Rita Murri

Variable Prediction of Antiretroviral Treatment Outcome by Different Systems for Interpreting Genotypic Human Immunodeficiency Virus Type 1 Drug Resistance

To determine the variability of genotypic human immunodeficiency virus (HIV) type 1 drug-resistance interpretation by available expert systems and its clinical implications, 261 subjects for whom a potent antiretroviral regimen was failing who were starting salvage therapy were evaluated. The association of the genotypic susceptibility score (GSS) of the salvage regimen, according to 11 interpretation systems, with HIV RNA outcomes for 6 months was examined. GSS was highly variable, as determined by the different interpretation systems, and showed independent correlation with changes from baseline HIV RNA levels at 6 months with 5 systems--Stanford hivdb, GuideLines 3.0, Retrogram 1.4, HIVresistanceWeb, and São Paulo University. Most GSSs predicted virologic response in regimens containing stavudine, lamivudine, efavirenz, or indinavir. Selected systems predicted response in regimens containing didanosine, abacavir, or nelfinavir, and no system predicted outcome of boosted protease inhibitors. GSSs predicted changes in HIV RNA levels better in adherent patients than in nonadherent individuals. Interpretation may be improved, and knowledge should be used uniformly throughout different expert systems.

Determinants of health-related quality of life in HIV-infected patients

In the era of new antiretroviral treatments that have dramatically reduced both morbidity and mortality, a primary goal is to maximize function and wellbeing in the everyday life of HIV-infected patients. To be able to do so, it would be important for clinicians and policy makers to identify factors that influence health-related quality of life (HRQoL). The objective of this multicentre prospective cohort study was to identify determinants of HRQoL in a cohort of Italian HIV-infected patients, the majority of whom were taking highly active antiretroviral therapy (HAART). A total of 809 patients were enrolled. The MOS-HIV Health Survey (summarized using two scores, physical health (PHS) and mental health (MHS)), and an HIV-related symptom scale were administered at enrolment and six months later. At baseline, low CD4+ cell count, hospitalization during the three months before the enrollment and symptoms were independently related to poor PHS; hospitalization during the three months before the enrollment, symptoms and poor satisfaction with information from providers were independently related to MHS. Predictors of PHS at six months included the stage of HIV infection, baseline CD4+ cells count, PHS and symptom score; while age, baseline MHS, symptom score and education predicted six-month MHS. Among these factors, symptoms, recent hospitalization and satisfaction with information are most amenable to clinical intervention.

Clinical and Virological Monitoring During Treatment with Intrathecal Cytarabine in Patients with AIDS-Associated Progressive Multifocal Leukoencephalopathy

We describe the clinical and virological outcome of human immunodeficiency virus-infected patients with progressive multifocal leukoencephalopathy (PML) treated with cytarabine. Twenty-seven patients received intrathecal cytarabine, 5 received concomitant intravenous cytarabine, and 20 received concomitant antiretroviral therapy. The median baseline CD4+ cell count was 28/mm3. After 4 weeks, 4 (19%) of 21 evaluable patients had stable disease, whereas the others progressed. The median survival from diagnosis and from onset was 66 and 128 days, respectively. Patients with Karnofsky scores of >50 and those previously taking antiretroviral medications had a higher probability of survival 3 months after diagnosis (P = .003 and P = .05, respectively). Overall, after 4 weeks, median JC virus load in CSF increased by 0.7 log10 copies/mL from baseline (P = NS). The mean JC virus load at 4 weeks was lower in patients with stable disease than in progressors (3.47 vs. 4.47 log10 copies/mL; P = .027). JC virus became undetectable in the only patient who had a long-term stable condition. The concentration of JC virus in CSF showed a correlation with clinical outcome.

