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.

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.

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.

Level, phenotype and activation status of CD4+FoxP3+ regulatory T cells in patients chronically infected with human immunodeficiency virus and/or hepatitis C virus.

CD4(+) regulatory T (T(reg)) cells have been involved in impaired immunity and persistence of viral infections. Herein, we report the level, phenotype and activation status of T(reg) cells in patients chronically infected with human immunodeficiency virus (HIV) and/or hepatitis C virus (HCV). Expression of CD25, CD45RA, CD27, CD127 and CD38 was assessed on these cells using polychromatic flow cytometry in 20 healthy controls, 20 HIV-monoinfected, 20 HCV-monoinfected and 31 HIV/HCV-co-infected patients. T(reg) cells were defined as CD4(+)forkhead box P3 (FoxP3)(+). The percentage of T(reg) cells was increased significantly in HIV patients compared with controls. Moreover, there was a significant inverse correlation between CD4 counts and T(reg) cell levels. Fewer than 50% of T(reg) cells expressed CD25, with differences in terms of CD127 expression between CD25(+) and CD25((-)) T(reg) cells. CD4(+)Foxp3(+) T(reg) cells displayed predominantly a central memory phenotype (CD45RA(-)CD27(+)), without differences between patients and healthy controls. Activated T(reg) cells were increased in HIV patients, particularly considering the central memory subset. In summary, HIV infection, but not HCV, induces an up-regulation of highly activated T(reg) cells, which increases in parallel with CD4 depletion. Hypothetically, this might contribute to the accelerated course of HCV-related liver disease in HIV-immunosuppressed patients.

Predictors of severe hepatic steatosis using abdominal ultrasound in HIV-infected patients.

OBJECTIVE: Multiple factors may lead to hepatic steatosis (HS) in HIV-positive patients. HS may result in severe liver damage on its own and/or by accelerating the progression of chronic viral hepatitis B or C. METHODS: The sensitivity/specificity of liver ultrasound (US) to recognize severe HS is above 85%. A cross-sectional case-control study of all HIV out-patients who underwent liver US since 2004 was conducted at our institution. RESULTS: Eight hundred and thirty (36.1%) out of 2300 HIV-positive patients on regular follow-up underwent liver US during the study period. Severe HS was diagnosed in 108 (13%) patients. A total of 117 matched HIV controls lacking HS were selected randomly. In patients with severe HS, we found significantly higher values of body mass index (BMI), plasma viral load, serum glucose, alkaline phosphatase, triglycerides and low-density lipoprotein cholesterol, as well as significantly higher prevalence of diabetes, elevated alcohol consumption, lipohypertrophy and advanced liver fibrosis. Furthermore, a trend towards longer exposure to nucleoside analogues was noticed. In the multivariate analysis, only elevated alcohol consumption [odds ratio (OR) 7, P=0.013], lipohypertrophy (OR 5.3, P=0.008), plasma viral load (OR 2.1, P=0.02), BMI (OR 1.2, P=0.013) and serum glucose (OR 1.03, P=0.027) were significantly associated with severe HS. CONCLUSIONS: Severe HS in HIV-positive patients is associated with predisposing factors that are similar to those of HIV-negative individuals. However, its characteristic association with elevated plasma viral load might suggest a direct involvement of HIV in liver fat deposition. Therefore, the benefit of controlling HIV replication with antiretroviral therapy should be balanced against its effect of occasionally inducing metabolic abnormalities and lipodystrophy.

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.

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.

[Role of bone gammagraphy in the diagnosis of secondary osteomalacia in a patient treated with tenofovir]. / Utilidad de la gammagrafía ósea en el diagnóstico de osteomalacia secundaria en un paciente en tratamiento con tenofovir.

It is reported a HIV infected patient under antiretroviral therapy including tenofovir therapy who was referred to the Nuclear Medicine Department to complete bone pain study. A bone scan was performed at 3 hours after the injection of 740 MBq of 99mTc-MDP, revealing an abnormal distribution with characteristic changes compatible with osteomalacia. In further analysis, a secondary hyperparathyroidism and osteomalacia were diagnosed in the context of Fanconi syndrome, an infrequent complication described in patients under treatment with tenofovir.

