Andrea Patroni

A Randomized Controlled Trial to Evaluate Antiretroviral Salvage Therapy Guided by Rules-Based or Phenotype-Driven HIV-1 Genotypic Drug-Resistance Interpretation With or Without Concentration-Controlled Intervention: The Resistance and Dosage Adapted Regimens (RADAR) Study

BACKGROUND It is not well defined whether concentration-controlled intervention (CCI) and rules-based human immunodeficiency virus (HIV) type 1 genotype drug-resistance interpretation (GI) or virtual phenotype drug-resistance interpretation (VPI) may improve the outcome of HIV salvage therapy. METHODS In a prospective, randomized, controlled trial, patients were randomized (on a factorial basis) to change treatment after either GI or VPI, and they then were further randomized to the control arm (no CCI) or the CCI arm. Protease inhibitor (PI) and nonnucleoside reverse-transcriptase inhibitor (NNRTI) trough concentration (Ctrough) values were determined at weeks 1, 4, 12, and 24 of the study. RESULTS Among 230 patients, virological benefit (defined by an HIV RNA load of <400 copies/mL at week 24) was not statistically different, either between patients in the GI and VPI arms or between patients in the CCI and control arms. A virological benefit was found for patients in the CCI arm, compared with patients in the control arm, but this benefit was not statistically significant (56.8% vs. 64.3% at week 4 and 63.6% vs. 74% at week 12). Dosage adaptation was possible for only a fraction of patients, because of low rates of treatment adherence or patient refusal to increase dosages. In the logistic regression analysis, independent predictors of virological response at week 24 were a PI Ctrough value and/or an NNRTI Ctrough value in the higher quartiles (or above cutoff levels) and a low number of PIs previously received. Moreover, receipt of a regimen that contained PIs boosted with ritonavir was an independent predictor of virological response. CONCLUSIONS The present study did not support the routine use of CCI for patients undergoing salvage treatment, probably as a result of existing difficulties associated with its clinical application. However, a higher Ctrough value appeared to be correlated with treatment response. No major differences were found between VPI or GI when they are used together with expert advice for the selection of salvage treatment combinations.

The Human Immunodeficiency Virus-Infected Traveler

As the number of travelers from industrialized countries who are infected with human immunodeficiency virus (HIV) increases as a consequence of the clinical benefits of highly active antiretroviral therapy (HAART), updated prophylactic knowledge is needed. Vaccine prophylaxis must balance the safety and immunogenicity of vaccines with the estimated risk of acquiring the disease. Further research is needed on antimalarial chemoprophylaxis for travelers who are HAART recipients, because of possible pharmacokinetic interactions. Safe sex practices must be adopted to avoid both spreading of the infection in the host country and superinfection with different HIV strains. Most individuals infected with HIV may travel safely, even though the infectious risk has been reported to be higher for patients with advanced infections than for the general population. These patients are also less likely to produce an effective immune response to vaccines. Migrants and refugees from poor countries are also at risk of acquiring HIV infection. Their legal-residency status may often prevent their access to adequate health services, thus necessitating urgent public health actions.

Adherence to hand hygiene in an Italian long-term care facility

In an Italian long-term-care facility (LTCF), we observed a 17.5% adherence to hand hygiene (HH), as well as 47.5% rate of glove use. Performing a procedure at high risk for cross-transmission of germs was the factor most strongly associated with noncompliance (odds ratio = 13.3; 95% confidence interval = 6.2 to 28.8; P < .0001). No significant differences in compliance related to health care worker category were found. Adherence to HH in the LTCF was similar to that found in a rehabilitation medicine unit of an acute care hospital (15.8%) but significantly lower than that reported in an infectious disease unit (53.7%; P < .0001). Our findings indicate that compliance with HH is a similar problem in LTCFs as in acute care facilities.

Modifications of health resource-use in Italy after the introduction of highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV) infection. Pharmaco-economic implications in a population-based setting

OBJECTIVE To assess the impact of highly active antiretroviral therapy (HAART) on health resource utilisation (HRU) and to estimate associated direct costs in a population based setting. DESIGN Retrospective study of all patients in the Institute of Infectious and Tropical Diseases (Brescia, Northern Italy) during a 4 years period related to the prescription of HAART has been performed: from 1997 (before HAART) to 2000 (after substantial period of HAART prescription). MAIN OUTCOME MEASURES AND RESULTS HIV inpatient admissions (IAs) decreased from 506.8/1000 patients (pts) in 1997 to 246.3/1000 pts in the year 2000. Day care admissions (DCAs) also decreased from 1658.3/1000 pts to 942/1000 pts, while outpatient consultations (OCs) increased from 2046.9/1000 pts to 2590.6/1000 pts in the same years, respectively. By contrast, a relative increase of IAs and DCAs of patients whose serostatus was HIV-negative or unknown has been found. Cost of antiretroviral therapy increased by 2582 Euro (2272 US Dollars), while cost of HIV care (IA+DCA+OC) decreased by 1546 Euro (1360.4 US Dollars) per patient, resulting in a saving in direct cost equal to 60% of the increase in the expenditure for antiretroviral drugs. CONCLUSIONS Our results demonstrate the shift of HIV care from inpatient to outpatient services that occurred after HAART had been introduced into clinical practice. Despite persisting clinical benefits, an increase in total direct cost for HIV pts has been seen for the first time during the HAART era in the year 2000, probably due to an over-prescription of HAART, according to actual Guideline for antiretroviral therapy use, to pts who were not at risk of clinical progression in the short term. Pharmacoeconomical surveillance of HAART is necessary while a favourable impact on the saving in cost is expected from the new treatment guidelines that suggest a relative delay in starting HAART.

