Claudio Arici

Similar Adherence Rates Favor Different Virologic Outcomes for Patients Treated with Nonnucleoside Analogues or Protease Inhibitors

BACKGROUND This prospective study verified the effect of adherence on the risk of virologic failure. METHODS At enrollment in the study, a total of 543 patients who were following a steady (duration, >or=6 months) and effective (viral load, <50 human immunodeficiency virus [HIV] RNA copies/mL) regimen of highly active antiretroviral therapy (HAART) completed a self-reported questionnaire derived from the Adult AIDS Clinical Trials Group Adherence Follow-up Questionnaire. Patients were followed up for the subsequent 6 months to document virologic failure, which was defined as 2 consecutive viral load measurements of >500 HIV RNA copies/mL. RESULTS Only the type of treatment and the adherence rate at baseline were significantly associated with the virologic end point. Among patients who reported an adherence rate of <or=75%, the rate of virologic failure was 17.4%; this rate decreased to 12.2% for patients whose adherence rate was 76%-85%, to 4.3% for patients whose adherence rate was 86%-95%, and to 2.4% for patients whose adherence rate was >95%. When analysis was adjusted according to the type of regimen received, patients who were receiving protease inhibitor (PI)-based HAART and who had an adherence rate of up to 85% had a virologic failure rate of >20%, whereas, only for patients who were receiving nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based HAART and who had an adherence rate of <or=75%, the virologic failure rate was >10%. For the comparison of NNRTI-treated patients and PI-treated patients with an adherence rate of 75%-95%, the odds ratio was 0.157 (95% confidence interval, 0.029-0.852). The number of pills and daily doses received correlated with the reported adherence rate. CONCLUSIONS Patients receiving NNRTIs report a higher rate of adherence than do patients receiving PIs. Adherence is significantly influenced by the number of pills and daily doses received. Low adherence is a major determinant of virologic failure; however, different therapies have different cutoff values for adherence that determine a significant increment of risk.

Man-to-woman sexual transmission of HIV: longitudinal study of 343 steady partners of infected men.

To study incidence and risk factors of heterosexually transmitted HIV infection, we followed a cohort of 343 seronegative women, stable, monogamous partners of infected men whose only risk of acquiring HIV was sexual exposure to the infected partner. Nineteen seroconversions occurred in 529.6 person years (py) of observation, yielding an incidence rate of 3.6 per 100 py. The incidence rate was 7.2 per 100 py among women who did not always use or never used condoms and 1.1 among those who always used them [relative risk (RR) 6.6, 95% confidence interval (CI) 1.9-21.9]. Anal sex was associated with a risk increase in only those women not always using condoms (RR 1.4, 95% CI 0.4-4.8). No seroconversions were observed among 22 women using oral contraceptives. One of the women using intrauterine devices seroconverted. In couples who did not always use condoms, seroconversions occurred more frequently in partners of men with symptomatic diseases, with a low CD4+ cell number (< 400 per mm3) or with a detectable p24 antigen. In couples not always using condoms and where the man had a low CD4+ cell count, the joint presence of blood viral antigens and AIDS symptoms conditioned a fivefold increased risk of seroconversion of the woman (RR 5.4, CI 1.4-20.3). At multivariate analysis, women with longer relationships (> or = 1 year) showed a lower risk of seroconversion (RR 0.3, CI 0.1-0.8), and those partners of men positive for p24 antigen in serum had an increased risk of seroconversion (RR = 4.0, CI 0.1-0.8).

Delayed presentation and late testing for HIV: Demographic and behavioral risk factors in a multicenter study in Italy

Summary:Ensuring timely access to care for persons with HIV is an important public health goal. To identify factors associated with delayed presentation to medical care after testing HIV-positive or with late HIV testing, we studied 968 patients at their first HIV care visit, enrolled in a multicenter study in Italy from 1997–2000. Patients completed a questionnaire on HIV-testing history, sexual behavior, and drug use behavior. Delayed presenters were patients with >6 months between their first HIV-positive test and presentation for HIV care; late testers were patients with CD4 count < 200 /mm3 or clinically defined AIDS at their first HIV-positive test. Among the study patients, 255 (26.3%) were delayed presenters, and 280 (28.9%) were late testers. In multinomial logistic regression analysis, injection drug use significantly increased (odds ratio [OR]= 5.04) the probability of delayed presentation but reduced (OR = 0.55) the chance of late testing. A previous HIV-negative test was associated with a reduced risk of both delayed presentation (OR = 0.39) and late testing (OR = 0.36). Unemployment was positively associated with delayed presentation and increasing age with late testing, whereas HIV counseling at the time of first positive HIV test strongly (OR = 0.42) reduced the odds of delayed presentation. Interventions aimed at promoting timely access to care of HIV-infected persons should consider differentiated programs for delayed presentation and late testing.

