Three-year efficacy of switching to dolutegravir plus lamivudine: A real-world study.

BACKGROUND: Dolutegravir (DTG) plus lamivudine (3TC) has proven highly efficacious as a switching strategy in virologically suppressed people with HIV (PWH). As this strategy was introduced relatively recently, real-world, long-term durability studies are lacking. METHODS: We performed a retrospective review of treatment-experienced patients who started DTG + 3TC in a cohort of PWH. HIV-RNA <50 copies/mL was analysed at 144 weeks in an intention-to-treat (ITT) analysis (missing = failure) and a per-protocol (PP) analysis (patients with missing data or changes for reasons other than virological failure were excluded). RESULTS: The study population comprised 358 PWH (19% women). Median age and time with HIV infection were 51.7 and 13.4 years, respectively. The median number of previous antiretroviral combinations was three. Previous virological failure was reported in 27.1% of patients, and the M184V resistance mutation was detected in 17 patients. At 144 weeks, the percentage of individuals with HIV-RNA <50 copies/mL was 77.4% (277/358) in the ITT analysis and 95.5% (277/290) in the PP analysis. A total of 68 participants were excluded from the PP analysis (data missing, 25, discontinuation due to toxicity, 19; other, 16; death, 8). Two people with virological failure selected resistance-associated mutations (M184V and M184V + R263K). HIV-RNA remained undetectable in 17 patients with a previous history of the M184V mutation. CONCLUSION: Our results confirm the real-world, long-term efficacy, tolerability and high genetic barrier of DTG + 3TC in treatment-experienced PWH. Although scarce, mutations causing resistance to nucleosides and integrase can emerge.

Genetic variants associated with steatohepatitis and liver fibrosis in HIV-infected patients with NAFLD.

Background and aims: Nonalcoholic fatty liver disease (NAFLD) is a common cause of liver damage in people living with HIV (PLWHIV). Several studies have investigated candidate genes for susceptibility to NAFLD and to steatohepatitis. PNPLA3, TM6SF2, and MBOAT7-TMC4 have been reported to be associated with elevated ALT levels and the histologic parameters of nonalcoholic steatohepatitis and severity of fibrosis. Our objective was to analyze the relationship between PNPLA3, TM6SF2, and MBOAT7-TMC4 and steatosis, steatohepatitis, and liver fibrosis in PLWHIV with NAFLD. Method: A cohort of PLWHIV with persistently elevated aminotransferase levels and suspected NAFLD who underwent liver biopsy and determination of genetic variants was assessed at two large centers in Spain. All participants included in the current study were genotyped for rs738409 (PNPLA3), rs58542926 (TM6SF2), and rs641738 (MBOAT7-TMC4). Results: The study population comprised PLWHIV who were on stable antiretroviral therapy [7.7% women; median age, 49.3 years (44-53.4)]. The median CD4 count was 829 (650-980), 60% had metabolic syndrome, and 18.5% were diabetic. The median BMI was 28.9 (25.5-30.8). Patients with liver steatosis (any grade) vs. nonsteatosis tended to harbor the PNPLA3 G allele variant [57.6% vs. 16.7% (p = 0.09)], but not TM6SF2 or MBOAT7-TMC4 variants. However, those with steatohepatitis vs. nonsteatohepatitis significantly more frequently had the PNPLA3 G allele variant [69.4% vs. 39.1% (p < 0.05)] and the MBOAT7-TMC4 A allele variant [75% vs. 42% (p < 0.05)]. In our cohort, the TM6SF2 gene variant was not associated with steatosis or steatohepatitis. The PNPLA3 G allele variant was associated with steatohepatitis [OR 4.9 (1.3-18); p 0.02] and liver fibrosis [OR 4.3 (1.1-17.4); p 0.04], and the MBOAT7-TMC4 A allele variant was associated with steatohepatitis [OR 6.6 (1.6-27.6); p 0.01]. Conclusion: The PNPLA3 G allele variant and MBOAT7-TMC4 A allele variant were associated with steatohepatitis and liver fibrosis in PLWHIV with persistently elevated aminotransferases and NAFLD. We recommend routine genotyping for PNPLA3 and MBOAT7-TMC4 in PLWHIV with NAFLD to identify those at higher risk of progression.