Hand hygiene and glove use behavior in an Italian hospital

In an Italian hospital, we observed that hand hygiene was performed in 638 (19.6%) of 3,253 opportunities, whereas gloves were worn in 538 (44.2%) 1,218 of opportunities. We observed an inverse correlation between the intensity of care and the rate of hand hygiene compliance (R2=0.057; P<.001), but no such association was observed for the rate of glove use compliance (R2=0.014; P=.078). Rates of compliance with hand hygiene and glove use recommendations follow different behavioral patterns.

Analysis of HIV‐1 mutation patterns in patients failing antiretroviral therapy

The emergence of mutations encoding drug resistance is supposed to be a significant limitation to the clinical efficacy of inhibitor compounds directed against specific HIV‐1 enzymatic targets. We have used a commercial test (Visible Genetics Inc., Paris, France) to study the prevalence of mutations occurred in HIV‐1 protease and reverse transcriptase (RT) genes in 93 HIV‐1 infected patients treated with at least one regimen containing a protease inhibitor (PI) and failing to the current therapeutic regimen. Protease mutations conferring resistance to at least one PI were detected in 46/93 (49.4%) of strains, 25 (26.8%) of which showed resistance to all PIs. Reverse transcriptase mutations conferring resistance to at least one RT inhibitor were detected in 57/93 (61.2%) of strains, 18 (19.3%) of which showed resistance to all RT inhibitors. The most frequent RT mutations were T215Y/F, M41L, and M184V (41.9, 40.8, and 40.8%, respectively), while L63P, L10R/V, and A71V/T (58, 41.9, and 34.4%, respectively) were the most represented protease substitutions. We have found no mutations encoding for multiple dideoxynucleoside resistance (Q151M or T69SS). Twelve of our patients (12.9%) had no mutation encoding drug resistance and were completely sensitive to all RT and protease inhibitors. Therefore, not all virological failures are caused by HIV‐1 genomic resistance. J. Clin. Lab. Anal. 15:43–46, 2001.

Immune Correlates of Virological Response in HIV-Positive Patients after Highly Active Antiretroviral Therapy (HAART)

Correlates of immune reconstitution after highly active antiretroviral therapy (HAART) are not completely understood, in particular as far as viro-immunological discordant responses are concerned. HIV-positive patients on stable HAART for > or = 1 year were recruited. Viro-immunological responses were categorized according to positive or negative area under the curve (AUC) variations for HIV plasma viral load (pVL) and CD4+ T-cell counts measured at least every 4 months. The following parameters were evaluated: lymphocyte spontaneous apoptosis (LSA), intracellular Bcl-2 expression in both CD4-CD45RA+ and CD4-CD45R0+, IL-7 and IL-15 plasma concentrations, and lymphocyte TRECs levels. Sixty-one patients were enrolled. A significant inverse correlation was found between CD4+ T-cell count and pVL AUC (r = 0.45; p = 0.0003). Patients with pVL response had higher levels of Bcl-2 in CD4-CD45R0+ (mean 65,409 MESF vs. 54,018 MESF; p = 0.089) and higher IL-15 (mean 1.34 pg/mL vs. 1.05 pg/mL; p = 0.069, respectively). Higher LSA and lower TRECs levels were found in viro-immunological non-responder patients with respect to those who had viro-immunological response (mean 24.84% vs. 14.89%; p = 0.01, and mean 17,796 copies/10(6) cells vs. 29,251 copies/10(6) cells; p = 0.68, respectively). Virological suppression may allow Bcl-2 and IL-15 hyperexpression during incomplete immune-reconstitution phase, while more complete immune reconstitution appeared to be marked by both high TRECs and low LSA levels, possibly indicating both central and peripheral CD4+ T-cell repopulations at this stage.

Vaginal colonization with Candida spp. in human immunodeficiency virus – infected women: a cohort study

We have conducted a longitudinal study on factors associated with candidal vaginal colonization, a precursor of vaginitis, in a cohort of HIV-infected women in Italy. All consecutive women attending a single, tertiary care clinical site were offered free screening for sexually transmitted infections and genital disorders every 6–12 months. Candidal vaginal colonization was defined as a positive culture for Candida spp. in an asymptomatic woman. From January 1998 to July 2002 we analysed 214 women. The baseline prevalence of candidal vaginal colonization was 16.8%. In the logistic regression analysis, the time since HIV infection ≥36 months (odds ratio [OR] = 0.18, 95% confidence interval [CI] 0.016–0.53, P = 0.002) and a plasma viral load ≥10,000 copies/mL (OR = 3.9, 95% CI 1.03–14.9, P = 0.045) were independently associated with candidal colonization. Among 130 women who were followed for a mean period of 24 months, the incidence of vaginal colonization was 10.7/100 women-years. In the Cox regression analysis, a CD4+ T-lymphocytes count <100 cells/μL during the follow-up was associated with an increased risk of candidal vaginal colonization (OR = 4.45, C.I. = 1.20–16.81, P = 0.03). Risk of candidal vaginal colonization episodes in HIV-infected women significantly increase when CD4+ T-lymphocytes are less than 100.