Changes in survival over time after a first episode of Pneumocystis carinii pneumonia for European patients with acquired immunodeficiency syndrome. Multicentre Study Group on AIDS in Europe.

BACKGROUND: Factors associated with improved survival over time for patients with the acquired immunodeficiency syndrome (AIDS) who have Pneumocystis carinii pneumonia at diagnosis are not clearly defined. METHODS: An inception cohort of 2533 patients with AIDS, diagnosed from 1979 to 1989, from 52 centers in 17 European countries was studied. Survival 3 months and 3 years after diagnosis was estimated by Kaplan-Meier life tables. Independent predictors of survival were analyzed by construction of Cox proportional hazards models. RESULTS: Patients in whom AIDS and P carinii pneumonia had been diagnosed before 1988 had a poorer 3-month (ie, short-term) survival, whereas the survival 1 and 2 years after P carinii pneumonia was lower only for patients whose disease was diagnosed before 1987 compared with those with more recent diagnoses. Other variables associated with poorer outcome were greater age, infection via blood transfusion, diagnosis made in south Europe, and coexisting illnesses. After controlling for these prognostic markers in multivariate analysis, improvement in survival over time was still evident. For patients who survived the P carinii pneumonia episode, both zidovudine and secondary prophylaxis for P carinii pneumonia initiated around the time of diagnosis were associated with improved survival, and, after controlling for these treatment variables, no statistically significant improvement in survival over time was observed. CONCLUSIONS: Survival after an episode of P carinii pneumonia has improved within recent years. Increased awareness of early symptoms of P carinii pneumonia and better treatment of the pneumonia may have led to improvement in short-term survival over time, whereas the introduction of zidovudine and increased use of secondary P carinii pneumonia prophylaxis may have resulted in the recent increase in survival 1 and 2 years after the diagnosis. However, 3-year survival remained unchanged over time, implying that the underlying human immunodeficiency virus infection and other complications are not effectively controlled.

Tuberculous meningitis with acellular cerebrospinal fluid in AIDS patients.

OBJECTIVE: To describe the clinical manifestations of tuberculous meningitis in HIV-positive patients with acellular cerebrospinal fluid (CSF). DESIGN: Retrospective analysis of case reports. METHODS: Four HIV-positive patients with acellular CSF and tuberculous meningitis are reported. RESULTS: Clinical presentation did not indicate meningeal infection in three of the four cases, and CSF tests were unusual in all cases. Two patients were diagnosed only after death. CONCLUSIONS: Acellular CSF may obstruct the diagnosis of tuberculous meningitis in AIDS patients.

Clearance of human herpesvirus type 8 viraemia in HIV-1-positive patients with Kaposi's sarcoma treated with liposomal doxorubicin. Caelyx/KS Spanish Study Group.

OBJECTIVE: To assess the impact of liposomal doxorubicin on human herpesvirus type 8 (HHV-8) cell viraemia in HIV-infected patients with Kaposi's sarcoma. DESIGN: Prospective, non-controlled, multicenter study. METHODS: The presence of HHV-8 DNA was investigated by polymerase chain reaction in peripheral blood mononuclear cells from 46 HIV-positive patients with Kaposi's sarcoma. Samples were tested at baseline and every 3 months during treatment with liposomal doxorubicin. CD4 cell counts, plasma HIV RNA, and clinical outcome were recorded at baseline and at follow-up visits. RESULTS: HHV-8 sequences were detected in 32 (70%) patients at baseline. No significant differences were found between subjects with HHV-8 positive and negative results. The proportion of patients with positive HHV-8 viraemia decreased to 38% (10 of 26) after 3 months of treatment with liposomal doxorubicin (P < 0.01). Overall, 12 of 22 (57%) subjects with positive HHV-8 cell viraemia at baseline became negative during the treatment period. However, in one of them HHV-8 reappeared 8 months later despite being on therapy. On the other hand, six of eight subjects with negative HHV-8 at baseline remained negative thereafter. There were no significant changes in plasma HIV RNA, total lymphocyte, or CD4 cell counts during the treatment period. Clinical response of Kaposi's sarcoma to liposomal doxorubicin and clearance of HHV-8 viraemia did not correlate well. CONCLUSIONS: HHV-8 cell viraemia significantly decreased during treatment with liposomal doxorubicin in HIV-infected patients with Kaposi's sarcoma, although the clinical response and HHV-8 clearance did not correlate well.

