50 years old who started combination antiretroviral therapy (cART). DESIGN: National, retrospective cohort analysis of patients >50 years old when they started cART (January 1, 2006-December 31, 2009). METHODS: We compared renal safety (changes in estimated glomerular filtration rate [eGFR] during the first year, and time to renal events during 4 years of follow-up) in FTC/TDF versus non-FTC/TDF users. Among FTC/TDF users, we compared protease inhibitors vs non-nucleoside reverse transcriptase inhibitors and Lopinavir/ritonavir vs Efavirenz. RESULTS: We included 103 patients: median age: 54.9 years, 84% males, median CD4 count 247 cells/µl, median viral load 4.7 log; median follow up 18 months (max: 48 months); 73 started with FTC/TDF and 30 with other NRTIs. Change in eGFR was significantly worse for ritonavir-boosted lopinavir (LPV/r) vs efavirenz (EFV) users in the FTC/TDF group (71.2 vs 98.9 ml/min/1.73 m(2) at month 12, P < 0.05). The risk of renal events (progression to an Chronic Kidney Disease Epidemiology Collaboration value < 60 ml/min/1.73 m(2) in subjects with baseline values >60) was comparable for FTC/TDF users and non users, but was higher and almost significant for LPV/r as compared to EFV users in the FTC/TDF group (adjusted hazard ratio 6.1, 95% CI 0.8-45.5). CONCLUSIONS: In our study with a population of HIV infected subjects ≥ 50 years old, renal safety was similar for FTC/TDF and other NRTI-based regimens, but worse for LPV/r as compared to other regimens.

[Executive summary of the recommendations on the evaluation and management of renal disease in human immunodeficiency virus-infected patients]. / Resumen ejecutivo del documento de consenso sobre el manejo de la patología renal en pacientes con infección por el virus de la inmunodeficiencia humana.

The aim of this article is to update the 2010 recommendations on the evaluation and management of renal disease in human immunodeficiency virus (HIV)-infected patients. Renal function should be monitored in all HIV-infected patients. 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 glycosuria. 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 provides indications for renal biopsy and advises on the optimal time for referral of a patient to the nephrologist. The indications for and evaluation and management of dialysis and renal transplantation are also addressed.

Safety, efficacy, and persistence of emtricitabine/tenofovir versus other nucleoside analogues in naive subjects aged 50 years or older in Spain: the TRIP study.

OBJECTIVES: Current antiretroviral guidelines state that being older than 50 to 55 years of age is an indication to start antiretroviral therapy (ART), regardless of CD4 status. However, no references to the preferred combination ART (cART) for these patients have been described. Our study compares emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) versus other nucleoside reverse transcriptase inhibitor (NNRTI) regimens in HIV ART-naïve patients who are ≥50 years. DESIGN: National, retrospective cohort analysis of patients who were ≥50 years old when they began the first cART (January 1, 2006 to December 31, 2009). METHODS: We compared safety, effectiveness, and persistence of treatment in FTC/TDF versus non-FTC/TDF users. Among FTC/TDF users, we compared protease inhibitor (PI) versus NNRTI users and lopinavir/r versus efavirenz users. RESULTS: We included 161 patients: median age was 54.6 years, 83% were men, median CD4 count was 191 cells/µL, median viral load was 4.7 log, and median follow-up was 19 months (maximum, 48 months). Of these participants, 112 started with FTC/TDF and 49 with other nucleotide reverse transcriptase inhibitors (NRTIs). During follow-up, 21.9% of subjects developed at least one laboratory event ≥grade 3, 5.6% interrupted cART due to adverse events,19.3% had virologic failure, and 49.1% modified cART. There were no statistically significant differences between FTC/TDF and non-FTC/TDF users for any output except for persistence: The proportion of subjects who changed cART was 71.4% for non-FTC/TDF users and 38.6% for FTC/TDF users (log rank 0.001; adjusted hazard ratio, 2.10; 95% CI, 1.34-3.29). CONCLUSIONS: In a population of HIV-infected subjects who were ≥50 years old, our study suggests that the use of FTC/TDF is generally safe and effective, with a longer persistence as compared to other regimens.

Daily tenofovir disoproxil fumarate/emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19: a double-blind placebo-controlled randomized trial in healthcare workers.

