Claudio Arici - Academia.edu (original) (raw)
Papers by Claudio Arici
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2010
Little is known about the incidence and risk factors for serious non-AIDS-defining events. The in... more Little is known about the incidence and risk factors for serious non-AIDS-defining events. The incidence of non-AIDS events (malignancies, end-stage renal disease, liver failure, pancreatitis, cardiovascular disease), and AIDS after January 1, 2001, was calculated; Poisson regression was used to investigate factors associated with non-AIDS and AIDS. Among 12,844 patients, 1058 were diagnosed with a non-AIDS event [incidence 1.77 per 100 person-years of follow-up; 95% confidence interval (CI): 1.66 to 1.87]; 462 patients (43.7%) died. The incidence of AIDS (1025 diagnoses; 339 deaths, 33.1%) was 1.72 per 100 person-years of follow-up (1.61 to 1.83). After adjustment, older age [incidence rate ratio (IRR): 1.71 per 10 years older, 95% CI: 1.60 to 1.83], diabetes (IRR: 1.49, 95% CI: 1.22 to 1.82) and hypertension (IRR: 1.63, 95% CI: 1.43 to 1.87) were associated with non-AIDS events. Compared with patients without an event, there was a 4-fold increased risk of death after an AIDS event (relative hazard: 4.14; 95% CI 3.47 to 4.94) and almost a 7-fold increased risk of death after a non-AIDS event (relative hazard: 6.72; 95% CI: 5.61 to 8.05). Non-AIDS events were common in the combination antiretroviral therapy era and associated with considerably mortality. Evidence on the impact of modifying immunodeficiency and lifestyle-related factors on the risk of non-AIDS events in HIV-infected persons is an important but unmet research need.
Antiviral Therapy
Background Complex antiretroviral regimens require optimal adherence to maintain long-lasting eff... more Background Complex antiretroviral regimens require optimal adherence to maintain long-lasting effectiveness. Simpler regimens, possibly with easy schedule and low pill burden, are needed for the long-term treatment of HIV infection. Objective To assess the efficacy and tolerability of a once-a-day highly active antiretroviral therapy (HAART) compared with two other conventional twice-a-day regimens. Methods In a prospective and randomized study, anti-retroviral-naive patients received either EFV+ddI+3TC (once-a-day regimen; OD), or EFV+Combivir® (twice-a-day and low-pill burden regimen; BID-low) or NFV+Combivir (twice-a-day and high-pill burden regimen; BID-high). Primary outcome was the proportion of patients with viral load <50 copies/ml at week 52 of follow-up. Results were evaluated according to intention-to-treat and on-treatment analysis. Results Thirty-four patients in each arm were enrolled. Baseline characteristics were similar in the three groups. The proportion of pati...
Antiviral Therapy
We evaluated in an open-label, randomized, controlled, pilot trial if the re-emergence of previou... more We evaluated in an open-label, randomized, controlled, pilot trial if the re-emergence of previously selected resistant strains, harbouring M184V mutation, could be modulated by the use of different drug associations as components of the new antiretroviral regimens. In addition, we assessed the clinical relevance of this mutation on the management of heavily pretreated HIV-infected patients. The primary end-point of the study was the re-selection of M184V mutation. Secondary end-points were the variation over time of HIV RNA plasma levels and CD4 cell counts and the progression of HIV disease. The primary population for efficacy analysis was the intention-to-treat exposed population. After a run-in phase consisting in a new treatment regimen excluding either lamivudine (3TC) or abacavir (ABC) so as to clear the previously documented M184V mutation, 18 patients with an HIV RNA plasma level greater than 10 000 copies/ml were randomized to receive an antiretroviral drug regimen (at lea...
Antiviral Therapy
Background One of the more vigorous debates in the field of highly active antiretroviral therapy ... more Background One of the more vigorous debates in the field of highly active antiretroviral therapy (HAART) is how to start it and what the optimal drug sequence is. Methods A retrospective cohort analysis was performed. The aim was to evaluate which variables could influence the virological response to second-line genotypic-based HAART in patients with virological documented first-line HAART failure. A positive response was defined as a confirmed HIV RNA level <50 copies/ml. Results Two hundred and eight patients were included. Demographic characteristics, risk factors for HIV acquisition, and drugs included in the initial treatment did not significantly influence the considered outcome. According to a multiple logistic model, the presence of thymidine analogue mutations (TAMs) had a negative association with the virological outcome ( P=0.006), whereas the use of a boosted protease inhibitor (PI) in second-line HAART was positively associated with the endpoint ( P=0.001). Patients ...
