Association of baseline CD4+ cell count and HIV-RNA on sustained virologic response to interferon-ribavirin in HIV/HCV coinfected patients.

UNLABELLED: BACKGROUND AND RATIONALE FOR THE STUDY: We assessed the association of CD4+ T-cell counts and HIV-RNA on sustained viral response (SVR) after therapy with pegylated interferon and ribavirin (PR) in HIV/HCV coinfected patients. We examined two large cohorts of coinfected patients treated with PR in Spain between 2000 and 2008. SVR was defined as undetectable HCV-RNA at 24 weeks after the end of PR. RESULTS: We studied 1682 patients, of whom 38% achieved SVR. Baseline factors independently associated with reduced odds of SVR included genotype 1 or 4, HCV-RNA > 500,000 IU/mL, advanced liver fibrosis, CDC clinical category C, and detectable HIV-RNA. By multivariate logistic regression analysis, we found that, in comparison with patients with combination antiretroviral therapy (cART) and undetectable HIV-RNA, the odds ratio [95% confidence interval (CI)] of SVR was 0.56 (0.41-0.78) for cART and detectable HIV-RNA, 0.86 (0.56-2.57) for no-cART and detectable HIV-RNA, and 1.38 (0.74-2.57) for no-cART and undetectable HIV-RNA. CONCLUSIONS: Detectable HIV-RNA, but not CD4+ T-cell count, was associated with reduced odds of SVR. However, this finding was only confirmed for cART and detectable HIV-RNA, raising the question as whether this represents a true association of HIV-RNA on response to PR or a spurious association due to poor adherence to treatment.

Executive summary of the consensus document on metabolic disorders and cardiovascular risk in patients with HIV infection.

The importance of the metabolic disorders and their impact on patients with HIV infection requires an individualized study and continuous updating. HIV patients have the same cardiovascular risk factors as the general population. The HIV infection per se increases the cardiovascular risk, and metabolic disorders caused by some antiretroviral drugs are added risk factors. For this reason, the choice of drugs with a good metabolic profile is essential. The most common metabolic disorders of HIV infected-patients (insulin resistance, diabetes, hyperlipidemia or osteopenia), as well as other factors of cardiovascular risk, such as hypertension, should also be dealt with according to guidelines similar to the general population, as well as insisting on steps to healthier lifestyles. The aim of this document is to provide a query tool for all professionals who treat HIV-patients and who may present or display any metabolic disorders listed in this document.

[Consensus statement on metabolic disorders and cardiovascular risks in patients with human immunodeficiency virus]. / Documento de consenso sobre alteraciones metabólicas y riesgo cardiovascular en pacientes con infección por el virus de la inmunodeficiencia humana.

OBJECTIVE: This consensus document is an update of metabolic disorders and cardiovascular risk (CVR) guidelines for HIV-infected patients. METHODS: This document has been approved by an expert panel of GEAM, SPNS and GESIDA after reviewing the results of efficacy and safety of clinical trials, cohort and pharmacokinetic studies published in biomedical journals (PubMed and Embase) or presented in medical scientific meetings. Recommendation strength and the evidence in which they are supported are based on the GRADE system. RESULTS: A healthy lifestyle is recommended, no smoking and at least 30min of aerobic exercise daily. In diabetic patients the same treatment as non-HIV infected patients is recommended. HIV patients with dyslipidemia should be considered as high CVR, thus its therapeutic objective is an LDL less than 100mg/dL. The antihypertensive of ACE inhibitors and ARAII families are better tolerated and have a lower risk of interactions. In HIV-patients with diabetes or metabolic syndrome and elevated transaminases with no defined etiology, the recommended is to rule out a hepatic steatosis Recommendations for action in hormone alterations are also updated. CONCLUSIONS: These new guidelines update previous recommendations regarding all those metabolic disorders involved in CVR. Hormone changes and their management and the impact of metabolic disorders on the liver are also included.

Comparison of the prognostic value of liver biopsy and FIB-4 index in patients coinfected with HIV and hepatitis C virus.