Assessment of Noninvasive Markers of Steatosis and Liver Fibrosis in Human Immunodeficiency Virus-Monoinfected Patients on Stable Antiretroviral Regimens.

Background: Nonalcoholic fatty liver disease (NAFLD) is a major nonacquired immune deficiency syndrome-defining condition for persons with human immunodeficiency virus (PWH). We aimed to validate noninvasive tests for the diagnosis of NAFLD in PWH. Methods: This is a cross-sectional study of PWH on stable antiretroviral therapy with persistently elevated transaminases and no known liver disease. The area under the receiver operating characteristic curve (AUROC) was calculated to compare the diagnostic accuracy of liver biopsy with abdominal ultrasound, transient elastography (TE) (including controlled attenuation parameter [CAP]), and noninvasive markers of steatosis (triglyceride and glucose index [TyG], hepatic steatosis index [HSI], fatty liver index [FLI]) and fibrosis ([FIB]-4, aminotransferase-to-platelet ratio index [APRI], NAFLD fibrosis score). We developed a diagnostic algorithm with serial combinations of markers. Results: Of 146 patients with increased transaminase levels, 69 underwent liver biopsy (90% steatosis, 61% steatohepatitis, and 4% F ≥3). The AUROC for steatosis was as follows: ultrasound, 0.90 (0.75-1); CAP, 0.94 (0.88-1); FLI, 0.81 (0.58-1); HSI, 0.74 (0.62-0.87); and TyG, 0.75 (0.49-1). For liver fibrosis ≥F3, the AUROC for TE, APRI, FIB-4, and NAFLD fibrosis score was 0.92 (0.82-1), 0.96 (0.90-1), 0.97 (0.93-1), and 0.85 (0.68-1). Optimal diagnostic performance for liver steatosis was for 2 noninvasive combined models of tests with TyG and FLI/HSI as the first tests and ultrasound or CAP as the second tests: AUROC = 0.99 (0.97-1, P < .001) and 0.92 (0.77-1, P < .001). Conclusions: Ultrasound and CAP performed best in diagnosing liver steatosis, and FLI, TyG, and HSI performed well. We propose an easy-to-implement algorithm with TyG or FLI as the first test and ultrasound or CAP as the second test to accurately diagnose or exclude NAFLD.

[Real-world efficacy of switching to bictegravir/ emtricitabine/tenofovir alafenamide in pretreated patients with triple therapy containing rilpivirine]. / Eficacia en vida real del cambio a bictegravir/ emtricitabina/tenofovir alafenamida en pacientes previamente tratados con pautas triples que contienen rilpivirina.

OBJECTIVE: To analyze the efficacy and tolerability of the strategy to change from rilpivirine (RPV) based regimens to bictegravir / emtricitabine / tenofovir alafenamide (B/F/TAF). METHODS: Single-center, observational and retrospective study. Patients who made the change to B/F/TAF before February 2020 were selected, analyzing the results after 24 and 48 weeks. The percentage that remained with an undetectable viral load was determined, as well as the changes in CD4 + lymphocytes, metabolic parameters and renal function. RESULTS: A total of 42 patients were included. Thirty-two of the 35 patients (91.4%) who completed the 48 weeks of follow-up had an undetectable viral load. The CD4 + lymphocyte count remained stable at 24 and 48 weeks. The response to B/F/TAF was not influenced by the two analogs previously received. CONCLUSIONS: Switching from triple therapy with RPV to B/F/TAF is a safe and effective strategy in real life.

[Helicobacter pylori infection in the HIV + population: a comorbidity to think about]. / Infección por Helicobacter pylori en la población VIH+: una comorbilidad en la que pensar.

OBJECTIVE: Gastrointestinal disorders are frequent in HIV+. Helicobacter pylori may be an underdiagnosed cause. METHODS: Patients with HIV and H. pylori were described since January 1998 up to December 2017. RESULTS: A total de 132 patients were included. The most frequent symptom was dyspepsia. 88.5% had chronic atrophic gastritis. Eradication was achieved in 102 (77.3%). Healing was more frequent with quadruple regimen (p=0.004) and in the youngest (p=0.041). CONCLUSIONS: H. pylori infection could be responsible for nonspecific digestive manifestations in HIV + patients.

¿Para cuándo la implantación de la profilaxis pre-exposición frente al VIH en España? / When should pre-exposure prophylaxis against HIV be implemented in Spain?

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Clinical experience with integrase inhibitors in HIV-2-infected individuals in Spain.

BACKGROUND: HIV-2 is a neglected virus despite estimates of 1-2 million people being infected worldwide. The virus is naturally resistant to some antiretrovirals used to treat HIV-1 and therapeutic options are limited for patients with HIV-2. METHODS: In this retrospective observational study, we analysed all HIV-2-infected individuals treated with integrase strand transfer inhibitors (INSTIs) recorded in the Spanish HIV-2 cohort. Demographics, treatment modalities, laboratory values, quantitative HIV-2 RNA and CD4 counts as well as drug resistance were analysed. RESULTS: From a total of 354 HIV-2-infected patients recruited by the Spanish HIV-2 cohort as of December 2017, INSTIs had been given to 44, in 18 as first-line therapy and in 26 after failing other antiretroviral regimens. After a median follow-up of 13 months of INSTI-based therapy, undetectable viraemia for HIV-2 was achieved in 89% of treatment-naive and in 65.4% of treatment-experienced patients. In parallel, CD4 gains were 82 and 126 cells/mm3, respectively. Treatment failure occurred in 15 patients, 2 being treatment-naive and 13 treatment-experienced. INSTI resistance changes were recognized in 12 patients: N155H (5), Q148H/R (3), Y143C/G (3) and R263K (1). CONCLUSIONS: Combinations based on INSTIs are effective and safe treatment options for HIV-2-infected individuals. However, resistance mutations to INSTIs are selected frequently in failing patients, reducing the already limited treatment options.

Eficacia de los regímenes basados en Sofosbuvir durante 12 semanas para el tratamiento de pacientes HCV genotipo 1 / Efficacy of 12 week length, Sofosbuvir based regimens for the treatment of HCV genotype 1 infected patients

Sofosbuvir (SOF) fue el primer antiviral de acción directa (AAD) comercializado. Ha formado y forma parte de muchas de las combinaciones utilizadas para el tratamiento del VHC. Se ha combinado con Simeprevir (SIM), Daclatasvir (DCV), Ledipasvir (LDV) (en comprimido único) y Velpatasvir (VEL) (también en comprimido único) con o sin ribavirina. Las tasas de respuesta viral sostenida (RVS) para genotipo 1 varían en función del fármaco acompañante (con SIM se obtienen tasas menores, mientras que con VEL se obtienen tasas superiores), del tipo de paciente (los pacientes cirróticos descompensados responden peor) y el uso concomitante de RBV con algunas combinaciones. En el perfil de paciente mayoritario en la actualidad en España, GT1 con grado de fibrosis F0-F2, la combinación pangenotípica SOF/VEL alcanza tasas de curación del 100%

Sofosbuvir (SOF) was the first available direct acting antiviral (DAA). It has been and remains part of many of the combinations used for HCV treatment. It has been combined with simeprevir (SIM), daclatasvir (DCV), ledipasvir (LDV) (as a single pill) and velpatasvir (VEL) (also as a single pill) with or without ribavirin. Sustained viral response rates (SVR) for genotype 1 vary according to the accompanying drug (with SIM there are lower rates, while with VEL higher rates are obtained), the type of patient (decompensated cirrhotic patients respond poorer) and the concomitant use of RBV with some combinations. In the profile of most patients currently in Spain, GT1 with fibrosis grade F0-F2, the pangenotypic combination SOF/VEL achieves 100% cure rates

Switching to an etravirine-containing regimen due to drug intolerance in clinical practice.

BACKGROUND: Drug intolerance is one of the main reasons for switching antiretroviral therapy in HIV-infected patients. Etravirine (ETR) has demonstrated good tolerability in clinical trials and may be an option for patients who switch therapy due to adverse events. METHODS: We retrospectively reviewed all patients who had switched to an ETR-containing regimen in our center due to side effects. Virological suppression, ETR discontinuation, and reasons for discontinuation were studied. RESULTS: A total of 78 patients started treatment with ETR in our center due to previous regimen toxicity. Most of them were men (83.3%), and the median time of infection was 14 years (IQR, 6.5-20 years). HIV RNA was <35 copies/mL in 88.3% of patients, although 33% had archived non-nucleos(t)ide reverse transcriptase inhibitor (NNRTI) mutations that did not compromise ETR efficacy. Efavirenz was the drug most often replaced (38.5%), followed by atazanavir (20.5%) and lopinavir (6.4%). The fixed combination of Trizivir was changed in another 10.3% of patients. After a median follow-up of 14 months (IQR, 6-23), the rate of virologic suppression was 79.5% and 98.4% in intention-to-treat and on-treatment analysis, respectively. Seven patients discontinued treatment due to adverse events (3 gastrointestinal disturbances, 2 rashes, 1 swelling, and 1 neuropathy). ETR was combined with 2 nucleos(t)ide analogues in 75.4% of patients. CONCLUSION: In HIV patients who report drug side effects, switching to an ETR-containing regimen is a safe strategy in terms of virological suppression and toxicity.

Treatment of chronic hepatitis C in HIV-infected patients with compensated liver cirrhosis.

The greatest benefit of hepatitis C virus (HCV) therapy is seen in cirrhotics attaining sustained virological response (SVR). However, concerns about toxicity and poorer responses often discourage treatment of cirrhotics. This may be particularly relevant in HIV-HCV-coinfected patients, in whom progression of liver fibrosis is faster and treatment responses lower. This is a retrospective analysis of HIV-HCV-coinfected patients who had received peginterferon-ribavirin therapy at our institution. Individuals naïve for interferon in whom liver fibrosis had been assessed using elastometry within the year before being treated were chosen. Response rates and toxicities were compared in cirrhotics (>14.5 KPa) and noncirrhotics. Patients with previous liver decompensation were excluded. Overall, 41 cirrhotics and 190 noncirrhotics entered the study. Groups were similar in age, gender, HCV genotypes and baseline serum HCV-RNA. SVR occurred at similar rates in cirrhotic and noncirrhotics, either considered by intention-to-treat (39%vs 45%; P = 0.4) or as treated (50%vs 52%, P = 0.8). In multivariate analysis (odds ratio, 95% CI, P), SVR was associated with HCV genotypes 2-3 (5, 2.9-11, <0.01) and lower serum HCV-RNA (2, 1.4-3.03 for every log decrease, <0.01) but not with cirrhosis (1.2, 0.4-3.6, 0.6). Treatment discontinuations because of adverse events tended to be more common in cirrhotics than in noncirrhotics (17%vs 12%; P = 0.2), but only severe thrombocytopenia was more frequent in cirrhotics than in non-cirrhotics (20%vs 3% at week 24; P < 0.01). Response to peginterferon-ribavirin therapy is similar in HIV-HCV coinfected patients with and without liver cirrhosis. Therefore, treatment must be encouraged in all compensated cirrhotic patients, although closer monitoring and management of side effects, mainly thrombocytopenia, may be warranted.

Hepatitis C virus (HCV) treatment uptake and changes in the prevalence of HCV genotypes in HIV/HCV-coinfected patients.

