Lamivudine or emtricitabine (XTC)/protease inhibitor dual therapy as a harm-reduction strategy in patients with tenofovir-related renal toxicity: a case-control study.

Tenofovir disoproxil fumarate (TDF) is widely used in HIV-infected patients. It is associated with tubular toxicity, but its management is controversial. A possible strategy is to switch to a dual therapy based on lamivudine or emtricitabine (XTC) and protease inhibitors (PIs). A case-control study was designed to evaluate the switch to XTC + PI therapy in patients with TDF-related renal toxicity. A case was defined as a patient who was on TDF/XTC + PI and who switched to XTC + PI. A control was defined as a patient with the same clinical features who remained on TDF/XTC + PI. Twenty-one cases and 21 controls were included. After 48 weeks, no differences in efficacy were observed. No improvement in the glomerular filtration rate as estimated with the Cockroft-Gault formula (eGFR) was seen, but the number of times that patients had values below 60 ml/min was higher with standard TDF/XTC 1 PI treatment than with dual XTC + PI treatment. A switch to dual therapy could be an option for patients at risk of TDF-related renal damage with no relevant risk of virological or immunological failure.

Prevalence, associated factors, and prognostic determinants of AIDS-related toxoplasmic encephalitis in the era of advanced highly active antiretroviral therapy.

BACKGROUND: Characteristics, associated factors, and survival probability of toxoplasmic encephalitis (TE) in the era of advanced highly active antiretroviral therapy (HAART) have not been fully clarified. METHODS: Data for 205 individuals with acquired immunodeficiency syndrome (AIDS)-related TE were derived from the Italian Registry Investigative NeuroAIDS database, and the cases were studied longitudinally to evaluate prevalence, clinical characteristics, and survival. Moreover, the relationship between the occurrence of TE and exposure to antiretroviral therapy and to TE prophylaxis was evaluated. RESULTS: With an overall prevalence of 26%, TE represented the most frequent neurological disorder in the cohort. Female sex, severe immunodeficiency, and absence of primary TE prophylaxis significantly increased the risk of TE, and previous exposure to antiretroviral therapy reduced the probability of disease occurrence. Thirty-six percent of patients who had received antiretroviral therapy developed TE, although in most of these cases, the patient experienced failure of antiretroviral therapy. Of note, 66% of patients who had experienced antiretroviral therapy did not receive prophylaxis for TE at TE diagnosis. The 1-year probability of that infection with human immunodeficiency virus (HIV) would progress or that death would occur after TE was 40% and 23%, respectively. Cognitive symptoms, low CD4(+) cell count, not receiving HAART after TE, and initiating HAART >2 months after TE diagnosis were all significantly associated with an increased probability of progression of HIV infection. Not receiving HAART after diagnosis negatively affected survival. CONCLUSIONS: TE remains a highly prevalent disorder of the central nervous system, even in the late HAART era, particularly among severely immunosuppressed patients and in absence of prophylaxis. Considering that persons with TE have a high probability of early death, prophylaxis should be maintained in immunosuppressed patients who experience failure of antiretroviral therapy, and HAART should be initiated as soon as possible after TE diagnosis.

Clinical epidemiology and survival of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy: data from the Italian Registry Investigative Neuro AIDS (IRINA).

Human immunodeficiency virus (HIV)-associated progressive multifocal leukoencephalopathy (PML) remains a relevant clinical problem even in the era of highly active antiretroviral therapy (HAART). Aims of the study were to analyze clinical and treatment-related features and the survival probability of PML patients observed within the Italian Registry Investigative Neuro AIDS (IRINA) during a 29-month period of HAART. Intravenous drug use, the presence of focal signs, and the involvement of white matter at neuroradiology increased the risk of having PML. A reduced probability of PML was observed when meningeal signs were reported. Patients starting HAART at PML diagnosis and previously naïve for antiretrovirals showed significantly higher 1-year probability of survival (.58), compared to those continuing HAART (.24), or never receiving HAART (.00). Higher CD4 cell count were associated with a higher survival probability (.45). At multivariate analysis, a younger age, higher CD4, starting HAART at PML diagnosis, the absence of previous acquired immunodeficiency syndrome (AIDS)-defining events, and the absence of a severe neurologic impairment were all associated with a reduced hazard of death. The use of cidofovir showed a trend towards a reduced risk of death.