BACKGROUND: We compared the prognostic value of liver biopsy (LB) and FIB-4 index in patients with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection. METHODS: We studied patients from the Grupo de Estudio del SIDA 3603 study cohort, in whom fibrosis was evaluated at baseline using both LB (Metavir score) and FIB-4 index. We assessed overall death (OD) and liver-related events (LREs), defined as decompensation or hepatocellular carcinoma, whichever occurred first. We used receiver operating characteristic (ROC) curves to determine the ability of LB and FIB-4 to predict outcomes. We also assessed the association between advanced fibrosis-LB (F3 or greater) or FIB-4 (≥3.25)-and outcomes using multivariate Cox regression analysis. RESULTS: The study sample comprised 903 patients (328 with sustained virologic response [SVR]). Baseline fibrosis by LB was as follows: F0, n = 71; F1, n = 242; F2, n = 236; F3, n = 236; F4, n = 118. Fibrosis by FIB-4 was as follows: ≤1, n = 148; >1 to <3.25, n = 597; ≥3.25, n = 158. After a median follow-up of 62 months, there were 46 deaths and 71 LREs. The area under the ROC curves for OD/LREs was 0.648 and 0.742 for LB and FIB-4, respectively (P = .006). Similar results were found for patients without SVR and for OD and LREs separately. The adjusted hazard ratios of OD or LRE were 1.740 (95% confidence interval [CI], 1.119-2.7.06; P = .014) for advanced fibrosis assessed by LB and 3.896 (95% CI, 2.463-6.160; P < .001) assessed by FIB-4. CONCLUSIONS: FIB-4 outperformed LB as a predictor of OD and LRE. These findings are of relevance for clinical practice and research and call into question the role of LB as a gold standard for assessing prognosis in HIV/HCV coinfection.

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.

Overall and cause-specific mortality in HIV-positive subjects compared to the general population.

INTRODUCTION: Emerging non-AIDS related causes of death have been observed in HIV-positive subjects in industrialized countries. We aimed to analyze overall and cause-specific excess of mortality of HIV-positive patients compared to the general population and to assess the effect of prognostic factors. MATERIAL AND METHODS: We used generalized linear models with Poisson error structure to estimate overall and cause-specific excess of mortality in HIV-positive patients from 2004 to 2012 in the cohort of the Spanish Network of HIV Research (CoRIS), compared to Spanish general population and to assess the impact of multiple risk factors. We investigated differences between short-term and long-term risk factors effects on excess of mortality. Multiple Imputation by Chained Equations was used to deal with missing data. RESULTS: In 9162 patients there were 363 deaths, 16.0% were non-AIDS malignancies, 10.5% liver and 0.3% cardiovascular related. Excess mortality was 1.20 deaths per 100 person years (py) for all-cause mortality, 0.16 for liver, 0.10 for non-AIDS malignancies and 0.03 for cardiovascular. Short-term (first-year follow-up) excess Hazard Ratio (eHR) for global mortality for baseline AIDS was 4.27 (95% CI 3.06-6.01) and 1.47 (95% CI 0.95-2.27) for HCV coinfection; long-term (subsequent follow-up) eHR for baseline AIDS was 0.88 (95% CI 0.58-1.35) and 4.48 (95% CI 2.71-7.42) for HCV coinfection. Lower CD4 count and higher viral load at entry, lower education, being male and over 50 years were predictors for overall excess mortality. Excess of liver mortality was higher in patients with CD4 counts at entry below 200 cells compared to those above 350 (eHR: 6.49, 95% CI 1.21-34.84) and in HCV-coinfected patients (eHR: 3.85, 95% CI 0.85- 17.37), although it was borderline significant. Patients over 50 years old (eHR: 5.55, 95%CI 2.4-12.85) and HCV coinfected (eHR: 5.81, 95% CI 2.6-13) showed a higher risk of non-AIDS malignancies mortality excess. Excess of cardiovascular mortality was related with HCV coinfection (eHR: 6.68, 95% CI 1.25-35.73). CONCLUSIONS: Our results show overall, liver, non-AIDS malignancies and cardiovascular excess of mortality associated with being HIV-positive, despite improvements in HIV disease management and antiretroviral therapies. Differential short-term and long-term effect of AIDS before entry and HCV coinfection was found for overall mortality.

