Drug-resistance development differs between HIV-1-infected patients failing first-line antiretroviral therapy containing nonnucleoside reverse transcriptase inhibitors with and without thymidine analogues.

OBJECTIVES: We evaluated the emergence of drug resistance in patients failing first-line regimens containing one nonnucleoside reverse transcriptase inhibitor (NNRTI) administered with zidovudine (ZDV) + lamivudine (the ZDV group) or non-thymidine analogues (non-TAs) (tenofovir or abacavir, + lamivudine or emtricitabine; the non-TA group). METHODS: Three hundred HIV-1-infected patients failing a first-line NNRTI-containing regimen (nevirapine, n = 148; efavirenz, n = 152) were included in the analysis. Virological failure was defined as viraemia ≥ 400 HIV-1 RNA copies/mL for the first time at least 6 months after starting the NNRTI-based regimen. For each patient, a genotypic resistance test at failure was available. The presence of drug-resistance mutations in HIV-1 reverse transcriptase was evaluated by comparing patients treated with NNRTI + zidovudine + lamivudine vs. those treated with NNRTI + non-TA. RESULTS: A total of 208 patients were failing with NNRTI + zidovudine + lamivudine and 92 with NNRTI + non-TA. No significant differences were observed between the non-TA group and the ZDV group regarding the time of virological failure [median (interquartile range): 12 (8-25) vs. 13 (9-32) months, respectively; P = 0.119] and viraemia [median (interquartile range): 4.0 (3.2-4.9) vs. 4.0 (3.3-4.7) log10 copies/mL, respectively; P = 0.894]. Resistance to reverse transcriptase inhibitors (RTIs) occurred at a significant lower frequency in the non-TA group than in the ZDV group (54.3 vs. 75.5%, respectively; P = 0.001). This difference was mainly attributable to a significantly lower prevalence of NNRTI resistance (54.3 vs. 74.0%, respectively; P = 0.002) and of the nucleoside reverse transcriptase inhibitor (NRTI) mutation M184V (23.9 vs. 63.5%, respectively; P < 0.001) in the non-TA group compared with the ZDV group. As expected, the mutation K65R was found only in the non-TA group (18.5%; P < 0.001). CONCLUSIONS: At first-line regimen failure, a lower prevalence of RTI resistance was found in patients treated with NNRTI + non-TA compared with those treated with NNRTI + zidovudine + lamivudine. These results confirm that the choice of backbone may influence the prevalence of drug resistance at virological failure.

Bone marrow toxicity in HCV genotype 5a-infected patient after peg-IFN alpha-2a and ribavirin therapy.

The optimal therapy for HCV-related chronic hepatitis is the combination of pegylated interferon alpha (peg-IFN alpha) plus ribavirin (RBV). Unfortunately, both peg-IFN alpha and RBV are responsible for a wide range of adverse events and potentially severe toxicities, particularly hematological alterations. Indeed, RBV is generally responsible for anemia through hemolysis, while peg-IFN alpha induces more commonly leukopoenia and thrombocytopenia, presumably through bone marrow toxicity. Actually, data regarding histopathological bone marrow alterations in HCV-infected patients following IFN-alpha therapy is scanty. We report a case of a HCV-infected cirrhotic patient, who developed bone marrow alterations following one-year peg-IFN alpha plus RBV treatment, and we describe the associated histopathological features. Our case report provides new significant insight on the histopathological changes occurring in bone marrow of HCV-infected cirrhotic patients during peg-IFN alpha-2a plus RBV treatment, providing also additional information on potential bone marrow toxicity in the course of IFN-based treatments.

Atypical disseminated leishmaniasis resembling post-kala-azar dermal leishmaniasis in an HIV-infected patient.

Post-kala-azar dermal leishmaniasis (PKDL) is very uncommon among HIV-positive patients, and very few cases have so far been documented. A case of atypical disseminated leishmaniasis resembling PKDL in an HIV-positive patient successfully treated with N-methylglucamine antimoniate is reported. The polymerase chain reaction performed on the skin lesions was positive for Leishmania infantum.

The epidemiology of recurrent bacterial pneumonia in people with AIDS in Europe.

Data from AIDS surveillance systems in the World Health Organization European region (1993-2001) were analysed to describe the main epidemiological aspects of recurrent bacterial pneumonia (RBP) as AIDS-defining illness (ADI) in Europe. Among the 153 756 AIDS cases analysed, 5796 (3.8%) had RBP. The proportion of RBP was higher (8.3%) in eastern than in western Europe (3.6%), possibly because of a greater propensity of certain countries to diagnose RBP. In western Europe, the proportion of RBP as ADI appeared to increase over time up to 1998 (from 2.5% to 4.5%), and declined thereafter (3.3% in 2001). RBP was strongly associated with intravenous drug use (odds ratio 3.0, 95% CI 2.7-3.3), whereas it did not differ in age groups or geographical areas. The study findings confirm the crucial role of intravenous drug use in the occurrence of RBP and suggest that highly active antiretroviral therapies mi.ht have had a postponing impact on the relative frequency of RBP as ADI.

[Guidelines for the management of HCV infection in HIV-infected patients. Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani]. / Linee-guida per la gestione clinica della infezione/malattia da HCV nei pazienti con infezione da HIV.

It is crucial to ensure an optimal clinical management of HCV infection in HIV-co-infected persons. The reasons for the development of guidelines on HCV-infection treatment in HIV-infected persons arise from the need for a standardised management of HIV/HCV coinfection in our Institute. The aim of these guidelines are: to clarify principles of clinical management of HCV infection in HIV-infected patients to care-providers; to improve the awareness of HIV-infected patients cared for our Institute on current management of HCV infection; to improve the quality of care on this topic. These guidelines, based on Evidence based Medicine principles, have been developed by a panel of experts, who conducted a systematic review of the literature, mainly taking into account current international recommendations. In the present document, the most frequent clinical presentation occurring in the management of HIV/HCV co-infected patients at our Institution are discussed. The adherence to present guidelines and their effectiveness at our Institution, outcome indicators will be evaluated. The present guidelines cannot entirely substitute the judgement of an expert clinician. However, adherence to these guidelines will contribute to the improvement of the standard of care of HIV/HCV-co-infected persons.

Remission of Behçet's disease and keratoconjunctivitis sicca in an HIV-infected patient treated with HAART.

A 34-year-old woman presented with a 10-year history of recurrent oral and genital ulcerations and recurrent episodes of bilateral conjunctivitis associated with HIV infection. A diagnosis of Behçet's disease (BD) in association with keratoconjunctivitis sicca (KCS) was made after exclusion of other viral and autoimmune diseases according to the international criteria for BD. This is the first reported case of a combination of BD and KCS in a patient with HIV infection in which a complete resolution was observed as a result of successful highly active antiretroviral therapy. The likelihood that a direct viral effect or HIV-induced autoimmune mechanisms act in the pathogenesis of both BD and KCS in HIV-infected patients is discussed.

Resection and transplantation: evaluation of surgical perspectives in HIV positive patients affected by end-stage liver disease.

PURPOSE: The aim of this study was to evaluate the opportunity of surgical treatment in terms of liver resection or liver transplantation in HIV positive patients affected by an end stage liver disease that referred to our liver unit. METHODS: Among 1350 outpatients who referred to our liver unit from January 2002 to September 2003, thirty-two (2,4%) were HIV positive. The routes of transmission of the viral infection, the related co-infections and the underlying liver disease were recorded. The therapeutic pathway was analysed. The kind and the duration of the surgical procedures were assessed. RESULTS: Fourteen (44%) of these thirty-two patients were not suitable for surgical treatment. Surgery was planned in 9 of 32 HIV positive patients (28%). Four patients (12%) were submitted to liver resection and OLT was performed in five patients (15%). Hepatocellular Carcinoma was present in 4 (44%) of the HIV positive patients considered for surgery. CONCLUSIONS: In conclusion in our centre the 28% of HIV positive out patients had the opportunity to receive a surgical treatment. The candidate to this surgery is mostly young, HCV and/or HBV coinfected and affected by HCC in 44% of cases.

Diagnosis of intra vascular catheter-related infection.

The use of central vascular catheters (CVC) is associated with a substantial number of complications, amongst which infections predominate. A diagnosis of CVC-related infection usually requires catheter removal for culture. Semiquantitative (roll-plate method) and quantitative methods (flush, vortex, centrifugation or sonication methods) are the most reliable diagnostic methodologies requiring catheter removal, because of their greater specificity. The roll-plate method is the simplest and most commonly used technique. This method only samples the external surface of the catheter, and is particularly indicated for recently inserted catheters in which extraluminal colonisation is the primary mechanism of infection. Luminal culture techniques, such as the quantitative methods, may be more relevant for catheters that have been in place for a long period of time. However, in up to 85% of removed CVC the culture is negative, and other diagnostic techniques that do not require catheter removal have been proposed, including paired quantitative blood cultures, endoluminal brushing, and differential time to positivity (DTP) of paired blood cultures. DTP, that compares the time to positivity for qualitative cultures of blood samples simultaneously drawn from the CVC and a peripheral vein, appears to be the most reliable in the routine clinical practice since many hospitals use automatic devices for qualitative blood culture positivity detection. More recently catheter-sparing direct diagnostic methods, which include Gram stain and acridin-orange leucocyte cytospin (AOLC) test, appeared to be especially useful because of the rapidity of results and the ability to distinguish different microorganisms, allowing early targeted antimicrobial therapy.

