Incidence of adipose tissue alterations in first-line antiretroviral therapy: the LipoICoNa Study.

Background: Adipose tissue alterations (ATAs) are a frequent untoward effect of antiretroviral therapy, the causes of which remain incompletely explained.

Objectives: To assess the incidence of ATAs and to identify the associated risk factors in patients infected with human immunodeficiency virus type 1 starting their first-line antiretroviral treatment.

Methods: In a multicenter investigation designed to study issues related to the treatment of patients starting antiretroviral therapy, physicians were requested to assess the presence of ATAs at enrollment and every 6 months thereafter.

The changing demographics of new HIV diagnoses at a London centre from 1994 to 2000.

Objective: To document the demographic changes in new HIV diagnoses at the Royal Free Hospital, London, UK, between 1994 and 2000.

Design: Retrospective case note review.

Methods: Data were extracted from the Royal Free HIV database identifying new diagnoses for 1994, 1997 and 2000.

An observational study on patients treated or not for acute HIV infection.

Background: A vast majority of HIV-infected subjects who experience HIV acute seroconversion actually receive treatment. Open questions are how can we identify patients who will be slow progressors or long-term non progressors, and, as a consequence, do not require treatment.

Methods: An observational retrospective study on patients who experienced acute HIV seroconversion from August 1995 to June 2001, who are still alive and followed as outpatients at the Clinic of Infectious Diseases of Modena, Italy.

Primary HIV-1 resistance in recently and chronically infected individuals of the Italian Cohort Naive for Antiretrovirals.

The risk of acquiring HIV-1 drug resistance at time of infection has become a public health problem following the widespread use of antiretroviral drugs in developed countries. Although a number of studies have reported data regarding the prevalence of HIV-1 primary resistance in developed countries over the past years, limited knowledge is available regarding the proportion of mutations related to drug resistance in antiretroviral naive subjects with chronic HIV-1 disease. In this study, we evaluated the prevalence of mutations in the reverse-transcriptase (RT) and protease region both in a representative group of recently HIV-1 infected subjects (n=68) and a cohort of chronically-infected HIV-positive patients (n=347) enrolled in the Italian Cohort of Antiretroviral Naive patients (I.

Virologic and immunologic response to regimens containing nevirapine or efavirenz in combination with 2 nucleoside analogues in the Italian Cohort Naive Antiretrovirals (I.Co.N.A.) study.

This nonrandomized study compared the virologic and immunologic responses to potent regimens containing either efavirenz or nevirapine after considering potential systematic differences between patients receiving these drugs. Virologic failure was defined as the first of 2 consecutive measurements of virus load >500 human immunodeficiency virus RNA copies/mL. Of the 694 patients included in the analysis, 460 (66.

Low prevalence of primary mutations associated with drug resistance in antiviral-naive patients at therapy initiation.

Objective: To assess the prevalence of mutations in the reverse-transcriptase (RT) and protease (PR) region in a cohort of chronically-infected HIV-positive patients requiring highly active antiretroviral therapy (HAART).

Methods: The study included 347 patients enrolled in the Italian Cohort of Antiretroviral Naive patients (I.CO.

Raised viral load in patients with viral suppression on highly active antiretroviral therapy: transient increase or treatment failure?

Objective: To assess the occurrence of viral load greater than 50 copies/ml in patients on highly active antiretroviral therapy (HAART) having achieved less than 50 copies/ml and the chance of whether a viral load greater than 50 copies/ml would lead to a sustained and increasing viral load.

Design: A cohort of 553 patients on HAART with viral loads of less than 50 copies/ml were followed.

Results: Over a median of 56 weeks 35% of patients experienced a transient increase and 8% virological failure (two consecutive viral loads of > 400 copies/ml).

Durability of HIV-1 viral suppression over 3.3 years with multi-drug antiretroviral therapy in previously drug-naive individuals.

Background: Relatively little is known about the long-term durability of viral suppression in individuals initially achieving a viral load of less than 50 copies/ml within 24 weeks of starting antiretroviral therapy, nor the extent to which therapy interruption accounts for the loss of suppression.

Methods: We intensely followed all 336 antiretroviral-naive patients attending the Goethe Universitat Clinic who began multi-drug combination regimens and in whom a viral load of less than 50 copies/ml was achieved within 24 weeks, in order to assess the risk of viral load rebound. Inspection of case notes allowed the distinction of viral rebound according to whether there was an associated complete interruption of therapy.

Participation in clinical studies among patients infected with HIV-1 in a single treatment centre over 12 years.

Objective: To examine a complete population of clinic attenders in order to compare the demographics of patients who participated in a clinical study with those who had not. These were subdivided into trials of antivirals, trials for drugs used in opportunistic infections or symptomatic HIV and epidemiological studies. The setting was an established London teaching hospital.

Non-Hodgkin lymphoma in HIV-infected patients in the era of highly active antiretroviral therapy.

This study was designed to assess the influence of highly active antiretroviral therapy (HAART) on non-Hodgkin lymphoma (NHL) among patients infected with human immunodeficiency virus (HIV). Within EuroSIDA, a multicenter observational cohort of more than 8500 patients from across Europe, the incidences of NHL and subtypes (Burkitt, immunoblastic, primary brain lymphoma [PBL], and other/unknown histology) were determined according to calendar time of follow-up, and for those who initiated HAART (> or =3 drugs) also time on HAART. Potential predictive factors of NHL were evaluated in Cox proportional hazard models.

Secondary mutations in the protease region of human immunodeficiency virus and virologic failure in drug-naive patients treated with protease inhibitor-based therapy.