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.

[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.

Effects of sustained viral response in patients with HIV and chronic hepatitis C and nonadvanced liver fibrosis.

OBJECTIVE: We assessed the effects of sustained viral response (SVR), after treating with interferon-ribavirin (IF-RB), on mortality, liver-related (LR) events (decompensation, hepatocellular carcinoma), HIV progression, and liver stiffness in HIV/hepatitis C virus (HCV)-coinfected patients with nonadvanced liver fibrosis. METHODS: From a cohort of HIV/HCV-coinfected patients treated with IF-RB, we selected those with baseline liver fibrosis stages F0, F1, or F2 according to METAVIR. The study started when IF-RB was stopped and ended at death or at the last follow-up visit. RESULTS: A total of 695 patients were included (HCV genotype 1 or 4, 431; F0, 77; F1, 290; and F2, 328), and 274 patients achieved SVR. After a median follow-up of 4.9 years, the adjusted hazard ratio (aHR) [95% confidence interval (CI)] of LR events or overall death, for patients with SVR taking the group of patients with no SVR as a reference was 0.217 (0.079 to 0.599) (P = 0.003) for the whole cohort with F0 to F2. For patients with F0, the aHR (95% CI) was 0.514 (0.040 to 6.593) (P = 0.609), for patients with F1, the aHR (95% CI) was 0.305 (0.053 to 1.762) (P = 0.185), and for patients with F2, it was 0.075 (0.009 to 0.662) (P = 0.020). We also found that, in comparison with no SVR, SVR was followed by less frequent HIV progression for the entire population (F0 to F2) and less frequent liver stiffness across all categories of fibrosis. CONCLUSIONS: SVR in HIV/HCV-coinfected patients with moderate stages of liver fibrosis is associated with a reduction of mortality and LR events, and with a reduction of progression of HIV and liver fibrosis.

Executive summary of the GeSIDA/National AIDS Plan consensus document on antiretroviral therapy in adults infected by the human immunodeficiency virus (updated January 2014).

In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation varies with clinical circumstances, number of CD4 cells, comorbid conditions and prevention of transmission of HIV. The objective of ART is to achieve an undetectable plasma viral load. Initial ART should always comprise a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors and a third drug from a different family (non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or integrase inhibitor). This update presents the causes and criteria for switching ART in patients with undetectable plasma viral load and in cases of virological failure. An update is also provided for the specific criteria for ART in special situations (acute infection, HIV-2 infection, and pregnancy) and with comorbid conditions (tuberculosis or other opportunistic infections, kidney disease, liver disease, and cancer).

HIV/hepatitis C virus-coinfected patients who achieved sustained virological response are still at risk of developing hepatocellular carcinoma.

OBJECTIVE: To describe the frequency and the characteristics of hepatocellular carcinoma (HCC) cases that appeared in HIV/hepatitis C virus (HCV)-coinfected patients with previous sustained virological response (SVR) and to compare these cases to those diagnosed in patients without SVR. METHODS: All HIV/HCV-coinfected patients diagnosed with HCC in 26 hospitals in Spain before 31 December 2012 were analyzed. Comparisons between cases diagnosed in patients with and without previous SVR were made. RESULTS: One hundred and sixty-seven HIV/HCV-coinfected patients were diagnosed with HCC in the participant hospitals. Sixty-five (39%) of them had been previously treated against HCV. In 13 cases, HCC was diagnosed after achieving consecution of SVR, accounting for 7.8% of the overall cases. The median (Q1-Q3) elapsed time from SVR to diagnosis of HCC was 28 (20-39) months. HCC was multicentric and was complicated with portal thrombosis in nine and six patients, respectively. Comparisons with HCC cases diagnosed in patients without previous SVR only yielded a significantly higher proportion of genotype 3 infection [10 (83%) out of 13 cases versus 34 (32%) out of 107; P = 0.001)]. The median (Q1-Q3) survival of HCC was 3 (1-39) months among cases developed in patients with previous SVR, whereas it was 6 (2-20) months in the remaining individuals (P = 0.7). CONCLUSION: HIV/HCV-coinfected patients with previous SVR may develop HCC in the mid term and long term. These cases account for a significant proportion of the total cases of HCC in this setting. Our findings reinforce the need to continue surveillance of HCC with ultrasound examinations in patients with cirrhosis who respond to anti-HCV therapy.