Sociodemographic and psychological variables influencing adherence to antiretroviral therapy.

OBJECTIVE: To assess the degree of compliance with antiretroviral therapy in HIV-infected patients, and identify which sociodemographic and psychological factors influence it, in order to develop strategies to improve adherence. DESIGN AND SETTING: Cross-sectional study in a reference HIV/AIDS institution located in Madrid, Spain. PATIENTS AND METHODS: A total of 366 HIV-infected patients who were on treatment with antiretroviral drugs were invited to complete a questionnaire which recorded sociodemographic data and psychological variables in relation to compliance with the prescribed medication. Clinical information was extracted from the hospital records. The Beck Depression Inventory was used to assess depression, while adherence to treatment was evaluated using patient's self report and the pill count method. RESULTS: A good adherence to antiretroviral therapy (> 90% consumption of the prescribed pills) was recorded in 211 (57.6%) patients. A good concordance for assessing adherence was found using the patient's self-report and the pill count method in a sub-group of patients. Predictors of compliance in the univariate analysis were age, transmission category, level of studies, work situation, CD4 cell count level, depression and self-perceived social support. In the multivariate model, only age, transmission category, CD4 cell count level, depression, self-perceived social support, and an interaction between the last two variables predicted compliance to treatment; adherence to antiretroviral therapy was better among subjects aged 32-35 years [odds ratio (OR), 2.31; 95% confidence interval (CI), 1.21-4.40], in non-intravenous drug users (IVDUs) (OR, 2.05; 95% CI, 1.28-3.29), subjects with CD4 cell counts from 200-499 x 10(6) cells/l at enrolment (OR, 2.78; 95% CI, 1.40-5.51) and in subjects not depressed and with a self-perceived good social support (OR, 1.86; 95% CI, 0.98-3.53). CONCLUSIONS: Sociodemographic and psychological factors influence the degree of adherence to antiretroviral therapy. Overall, IVDUs and younger individuals tend to have a poorer compliance, as well as subjects with depression and lack of self-perceived social support. An increased awareness of these factors by practitioners attending HIV-infected persons, recognizing and potentially treating some of them, should indirectly improve the effectiveness of antiretroviral therapy.

Latent Haemophilus influenzae pneumonia in patients infected with HIV.

Pneumonia caused by common pyogenic bacteria occurs frequently in HIV-infected patients. Its clinical presentation has been described as being similar to that seen in non-immunosuppressed hosts but clearly different to that of opportunistic pneumonias. An atypical presentation has rarely been seen. In a 10-month period, we saw 12 HIV-infected patients who presented with Haemophilus influenzae pneumonia which was clinically and radiologically indistinguishable from Pneumocystis carinii pneumonia. Ten of the patients were intravenous drug users and were in different stages of HIV disease. The clinical picture was characterized by a prolonged course (median 4 weeks), non-productive cough, dyspnoea, and absence of findings usually present in bacterial pneumonia. Laboratory data frequently showed absence of leukocytosis, increased lactate dehydrogenase levels, hypoxaemia, and decreased CD4+ cell counts. All presented with interstitial or mixed bilateral infiltrates. Resistance to ampicillin and trimethoprim-sulphamethoxazole were each found in seven cases. Eleven patients were cured with antibiotic therapy, although five relapsed. H. influenzae pneumonia should be considered in HIV-infected patients who present with pulmonary symptoms and bilateral infiltrates of subacute or chronic onset. Clinical resolution of pneumonia is the usual outcome, but recurrences of infection are frequent.