Giornale di malattie infettive e parassitarie, 1990
Scandinavian Journal of Infectious Diseases, 2003
A case of human immunodeficiency virus (HIV)-associated lymphocytic interstitial pneumonia is des... more A case of human immunodeficiency virus (HIV)-associated lymphocytic interstitial pneumonia is described, in which improvement occurred soon after starting antiviral therapy. A 20-y-old black female with HIV infection (CD4+ count 228 x 10(6) cells and plasma viral load 379,670 copies/ml) showed radiological signs of reticulonodular infiltrates of the lungs and pulmonary functional tests indicative of a severe restrictive syndrome. Bronchoalveolar and blood cultures yielded no organism and transbronchial biopsy disclosed findings consistent with lymphocytic interstitial pneumonia. After 4 weeks on triple HIV combination therapy, she was well and respiratory tests had normalized. Six months later, a computed tomographic scan of the chest showed only residual alterations. Despite a good sirological response to treatment, no significant immune recovery occurred over a 2 y follow-up.
Journal of Antimicrobial Chemotherapy, 2005
This retrospective longitudinal cohort study compared the virological and immunological responses... more This retrospective longitudinal cohort study compared the virological and immunological responses to highly active antiretroviral therapy containing either efavirenz or lopinavir/ritonavir in previously antiretroviral-naive HIV-infected patients. Patients and methods: A total of 472 patients were selected (348 efavirenz and 124 lopinavir/ritonavir). The primary endpoint of this study was virological success (HIV RNA <50 copies/mL). The immunological response was assessed on the basis of either CD4+ T cell count variations (absolute and percentage) with respect to baseline values or categorical endpoints (defined as either a CD4+ T cell increase of-> 50 cells/mm 3 at week 24 or of-> 75 cells/mm 3 at week 48). Results: At intention-to-treat (ITT) analysis, the adjusted odds ratio of virological success for patients who started lopinavir/ritonavir, compared with those who started efavirenz, was 0.54 (95% CI: 0.33-0.89, P = 0.016) at week 24 and 0.40 (95% CI: 0.33-0.89, P = 0.002) at week 48. However, patients receiving lopinavir/ ritonavir had a more pronounced CD4+ T cell recovery, demonstrating both a mean absolute and percentage increase up to week 48 (MANOVA P < 0.0001). Conclusions: Although comparisons of drug efficacy in non-randomized studies should be viewed with caution, from a virological point of view efavirenz-containing regimens performed as well (on-treatment analysis) or better (ITT analysis) than those containing lopinavir/ritonavir. In contrast, immunological outcome appeared to favour lopinavir/ritonavir.
International Journal of STD & AIDS, 2001
Severe lactic acidosis has been increasingly reported as a potentially fatal complication of HIV ... more Severe lactic acidosis has been increasingly reported as a potentially fatal complication of HIV treatment. We report on an asymptomatic HIV-infected woman treated with stavudine, lamivudine and indinavir for one year. She was hospitalized because of progressive dispnoea, oedema, cyanosis and severe lactic acidosis. Arterial blood pH was 6.98, bicarbonate 4.4 mmol/l (normal value 22-26), blood lactate: 29.7 mmol/l (normal value <2.2). Hepatic function was normal. She had an impressively rapid response (within a few hours) to empirical treatment with thiamine (100 mg i.v.). No evidence of sepsis or malabsorption were identified and vitamin B1 level was not tested before thiamine infusion. Three months later she was re-started successfully on nelfinavir plus nevirapine. The rapid response to thiamine infusion deserves a careful attention and such an approach should be considered in similar cases as a support treatment of this potentially life-threatening complication of HIV therapy.
International Journal of STD & AIDS, 2001
Our objective was to assess, in the clinical setting, the predictors of immune reconstitution (IR... more Our objective was to assess, in the clinical setting, the predictors of immune reconstitution (IR) and its relation with long-term clinical benefit, in HIV patients with advanced disease after highly active antiretroviral therapy (HAART) through an observational study. A retrospective cohort study in a clinical setting of 383 consecutive adult patients with advanced HIV infection (CD4+ cells &amp;lt;200/mm(3) at baseline), starting their first protease inhibitor (PI)-containing regimen was observed. Immune reconstitution was defined as CD4 count &amp;gt;200 cells/mm(3) and an increase &amp;gt; or =100 cells from baseline, anytime since starting HAART. Clinical benefit was defined as decreased mortality and reduction in AIDS-defining events, AIDS-related complex (ARC) events, major infections and hospitalization (days spent in hospital). During a mean follow-up of 808 days, 261 patients (68.1%) achieved IR. About 50% of these patients reached this result within one year after starting HAART. In multivariate analysis, predictors of immune recovery were sex (female) and baseline CD4 count higher than 50 cells/mm(3). The group of patients with IR had greater clinical benefit with lower mortality, fewer AIDS-defining events, shorter lengths of stay in hospital, fewer ARC events and fewer major infections during all the follow-up (P &amp;lt; 0.0001, tests for trends). However, although they did less remarkably than the first group of patients, even those patients who did not achieve IR experienced a significant decrease in the incidence of all the above events, as compared with the first and sometimes the second trimester after starting their HIV therapy. About 70% of HIV patients with advanced disease achieved IR after starting HAART. Such a benefit is a time-dependent effect and may even take more than 2 years to occur. Predictors of IR were sex (female) and higher baseline CD4 count (&amp;gt;50 cells/mm(3)). The patients who achieved immune recovery performed clinically better than patients who did not. Also the patients who failed to gain such a strong immunological recovery experienced a long-term clinical benefit. This suggests that PI-containing regimens, in advanced HIV disease, may produce a significant clinical benefit, at least temporary, even for patients who do not achieve a substantial immune response.
HIV Clinical Trials, 2007
Background: The effect of adherence on the risk of virologic failure and mutations selection was ... more 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.
HIV Clinical Trials, 2007
To investigate future drug options (FDOs), resistance cost (RCVF), and virologic response to geno... more To investigate future drug options (FDOs), resistance cost (RCVF), and virologic response to genotypic-driven rescue highly active antiretroviral therapy (HAART), according to type of therapy. This was a retrospective analysis in naïve or antiretroviral-experienced patients. Virologic response was defined as HIV RNA &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;50 copies. There were 108 patients failing first-line HAART; there were 328 experienced patients. FDOs were reduced in subjects failing a thymidine-analogue (TA) regimen (median 3.65, IQR 1.29 ) compared to patients without TA (median 3.82, IQR 1.12) (p = .011). FDOs after first failure were higher for patients with non-nucleoside reverse transcriptase inhibitor (NNRTI; median 3.82; IQR 1.24) than with protease inhibitor (PI; median 3.64, IQR 1.15) (p = .027). In experienced patients, FDOs were much higher for TA (p = .005). Patients responding to genotypic-modified regimens had higher FDOs (median 3.9 4, IQR 2.53) than patients not responding (median 2.18, IQR 3.65) (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; .0001). Switching from an NNRTI-based HAART to a boosted PI had a higher chance (48.1%) of achieving a full virologic suppression, compared to switching from PI to NNRTI (21.4%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .0001). FDOs and RCVF are parameters that can quantify the therapeutic choices at virologic failure. Different drugs induce different FDOs and RCVF. In successive-line regimens, the higher antiviral effect and genetic barrier of boosted PIs may overcome the limits of using nucleoside reverse transcriptase backbones, with only partial effectiveness.
HIV Clinical Trials, 2002
Optimal adherence to highly active antiretroviral therapy (HAART) is necessary to achieve the bes... more Optimal adherence to highly active antiretroviral therapy (HAART) is necessary to achieve the best and the most durable benefit. Many factors may influence compliance to such demanding regimens, and their identification may help in the design of strategies to enhance adherence. To assess the factors associated with lower compliance to therapy, the causes of nonadherence, and the relation of nonadherence with virologic response. We performed an observational, cross-sectional study on HIV-infected patients (pts) receiving unrestricted HAART and attending our clinic from January to May 2001. Pts completed a self-administered (ACTG modified) questionnaire on adherence to their therapy. Virologic response was defined as undetectable viral load at the time of interview. A regression model was used to determine predictors of adherence. 597 out of 623 pts (95.8%) completed the survey. Mean age was 38.2 years (range, 18-79). A total of 448 pts (75.0%) were men, 323 (54.1%) were intravenous drug users, 196 (32.8%) were heterosexuals, 76 (12.7%) were men who have sex with men. Mean time on therapy was 49.3 months (range, 4-145). All pts were on stable therapy (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 4 months), 173 pts (29%) were on their first HAART regimen, 309 pts (51.7%) were on NNRTI-based regimen, and 288 pts (48.2%) were on a PI-containing treatment. A total of 304 pts (50.9%) were categorized as adherent (p = .024). Multiple logistic regression showed that older age (p = .002), lower number of pills (p = .024), fewer daily doses (p = .002), and shorter time on therapy (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001) were factors associated with adherent behavior. Forgetfulness (59.3%), being away from home (50.2%), and problems with schedule (37.6%) were the most frequent causes of nonadherence. Adherent pts were more likely to have undetectable viral load than nonadherent pts (76.5% vs. 55.3%; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.0001). Younger age, higher number of pills, higher frequency of doses, and longer time on therapy were predictors of nonadherent behavior. Optimal adherence correlated with the best virologic response. Simpler regimens with a lower number of pills and doses may help patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; compliance to therapy.
Clinical Infectious Diseases, 2006
Clinical Infectious Diseases, 2005
Background. This prospective study verified the effect of adherence on the risk of virologic fail... more 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, у6 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 1500 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 р75%, 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 195%. 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 120%, whereas, only for patients who were receiving nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based HAART and who had an adherence rate of р75%, the virologic failure rate was 110%. 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. The positive influence of HAART on survival, disease progression, immune function, and overall quality of life can be tempered by reduced adherence. Many variables, including depression, alcohol and drug use, work schedules, changes in daily routines, and decrease in cognitive function may have an influence on the ability
Clinical Infectious Diseases, 2003
Clinical Infectious Diseases, 2002
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2010
Little is known about the incidence and risk factors for serious non-AIDS-defining events. The in... more Little is known about the incidence and risk factors for serious non-AIDS-defining events. The incidence of non-AIDS events (malignancies, end-stage renal disease, liver failure, pancreatitis, cardiovascular disease), and AIDS after January 1, 2001, was calculated; Poisson regression was used to investigate factors associated with non-AIDS and AIDS. Among 12,844 patients, 1058 were diagnosed with a non-AIDS event [incidence 1.77 per 100 person-years of follow-up; 95% confidence interval (CI): 1.66 to 1.87]; 462 patients (43.7%) died. The incidence of AIDS (1025 diagnoses; 339 deaths, 33.1%) was 1.72 per 100 person-years of follow-up (1.61 to 1.83). After adjustment, older age [incidence rate ratio (IRR): 1.71 per 10 years older, 95% CI: 1.60 to 1.83], diabetes (IRR: 1.49, 95% CI: 1.22 to 1.82) and hypertension (IRR: 1.63, 95% CI: 1.43 to 1.87) were associated with non-AIDS events. Compared with patients without an event, there was a 4-fold increased risk of death after an AIDS event (relative hazard: 4.14; 95% CI 3.47 to 4.94) and almost a 7-fold increased risk of death after a non-AIDS event (relative hazard: 6.72; 95% CI: 5.61 to 8.05). Non-AIDS events were common in the combination antiretroviral therapy era and associated with considerably mortality. Evidence on the impact of modifying immunodeficiency and lifestyle-related factors on the risk of non-AIDS events in HIV-infected persons is an important but unmet research need.
Antiviral Therapy
Background Complex antiretroviral regimens require optimal adherence to maintain long-lasting eff... more Background Complex antiretroviral regimens require optimal adherence to maintain long-lasting effectiveness. Simpler regimens, possibly with easy schedule and low pill burden, are needed for the long-term treatment of HIV infection. Objective To assess the efficacy and tolerability of a once-a-day highly active antiretroviral therapy (HAART) compared with two other conventional twice-a-day regimens. Methods In a prospective and randomized study, anti-retroviral-naive patients received either EFV+ddI+3TC (once-a-day regimen; OD), or EFV+Combivir® (twice-a-day and low-pill burden regimen; BID-low) or NFV+Combivir (twice-a-day and high-pill burden regimen; BID-high). Primary outcome was the proportion of patients with viral load <50 copies/ml at week 52 of follow-up. Results were evaluated according to intention-to-treat and on-treatment analysis. Results Thirty-four patients in each arm were enrolled. Baseline characteristics were similar in the three groups. The proportion of pati...
Antiviral Therapy
We evaluated in an open-label, randomized, controlled, pilot trial if the re-emergence of previou... more We evaluated in an open-label, randomized, controlled, pilot trial if the re-emergence of previously selected resistant strains, harbouring M184V mutation, could be modulated by the use of different drug associations as components of the new antiretroviral regimens. In addition, we assessed the clinical relevance of this mutation on the management of heavily pretreated HIV-infected patients. The primary end-point of the study was the re-selection of M184V mutation. Secondary end-points were the variation over time of HIV RNA plasma levels and CD4 cell counts and the progression of HIV disease. The primary population for efficacy analysis was the intention-to-treat exposed population. After a run-in phase consisting in a new treatment regimen excluding either lamivudine (3TC) or abacavir (ABC) so as to clear the previously documented M184V mutation, 18 patients with an HIV RNA plasma level greater than 10 000 copies/ml were randomized to receive an antiretroviral drug regimen (at lea...
Antiviral Therapy
Background One of the more vigorous debates in the field of highly active antiretroviral therapy ... more Background One of the more vigorous debates in the field of highly active antiretroviral therapy (HAART) is how to start it and what the optimal drug sequence is. Methods A retrospective cohort analysis was performed. The aim was to evaluate which variables could influence the virological response to second-line genotypic-based HAART in patients with virological documented first-line HAART failure. A positive response was defined as a confirmed HIV RNA level <50 copies/ml. Results Two hundred and eight patients were included. Demographic characteristics, risk factors for HIV acquisition, and drugs included in the initial treatment did not significantly influence the considered outcome. According to a multiple logistic model, the presence of thymidine analogue mutations (TAMs) had a negative association with the virological outcome ( P=0.006), whereas the use of a boosted protease inhibitor (PI) in second-line HAART was positively associated with the endpoint ( P=0.001). Patients ...
Giornale di malattie infettive e parassitarie, 1990
Scandinavian Journal of Infectious Diseases, 2003
A case of human immunodeficiency virus (HIV)-associated lymphocytic interstitial pneumonia is des... more A case of human immunodeficiency virus (HIV)-associated lymphocytic interstitial pneumonia is described, in which improvement occurred soon after starting antiviral therapy. A 20-y-old black female with HIV infection (CD4+ count 228 x 10(6) cells and plasma viral load 379,670 copies/ml) showed radiological signs of reticulonodular infiltrates of the lungs and pulmonary functional tests indicative of a severe restrictive syndrome. Bronchoalveolar and blood cultures yielded no organism and transbronchial biopsy disclosed findings consistent with lymphocytic interstitial pneumonia. After 4 weeks on triple HIV combination therapy, she was well and respiratory tests had normalized. Six months later, a computed tomographic scan of the chest showed only residual alterations. Despite a good sirological response to treatment, no significant immune recovery occurred over a 2 y follow-up.
