Atypical pyoderma gangrenosum mimicking an infectious process.

We present a patient with atypical pyoderma gangrenosum (APG), which involved the patient's arm and hand. Hemorrhagic bullae and progressive ulcerations were initially thought to be secondary to an infectious process, but a biopsy revealed PG. Awareness of APG by infectious disease services may prevent unnecessary use of broad-spectrum antibiotics.

Hepatitis C virus treatment rates and outcomes in HIV/hepatitis C virus co-infected individuals at an urban HIV clinic.

OBJECTIVES: The factors associated with hepatitis C virus (HCV) treatment uptake and responses were assessed among HCV/HIV co-infected individuals referred for HCV therapy at an urban HIV clinic. METHODS: Retrospective review of HIV/HCV patients enrolled in the HCV treatment program at the John Ruedy Immunodeficiency Clinic in Vancouver. The factors associated with treatment uptake were assessed using multivariate analysis. RESULTS: A total of 134 HCV/HIV co-infected individuals were recalled for assessment for HCV therapy. Overall 64 (48%) initiated treatment, and of those treated 49 (76.6%) attained end treatment response, whereas 35 (57.8%) achieved sustained virological response (SVR). When evaluated by genotype, 53% (17/32) of those with genotype 1, and 65% (20/31) of those with genotype 2 or 3 infections attained SVR. In treated individuals, alanine aminotransferase dropped significantly after treatment (P<0.001). During treatment, CD4 counts dropped significantly (P<0.001) in all patients. The counts recovered to baseline in patients who achieved SVR, but remained lower in patients who failed the therapy (P=0.015). On multivariate analysis, history of injection drug use (odds ratio: 3.48; 95% confidence interval: 1.37-8.79; P=0.009) and low hemoglobin levels (odds ratio: 4.23; 95% confidence interval: 1.36-13.10; P=0.013) were associated with those who did not enter the treatment. CONCLUSION: Only half of treatment-eligible co-infected patients referred for the therapy initiated treatment. Of those referred for the therapy, history of injection drug use was associated with lower rates of treatment uptake. Treated HIV/HCV co-infected individuals benefitted from both decreased alanine aminotransferase (independent of SVR), and rates of SVR similar to those described in HCV monoinfected patients.

Liver ultrastructural morphology and mitochondrial DNA levels in HIV/hepatitis C virus coinfection: no evidence of mitochondrial damage with highly active antiretroviral therapy.

Liver mitochondrial toxicity is a concern, particularly in HIV/hepatitis C virus (HCV) coinfection. Liver biopsies from HIV/HCV co-infected patients, 14 ON-highly active antiretroviral therapy (HAART) and nine OFF-HAART, were assessed by electron microscopy quantitative morphometric analyses. Hepatocytes tended to be larger ON-HAART than OFF-HAART (P = 0.05), but mitochondrial volume, cristae density, lipid volume, mitochondrial DNA and RNA levels were similar. We found no evidence of increased mitochondrial toxicity in individuals currently on HAART, suggesting that concomitant HAART should not delay HCV therapy.

Tenofovir-based rescue therapy for advanced liver disease in 6 patients coinfected with HIV and hepatitis B virus and receiving lamivudine.

We summarize the clinical history and laboratory results following the introduction of tenofovir among 6 patients coinfected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) who presented with severe liver disease while receiving lamivudine-based highly active antiretroviral therapy. In all cases, the introduction of tenofovir led to a sustained undetectable HBV and HIV loads, with marked clinical and laboratory improvement in liver function. We provide supporting evidence for the role of tenofovir in the management of advanced HBV infection in HIV-positive patients after the development of lamivudine resistance.

Ethical and scientific issues surrounding solid organ transplantation in HIV-positive patients: Absence of evidence is not evidence of absence.

End-stage liver disease is emerging as a leading cause of death among HIV-positive patients. Historically, an HIV diagnosis was a contraindication for a liver transplant; however, because of the efficacy of highly active antiretroviral therapy (HAART), HIV-positive patients have one-year, two-year, and three-year post-transplantation survival rates similar to that of HIV-negative patients. Based on this evidence, HIV-positive patients are now considered eligible for transplantation. However, newly emerging guidelines include the stipulation that HIV-positive patients must be on HAART to be placed on a waiting list for transplantation. The purpose of the present paper is to evaluate the scientific and ethical probity of requiring HIV-positive patients to be on HAART as a condition for being on a liver transplant waiting list. It is argued that the emphasis should be placed on the probability of post-transplantation HAART tolerance, and that concerns about pretransplantation HAART tolerance are of secondary importance.

Effect of serostatus for hepatitis C virus on mortality among antiretrovirally naive HIV-positive patients.