The role of mutations in protease (PR) and reverse-transcriptase (RT) of human immunodeficiency virus (HIV) in predicting virologic failure was assessed in 248 antiretroviral-naive HIV-positive patients who began a PR inhibitor-containing antiretroviral regimen. Genotypic testing was performed on plasma samples stored before the start of therapy. Twenty-seven patients (10.

Increasing prevalence of non-clade B HIV-1 strains in heterosexual men and women, as monitored by analysis of reverse transcriptase and protease sequences.

Objective: We evaluated the prevalence of HIV-1 non-clade B over time in a formerly clade B-restricted area. Protease and reverse transcriptase regions of the pol gene were used for phylogenetic and recombination analysis and for clade assignment to HIV-1 A-D, F-H, J, and K strains of the M group.

Methods: The pol gene of 349 HIV-1 patients belonging to the Italian Cohort Naive for Antiretrovirals (ICONA) were genotypically analyzed to study the prevalence of antiretroviral-associated resistance mutations.

When to start highly active antiretroviral therapy in chronically HIV-infected patients: evidence from the ICONA study.

Objectives: To compare the response to highly active antiretroviral therapy (HAART) in individuals starting HAART at different CD4 cell counts.

Design: The mean increase in CD4 cell count and rate of virological failure after commencing HAART were measured in antiretroviral-naive patients (1421) in a large, non-randomized multicentre, observational study in Italy (ICONA). Clinical endpoints were also evaluated in a subset of patients who started HAART with a very low CD4 cell count.

HIV drug susceptibility and treatment response to mega-HAART regimen in patients from the Frankfurt HIV cohort.

Objective: To assess the relationship between viral susceptibility at baseline and virological response in human immunodeficiency virus (HIV)-infected patients treated with multi-drug salvage regimens after multiple previous treatment failures.

Design: Retrospective analysis of 50 patients from the Frankfurt HIV cohort who had received treatment with a minimum of six drugs, and for whom a sample for baseline viral phenotyping was available.

Methods: Viral drug susceptibility was measured retrospectively from stored samples using the Antivirogram, a recombinant virus assay based method.

Resistance profiles in patients with viral rebound on potent antiretroviral therapy.

The prevalence of phenotypic drug resistance was assessed in 60 patients with a viral rebound after they received a protease inhibitor (PI)- or nonnucleoside reverse transcriptase inhibitor (NNRTI)-containing regimen (baseline). Resistance testing was done within 36 weeks of viral rebound; no resistance testing was available at baseline. All patients had previously received zidovudine; 86.

Adrenaline-induced mobilization of T cells in HIV-infected patients.

The present study aimed to investigate lymphocyte mobilization from peripheral cell reservoirs in HIV-infected patients. Nine HIV-infected patients on stable highly active anti-retroviral therapy (HAART), eight treatment-naive HIV-infected patients and eight HIV- controls received a 1-h adrenaline infusion. The adrenaline infusion induced a three-fold increase in the concentration of lymphocytes in all three groups.

Natural immunity and HIV disease progression.

Objective: To investigate the clinical implications of impaired levels of the natural immunity mediated by natural killer (NK) cells and lymphokine activated killer (LAK) cells during infection with HIV-1.

Design: Data used were from 172 individuals with an estimated measure of NK cell activity and 146 with an estimated measure of LAK cell activity. Patients had active HIV infection at the time of enrolment in the study and have been followed-up prospectively for a median of 3.

The rate of CD4 decline as a determinant of progression to AIDS independent of the most recent CD4 count. The Italian Seroconversion Study.

The data of two cohort studies of HIV-infected individuals were used to examine whether the rate of CD4 decline is a determinant of HIV progression, independent of the most recent CD4 count. Time from seroconversion to clinical AIDS was the main outcome measure. Rates of CD4 decline were estimated using the ordinary least squares regression method.

The relative prognostic value of plasma HIV RNA levels and CD4 lymphocyte counts in advanced HIV infection.

Objective: It has been suggested that the plasma HIV RNA level is a better predictor of AIDS and death than the CD4 lymphocyte count. We assessed whether the prognostic value of plasma virus levels was different according to the CD4 count.

Design: Prospective cohort study of HIV-infected patients followed for a median of 2.

Evaluating the effect of year of seroconversion on HIV progression in cohort studies. Italian Seroconversion Study.

Objectives: To show how a spurious association between the calendar year of seroconversion and HIV progression arises as a result of censoring the follow-up of individuals at their last visit, when the individuals' visits are intermittent.

Design: A notional cohort of 1140 seroconverters and a cohort study of 1270 HIV-infected individuals seroconverted between 1985 and 1994, and followed up to December 1995 (the Italian Seroconversion Study cohort).

Methods: Failure times and rate of the patients attending the clinic over the study period were simulated for the notional cohort.

A practical approach to adjusting for attrition bias in HIV clinical trials with serial marker responses.

Objectives: To illustrate a simple approach to adjusting for bias due to drop-outs (i.e., attrition bias) when evaluating the effect of a certain therapy in HIV clinical trials using the mean change in plasma viral load.

Production of beta-chemokines in human immunodeficiency virus (HIV) infection: evidence that high levels of macrophage inflammatory protein-1beta are associated with a decreased risk of HIV disease progression.

Macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES production were measured by ELISA in whole blood that had been stimulated for 4.5 h with phytohemagglutinin. The blood was from 90 healthy human immunodeficiency virus (HIV)-negative controls and from 245 HIV-infected subjects who were followed for < or = 4.