Journal of Antimicrobial Chemotherapy, 2005
This retrospective longitudinal cohort study compared the virological and immunological responses... more This retrospective longitudinal cohort study compared the virological and immunological responses to highly active antiretroviral therapy containing either efavirenz or lopinavir/ritonavir in previously antiretroviral-naive HIV-infected patients. Patients and methods: A total of 472 patients were selected (348 efavirenz and 124 lopinavir/ritonavir). The primary endpoint of this study was virological success (HIV RNA <50 copies/mL). The immunological response was assessed on the basis of either CD4+ T cell count variations (absolute and percentage) with respect to baseline values or categorical endpoints (defined as either a CD4+ T cell increase of-> 50 cells/mm 3 at week 24 or of-> 75 cells/mm 3 at week 48). Results: At intention-to-treat (ITT) analysis, the adjusted odds ratio of virological success for patients who started lopinavir/ritonavir, compared with those who started efavirenz, was 0.54 (95% CI: 0.33-0.89, P = 0.016) at week 24 and 0.40 (95% CI: 0.33-0.89, P = 0.002) at week 48. However, patients receiving lopinavir/ ritonavir had a more pronounced CD4+ T cell recovery, demonstrating both a mean absolute and percentage increase up to week 48 (MANOVA P < 0.0001). Conclusions: Although comparisons of drug efficacy in non-randomized studies should be viewed with caution, from a virological point of view efavirenz-containing regimens performed as well (on-treatment analysis) or better (ITT analysis) than those containing lopinavir/ritonavir. In contrast, immunological outcome appeared to favour lopinavir/ritonavir.
International Journal of STD & AIDS, 2001
Severe lactic acidosis has been increasingly reported as a potentially fatal complication of HIV ... more Severe lactic acidosis has been increasingly reported as a potentially fatal complication of HIV treatment. We report on an asymptomatic HIV-infected woman treated with stavudine, lamivudine and indinavir for one year. She was hospitalized because of progressive dispnoea, oedema, cyanosis and severe lactic acidosis. Arterial blood pH was 6.98, bicarbonate 4.4 mmol/l (normal value 22-26), blood lactate: 29.7 mmol/l (normal value <2.2). Hepatic function was normal. She had an impressively rapid response (within a few hours) to empirical treatment with thiamine (100 mg i.v.). No evidence of sepsis or malabsorption were identified and vitamin B1 level was not tested before thiamine infusion. Three months later she was re-started successfully on nelfinavir plus nevirapine. The rapid response to thiamine infusion deserves a careful attention and such an approach should be considered in similar cases as a support treatment of this potentially life-threatening complication of HIV therapy.
International Journal of STD & AIDS, 2001
Our objective was to assess, in the clinical setting, the predictors of immune reconstitution (IR... more Our objective was to assess, in the clinical setting, the predictors of immune reconstitution (IR) and its relation with long-term clinical benefit, in HIV patients with advanced disease after highly active antiretroviral therapy (HAART) through an observational study. A retrospective cohort study in a clinical setting of 383 consecutive adult patients with advanced HIV infection (CD4+ cells &amp;lt;200/mm(3) at baseline), starting their first protease inhibitor (PI)-containing regimen was observed. Immune reconstitution was defined as CD4 count &amp;gt;200 cells/mm(3) and an increase &amp;gt; or =100 cells from baseline, anytime since starting HAART. Clinical benefit was defined as decreased mortality and reduction in AIDS-defining events, AIDS-related complex (ARC) events, major infections and hospitalization (days spent in hospital). During a mean follow-up of 808 days, 261 patients (68.1%) achieved IR. About 50% of these patients reached this result within one year after starting HAART. In multivariate analysis, predictors of immune recovery were sex (female) and baseline CD4 count higher than 50 cells/mm(3). The group of patients with IR had greater clinical benefit with lower mortality, fewer AIDS-defining events, shorter lengths of stay in hospital, fewer ARC events and fewer major infections during all the follow-up (P &amp;lt; 0.0001, tests for trends). However, although they did less remarkably than the first group of patients, even those patients who did not achieve IR experienced a significant decrease in the incidence of all the above events, as compared with the first and sometimes the second trimester after starting their HIV therapy. About 70% of HIV patients with advanced disease achieved IR after starting HAART. Such a benefit is a time-dependent effect and may even take more than 2 years to occur. Predictors of IR were sex (female) and higher baseline CD4 count (&amp;gt;50 cells/mm(3)). The patients who achieved immune recovery performed clinically better than patients who did not. Also the patients who failed to gain such a strong immunological recovery experienced a long-term clinical benefit. This suggests that PI-containing regimens, in advanced HIV disease, may produce a significant clinical benefit, at least temporary, even for patients who do not achieve a substantial immune response.
HIV Clinical Trials, 2007
Background: The effect of adherence on the risk of virologic failure and mutations selection was ... more 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.