AIDS-Associated Cerebral Toxoplasmosis: An Update on Diagnosis and Treatment

Toxoplasmic encephalitis (TE) is one of the major opportunistic infections of the central nervous system (CNS) and the most frequent cause of focal brain lesions (FBL) in patients with acquired immunodeficiency syndrome (AIDS) (Luft et al. 1993). CNS toxoplasmosis is rapidly progressive and fatal without treatment and has been reported to be the AIDS index diagnosis in 22%-51% of patients infected with human immunodeficiency virus (HIV) (Leport et al. 1988; Cohn et al. 1989; Dannemann et al. 1991; Zangerle et al. 1991; Porter and Sande 1992).

Safety and efficacy of treatment switch to raltegravir plus tenofovir/emtricitabine or abacavir/lamivudine in patients with optimal virological control: 48-week results from a randomized pilot study (Raltegravir Switch for Toxicity or Adverse Events, RASTA Study)

Abstract Background: The Raltegravir Switch for Toxicity or Adverse Events (RASTA) Study is a 2-arm randomized pilot study exploring the safety and efficacy at 48 weeks of a treatment switch to raltegravir associated with tenofovir/emtricitabine or abacavir/lamivudine in patients with regimens with optimal virological control. Methods: Patients treated with stable protease inhibitor (PI)-, non-nucleoside reverse transcriptase inhibitor (NNRTI)-, or nucleoside reverse transcriptase inhibitor (NRTI)-based regimens, with HIV-RNA levels < 50 copies/ml for ≥ 3 months and a CD4 cell count > 200 cells/μl were eligible. Enrollment of 40 patients was planned: at baseline patients were randomized 1:1 to switch to raltegravir plus tenofovir/emtricitabine (arm A) or abacavir/lamivudine (arm B). Laboratory parameters, raltegravir plasma levels, self- reported adherence, quality of life parameters, neurocognitive performance, bone composition, and body fat distribution were monitored. Virological failure was defined as HIV-RNA > 50 copies/ml on 2 consecutive determinations. Results: After 48 weeks, 5/40 (12.5%) regimen discontinuations occurred: 2 were for low-level viremia virological failure (both in arm A, at weeks 24 and 48) and 3 were for adverse events (neurological disturbances and skin rash in arm B; proximal tubulopathy in arm A). Overall, a significant CD4 increase was observed at weeks 36 and 48, and a significant decrease in total cholesterol, non-high density lipoprotein cholesterol, and triglycerides was observed at each study visit. Physical health/satisfaction in therapy scores and neuropsychological performance improved. The lumbar column Z-score improved, with no modification in other bone composition and fat distribution parameters. Conclusions: The investigated switch strategy was associated with rare virological failure. Improvements in lipid levels, quality of life measures, neuropsychological performance, and bone composition suggest good tolerability of raltegravir-based regimens.

Fluconazole for primary prophylaxis of AIDS-associated cryptococcosis: A case-control study

In order to verify whether fluconazole has a prophylactive effect against the occurrence of cryptococcosis in HIV-infected patients and to identify other factors capable of increasing or reducing the risk of this infection, we arranged a case-control study of 17 patients with cryptococcal infection. 34 controls were selected, matched by presence of an AIDS-defining event, CD4 cell count, and date of T-cell phenotyping. No significant difference in exposure to fluconazole, in total days of treatment, or in total dose administered was observed between cases and controls. However, control patients took a significantly higher average daily dosage of fluconazole and a linear tendency in risk reduction (p = 0.04) in relation to increasing dosage was observed. Antiretroviral therapy and an average daily fluconazole dose exceeding 150 mg both each reduced the risk of a cryptococcal infection.