The efficacy of current hepatitis C therapy in HIV/HCV-coinfected patients is largely dependent on HCV genotype. The annual prevalence of HCV genotypes/subtypes and their influence on HCV clearance with antiviral treatment were examined in a dynamic cohort of HIV/HCV-coinfected patients followed up in Madrid since 2000. Patients entered the cohort at first visit and left the cohort when HCV clearance was achieved with HCV therapy or when follow-up was interrupted for any reason, including death. A total of 672 HIV/HCV-coinfected patients constituted the cohort. The mean follow-up time was 5.5 years, corresponding to 4108 patient-years. Mean age at entry was 37 years, and 73% were men and 86% were intravenous drug users. Overall distribution of HCV genotypes was as follows: 57.1% HCV-1 (1a: 29.2%, 1b: 20.4%, unknown: 7.6%), 1.3% HCV-2, 25.4% HCV-3 and 15.9% HCV-4. A total of 274 (40.8%) patients were treated with peginterferon-ribavirin, of whom 116 (42.3%) achieved HCV clearance following 1-3 courses of therapy. The proportion of HCV-1/4 rose from 71.7% in 2000 to 76.8% in 2008, whereas the proportion of HCV-2/3 fell from 28.1% in 2000 to 23.2% in 2008. The yearly prevalence increased for HCV-1 (R(2) : 0.92, b: 0.59, P < 0.001) and HCV-4 (R(2) : 0.77, b: 0.33, P < 0.005) and conversely diminished for HCV-3 (R(2) : 0.94, b: -0.82, P < 0.001). In summary, the prevalence of HCV-1 and HCV-4 has increased over the last decade in HIV/HCV-coinfected patients, whereas conversely it has declined for HCV-3, in association with the wider use of HCV therapy (41%) in this population.

Risk factors for advanced liver fibrosis in HIV-infected individuals: role of antiretroviral drugs and insulin resistance.

Liver damage may result from multiple factors in HIV-infected patients. The availability of reliable noninvasive tools to measure liver fibrosis has permitted the screening of large patient populations. Cross-sectional study of all consecutive HIV outpatients who underwent examination by transient elastometry (FibroScan) at one HIV reference clinic during 2007. Advanced liver fibrosis (ALF) was defined as hepatic stiffness >9.5 kilopascals, which corresponds to Metavir stages F3-F4 in the liver biopsy. A total of 681 consecutive HIV-infected patients (64% injecting drug users; mean age 43; 78% male; 98% on antiretroviral therapy) had at least one valid FibroScan evaluation. ALF was diagnosed in 215 (32%) of them. In the univariate analysis, ALF was significantly associated with older age, low CD4 counts, chronic hepatitis C, past alcohol abuse, elevated ALT, high triglycerides, low cholesterol, high homeostasis model assessment (HOMA) index and exposure to didanosine and/or stavudine. In a multivariate model (OR, 95% CI), chronic hepatitis C (2.83, 1.57-5.08), past alcohol abuse (2.26, 1.37-3.74), exposure to didanosine and/or stavudine (1.85, 1.14-3.01), high HOMA index (1.25, 1.04-1.51), older age (1.09, 1.05-1.14) and elevated ALT (1.04, 1.03-1.06) remained as independently associated with ALF. Therefore, in addition to chronic hepatitis C and alcohol abuse, insulin resistance and/or exposure to dideoxy-nucleosides may contribute to ALF in HIV-infected patients.

Differences in liver fibrosis and response to pegylated interferon plus ribavirin in HIV/HCV-coinfected patients with normal vs elevated liver enzymes.

Severity of liver fibrosis and response to pegylated interferon plus ribavirin (pegIFN-RBV) are not well known in HIV/HCV-coinfected patients with persistently normal alanine aminotransferase (PNALT). All HIV/HCV-coinfected patients who had been assessed for liver fibrosis using elastometry during 2005 at our clinic were evaluated. Those with at least 1 year with three prior consecutive ALT measurements below the upper limit of normality were compared with patients with elevated ALT. Response to pegIFN-RBV was assessed in a subset of these patients. We analysed 87 patients with PNALT and 122 with elevated ALT. Compared to patients with elevated ALT, those with PNALT were significantly more often women (42%vs 26%), had greater mean CD4 counts (565 vs 420 cells/mm³), had lower mean serum HCV-RNA (5.8 vs 6.2 log IU/ml) and were infected by HCV genotype 4 (33%vs 6%). Liver fibrosis was considered as severe (Metavir F3) in 10% of patients with PNALT, and another 4% had cirrhosis based on stiffness values. These numbers were 16% and 35% in patients with elevated ALT. Treatment with pegIFN-RBV was given to 22 and 45 patients with PNALT and elevated ALT, respectively. Sustained virological response was achieved in 50% and 29% of them. In the multivariate analysis, PNALT was independently associated with response (OR: 7.9; 95% CI: 1.4-45.2; P = 0.02). Nearly 15% of HIV/HCV-coinfected patients with PNALT showed advanced liver fibrosis (Metavir F3-F4 estimates by elastometry). In summary, response to pegIFN-RBV is higher in patients with PNALT than in those with elevated ALT. Therefore, treatment should not be denied in HIV/HCV-coinfected patients with PNALT.