OBJECTIVES: To assess the effect of hydroxychloroquine (HCQ) and Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) as pre-exposure prophylaxis on COVID-19 risk. METHODS: EPICOS is a double-blind, placebo-controlled randomized trial conducted in Spain, Bolivia, and Venezuela. Healthcare workers with negative SARS-CoV-2 IgM/IgG test were randomly assigned to the following: daily TDF/FTC plus HCQ for 12 weeks, TDF/FTC plus HCQ placebo, HCQ plus TDF/FTC placebo, and TDF/FTC placebo plus HCQ placebo. Randomization was performed in groups of four. Primary outcome was laboratory-confirmed, symptomatic COVID-19. We also studied any (symptomatic or asymptomatic) COVID-19. We compared group-specific 14-week risks via differences and ratios with 95% CIs. RESULTS: Of 1002 individuals screened, 926 (92.4%) were eligible and there were 14 cases of symptomatic COVID-19: 220 were assigned to the TDF/FTC plus HCQ group (3 cases), 231 to the TDF/FTC placebo plus HCQ group (3 cases), 233 to the TDF/FTC plus HCQ placebo group (3 cases), and 223 to the double placebo group (5 cases). Compared with the double placebo group, 14-week risk ratios (95% CI) of symptomatic COVID-19 were 0.39 (0.00-1.98) for TDF + HCQ, 0.34 (0.00-2.06) for TDF, and 0.49 (0.00-2.29) for HCQ. Corresponding risk ratios of any COVID-19 were 0.51 (0.21-1.00) for TDF + HCQ, 0.81 (0.44-1.49) for TDF, and 0.73 (0.41-1.38) for HCQ. Adverse events were generally mild. DISCUSSION: The target sample size was not met. Our findings are compatible with both benefit and harm of pre-exposure prophylaxis with TDF/FTC and HCQ, alone or in combination, compared with placebo.

Low-Level Viremia Is Associated With Clinical Progression in HIV-Infected Patients Receiving Antiretroviral Treatment.

BACKGROUND: The objective of this study was to investigate the long-term impact of low-level viremia (LLV) on all-cause mortality, AIDS and non-AIDS events (NAEs), and virological failure in patients receiving antiretroviral therapy (ART). METHODS: We analyzed ART-naive adults from the cohort of the Spanish AIDS Research Network (CoRIS) who initiated ART from 2004 to 2015 and achieved plasma viral load (VL) below 50 copies per milliliter. LLV50-199 was defined as 2 consecutive VL between 50 and 199 copies per milliliter, and LLV200-499 as 2 consecutive VL between 50 and 499 copies per milliliter with at least one between 200 and 499 copies per milliliter. Multivariable Cox models were used to estimate the association of LLV with AIDS events/death, non-AIDS events, and virological failure. RESULTS: Of 5986 patients included, 237 (4.0%) experienced LLV50-199 and 168 (2.8%) developed LLV200-499. One hundred seventy-one patients died or developed an AIDS event, 245 had any serious NAE and 280 had virological failure. LLV200-499 was strongly associated with a higher risk of both AIDS events/death [adjusted hazard ratio (aHR), 2.89; 95% confidence interval (CI), 1.41 to 5.92] and virological failure (aHR, 3.25; 95% CI: 1.77 to 5.99), whereas no differences were observed between LLV50-199 and no LLV neither for AIDS events/death (aHR, 1.84; 95% CI: 0.89 to 3.82) nor virological failure (aHR, 1.42; 95% CI: 0.78 to 2.58). LLV was not associated with the occurrence of any serious NAE. CONCLUSIONS: In this cohort, LLV200-499 was strongly associated with AIDS events/death and virological failure, but not with any serious NAE. Therefore, vigorous treatment should be implemented in patients with more than 200 copies per milliliter.

Premature treatment discontinuation in HIV/HCV-coinfected patients receiving pegylated interferon plus weight-based ribavirin.