Discontinuation of secondary prophylaxis for opportunistic infections in HIV-infected patients receiving highly active antiretroviral therapy.

BACKGROUND: Immune reconstitution following the introduction of highly active antiretroviral therapies (HAART) has lead to a remarkable reduction in the incidence of opportunistic infections (OI) in subjects with advanced HIV disease. Moreover, discontinuation of primary prophylaxis for some OI can be attempted without risk in patients experiencing a favourable response to treatment. However, data on the feasibility of discontinuing secondary prophylaxis are much more scarce, and restricted mainly to the withdrawal of maintenance treatment for cytomegalovirus (CMV) retinitis. PATIENTS AND METHODS: Retrospective review of the clinical outcome at 18 months in HIV-infected patients in whom discontinuation of secondary prophylaxis, for different OI, was recommended 3 months after the introduction of HAART, if both CD4 counts > 100 x 10(6) CD4 lymphocytes/l and plasma HIV-RNA < 500 copies/ml had been achieved. RESULTS: Fifty-three subjects were analysed. Secondary chemoprophylaxis was discontinued for the following OI: Pneumocystis carinii pneumonia (PCP) (n = 29), cerebral toxoplasmosis (n = 9), disseminated Mycobacterium avium complex infection (n = 7), CMV retinitis (n = 5), recurrent oroesophageal candidiasis (n = 5), Visceral leishmaniasis (n = 2), recurrent herpes zoster (n = 2), and chronic mucocutaneous herpes simplex infection (n = 1). In six individuals, OI prophylaxis was discontinued for two or more entities. Only two episodes of OI were recorded in these individuals during 18 months of follow-up. One developed tuberculous lymphadenitis despite having a good response to treatment, and another suffered a new episode of PCP after voluntary treatment interruption for 6 weeks. CONCLUSION: Secondary prophylaxis for OI can be attempted without major risk in HIV-infected patients experiencing a favourable response to HAART. The benefit of this intervention should reduce costs, drug side-effects and pharmacologic interactions, and indirectly will improve patient's quality of life and adherence to antiretroviral treatment.

Risks and benefits of replacing protease inhibitors by nevirapine in HIV-infected subjects under long-term successful triple combination therapy.

OBJECTIVE: To analyse the safety and efficacy of replacing the protease inhibitor (PI) by nevirapine (NVP) in subjects experiencing a long-term control of virus replication under a triple PI-containing antiretroviral combination. DESIGN: Prospective evaluation of 138 HIV-positive subjects with plasma viral load below 50 HIV-RNA copies/ml for the last 6 months under a triple PI-containing regimen, who were randomly assigned to either replace the PI by NVP (n = 104) or continue on the same treatment (n = 34). METHODS: Viral load, CD4 count, lipid profile, body-shape features, and quality of life parameters were all assessed at the time of randomization and every 3 months thereafter. RESULTS: In an intent-to-treat analysis, a rebound in viral load occurred in 11% of subjects during the first 6 months after replacing the PI by NVP, whereas it appeared in 29% of those who remained on PI (P = 0.007). Treatment failure was related to lack of adherence in 90% of subjects on PI, but only in 22% of those receiving NVP (P = 0.006). The CD4 cell count outcome did not differ significantly comparing both groups at 6 months, although in patients receiving NVP an average reduction of 35 x 10(6) cells/l was observed, whereas in those on PI a positive trend was still recorded (+54 x 10(6) cells/l). At the time of randomization, 77.5 and 57.5% of subjects had cholesterol and triglyceride values above 200 mg/dl, respectively. No significant changes in the lipid profile were observed in any of the groups thereafter. Body-shape abnormalities were recorded in 70% of persons at the time of randomization, and partially reversed at 6 months in 50% of subjects who replaced the PI by NVP. A quality of life score recorded a significant improvement in subjects who switched to NVP compared with those who continued on PI. CONCLUSIONS: The replacement of PI by NVP seems to be safe both virologically and immunologically, provides a significant improvement in the quality of life and in half of patients ameliorate lipodystrophic body-shape changes at 6 months, although serum lipid abnormalities still remain unmodified.