Clinical effects of viral relapse after interferon plus ribavirin in patients co-infected with human immunodeficiency virus and hepatitis C virus.

BACKGROUND & AIMS: Sustained viral response (SVR) after therapy with interferon-ribavirin (IF-RB) reduces liver-related (LR) complications and mortality in HIV/HCV-co-infected patients. Here, we assess the impact of end-of-treatment response with subsequent relapse (REL) on LR events (LR death, liver decompensation, hepatocellular carcinoma, or liver transplantation), and liver stiffness (LS) by transient elastography. METHODS: We analyzed the GESIDA 3603 Cohort (HIV/HCV-co-infected patients treated with IF-RB in 19 centers in Spain). Response to IF-RB was categorized as SVR, REL, and no response (NR). The study started when IF-RB was stopped and ended at death or the last follow-up visit. Multivariate regression analyses were adjusted for age, sex, HIV category of transmission, CDC clinical category, nadir CD4+ cell count, HCV genotype, HCV-RNA viral load, and liver fibrosis. RESULTS: Of 1599 patients included, response was categorized as NR in 765, REL in 250 and SVR in 584. Median follow-up was more than 4 years in each group. Taking the group of patients with NR as reference, we found that the adjusted hazard ratios (95% confidence interval) of liver-related events (liver-related death, liver decompensation, hepatocellular carcinoma, liver transplantation) for patients with REL and for patients with SVR were 0.17 (0.05; 0.50) and 0.03 (0; 0.20), respectively. We also found that SVR was followed by less liver stiffness than both REL and NR. However, REL was associated with less liver stiffness than NR. CONCLUSIONS: Best outcomes were achieved with an SVR. However, REL was associated with less LR mortality, decompensation, and liver stiffness than NR.

Increasing incidence of hepatocellular carcinoma in HIV-infected patients in Spain.

BACKGROUND: To report the clinical and epidemiological characteristics of hepatocellular carcinoma (HCC) diagnosed in a cohort of human immunodeficiency virus (HIV)-infected patients in Spain. METHODS: All HIV-infected patients diagnosed of HCC in 18 hospitals in Spain before 31 December 2010 were included. The main characteristics of HCC cases are described and comparisons between cases according to the year of diagnosis are presented. RESULTS: Eighty-two cases of HCC in HIV-infected patients were included, all of them related to viral hepatitis coinfection: hepatitis C virus (HCV) in 66 (81%), hepatitis B virus (HBV) in 6 (7%), and HBV/HCV in 10 (12%). From 1999, when the first case of HCC was diagnosed, a progressive increment in the incidence of HCC in the cohort has occurred. In patients coinfected with HIV/HCV-coinfected patients, the incidence HCC increased from 0.2 to 2.8 cases per 1000 person-years between 2000 and 2009. Death occurred in 65 patients (79%), with a median survival of 91 days (interquartile range, 31-227 days). Three of 11 patients (28%) who received potentially curative therapy died, compared with 62 of 71 patients (87%) who did not receive curative therapy (P = .0001). Compared with cases of HCC diagnosed before 2005, cases diagnosed later did not show a higher survival rate. CONCLUSIONS: HCC is an emerging complication of cirrhosis in HIV-infected patients. A sharp increase in its incidence has occurred in those also infected by HCV in the recent years. Unfortunately, HCC is frequently diagnosed at an advanced stage, and mortality continues to be very high, with no significant changes in recent years. Earlier diagnosis, which may allow potentially curative therapy, is necessary.

Fat redistribution syndromes associated with HIV-1 infection and combination antiretroviral therapy.