Management of Recurrent Cutaneous Abscesses During Therapy With Infliximab

BACKGROUND Infliximab is a chimeric monoclonal antibody, belonging to the class of anti-tumor necrosis factor-α (TNF-α) agents, approved for the treatment of psoriasis and psoriatic arthritis. Drugs of this class are known to be associated with an infective risk, probably because they interfere with inflammatory and immune response at different levels. Although cutaneous Staphylococcus aureus infections seem to be more frequent than any other infection in the course of anti-TNF-α treatment, only a few case reports in the literature deal with this side effect, and, in particular, with its management. OBJECTIVE Our aim was to report a case of recurrent methicillin-sensitive S aureus (MSSA) cutaneous abscesses during therapy with infliximab and successful management. CASE SUMMARY In July 2009, a 53-year-old white woman (weighing 85 kg) affected by psoriasis and psoriatic arthritis was administered infliximab (5 mg/kg IV), based upon clinical appearance and previous unsuccessful treatment with cyclosporine, methotrexate, etanercept, and adalimumab. Three days after the first 3 infusions (at weeks 0, 2, and 6) she complained about the recurrent onset of painful, erythematous, indurated, and pus-draining cutaneous nodules located on her abdomen. The swab always revealed the presence of MSSA, and antibiotic oral therapy with amoxicillin + clavulanic acid (875 + 125 mg BID for 7 days) was established, with complete resolution of the abscesses. Routine laboratory findings were in normal ranges, with the exception of an elevated erythrosedimentation rate and an increased white blood cell count (range, 13,000-15,000/mm(3)) with neutrophilia (range, 75%-80%). HIV infection was ruled out. In agreement with the infectious disease consultant, 1 day before the fourth infusion, a prophylactic antibiotic therapy with amoxicillin + clavulanic acid (875 + 125 mg BID for 5 days) was added to the therapeutic regimen. This treatment schedule was successfully repeated at each following infusion (every 8 weeks), and no recurrence of skin abscesses was observed. The patient provided signed authorization for publication of this case. CONCLUSIONS This case report describes a woman with psoriasis and psoriatic arthritis who developed MSSA skin abscesses after each of the first 3 infliximab infusions, which did not recur for the next 6 infusions after amoxicillin + clavulanic acid was added to her regimen, pre- and 4 days postinfusion. Adequately designed, placebo-controlled, double-blind trials are needed to determine whether such prophylactic antibiotic treatment is well tolerated or effective for this common complication of therapy with anti-TNF-α agents, when withdrawal of the drug is not advisable, as in this case.

Relationship between self-reported adherence, antiretroviral drug concentration measurement and self-reported symptoms in patients treated for HIV-1 infection

Background: The aim of the study was to explore relationships between self-reported adherence, antiretroviral drug concentration measurement (TDM) and self-reported symptoms. Methods: We systematically administered to human immunodeficiency (HIV)-infected outpatients a questionnaire evaluating measures of self-reported adherence (missing doses during last week, deviations from the prescribed timing of therapy, self-initiated discontinuations for > 24 or 48 h, exhausting drugs and present sense of how patients are taking therapy) and a panel of referred symptoms (a symptom score was built summing self-reported scores for each listed symptom). We selected patients who completed the questionnaire and also had a TDM (mainly reflecting adherence in the past few days or weeks), thus comparing these two tools as measures of adherence. Results: A total of 130 patients (64.6% males, median age 44 years, 76.2% with HIV RNA < 50 copies/ml, median CD4 540 cells/μl) were included. Mean self-reported adherence (on a 0–100 visual analogue scale) was 80% (standard deviation, 18.7). Drug concentration was subtherapeutic in 16 patients (12.3%), of which 7 (5.4%) had undetectable drug levels (< 0.05 mg/L). Of these last seven patients, five (71.4%) reported an adherence below 80%. In a multivariable analysis, females and patients with undetectable drug levels (mean change −18.43%, 95% confidence intervals (CIs) −31.83 to −5.03, p = 0.007) showed a lower self-reported adherence, while those with HIV RNA < 50 copies/ml showed a higher adherence. Lower self-reported adherence (odds ratio 0.62 per 10% increase, 95% CI = 0.43–0.89, p = 0.009) and longer time from last drug intake were independently related to the development of undetectable drug levels. We also found that a higher symptom score was associated with a lower self-reported adherence and with a higher proportion of undetectable drug levels. Conclusions: Self-reported adherence and TDM showed a correlation and seemed to be comparable tools for adherence estimation. Self-reported symptoms were associated with lower adherence and undetectable drug levels.

Detrimental clinical interaction between ritonavir-boosted protease inhibitors and vinblastin in HIV-infected patients with Hodgkin lymphoma

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK