Sara Melzi - Academia.edu (original) (raw)
Papers by Sara Melzi
![Research paper thumbnail of [Renal toxicity in HIV-infected patients receiving HAART including tenofovir]](https://attachments.academia-assets.com/49512742/thumbnails/1.jpg)
](Le Infezioni in Medicina Rivista Periodica Di Eziologia Epidemiologia Diagnostica Clinica E Terapia Delle Patologie Infettive, Sep 1, 2006
HIV-infected patients may undergo renal damage related to the HIV infection itself, to the presen... more HIV-infected patients may undergo renal damage related to the HIV infection itself, to the presence of co-infections, arterial hypertension, diabetes or to the exposure to nephrotoxic drugs. Tenofovir has been associated with the development of acute renal failure with Fanconi syndrome and acute tubular necrosis and, albeit rarely, with chronic liver disease. Patients with low CD4 cell count, low body weight and with concomitant diseases such as arterial hypertension and diabetes or co-infections with HCV, HBV or Treponema pallidum seem at higher risk of tenofovir-related nephrotoxicity. Other risk factors include previous exposure to nephrotoxic drugs and the association of tenofovir with boosted protease inhibitors or with didanosine. However, from the analysis of published papers the incidence of tenofovir-related renal toxicity seems low, as confirmed also by our personal casuistry (SCOLTA Project). Thus, a careful selection of patients including the evaluation of existent renal disease before starting an antiretroviral regimen including tenofovir is necessary to prevent renal damage. Furthermore, frequent monitoring of renal function in patients at higher risk of renal damage is strongly recommended, as well as a tenofovir dose adjustment if an alteration of renal function is detected.
Jaids Journal of Acquired Immune Deficiency Syndromes, Jun 1, 2006
The SIMONE study (SIndrome Metabolica ONE) was a cross-sectional survey designed to assess the pr... more The SIMONE study (SIndrome Metabolica ONE) was a cross-sectional survey designed to assess the prevalence and characteristics of MS in a population of Italian HIV-infected patients, employing the National Education Cholesterol Program criteria. 6 The study started in February and ...
Il presente elaborato ha la fi nalità di porre il lettore di fronte alla problematica della valut... more Il presente elaborato ha la fi nalità di porre il lettore di fronte alla problematica della valutazione dei costi nel contesto sanitario e dei possibili approcci percorribili, in tema di strumenti per la raccolta di dati inerenti il percorso diagnostico e clinico del paziente. Nello specifi co si prenderà in considerazione la metodica patient-based come sistema di assoluto interesse, sia per l'applicazione all'interno del contesto del fi nanziamento dell'offerta sanitaria, sia come strumento di valorizzazione della storia dell'utente-paziente. Differenti applicazioni a livello di sistemi informativi e di database da cui attingere informazioni saranno presi in considerazione. In particolar modo si cercherà di proporre una adeguata applicazione della metodica all'interno del contesto dei pazienti HIV positivi, nel quadro territoriale della Regione Lombardia.
![Research paper thumbnail of [Renal toxicity in HIV-infected patients receiving HAART including tenofovir]](https://attachments.academia-assets.com/49512741/thumbnails/1.jpg)
](Le infezioni in medicina : rivista periodica di eziologia, epidemiologia, diagnostica, clinica e terapia delle patologie infettive, 2006
HIV-infected patients may undergo renal damage related to the HIV infection itself, to the presen... more HIV-infected patients may undergo renal damage related to the HIV infection itself, to the presence of co-infections, arterial hypertension, diabetes or to the exposure to nephrotoxic drugs. Tenofovir has been associated with the development of acute renal failure with Fanconi syndrome and acute tubular necrosis and, albeit rarely, with chronic liver disease. Patients with low CD4 cell count, low body weight and with concomitant diseases such as arterial hypertension and diabetes or co-infections with HCV, HBV or Treponema pallidum seem at higher risk of tenofovir-related nephrotoxicity. Other risk factors include previous exposure to nephrotoxic drugs and the association of tenofovir with boosted protease inhibitors or with didanosine. However, from the analysis of published papers the incidence of tenofovir-related renal toxicity seems low, as confirmed also by our personal casuistry (SCOLTA Project). Thus, a careful selection of patients including the evaluation of existent renal...
Antiviral therapy, 2003
To describe the immunological and virological outcome, and the factors associated to discontinuat... more To describe the immunological and virological outcome, and the factors associated to discontinuation in patients switching to a regimen containing efavirenz (EFV), nevirapine (NVP) or abacavir (ABC) after long-term viral suppression under protease inhibitor-including HAART. Observational study at three outpatient clinics for HIV care in Italy. Patients with HIV RNA <80 copies/ml and CD4 >200 cells/ml for at least 6 months on a protease inhibitor-containing treatment who switched to NVP, EFV or ABC were included in the study. End-points were immunological failure, virological failure and discontinuation due to toxicity. Survival analyses were performed to find out any independent variables predictive of reaching the end-points. 177 patients were enrolled; 85 started EFV, 54 NVP and 38 ABC as part of the simplification regimen. 16/159 patients experienced immunological failure: the variables associated to CD4 count decrease were HIV RNA set point value (HR 2.32 for each log10 co...
Antiviral therapy, 2004
We studied the predictive value of self-reported adherence and plasma drug concentrations on viro... more We studied the predictive value of self-reported adherence and plasma drug concentrations on virological rebound to HAART. Among 238 participants in the AdICoNA study who had viral load < or = 500 copies/ml, 42 (17.6%) experienced virological rebound by 96 weeks. Both self-reported non-adherence and sub-optimal concentration were independently associated with a higher risk of virological rebound.
Cholesterol, 2010
Many infections favor or are directly implicated with lipid metabolism perturbations and/or incre... more Many infections favor or are directly implicated with lipid metabolism perturbations and/or increased risk of coronary heart disease (CHD). HIV itself has been shown to increase lipogenesis in the liver and to alter the lipid profile, while the presence of unsafe habits, addiction, comorbidities, and AIDS-related diseases increases substantially the risk of cardiovascular disease (CVD) in the HIV-infected population. Antiretroviral therapy reduces such stimuli but many drugs have intrinsic toxicity profiles impacting on metabolism or potential direct cardiotoxicity. In a moment when the main guidelines of HIV therapy are predating the point when to start treating, we mean to highlight the contribution of HIV-1 to lipid alteration and inflammation, the impact of antiretroviral therapy, the decisions on what drugs to use to reduce the probability of having a cardiovascular event, the increasing use of statins and fibrates in HIV-1 infected subjects, and finally the switch strategies, that balance effectiveness and toxicity to move the decision to change HIV drugs. Early treatment might reduce the negative effect of HIV on overall cardiovascular risk but may also evidence the impact of drugs, and the final balance (reduction or increase in CHD and lipid abnormalities) is not known up to date.
PLoS ONE, 2012
Background: Long term efficacy of raltegravir (RAL)-including regimens in highly pre-treated HIV-... more Background: Long term efficacy of raltegravir (RAL)-including regimens in highly pre-treated HIV-1-infected patients has been demonstrated in registration trials. However, few studies have assessed durability in routine clinical settings.
Journal of Antimicrobial Chemotherapy, 2003
The immunovirological outcome of lopinavir/ritonavir was evaluated in 70 antiretroviralexperience... more The immunovirological outcome of lopinavir/ritonavir was evaluated in 70 antiretroviralexperienced HIV patients; at baseline, median CD4+ cell count was 218 cells/mm 3 and median plasma viraemia 4.58 log 10 copies/mL. After 12 months, we observed an increase in CD4+ cell count to 322 cells/mm 3 (P = 0.0001) and a decrease in plasma viraemia to 2.35 log 10 copies/mL (P = 0.0001). Four patients discontinued lopinavir/ritonavir during observation. Among metabolic parameters, only triglyceride concentrations increased during treatment (P = 0.02). Twenty-six patients had a genotypic resistance test at baseline; four had ≥6 mutations known to reduce susceptibility to lopinavir/ritonavir. Undetectable plasma viraemia was obtained only in patients with ≤5 mutations (61.9%).
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2002
Adherence to highly active antiretroviral therapy (HAART) plays a critical role in the effectiven... more Adherence to highly active antiretroviral therapy (HAART) plays a critical role in the effectiveness of HIV treatment. Nevertheless, the complexity of regimens and frequent side effects make HAART extraordinarily difficult to take, and many HIV-infected persons fail to adhere. The current study offers an overview of the relationship between adherence and antiretroviral treatment-related variables. As for other chronic diseases, medication regimen complexity also has an impact on adherence in the management of HIV infection. In particular, the authors discuss the effect of pill burden, dosing frequency, dietary instructions, number and type of different medications prescribed, short- and long-term side effects, convenience, and ability to incorporate the treatment regimen into a daily routine. Medication side effects are common in HAART-treated persons and are associated with concurrent and future nonadherence. Simplification of regimens, adjustment of the drug schedule to the patient&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;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;s specific lifestyle, and anticipation and self-management of side effects are treatment-based strategies to optimize HAART adherence and ensure the most effective, convenient, safe, and well-tolerated antiretroviral treatment.