More than 15 years after the introduction of highly active antiretroviral therapy, HIV/HAART-associated lipodystrophy syndrome still shadows the indisputable efficacy of antiretroviral therapy. Several issues related to this complication (prevalence, diagnosis, pathogenesis, prevention, or clinical management) have not been completely clarified. However, in the last years, substantial progress has been made in elucidating some of these basic aspects. This includes a better knowledge of the pathogenic mechanisms underlying HIV/HAART-associated lipodystrophy syndrome such as genetic host determinants, the impact of HIV infection per se, as well as the contribution of antiretroviral therapy. In regard to treatment, we have learned that certain drugs are especially prone to cause HIV/HAART-associated lipodystrophy syndrome (i.e. thymidine analogues). Pharmacological interventions to treat this condition have yielded mostly disappointing results, and the only intervention which offers an immediate aesthetical improvement for patients with HIV/HAART-associated lipodystrophy syndrome is plastic surgery. Even under the most favorable conditions (ideal host genetic make-up, and the timely initiation of HIV therapy with less toxic drugs), current data show that HIV/HAART-associated lipodystrophy syndrome is a complication of HIV infection and/or antiretroviral treatment that we are unable to avoid. In the context of HIV-1-infected patients under long-term antiretroviral therapy, fat toxicity is still the dark side of the rainbow.

[Cardiovascular risk in human immunodeficiency virus-infected patients in Spain. CoRIS cohort, 2011]. / Riesgo cardiovascular en pacientes con infección por el virus de la inmunodeficiencia humana en España. Cohorte CoRIS, 2011.

INTRODUCTION: Current information on cardiovascular risk (CVR) in HIV-infected patients in Spain is limited. METHODS: An analysis was made of a prospective multicentre cohort of Spanish HIV-infected patients (CoRIS) between January-2010 and July-2011. CVR was evaluated using Framingham, REGICOR and SCORE equations. RESULTS: The study included 1019 patients (76% males, mean age 40 years) recruited from 13 hospitals belonging to 10 autonomous communities in Spain. Almost two-thirds (65.4%) of patients were on antiretroviral therapy (ART), 36.7% with non-nucleoside analogs, 24% with protease inhibitors (PIs) (52% with atazanavir/r or darunavir/r) and 4,6% with raltegravir. More than half (56.2%) of the patients had an HIV viral load <50 copies/ml. Smoking prevalence was 46%, HDL cholesterol (HDL-C) <40mg/dl 36.1%, total cholesterol (total-C) >200mg/dl 27.8%, age >45years 27.2%, metabolic syndrome 11.5%, hypertension 9.4%, cocaine use 7%, and diabetes 2.9%. ART was associated with higher total-C and LDL-C concentrations, although also higher HDL-C and lower total-C/HDL-C ratio; patients receiving PIs boosted with a high ritonavir dose showed higher total-C levels and higher total-C/HDL-C ratio. According to Framingham cardiovascular, and coronary, REGICOR, and SCORE equations, 15.2%, 6.4%, 4.2% and 3.9% of patients, respectively, were classified as having moderate or high CVR. CONCLUSION: In HIV-infected patients from CoRIS, prevalence of modifiable CVR factors is still high. Commonly used scores identify a relatively low number of patients with high CVR.

Outcomes in HIV-infected patients admitted due to pandemic influenza.