HIV Clinical Trials, 2007
To investigate future drug options (FDOs), resistance cost (RCVF), and virologic response to geno... more To investigate future drug options (FDOs), resistance cost (RCVF), and virologic response to genotypic-driven rescue highly active antiretroviral therapy (HAART), according to type of therapy. This was a retrospective analysis in naïve or antiretroviral-experienced patients. Virologic response was defined as HIV RNA &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;50 copies. There were 108 patients failing first-line HAART; there were 328 experienced patients. FDOs were reduced in subjects failing a thymidine-analogue (TA) regimen (median 3.65, IQR 1.29 ) compared to patients without TA (median 3.82, IQR 1.12) (p = .011). FDOs after first failure were higher for patients with non-nucleoside reverse transcriptase inhibitor (NNRTI; median 3.82; IQR 1.24) than with protease inhibitor (PI; median 3.64, IQR 1.15) (p = .027). In experienced patients, FDOs were much higher for TA (p = .005). Patients responding to genotypic-modified regimens had higher FDOs (median 3.9 4, IQR 2.53) than patients not responding (median 2.18, IQR 3.65) (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; .0001). Switching from an NNRTI-based HAART to a boosted PI had a higher chance (48.1%) of achieving a full virologic suppression, compared to switching from PI to NNRTI (21.4%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .0001). FDOs and RCVF are parameters that can quantify the therapeutic choices at virologic failure. Different drugs induce different FDOs and RCVF. In successive-line regimens, the higher antiviral effect and genetic barrier of boosted PIs may overcome the limits of using nucleoside reverse transcriptase backbones, with only partial effectiveness.
HIV Clinical Trials, 2002
Optimal adherence to highly active antiretroviral therapy (HAART) is necessary to achieve the bes... more Optimal adherence to highly active antiretroviral therapy (HAART) is necessary to achieve the best and the most durable benefit. Many factors may influence compliance to such demanding regimens, and their identification may help in the design of strategies to enhance adherence. To assess the factors associated with lower compliance to therapy, the causes of nonadherence, and the relation of nonadherence with virologic response. We performed an observational, cross-sectional study on HIV-infected patients (pts) receiving unrestricted HAART and attending our clinic from January to May 2001. Pts completed a self-administered (ACTG modified) questionnaire on adherence to their therapy. Virologic response was defined as undetectable viral load at the time of interview. A regression model was used to determine predictors of adherence. 597 out of 623 pts (95.8%) completed the survey. Mean age was 38.2 years (range, 18-79). A total of 448 pts (75.0%) were men, 323 (54.1%) were intravenous drug users, 196 (32.8%) were heterosexuals, 76 (12.7%) were men who have sex with men. Mean time on therapy was 49.3 months (range, 4-145). All pts were on stable therapy (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 4 months), 173 pts (29%) were on their first HAART regimen, 309 pts (51.7%) were on NNRTI-based regimen, and 288 pts (48.2%) were on a PI-containing treatment. A total of 304 pts (50.9%) were categorized as adherent (p = .024). Multiple logistic regression showed that older age (p = .002), lower number of pills (p = .024), fewer daily doses (p = .002), and shorter time on therapy (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001) were factors associated with adherent behavior. Forgetfulness (59.3%), being away from home (50.2%), and problems with schedule (37.6%) were the most frequent causes of nonadherence. Adherent pts were more likely to have undetectable viral load than nonadherent pts (76.5% vs. 55.3%; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.0001). Younger age, higher number of pills, higher frequency of doses, and longer time on therapy were predictors of nonadherent behavior. Optimal adherence correlated with the best virologic response. Simpler regimens with a lower number of pills and doses may help patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; compliance to therapy.
Clinical Infectious Diseases, 2006
Clinical Infectious Diseases, 2005
Background. This prospective study verified the effect of adherence on the risk of virologic fail... more 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, у6 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 1500 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 р75%, 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 195%. 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 120%, whereas, only for patients who were receiving nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based HAART and who had an adherence rate of р75%, the virologic failure rate was 110%. 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. The positive influence of HAART on survival, disease progression, immune function, and overall quality of life can be tempered by reduced adherence. Many variables, including depression, alcohol and drug use, work schedules, changes in daily routines, and decrease in cognitive function may have an influence on the ability
Clinical Infectious Diseases, 2003
Clinical Infectious Diseases, 2002