Community-acquired Acinetobacter radioresistens bacteremia in an HIV-positive patient.

We describe the first case of community-acquired bacteremia caused by Acinetobacter radioresistens; the patient was a 32-year-old HIV-positive neutropenic woman. Ambiguous Gram staining and poor biochemical reactivity of blood culture isolates misguided early diagnosis and therapy. Bacterial identification was based on 16S rDNA sequence analysis. A. radioresistens can be considered as a cause of opportunistic infection in immunodeficient patients.

Clinical manifestation of HIV-related pulmonary hypertension.

In recent years, much more thought has been given to the pathogenic role of HIV and to the clinical manifestations of HIV-related pulmonary hypertension (HRPH), which currently represents one of the most severe events during HIV disease. HRPH occurs in early and late stages of HIV infection and does not seem to be related to the degree of immune deficiency. Many of the symptoms in HRPH result from right ventricular dysfunction: the first clinical manifestation is effort intolerance and exertional dyspnea that will progress to the point of breathlessness at rest. The diagnosis of HRPH can be made only after all etiologies for pulmonary hypertension have been excluded. Echocardiography has been proven to be an extremely useful tool for diagnosing HRPH, and Doppler echocardiography can be used to estimate systolic pulmonary artery pressure and to monitor the effects of therapy. Assessment of hemodynamic measures by catheterization remains, however, the best test for evaluating response to therapy. Cardiac catheterization is mandatory to characterize the disease and exclude an underlying cardiac shunt as etiology. Vasodilators have been extensively used in the treatment of pulmonary hypertension, since vasoconstriction is a determinant characteristic of this disease. However, HRPH remains a progressive disease for which treatment is often unsatisfactory and there is no cure. As new, more efficient antiretroviral treatment are introduced, clinicians should expect to encounter an increasing number of cases of pulmonary hypertension in HIV+ patients in the future.

Role of human immunodeficiency virus in primary pulmonary hypertension--case reports.

Previous cases of pulmonary hypertension (PH) in human immunodeficiency virus (HIV) infection have been reported in the literature. The role of HIV in PH is still debatable. The purpose of this report was to analyze whether HIV plays a direct or indirect role in PH pathogenesis. Between February and November 1997, 56 HIV-infected patients with cardiac symptoms and signs were studied by serial color Doppler echocardiography. In four patients (7.1%), PH not related to other well-known associated conditions, was disclosed. In spite of a low serum HIV RNA viral load and a high-efficacy antiretroviral therapy, including a protease inhibitor in two patients, PH developed and worsened. It could be hypothesized that in some patients with an individual immunogenetic predisposition, a high secretion of cytokines and endothelin-1 stimulated by an unidentified pathogen different from HIV could lead to PH. Antiretroviral therapy seems not to prevent or reduce right ventricle pressure gradient in PH.

Occupational hepatitis C virus infection in Italian health care workers. Italian Study Group on Occupational Risk of Bloodborne Infections.

The risk of exposed health care workers in 16 Italian hospitals becoming infected with hepatitis C virus was assessed through two serosurveys at a 1-year interval and at follow-up. Prevalence, which was 2.2%, was significantly associated with previous acute hepatitis, blood transfusions, housekeeping, and older age (> 46 years) but not with occupational risk factors. After 1 year, 2622 (87%) of the 3006 seronegative health care workers were retested, and 3 (0.1%), who did not acknowledge occupational or community risk factors, seroconverted. Additionally, 133 (97 needlesticks) out of 370 reported occupational exposures were to hepatitis C virus; one pricked nurse seroconverted (0.75%). Although the risk is not negligible, hepatitis C virus infection does not seem to be easily occupationally transmitted.

Long-term effects of recombinant leukocyte alpha interferon in the treatment of chronic delta hepatitis.

A pilot study is described, in which 25 chronic CDH patients were treated with 3 MU recombinant alpha-interferon per week for 4 months. Improvement was transient and no long-term effects were noted. Side effects were well tolerated and reversible so that longer treatment and higher dosages should be possible.