BACKGROUND: Chronic hepatitis C therapy in HIV patients is often penalized by more frequent premature treatment discontinuations. It is unclear what the relative contribution of more adverse events and/or early virological failures are. METHODS: PRESCO was a prospective, multicentre, comparative trial, in which 389 HIV/HCV-coinfected patients with CD4+ T-cell counts >300 cells/ml and elevated aminotransferases received pegylated interferon-alpha2a (peg IFN-alpha2a) 180 mg per week plus ribavirin (RBV) 1,000-1,200 mg daily. Patients with HCV genotypes 1 or 4 were treated for 48 or 72 weeks while HCV genotypes 2 or 3 carriers were treated for 24 or 48 weeks. Use of didanosine was not allowed. RESULTS: Sustained virological response (SVR) was achieved by 193 (49.6%), and was significantly greater in HCV-2/3 than in HCV-1/4 patients (72.4% versus 35%; P<0.0001). Premature treatment discontinuations occurred in 174 patients (44.7%). This was due to early virological failure in 66 (17%), serious adverse events in 32 (8.2%), loss-to-follow-up in 12 (3.1%) and voluntary withdrawal in 64 (16.4%). Only 10 patients (2.6%) stopped HCV therapy due to severe anaemia. Two patients stopped HCV medication due to symptomatic mitochondrial toxicity. There were no episodes of hepatic decompensation. CONCLUSIONS: Treatment with RBV 1,000-1,200 mg/day plus peg IFN-alpha2a is relatively safe and provided SVR in nearly half of the HIV/HCV-coinfected patients, twice as many amongst the HCV-2/3 than HCV-1/4 carriers. Avoidance of didanosine, limited use of zidovudine and therapy restricted to patients with CD4+ T-cell counts >300 cells/ml most probably explains the lower and different spectrum of serious adverse events in PRESCO compared with prior trials conducted in coinfected patients.

Role of weight-based ribavirin dosing and extended duration of therapy in chronic hepatitis C in HIV-infected patients: the PRESCO trial.

The response to pegylated interferon (pegIFN) plus ribavirin (RBV) as treatment of chronic hepatitis C virus (HCV) infection is lower in HIV-coinfected than in HCV-monoinfected patients and could be due to suboptimal RBV dosing and/or insufficient duration of therapy in prior trials. In a prospective, multicenter, open, comparative trial, HCV/HIV-coinfected patients received pegIFN plus weight-based RBV for 48 or 72 weeks (HCV genotypes 1 and 4) and 24 or 48 weeks (HCV genotypes 2 and 3). Use of didanosine was not allowed. Out of 389 patients included in the trial, 61% were infected by HCV-1/4 and 67% had serum HCV-RNA >500,000 IU/ml. Sustained virological response (SVR) was achieved by 49.6%, significantly higher in HCV-2/3 than HCV-1/4 (72.4% vs. 35%; p < 0.0001). A high drop-out rate in the longer treatment arms precluded obtaining definitive conclusions about the efficacy of prolonging therapy. Premature treatment discontinuations due to serious adverse events occurred in 8.2%. Infection with HCV-2/3, lower baseline HCV-RNA, and negative HCV-RNA at week 12 were all independent predictors of SVR in the multivariate analysis. The use of RBV 1000-1200 mg/day plus pegIFN is relatively safe and provides SVR in nearly half of coinfected patients, twice as high in HCV-2/3 than HCV-1/4.

Effectiveness and safety of simplification therapy with once-daily tenofovir, lamivudine, and efavirenz in HIV-1-infected patients with undetectable plasma viral load on HAART.

OBJECTIVE: To evaluate the effectiveness and tolerability of a simplification regimen with tenofovir DF (TDF), lamivudine (3TC), and efavirenz (EFV) in HAART-experienced HIV-1-infected subjects with sustained viral suppression. METHOD: Patients with HIV-1 RNA <200 copies/mL during the previous 6 months and who switched their current twice-daily or three-times-daily HAART to a simplified once-daily regimen of TDF (300 mg), 3TC (300 mg), and EFV (600 mg) were included. RESULTS: 154 patients (70% males, mean age 42 years) were included. Previous HAART included a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen in 55% of the patients and a thymidine analog in 87%. The percentage of patients with viral load <200 copies/mL in the intent-to-treat (ITT) data set was 83% at 6 months and 75% at 12 months (98% and 96%, respectively, in the on-treatment [OT] analysis). Five patients (3%) were identified as virologic failures according to the study protocol. The mean CD4 T-cell count increased significantly 12 months after simplification (from 570 to 632 cells/mm3; p < .01). At 12 months, mean triglyceride levels decreased from 233 to 170 mg/dL (p < .01) and mean cholesterol levels decreased from 205 to 189 mg/dL (p < .01). Thirty-three patients (21%) discontinued the study treatment prior to completing the 12-month follow-up. CONCLUSION: Simplification to a once-daily regimen containing TDF, 3TC, and EFV is virologically and immunologically effective, well-tolerated, and safe with benefits in the lipid profile in the majority of patients.