Diagnosis of visceral leishmaniasis in HIV-infected individuals using peripheral blood smears.

OBJECTIVE: To compare the clinical and laboratory features of visceral leishmaniasis (kala-azar) in HIV-infected and non-infected subjects, and to determine the presence of Leishmania amastigotes in circulating leukocytes using peripheral blood smears. PATIENTS: Twenty-eight HIV-infected and six HIV-negative adult patients diagnosed as having kala-azar presenting at one institution over a 7-year period. METHODS: Retrospective review of clinical charts and re-examination of peripheral blood smears. RESULTS: There were no significant differences in the clinical presentation and laboratory features of HIV-positive and HIV-negative patients. However, Leishmania amastigotes were observed in circulating leukocytes in eight out of the 17 available peripheral blood smears (15 from HIV-infected patients). All eight individuals presenting with Leishmania in peripheral blood leukocytes were HIV-positive. CONCLUSIONS: Direct visualization of Leishmania amastigotes in leukocytes on peripheral blood smears enabled the diagnosis of kala-azar in a high proportion [eight out of 15 (53%)] of our HIV-infected patients.

Prevention of nevirapine-associated exanthema using slow dose escalation and/or corticosteroids.

OBJECTIVE: The appearance of rash is one of the most frequent and limiting side-effects during the first 4 weeks of treatment with nevirapine (NVP). We explored the efficacy and safety of four different strategies for reducing the incidence of this complication. PATIENTS AND METHODS: Four-hundred and sixty-nine patients were assigned randomly to accomplish the induction phase of NVP following either the standard recommendation of 200 mg daily during the first 2 weeks (n = 166), or any of three new strategies: adding prednisone 50 mg each other day during the first 2 weeks (n = 93); using a slowly escalating dose, beginning with 100 mg daily the first week, and increasing the dose by 100 mg/week up to the full daily dose of 400 mg (n = 107); and combining both the addition of prednisone with the slowly escalating dose (n = 103). A pharmacokinetic substudy was performed in seven patients receiving 100 mg of NVP during the first week. RESULTS: The incidence of rash diminished from 18.7% using the standard recommendation to 9.2% using the alternative approaches (P = 0.003). Rash appeared in 11.2%, 8.6%, and 7.7% of subjects assigned to receive the slowly escalating dose, prednisone, or both, respectively, without significant differences among them. The rate of drug discontinuation was also diminished by one-half using the new approaches (8.5% versus 4.3%; P = 0.06). NVP plasma concentrations within the first week of treatment using 100 mg daily were above the 90% inhibitory concentration for wild-type HIV-1 in all instances. CONCLUSION: The incidence of rash complicating the first few weeks of treatment with NVP can be diminished by adding corticosteroids for 2 weeks to the standard recommendation, or by using a slowly escalating dose. This second approach is proven to be pharmacokinetically safe.

Opportunistic infections shortly after beginning highly active antiretroviral therapy.

The clinical benefit of highly active antiretroviral therapy (HAART) has been attributed to its suppression of viral replication and improvement in the CD4 lymphocyte count. However, the development of clinical symptoms secondary to previously silent opportunistic pathogens shortly after beginning HAART has been reported as a distinct clinical syndrome and seems to be associated with inflammatory phenomena surrounding a rapid restoration of the immune system in previously immunosuppressed patients. Herein, we report nine (3.6%) episodes of opportunistic infections (OI) in 247 human immunodeficiency virus (HIV)-infected patients undergoing HAART in a reference HIV/AIDS institution located in Madrid, Spain. In all instances, OI clustered within the first 3 months after beginning HAART. Episodes of cerebral toxoplasmosis (three cases), Pneumocystis carinii pneumonia (two cases), and herpes zoster (two cases) occurred in persons without a previous AIDS-defining illness, in addition a relapse of cytomegalovirus retinitis and a rebound in Kaposi's sarcoma were seen, respectively, in another two patients. Four of the nine subjects had a CD4 count above 200 cells/mm3 before HAART began. Of these, one developed Pneumocystis pneumonia and one other cerebral toxoplasmosis. In conclusion, prophylaxis and close clinical monitoring of HIV-infected patients should be considered for the first 3 months after beginning HAART, even for subjects without severe immunosuppression.