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2005
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2006
The SIMONE study (SIndrome Metabolica ONE) was a cross-sectional survey designed to assess the pr... more The SIMONE study (SIndrome Metabolica ONE) was a cross-sectional survey designed to assess the prevalence and characteristics of MS in a population of Italian HIV-infected patients, employing the National Education Cholesterol Program criteria. 6 The study started in February and ...
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2000
The outcome of second-line protease inhibitor (PI)-containing highly active antiretroviral therap... more The outcome of second-line protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) was investigated in 263 patients who were failed by (n = 148) or intolerant of (n = 115) a first HAART regimen. The endpoints were virologic failure (decline in HIV RNA &amp;amp;amp;amp;amp;lt; 1 log10 copies/ml after &amp;amp;amp;amp;amp;gt; or = 2 months) and discontinuation due to intolerance/toxicity. During a median follow-up of 483 days (33-1087 days), 154 patients (59%) discontinued the second regimen, 86 (33%) because of intolerance/toxicity; another 135 patients (51.3%) showed virologic failure. Independent factors associated with virologic failure (Cox&amp;amp;amp;amp;amp;#39;s model) were 7 to 12 months of first HAART (hazard ratio [HR] 1.70 versus &amp;amp;amp;amp;amp;lt; or = 6 months: 95% confidence interval [CI], 1.08-2.70) and gender (HR 1.58 males versus females: 95% CI, 1.04-2.30); the negatively associated factors were advanced age (HR 0.61 &amp;amp;amp;amp;amp;gt; 34 years versus &amp;amp;amp;amp;amp;lt; or = 34 years: 95% CI, 0.42-0.88), a saquinavir-containing first HAART (HR 0.57 versus indinavir: 95% CI, 0.34-0.93) and change due to intolerance/toxicity (HR 0.58 versus failure: 95% CI, 0.35-0.98). The independent variables predictive of discontinuation due to intolerance/toxicity were the reason for switching (HR 1.79 intolerance versus failure: 95% CI, 1.02-3.16) and the first protease inhibitor (PI) regimen (HR 0.42 ritonavir versus indinavir: 95% CI, 0.22-0.80). Given that patients who are failed by a first regimen are at high risk of having rescue therapy fail as well, second-line regimens including therapies directed by testing of drug resistance patterns of clinical viral isolates are warranted. Patients experiencing toxicity due to a first PI-containing regimen are at risk of toxicity to other PIs and should be addressed to PI-sparing HAART.
International Journal of Antimicrobial Agents, 2014
Apart from the BENCHMRK study, there are no large observational experiences describing the longte... more Apart from the BENCHMRK study, there are no large observational experiences describing the longterm efficacy and safety of rescue regimens for human immunodeficiency virus type 1 (HIV-1) infection. Antiretroviral-experienced patients with detectable viraemia starting a raltegravir (RAL)-based regimen between March 2007 and June 2009 were consecutively enrolled and followed for ≥4 years. Data were censored at Week 206 for homogeneity. Of 333 patients, 258 (77.5%) were still on RAL-based therapy at Week 206, and 241 had undetectable HIV-1 RNA (73% in intention-to-treat analysis). Of the 75 subjects who discontinued RAL therapy, 36 were lost to follow-up, 15 changed their regimen due to virological failure, 2 simplified their regimen stopping RAL, 9 stopped all antiretrovirals and 13 died. Overall, 100 subjects (30.0%) had at least one detectable viraemia, but only 32 (9.6%) had true viral failure. Seventeen patients continued their failing regimen. 'Blips' were experienced by 53 patients (15.9%), whilst 15 (4.5%) had confirmed viral rebound due to adherence issues and were re-suppressed upon treatment re-introduction. In a multivariate analysis of predictors of interruption or failure, each baseline HIV-1 RNA log 10 increase was associated with an adjusted hazard ratio for failure of 1.6; having more than 13 previous treatment courses also emerged as a predictor. Overall, adverse events were rare (n = 64), with 13 deaths. Tumours were mainly early events, often fatal (7/15), mainly non-Hodgkin's lymphomas (8), followed by hepatocarcinoma (2). RAL proved effective and well tolerated in this cohort, and few patients experienced viral failure after 4 years.