BACKGROUND: We examined the effect of hepatitis C virus (HCV) seropositivity on risk of death among people receiving their first antiretroviral treatment (ART) for HIV infection. METHODS: In British Columbia, the HIV/ AIDS Drug Treatment Program is the only source of free ART. Patients who initiated a triple-drug ART regimen between July 31, 1996, and July 31, 2000, were included if they were ART-naive and had baseline HCV serological data. Outcomes of interest for survival analysis were deaths from natural and HIV-related causes, with a data cutoff of June 30, 2003. RESULTS: Of 1186 eligible subjects, 606 (51%) were HCV positive and 580, negative. Fewer HCV-positive people were male (78% v. 93%, p < 0.001) and had an AIDS diagnosis at baseline (11% v. 15%, p = 0.028). Their CD4 fraction was significantly higher at baseline (19% v. 16% of T lymphocytes, p < 0.001) but their absolute CD4 counts, log HIV viral load and the type of ART initiated were similar to those of HCV negative people. Of 163 deaths (from natural causes only) during the study period, 118 (19%) were in HCV positive and 45 (8%) in HCV negative patients (p < 0.001); of the 114 deaths attributed to HIV infection, these proportions were 79 (13%) versus 35 (6%; p < 0.001). After adjustment for potential confounders, HCV seropositivity remained predictive of death (adjusted hazard ratio [HR] 2.20, 95% confidence interval [CI] 1.50- 3.21, p < 0.001), especially HIV-related death (adjusted HR 1.75, 95% CI 1.13- 2.72, p = 0.012). INTERPRETATION: In this population-based HIV treatment program, we found HCV seropositivity to be an independent predictor of mortality, especially death related to HIV infection.

Adverse effects of antiretroviral therapy for HIV infection.

Long-term remission of HIV-1 disease can be readily achieved by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients.

Hepatotoxicity of nucleoside reverse transcriptase inhibitors.

Hepatotoxicity is an adverse effect of all available classes of antiretrovirals, including nucleoside reverse transcriptase inhibitors (NRTI). A syndrome of hepatic steatosis and lactic acidosis has been recognized as a rare, potentially fatal complication since the advent of NRTI monotherapy in the early 1990s. Today, NRTI remain the backbone of antiretroviral combination regimens, and, with the success of current treatment strategies, exposure to two or more of these agents may occur over a number of years. Hepatic steatosis and lactic acidosis are accordingly being observed more frequently, along with a more recently recognized syndrome of chronic hyperlactatemia. These as well as other adverse effects of NRTI are mediated by inhibition of human DNA polymerase gamma, resulting in mitochondrial dysfunction in the liver and other tissues. Early recognition and intervention are essential to avert serious outcomes.

Factors other than the Duke criteria associated with infective endocarditis among injection drug users.

BACKGROUND: Modified Duke criteria were applied to consecutive injection drug users (IDUs) who were admitted to an inner-city hospital with a clinical suspicion of infective endocarditis, and the presence of any other clinical variables that were predictive of the presence of infective endocarditis was determined. METHODS: Clinical data on consecutive IDUs who were hospitalized over 15 months in Vancouver were collected. Data included the admission history, and findings on physical examination and on initial laboratory investigations. Each subject's course in hospital was followed until discharge or death during the index hospitalization. Follow-up data collected included culture results, the interpretation of the echocardiogram and the discharge diagnosis. The modified Duke criteria were used for the diagnosis of infective endocarditis (definite, possible or rejected). Multiple logistic regression was used to determine what clinical variables (exclusive of the Duke criteria) available within 48 hours of presentation were independent predictors of infective endocarditis. RESULTS: One hundred IDUs were enrolled. Fifty-one were female, and 58 were HIV-positive. Twenty-three met the modified Duke criteria for definite infective endocarditis, and 25 had possible infective endocarditis. IDUs with definite infective endocarditis were more commonly noted to have evidence of vascular phenomena (arterial embolism, septic pulmonary infarction, mycotic aneurysm, intracranial hemorrhage or Janeway lesions) (6 [26%]) than those who had possible endocarditis (1 [4%]). Those with definite infective endocarditis more often had multiple opacities on chest radiography (56% v. < 12%), and fewer had an obvious source of infection (52% v. 72% and 81% of possible and rejected infective endocarditis, respectively). Among febrile IDUs, definite endocarditis was highly associated with having no obvious source of infection (odds ratio 3.1 [95% confidence interval 1.1-8.7]) compared with febrile IDUs with an obvious source of infection. In similarly compared groups, the presence of hematuria, proteinuria or pyuria was also predictive of definite endocarditis (odds ratio 2.9 [95% CI 1.1-8.6]). CONCLUSIONS: Among IDUs, the modified Duke criteria are useful for classifying cases with definite infective endocarditis and rejecting cases without infective endocarditis. The classification of possible infective endocarditis is suitable for this population.

Prevalence and response to antiretroviral therapy of non-B subtypes of HIV in antiretroviral-naive individuals in British Columbia.

In North America, the B subtype of the major group (M) of HIV-1 predominates. Phylogenetic analysis of HIV reverse transcriptase and protease sequences isolated from 479 therapy-naive patients, first seeking treatment in British Columbia between June 1997 and August 1998, revealed a prevalence of 4.4% non-B virus. A range of different subtypes was identified, including one subtype A, 11 C, two D, five CRF01_AE, and one sample that could not be reliably subtyped. Baseline CD4 courts were significantly lower in individuals harbouring the non-B subtypes (P = 0.02), but baseline viral loads were similar (P = 0.80). In this study, individuals infected with non-B variants did not have a significantly different virological response to therapy after up to 18 months.