[Efficacy and safety of a reduced-dose of stavudine in HIV-infected patients under immunological and virological stable conditions]. / Impacto de la reducción de dosis de estavudina en su perfil de eficacia/seguridad en pacientes con infección por el virus de la inmunodeficiencia humana inmunológica y virológicamente estables.

BACKGROUND AND OBJECTIVE: Stavudine (d4T) has shown a favourable short and long-term tolerability profile. Nevertheless, its usage is currently decreasing due to some safety concerns. We aimed to evaluate the efficacy and safety of d4T low-dose-based regimens. PATIENTS AND METHOD: This was a multicenter and retrospective review chart of patients receiving standard doses of d4T for > or = 6 months (weight > 60 kg: 40 mg/12 h; weight < 60 kg: 30 mg/12 h) and having undetectable viral load for at least 3 months before the d4T dose reduction (weight > 60 kg: 30 mg/12 h; weight < 60 kg: 20 mg/12 h). Immunological and viral parametres, lipid profile and side effects were determined. RESULTS: A total of 982 patients were included. The main reason for reducing the dose was prevention of toxicity (76%). After 6 months of follow-up, 97% and 84% patients had less than 400 and 50 cp/ml, respectively, and the CD4 cell count increased by 38 cel/ml. Lipids, lipodystrophy and peripheral polineuropathy improved but there was no statistical significance. CONCLUSIONS: A d4T dose reduction in an immuno-virologically stable population does not affect treatment efficacy. Longer follow-ups are required to confirm improvements in the safety profile.

Impact of ribavirin exposure on early virological response to hepatitis C therapy in HIV-infected patients with chronic hepatitis C.

BACKGROUND: The use of pegylated interferon (PEG-IFN) plus ribavirin (RBV) is currently the recommended treatment for chronic hepatitis C virus (HCV) infection. Coinfection with HIV is a negative predictor of response, for reasons not well understood. METHODS: We examined the virological response at weeks 4 and 12 in 198 HCV/HIV-coinfected patients enrolled in a prospective trial in which PEG-IFN alpha 2a (180 microg per week) and RBV (1000-1200 mg daily) were provided. RESULTS: In an on-treatment analysis, 52.8% of patients achieved undetectable HCV-RNA (<600 IU/ml) at week 4, while 63% and 77.2% of patients had a decline of at least 2 and 1 log10, respectively. At week 12, 73.1% of patients reached undetectable HCV-RNA, and 83.5% and 89% achieved at least a 2- and 1-log10 drop, respectively. More than 85% of HCV genotypes 2/3 cleared HCV-RNA at week 4, a proportion significantly higher when compared with genotypes 1 (33.8%) and 4 (28.6%). Multivariate logistic regression analysis identified genotype 3 and RBV exposure (mg/kg of body weight) as independent predictors of virological response at week 12 of therapy. CONCLUSION: Early virological response rates to PEG-IFN plus RBV in HCV/HIV-coinfected patients seem to be similar to those reported for HCV-monoinfected subjects. The use of suboptimal doses of RBV in most earlier trials might account for the low response rates seen in coinfected patients. To our knowledge, this is the first report demonstrating that RBV exerts a significant independent effect on early virological response. Therefore, strategies aimed at optimizing doses and adherence to RBV might help to improve responses to HCV therapy in coinfected patients.

Treatment-limiting toxicities associated withnucleoside analogue reverse transcriptase inhibitor therapy: A prospective, observational study.