Liver fibrosis in patients with chronic hepatitis C and persistently normal liver enzymes: influence of HIV infection.

Liver fibrosis progress slowly in patients with chronic hepatitis C and persistently normal alanine aminotransferase (PNALT) compared to subjects with elevated aminotransferases. Differences in liver fibrosis according to human immunodeficiency virus (HIV) status in this population have not been examined. All patients with serum hepatitis C virus (HCV)-RNA and PNALT who underwent liver fibrosis assessment using elastometry since 2004 at three different European hospitals were evaluated. Patients previously treated with interferon were excluded. PNALT was defined as ALT below the upper limit of normality in at least three consecutive determinations within the last 12 months. Fibrosis stage was defined as mild (Metavir F0-F1) if stiffness < or =7.1 kPa; moderate (F2) if 7.2-9.4 kPa; severe (F3) if 9.5-14 kPa, and cirrhosis (F4) if >14 kPa. A total of 449 HIV-negative and 133 HIV-positive patients were evaluated. HIV-negative patients were older (mean age 51.8 vs 43.5 years) and more frequently females (63%vs 37%) than the HIV counterparts. Mean serum HCV-RNA was similar in both the groups (5.9 vs 5.8 log IU/mL). Overall, 78.8% of the HIV patients were on HAART and their mean CD4 count was 525 (+/-278) cells/microL. In HIV-negatives, liver fibrosis was mild in 84.6%; moderate in 8.7%, severe in 3.3% and cirrhosis was found in 3.3%. In HIV patients, these figures were 70.7%, 18.8%, 6%, and 4.5%, respectively. In the multivariate logistic regression analysis, older age (odds ratio or OR: 1.04; 95% confidence interval or CI: 1.02-1.07; P < 0.001) and being HIV+ (OR: 2.6; 95% CI: 1.21-5.85; P < 0.01) were associated with severe liver fibrosis or cirrhosis (F3-F4). Thus, severe liver fibrosis and cirrhosis are seen in 6.6% of the HCV-monoinfected and in 10.5% of HCV-HIV co-infected patients with PNALT. Some degree of liver fibrosis that justifies treatment is seen in 15% of the HCV-monoinfected but doubles to nearly 30% in HIV-HCV co-infected patients with PNALT.

Response to pegylated interferon plus ribavirin in HIV-infected patients with chronic hepatitis C due to genotype 4.