PURPOSE: To determine the clinical, epidemiological and prognostic factors of HIV-infected patients with influenza A H1N1 admitted to hospital. METHODS: The study population was HIV infected patients with confirmed influenza infection admitted to hospital in a multicenter cohort. We analyzed demographic data, comorbid conditions, severe events (bronchopneumonia, respiratory insufficiency, respiratory distress, sepsis, admission to intensive care unit, death) and outcome. Data were analyzed using descriptive statistics. Proportions were compared using the χ(2) test or Fisher exact test, when applicable. Quantitative variables were compared using the Student t test or Mann-Whitney test. Prognostic impact was analyzed using logistic regression. RESULTS: A total of 43 patients, of whom 62.8% were male, were included from 22 hospitals. The mean age was 43.3 years (interquartile range [IQR], 38.4-48.4). HIV was diagnosed for a mean of 14.5 years (IQR, 8.4-20.3). CD4 lymphocyte was <200 cells/µL in 38%; 85.7% were on antiretroviral therapy, and 66.7% virologically suppressed. Comorbid conditions were hepatitis B or C (74.4%), smoking (67.4%), chronic obstructive pulmonary disease (30.2%), asthma (14%), and obesity (8.6%). Seven patients had received seasonal influenza vaccination, and 2 the H1N1 vaccine. Cough (100%), fever (93%), gastrointestinal disorders (27.9%) or general--myalgia, general malaise--(67.4%) were the presenting symptoms. These were severe in 24 (55.8%) with 7 (16.3%) requiring intensive care. Two patients died. A lower CD4 lymphocyte count was associated with bacterial infection (P=.063) and longer hospital stay (P=.007). Early oseltamivir reduced severe cases (OR, 4.5; 1.1-18.3; P=.035). CONCLUSIONS: HIV-infected patients admitted to hospital due to influenza A H1N1 had severe morbidity. Low CD4 lymphocytes correlated with longer hospitalization and bacterial infections. Early oseltamivir treatment reduced severe symptoms.

Sustained virological response to interferon plus ribavirin reduces liver-related complications and mortality in patients coinfected with human immunodeficiency virus and hepatitis C virus.

UNLABELLED: Human immunodeficiency virus (HIV) infection modifies the natural history of chronic hepatitis C, thus promoting more rapid progression to cirrhosis and end-stage liver disease. The objective of our study was to determine whether hepatitis C virus (HCV) clearance is associated with improved clinical outcomes in patients positive for HIV and HCV. It was an ambispective cohort study carried out in 11 HIV units in Spain and involved 711 consecutive patients positive for HIV/HCV who started interferon plus ribavirin therapy between 2000 and 2005. We measured sustained virologic response (SVR), i.e., undetectable HCV RNA at 24 weeks after the end of treatment, and clinical outcomes, defined as death (liver-related or non-liver-related), liver decompensation, hepatocellular carcinoma, and liver transplantation. Of 711 patients who were positive for HIV/HCV, 31% had SVR. During a mean follow-up of 20.8 months (interquartile range: 12.2-38.7), the incidence rates per 100 person-years of overall mortality, liver-related mortality, and liver decompensation were 0.46, 0.23, and 0.23 among patients with SVR and 3.12, 1.65, and 4.33 among those without SVR (P = 0.003, 0.028, and <0.001 by the log-rank test), respectively. Cox regression analysis adjusted for fibrosis, HCV genotype, HCV RNA viral load, Centers for Disease Control and Prevention clinical category, and nadir CD4+ cell count showed that the adjusted hazard ratio of liver-related events was 8.92 (95% confidence interval, 1.20; 66.11, P = 0.032) for nonresponders in comparison with responders and 4.96 (95% confidence interval, 2.27; 10.85, P < 0.001) for patients with fibrosis grade of F3-F4 versus those with F0-F2.Because this was not a prospective study, selection and survival biases may influence estimates of effect. CONCLUSION: Our results suggest that the achievement of an SVR after interferon-ribavirin therapy in patients coinfected with HIV/HCV reduces liver-related complications and mortality.

[Lopinavir/ritonavir monotherapy. Possible indications]. / Lopinavir potenciado con ritonavir en monoterapia. Posibles indicaciones.

Monotherapy with LPV/r maintains blocked viral replication when used as a simplification strategy from antiretroviral therapy with a boosted protease inhibitor and two nucleoside analogs in patients with an undetectable viral load for at least 6 months. This simplification strategy can be recommended to patients in these circumstances and who are able to maintain near perfect adherence. As recommended by the GESIDA guidelines, LPV/r monotherapy could be offered to patients with undetectable viral loads but who show symptoms or laboratory abnormalities attributable to nucleoside analog toxicity, or co-morbidities such as liver disease or nephropathy; LPV/r monotherapy could also be offered to patients who simply wish to take a lower number of pills. This strategy reduces treatment toxicity and costs, without jeopardizing the patient's future.