BACKGROUND: The Recover Study is an ongoing, prospective study designed 10 to assess toxicity associated with the use of nucleoside analogue reverse transcriptase inhibitors (NRTIs) (stavudine, zidovudine, lamivudine, didanosine, abacavir) in HIV-1-infected patients receiving highly active antiretroviral therapy (HAART) in routine clinical practice. This project is being conducted at 120 HIV units at teaching hospitals across Spain. OBJECTIVE: The aim of this study was to identify the most common treatment-limiting 10 moderate to severe clinical and laboratory adverse effects (AEs), and the individual NRTIs involved in the development of these effects, in HIV-1-infected patients receiving HAART who discontinued use of an NRTI in the Recover Study. METHODS: Patients eligible for participation in the Recover Study are aged10 ≥18 years; have virologically documented HIV-1 infection; have sustained viral suppression (viral load <200 cells/mL or stable, heavily experienced [ie, have received ≥3 antiretroviral regimens] patients with viral load <5000 cells/mL) for ≥6 months; are receiving HAART; are undergoing active follow-up; and have developed 2:1 NRTI-associated AE that, in the opinion of a study investigator and under the conditions of routine clinical practice, justified discontinuation of treatment with the offending drug (principal AE/offending NRTI). The present study included patients recruited for the Recover Study between September 2002 and May 2003. RESULTS: A total of 1391 patients were enrolled (966 men, 425 women; mean 1 age, 42 years [range, 18-67 years]). Five hundred six patients (36.4%) had been diagnosed with AIDS. The mean duration of treatment with the offending NRTI was 74 months (range, 6-156 months). Seven hundred nine patients (51.0%) were receiving fourth-line (or more) therapy. Eight hundred twenty-one patients (59.0%) were receiving nonnucleoside analogues, and 552 patients (39.7%), protease inhibitors, as components of their HAART regimens. The NRTIs with the highest discontinuation rates were stavudine (914 patients [65.7%]) and zidovudine (177 [12.7%]). The most frequent NRTI-related AEs were lipoatrophy (550 patients [39.5%]) and peripheral neuropathy (170 [12.2%]). Lipoatrophy was most commonly associated with stavudine (480/550 cases [87.3%]); periph eral neuropathy, with stavudine and didanosine (107/170 [62.9%] and 48/170 [28.2%] cases, respectively); and anemia, with zidovudine (70/77 cases [90.9%]). CONCLUSIONS: The results of this study in patients with HIV-1 recruited in the10 Recover Study and undergoing HAART suggest that long-term treatment with NRTIs is associated with AEs (lipoatrophy, peripheral neuropathy, and lipodystrophy), with morphologic disorders (lipoatrophy, lipodystrophy) being the most common AEs leading to discontinuation. Minimizing these AEs by switching to an NRTI not associated with these AEs (eg, tenofovir) would contribute to adherence and hence efficacy of long-term HAART.

Liver Fibrosis progression using Fibroscan in HIV/HCV coinfected patients with undetectable HIV viral load.

INTRODUCTION: Several factors such as duration of infection, age, male gender, consumption of alcohol, HIV infection and low CD4 count have been associated with fibrosis progression rate. However, it is relatively scarce, the knowledge about the liver fibrosis progression rate in HIV-infected patients with undetectable HIV viral load (VL). For this reason, we performed the present study. MATERIALS AND METHODS: Observational and multicenter study (2008-2012) conducted in four hospitals of the northern Spain. HIV/HCV (hepatitis c) virus coinfected patients ≥18 years on stable combination antiretroviral therapy (cART) (≥6 months) and with a HIV VL <50 copies/mL were selected to analyze their liver fibrosis progression. Fibrosis progression was assessed using a Fibroscan® (502 STEP 3 model) and measuring a basal test and a second one at least 12 months apart from baseline. This evolution was compared with different variables such as duration of HIV/HCV coinfection, gender, age, previous treatment for HCV, HCV genotype, CD4 lymphocyte counts and the cART employed at the basal test. RESULTS: A total of 608 patients were included (median age 29.4 years, 71.7% men). Of these, 463 patients met the inclusion criteria. In these patients, the liver fibrosis progression was nearly flat and the only variables related to a higher liver fibrosis progression were the increasing age of the patients (p=0.02) and the duration of the coinfection (p=0.001). CD4 lymphocyte counts showed a tendency to improved liver fibrosis (p=0.056). CONCLUSIONS: In HIV/HCV coinfected patients on stable cART and HIV undetectable VL, the increase in liver fibrosis rate progression was nearly flat, although it was significantly associated with the duration of the coinfection and the age of the patient. The beneficial effects of the cART were independent of the antiretroviral drug employed. A tendency to a lower fibrosis progression was observed in those patients with a higher CD4 count.

Dual therapy with darunavir/r plus etravirine is safe and effective as switching therapy in antiretroviral experienced HIV-patients. The BITER Study.