Effect of Adherence to HAART on Virologic Outcome and on the Selection of Resistance-Conferring Mutations in NNRTI- or PI-Treated Patients

Abstract Background: The effect of adherence on the risk of virologic failure and mutations selection was verified in a prospective study. Method: At baseline, all patients had a viral load (VL) <50 copies/mL and completed a self-reported questionnaire. Patients were followed for the subsequent 4 months to document virologic rebound (VL > 50 copies/mL). Results: 1,133 patients completed 2,240 questionnaires/follow-up (non-nucleoside reverse transcriptase inhibitor [NNRTI] = 1,479; single protease inhibitor [PI] = 200; boosted PI = 561). Only the type of treatment and the baseline adherence rate were significantly associated with the virologic endpoint. A viral rebound rate >10% was observed in patients treated with single PI (14.7%) or boosted PI (11.7%) up to an adherence rate of 95%, whereas a similar (17.6%) rebound rate was observed only in NNRTI-treated patients with very low adherence (<55%). After adjustment for other baseline predictors of adherence, patients on NNRTIs showed a higher adherence rate than those on PIs but not higher than those on boosted PIs. The same adherence rate did not have the same result, in terms of virologic rebound, in patients on the same HAART for shorter or longer periods of time. Overall, the risk of virologic rebound for patients with >95% adherence rate was 6.2% in the first 6 months of therapy, lowered to 5.0% in the following 6 months, and was 3.2% thereafter. The risk of selecting for resistance-inducing viral mutation for NNRTI-treated patients was higher (4.9%) at very low adherence rates (<75%); the opposite was true for single PI-treated patients (4.2% for adherence >95%). Boosted PI-treated patients showed an intermediate pattern, even if at a much lower level of risk. Conclusion: Low adherence is a major determinant of virologic failure, however different therapies have different adherence cutoffs determining a significant increment of risk.

Factors associated with the failure of HIV-positive persons to return for scheduled medical visits

Abstract PURPOSE: To assess in an HIV-positive cohort the cumulative probability of failing to return for scheduled medical visits and to address the factors associated with follow-up discontinuation. METHOD: This was a hospital-based cohort study conducted from January 1985 through September 1999. Out of 3,300 HIV-1 infected patients, 1,680 patients with CD4 count <500 cells/mL or with AIDS diagnosis were included in the analysis because they received scheduled medical visits for follow-up at our center. Baseline visit was the first visit when patients met the criteria for enrollment. The main outcome measure was failure to return for scheduled medical visits for at least 12 consecutive months. RESULTS: The probability of returning decreased rapidly in the first months after the baseline visit. After 1 year since enrollment, 25% of patients failed to return and after 2 years 34% of patients failed to return. Most patients who failed to return for visits (78%) discontinued their follow-up within 6 months since enrollment. In multivariate analysis, patients in the intravenous drug use (IDU) category were most likely to fail to return for scheduled appointments, as were patients with higher CD4 count (CD4 >50 cells/μL) or patients without AIDS diagnosis. Patients with shorter follow-up had a higher risk of failing to return (odds ratio [OR]: 0.12, 0.36, 0.45, and 0.74 for >36, 24-36, 12-24, and 6-12 months of follow-up respectively vs. <6 months). Patients who were enrolled in more recent years had a higher compliance to follow-up visits (OR: 0.33, 0.63, and 0.61 for ≥1997, 1995-1996, and 1988-1994 vs. <1988). CONCLUSION: Patients in the IDU category, patients without AIDS diagnosis, or patients with higher CD4 counts are more likely to miss medical appointments and discontinue their follow-up. More recently enrolled patients have a lower risk of failing to return. It is possible that the recent and more effective anti-HIV treatment played a major role in increasing adherence to follow-up.

Nosocomial Bloodstream Infections among Human Immunodeficiency Virus–Infected Patients: Incidence and Risk Factors

To assess the incidence of nosocomial bloodstream infections (NBSIs) in human immunodeficiency virus (HIV)-infected patients, and to analyze the main associated risk factors, we performed a 1-year multicenter prospective study of patients with advanced HIV infection who were consecutively admitted to 17 Italian infectious diseases wards. As of May 1999, a total of 65 NBSIs (4.7%) occurred in 1379 admissions, for an incidence of 2.45 NBSIs per 1000 patient-days. Twenty-nine NBSIs were catheter-related bloodstream infections, with a rate of 9.6 central venous catheter-associated infections per 1000 device-days. Multivariate analysis indicated that variables independently associated with NBSIs included active injection drug use, a Karnofsky Performance Status score of <40, presence of a central venous catheter, and length of hospital stay. Mortality rates were 24.6% and 7.2% among patients with and without NBSIs, respectively (P<.00001). In the era of highly active antiretroviral therapy, NBSIs continue to occur frequently and remain severe and life-threatening manifestations.