Short-term efficacy and safety of stavudine in pretreated HIV-infected patients.

Most of the information available on stavudine (d4T) comes from studies in patients with advanced human immunodeficiency virus (HIV) disease to whom stavudine was administered as monotherapy. Herein, we summarize the results of adding 40 mg stavudine twice daily to previous therapies in patients with mild to advanced immunological disease (mean CD4 T cell count 178 cells/mm3; range 6-480 cells/mm3). In an intention-to-treat, prospective, open trial, 64 patients (84.4% men; mean age 35.2 years) were analysed. Their average time on previous antiretroviral therapy was 19.8 months (range 6-52). Plasma HIV RNA load fell by a mean of 0.64 and 0.74 log at 1 and 3 months, respectively, after the start of stavudine therapy (P <0.001 Sign rank test). The CD4 cell count increased by a mean of 25.1 cells/mm3 in the third month (P = 0.002 Sign rank test). Antiviral activity was independent of the CD4 cell count at baseline, but more pronounced declines in viral load were seen in patients with shorter periods of previous antiretroviral therapy and in those in whom stavudine was combined with didanosine or lamivudine rather than zidovudine. Ten (15.6%) patients discontinued the drug during the first 6 months of treatment because of the development of toxicity (neuropathy in six cases, hepatitis in two, oedema in one and rash in another); all but one of them had CD4 counts < 200 cells/mm3. Another two patients stopped treatment voluntarily. The remaining 52 patients tolerated the drug well for the first 6 months and had a high level of compliance with treatment. In conclusion, stavudine is generally well tolerated and has significant antiretroviral activity when it is administered to patients with extensive previous treatment with multiple reverse transcriptase (RT) inhibitors. It should be expected that the short-term favourable effects of stavudine on laboratory markers will further translate into a reduced progression of disease and improved survival.

Increasing impact of chronic viral hepatitis on hospital admissions and mortality among HIV-infected patients.

To assess the impact of chronic viral liver disease (CVLD) on hospital admissions and death in HIV-infected patients since the introduction of highly active antiretroviral therapy, all hospital charts, from January 1996 to December 2000, in a large HIV/AIDS reference center in Madrid were reviewed. Discharge diagnosis, complications during the inpatient period, and number and causes of death were recorded. A total of 1334 hospital admissions involving 875 HIV-infected individuals was recorded. Up to 82% of them were either active or former intravenous drug users. Overall, 158 (11.8%) were admitted because of complications of CVLD, or developed complications of CVLD during their admission for another reason. The absolute number and proportion of admissions caused by CVLD increased over time, from 9.4% (31 of 330) in 1996 to 16% (46 of 287) in 2000 (p < 0.05). Likewise, the total number and proportion of deaths due to CVLD increased from 9.3% (5 of 54) in 1996 to 45% (9 of 20) in 2000 (p < 0.05). Chronic hepatitis C was the only etiology in nearly three-quarters of patients who were admitted or died of CVLD. In conclusion, the proportion of hospital admissions caused by liver failure in HIV-infected patients has increased in the last 5 years, accounting for 16% of cases in 2000. End-stage liver disease currently represents 45% of causes of in-hospital death among HIV-infected individuals. Therefore, strategies to prevent infection by hepatitis viruses (hepatitis B vaccine) and specific treatment (interferon plus ribavirin for hepatitis C virus) should be encouraged among HIV-infected persons.