INTRODUCTION: Switching therapy studies are usually designed as second-line antiretroviral treatment (ART) in patients without previous virologic failures. Combined ART (cART) with DRV/r and ETR has a good pharmacokinetic profile, high genetic barrier and has been proved as rescue therapy. The aim of our study was to analyze efficacy and safety of therapy with DRV/r plus ETR in treatment experienced HIV-patients with previous therapeutic failures that need to switch ART. We present results at first 24 weeks. METHODS: Multicentre retrospective observational study. INCLUSION CRITERIA: adult HIV-patients on ART with HIV-VL <1000 cop/mL who started their ART with DRV/r (600/100 bid or 800/100 qd)+ETR by adverse events, non-adherence, tolerability or prevention of future complications. Patients with acute AIDS events, HBV, pregnancy, drug addiction or previous selected mutations to DRV or ETR were excluded. RESULTS: Ninety-nine patients were included, mean age: 47 years (r: 22-79); 70% men, 40.4% previous AIDS event and 39.3% HCV. Ninety-one patients had received ≥3 cART regimens and 45≥5, 75 patients had HIV-VL <50 cop/mL and 24 low-level viremia (LLV): 297.5±261.4 cop/mL, CD4+ 568±279 cells/µL. ART before switching: NRTI+PI/r (33%), NNRTI (17%), PI/r+NNRTI (23%), PI/r+INI (13%), other (14%). Main reason to switching was: toxicity/intolerance 50 patients (renal 32%, gastrointestinal: 14%, hyperlipidaemia 10%; osteopenia/osteoporosis: 6%); improving adherence 26 patients; prevention of complications 19 patients. Nine subjects withdrew ART during follow-up because: intolerance or new toxicity three; non-adherence two; simplification to DRV/r monotherapy two; persistence of previous toxicity one; virologic failure one. At week 24, among patients who continued with DRV/r+ETR (n=90): 81 (89%) had VL<50 cop/mL, in those with with HIV-VL<50 at baseline (67/90), 94% persisted with <50 cop., and in those with LLV (24/90), 61% (n=14) achieved a VL<50 cop. We didn't observe any significant difference in lab parameters between baseline and week 24. Estimated glomerular filtrate rate increased from 83.4±24.7 to 88.5±56.8 mL/min, p=NS. Regarding reason to switching, it improved in 42 cases, no changes: 20 cases; worsened: 4 cases, and non-applicable or unknown: 24 cases. CONCLUSIONS: Switching to dual therapy with DRV/r+ETR is an effective strategy in selected heavily experienced ART patients, even in those with LLV (<1000 cop/mL). This cART is safe and well tolerated, can reduce number of pills and improve adherence.

Executive summary of the consensus document on the management of renal disease in HIV-infected patients.

The aim of this article is to update the 2010 recommendations on the evaluation and management of renal disease in HIV-infected patients. Renal function should be monitored in all HIV-infected patients. 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 provides indications for renal biopsy and advises on the optimal time for referral of a patient to the nephrologist. The indications for and evaluation and management of dialysis and renal transplantation are also addressed.

Consensus document on the management of renal disease in HIV-infected patients.

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.

Prevention and treatment of opportunistic infections and other coinfections in HIV-infected patients: may 2015 / Prevención y tratamiento de infecciones oportunistas y otras coinfecciones en pacientes infectados por el VIH: mayo de 2015

Despite the huge advance that antiretroviral therapy represents for the prognosis of infection by the human immunodeficiency virus (HIV), opportunistic infections (OIs) continue to be a cause of morbidity and mortality in HIV-infected patients. OIs often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an OI. The present article updates our previous guidelines on the prevention and treatment of various OIs in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome

A pesar del gran avance que ha supuesto el tratamiento antirretroviral (TAR) para el pronóstico de la infección por el VIH, las infecciones oportunistas (IO) continúan siendo causa de morbilidad y mortalidad en estos pacientes. Ello ocurre en muchos casos debido a la inmunodepresión grave, bien ante la falta de adherencia al TAR, el fracaso del mismo o el desconocimiento de la existencia de la infección por el VIH en pacientes que comienzan con una IO. El presente artículo actualiza las recomendaciones de prevención y tratamiento de diferentes infecciones en pacientes con infección por VIH: parasitarias, fúngicas, víricas, micobacterianas, bacterianas e importadas, además del síndrome de reconstitución inmune