Changes in hospital admissions across Europe: 1995-2003. Results from the EuroSIDA study

To describe changes in the proportions of patients admitted to hospital and the duration of admission during the month of March between 1995 and 2003 and to describe the factors related to admission for 9802 patients from EuroSIDA, a pan‐European, observational cohort study.

Outcome of 2 Simplification Strategies for the Treatment of Human Immunodeficiency Virus Type 1 Infection

In a prospective, open-label, 104-week study, patients who were infected with human immunodeficiency virus type 1 (virus load, <50 copies/mL) and who were receiving protease inhibitor-based therapy were randomly assigned to continue treatment with a protease inhibitor or to replace it with abacavir or efavirenz. Treatment failure, defined as virological failure (virus load, >500 copies/microL) or any clinical or biochemical adverse event with a grade of >or=3 (on the basis of the World Health Organization [WHO] or American Heart Association [AHA] scales), was the primary outcome measurement. Failure rates were more frequent in the group treated with protease inhibitors (P<.01), and there were no significant differences in the rate of treatment failure between the group treated with efavirenz and the group treated with abacavir. Tolerability was better in the groups treated with abacavir or with efavirenz versus those treated with protease inhibitors. Fewer patients who received efavirenz experienced viral rebound. Among all groups, the mean increase in the CD4 cell count was 131 cells/microL (P<.001), with no significant difference between groups. This switching strategy maintains optimal levels of virological suppression and may improve lipid profiles in most patients.

Behavioral correlates of adherence to antiretroviral therapy

Summary: The objective of this study was to analyze the relationships between adherence to treatment and sexual and drug‐taking behaviors among persons with HIV, who started combination antiretroviral therapy as their first regimen. The authors analyzed data from 366 patients enrolled in a multicenter observational cohort study conducted in infectious disease hospital units in Italy. Adherence measurement was based on responses to a self‐administered questionnaire regarding following HIV physician advice on taking medications and missed appointments. Questions on sexual and drug‐taking behaviors were also included in the questionnaire. The median time since starting antiretroviral therapy was 11.8 months; 37.4% of patients were on a two‐drug regimen and 62.6% were on a three‐drug regimen. Overall, 68 patients (18.6%) could be classified as nonadherent. The proportion of patients with viral load ≤ 500 copies/mL was significantly higher among adherent patients (68%) compared with nonadherent patients (40.4%; p = .001). In multivariable analysis, age (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.42‐0.98, per 10‐year increment) and current use of injection (OR, 3.47; 95% CI, 1.40‐8.5) or noninjection drugs (OR, 4.23; 95% CI, 1.85‐9.67) were significantly associated with nonadherence. No significant association was found between adherence and sexual behaviors. The data do not support the hypothesis that among HIV‐infected person on antiretroviral therapy, poor adherence is associated with high‐risk sexual behaviors that may further spread the infection.

Zidovudine prophylaxis after accidental exposure to HIV : the Italian experience

ObjectivesTo evaluate the use of zidovudine prophylaxis in HIV-exposed health-care workers (HCW) in Italy and to determine its short-term toxicity. DesignLongitudinal, open study with retrospective and prospective collection of data. SettingAll Italian clinical centres that care for HIV-infected patients and are licensed by the Ministry of Health to dispense zidovudine and 30 hospitals participating in the Italian Multicentre Study on Occupational Risk of HIV Infection. Study populationHCW and other individuals who accepted zidovudine prophylaxis after accidental exposure to HIV. ResultsData were collected for 224 HIV-exposed individuals until 30 )une 1991. An increase in zidovudine prophylaxis was observed. All but 10 subjects received 1000–1250 mg zidovudine per day. Anaemia (five cases), neutropenia (one case) and an increase in serum alanine aminotransferase levels (two cases) were the only haematochemical side-effects observed; none of the subjects ceased prophylaxis because of side-effects. More than 50% of subjects had constitutional reactions; as a result, prophylaxis was stopped by 29 patients. These adverse effects began within 10 days of prophylaxis; all resolved after prophylaxis was stopped. No HIV-antibody seroconversions were observed after a mean follow-up of 8 months. ConclusionsZidovudine prophylaxis has become a feature of the management of occupational exposures to HIV in health-care settings; short-term toxicity is mild, dose-related and reversible. Further studies are needed to assess the risk of long-term sequelae.