SUMMARY: Hepatitis C virus (HCV) genotypes 1 and 4 respond less well to pegylated interferon (pegIFN) plus ribavirin (RBV) therapy. For this reason most studies merge these two genotypes when assessing virological response. However, in most trials the HCV genotype 4 population is rather small, and conclusions are mainly derived from what occurs in HCV-1 patients. All HCV-4 patients coinfected with HIV who received pegIFN plus RBV in two different multicentre studies, PRESCO and ROMANCE, conducted respectively in Spain and Italy, were retrospectively analyzed. Baseline plasma HCV-RNA, proportion of patients with HCV-RNA <10 IU / mL at week 4 (rapid virological response), and HCV-RNA declines >2 logs at week 12 (early virological response, EVR) were all assessed as predictors of sustained virological response (SVR). Overall, 75 patients (60 men) were evaluated. Median age was 40 years and median CD4 count 598 cells / mm(3); 49% had plasma HIV-RNA <50 copies / mL; 71% had elevated liver enzymes and 31% had advanced liver fibrosis (Metavir F3-F4). Median serum HCV-RNA was 5.7 log IU / mL. Rapid virological response was attained by 10 (20%) patients and EVR by 26 (42%). Using intention-to-treat and on-treatment (OT) analyses, SVR was achieved by 21 / 75 (28%) and 21 / 62 (34%) of HCV-4 patients, respectively. In the multivariate analysis (OT), baseline HCV-RNA (OR 0.09 for every log increment; 95% CI: 0.01-0.7) and EVR (OR: 7.08; 95% CI: 1.8-27.2) were significantly and independently associated with SVR. This is the largest series of HIV-infected patients with chronic hepatitis C due to HCV-4 treated with pegIFN plus RBV examined so far and the results show that HCV-4 behaves similarly to HCV-1. Therefore, these patients should be considered as difficult to treat population. Baseline serum HCV-RNA and EVR are the best predictors of SVR in HCV-4 / HIV-coinfected patients.

Long-term prognosis of HIV-infected patients with Kaposi sarcoma treated with pegylated liposomal doxorubicin.

INTRODUCTION: Incidence of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected persons has dramatically decreased in the highly active antiretroviral therapy era. However, this tumor still represents the most common cancer in this population. OBJECTIVES: The objectives of this study were to evaluate long-term prognosis of HIV-infected patients with KS who had received pegylated liposomal doxorubicin (PLD) and, more specifically, to assess tumor relapse rate, mortality, and cause of death in these subjects. DESIGN: This study was a retrospective review of all patients with KS who had received PLD in centers belonging to the Caelyx/KS Spanish Group. Kaplan-Meier analysis and univariate and multivariate Cox-regression analysis were used to assess the rate of and factors associated with relapse and death through January 2006. RESULTS: A total of 98 patients received PLD from September 1997 through June 2002. Median follow-up after initiation of treatment was 28.7 months (interquartile range, 6.6-73.2 months); during follow-up, 29 patients died (a mortality rate of 14.6% per year). In 9 patients (31%), the cause of death was related to the appearance of other tumors (including 7 lymphomas, 1 gastrointestinal adenocarcinoma, and 1 tongue epidermoid cancer). Death caused by progression of KS occurred in 3 cases. Death risk was inversely related to CD4(+) cell counts at the end of follow-up (hazard ratio for every increase in CD4(+) cell count of 100 cells/microL, 0.7; 95% confidence interval, 0.5-0.9). A relapse study was performed for 61 patients who had complete or partial response to PLD and who attended a control visit after treatment completion. After a median follow-up of 50 months (interquartile range, 17.2-76 months), 8 patients (13%) had experienced relapse; 5 of these patient experienced relapse within the first year after stopping PLD. The only factor that was independently related to risk of relapse was having a CD4(+) cell count >200 cells/microL at baseline (hazard ratio, 6.2; 95% confidence interval, 1.2-30). Lower CD4(+) cell count at the end of follow-up was marginally associated with relapse (hazard ratio for every increase in CD4(+) cell count of 100 cells/microL, 0.7; 95% confidence interval, 0.6-1.01). CONCLUSIONS: Treatment of KS with PLD in HIV-infected patients is followed by a low relapse rate, with most relapses occurring during the first year after stopping chemotherapy. However, the mortality rate in this population was high, in part because of an unexpectedly high incidence of other tumors, mainly lymphomas.

Liver cirrhosis in HIV-infected patients: prevalence, aetiology and clinical outcome.

Liver disease is frequently seen in HIV+ patients as a result of coinfection with hepatitis B (HBV) or C (HCV) viruses, alcohol abuse and/or exposure to hepatotoxic drugs. The aim of this study was to assess the prevalence of liver cirrhosis, its main causes and clinical presentation in HIV+ patients. Observational, cross-sectional, retrospective study of all HIV+ individuals followed at one reference HIV outpatient clinic in Madrid. Liver fibrosis was measured in all cases using transient elastometry (FibroScan). All 2168 HIV+ patients on regular follow-up (76% males, 46% injecting drug users) were successfully examined by FibroScan) between October 2004 and August 2006. Liver cirrhosis was recognized in 181 (overall prevalence, 8.3%), and the main aetiologies were HCV, 82.3%; HBV, 1.6%; dual HBV/HCV, 2.8%; and triple HBV/HCV/ hepatitis delta virus (HDV) infection, 6.6%. The prevalence of cirrhosis differed among patients with distinct chronic viral hepatitis: HCV, 19.2%; HBV, 6.1%; HBV/HCV, 41.7%; and HBV/HCV/HDV, 66.7%. In 12 patients with cirrhosis (6.7%), no definite aetiology was recognized. Overall, cirrhotics had lower mean CD4 counts than noncirrhotics (408 vs 528 cells/microL respectively; P = 0.02), despite similar proportion of subjects with undetectable viraemia on highly active antiretroviral therapy. Clinical manifestations of liver cirrhosis were: splenomegaly, 61.5%; oesophageal varices, 59.8%; ascites, 22.6%; encephalopathy, 12.1%; and variceal bleeding, 6.1%. Liver cirrhosis and hepatic decompensation events are relatively frequent in HIV+ individuals. Chronic HCV and alcohol abuse, but not chronic HBV, play a major role. Transient elastometry may allow the identification of a significant number of HIV+ individuals with asymptomatic liver cirrhosis.

Liver fibrosis on account of chronic hepatitis C is more severe in HIV-positive than HIV-negative patients despite antiretroviral therapy.

The recent availability of non-invasive tools to measure liver fibrosis has allowed examination of its extent and determination of predictors in all patients with chronic hepatitis C virus (HCV) infection. On the other hand, most information on hepatic fibrosis in HCV/human immunodeficiency virus (HIV)-coinfected patients has been derived from liver biopsies taken before highly active antiretroviral therapy (HAART) was widely available. All consecutive HCV patients with elevated aminotransferases seen during the last 3 years were evaluated and liver fibrosis measured using transient elastography (FibroScan) and biochemical indexes. Patients were split according to their HIV serostatus. A total of 656 (69.6%) HCV-monoinfected and 287 (30.4%) HIV/HCV-coinfected patients were assessed. Mean CD4 count of coinfected patients was 493 cells/muL and 88% were under HAART (mean time, 4.2 +/- 2.4 years). Advanced liver fibrosis or cirrhosis was recognized in 39% of the coinfected and 18% of the monoinfected patients (P < 0.005). A good correlation was found between FibroScan) and biochemical indexes [AST to platelet ratio index (r = 0.405, P < 0.0001), FIB-4 (r = 0.393, P < 0.0001) and Forns (r = 0.407, P < 0.0001)], regardless of the HIV status. In the multivariate analysis, age >45 years, body mass index (BMI) >25 kg/m(2), and HIV infection were independently associated with advanced liver fibrosis or cirrhosis. HIV/HCV-coinfected patients have more advanced liver fibrosis than HCV-monoinfected patients despite the immunologic benefit of HAART.

Clearance of hepatitis C virus in HIV-infected patients with multiple chronic viral hepatitis.

Viral interferences between hepatitis C (HCV) and hepatitis B (HBV) viruses were investigated in a case-control study conducted in 107 human immunodeficiency virus (HIV)-infected patients with HCV antibodies. Overall, 15 (68%) of 22 hepatitis B surface antigen (HBsAg)-positive patients had negative serum HCV-RNA while it occurred in only nine (10%) of 85 HBsAg-negative counterparts (P = 0.02). After adjusting for age, antiretroviral therapy, plasma HIV-RNA and CD4 counts, being HBsAg-positive was strongly associated with having negative serum HCV-RNA (odds ratio: 23; 95% confidence interval: 6-59; P < 0.001). Thus, HBV may favour the elimination of HCV in HIV-infected patients, which may influence liver disease and therapeutic decisions.