International Journal of Antimicrobial Agents, 2004
The use of tenofovir as part of a HAART regimen has been widely used in HIV-multi-experienced-pat... more The use of tenofovir as part of a HAART regimen has been widely used in HIV-multi-experienced-patients because of its favourable resistance profile. Tenofovir is mainly eliminated by the kidneys and renal toxicity should be carefully monitored. We describe here the case of an HIV-infected patient, without a prior history of renal failure who developed nephrolithiasis and hydronephrosis after starting a tenofovir-containing HAART regimen.
Infection, 2009
Objectives: The protease inhibitor atazanavir (ATV) can be used either boosted by ritonavir (ATV3... more Objectives: The protease inhibitor atazanavir (ATV) can be used either boosted by ritonavir (ATV300/r) or unboosted (ATV400). To date, however, genotypic resistance scores (GRSs) have been developed only for boosted-ATV. We have determined GRS associated with virologic response (VR) for both ATV300/r and ATV400 in highly pre-treated HIV-1 infected patients. Patients and Methods: We analyzed the results of genotypic tests available 0-3 months before the initiation of an ATV-containing regimen in 159 patients with HIV-RNA ‡ 500 copies/ml (ATV300/r group: 74; ATV400 group: 85) who were enrolled in the CARe study through an Early Access Program. The impact of baseline protease mutations on VR ( ‡ 1 log 10 copies/ml HIV-RNA decrease at 12-24 weeks) was analyzed using Fisher's exact test. Mutated protease amino acid positions (MPP) with p < 0.20 were retained for further analysis. The GRSs were determined by a step-by-step analysis using the v 2 test for trend. Results: The GRSs for ATV300/r and ATV400 revealed differing sets of mutations. For ATV300/r, 12 MPPs (10C/ I/V + 32I + 34Q + 46I/L + 53L + 54A/M/V + 82A/F/I/ T + 84V + 90M -15E/G/L/V -69K/M/N/Q/R/T/Y -72M/ T/V; p = 1.38 · 10 -9 ) were the most strongly associated with VR (VR: 100%, 78.3%, 83.3%, 75% and 0% of patients with a score of -2/-1, 0, 1, 2, and ‡ 3, respectively); the last three MPPs (I15/H69/I72) were associated with a better VR. For ATV400, nine MPPs (16E + 20I/M/R/T/V + 32I + 33F/I/V + 53L/Y + 64L/M/ V + 71I/T/V + 85V + 93L/M; p = 9.42 · 10 -8 ) were most strongly associated with VR (VR: 83.3%, 66.7%, 5.9%, 0% of patients with 0, 1/2, 3, and ‡ 4 MPP, respectively). Differences between GRSs for ATV300/r and ATV400 may be due to different ATV drug levels (boosted vs unboosted), favoring different pathways of escape from antiviral pressure. Conclusions: Both GRSs were independent predictors of response in a multivariable logistic regression model. Nevertheless, cross-validation of these GRSs on different patient databases is required before their implementation in clinical practice.
Journal of general internal medicine, 2004
To evaluate the rate of discordance between patients and physicians on adherence to highly active... more To evaluate the rate of discordance between patients and physicians on adherence to highly active antiretroviral therapy (HAART) and identify factors related to discordance in these two assessments.
Le Infezioni in Medicina Rivista Periodica Di Eziologia Epidemiologia Diagnostica Clinica E Terapia Delle Patologie Infettive, Sep 1, 2006
HIV-infected patients may undergo renal damage related to the HIV infection itself, to the presen... more HIV-infected patients may undergo renal damage related to the HIV infection itself, to the presence of co-infections, arterial hypertension, diabetes or to the exposure to nephrotoxic drugs. Tenofovir has been associated with the development of acute renal failure with Fanconi syndrome and acute tubular necrosis and, albeit rarely, with chronic liver disease. Patients with low CD4 cell count, low body weight and with concomitant diseases such as arterial hypertension and diabetes or co-infections with HCV, HBV or Treponema pallidum seem at higher risk of tenofovir-related nephrotoxicity. Other risk factors include previous exposure to nephrotoxic drugs and the association of tenofovir with boosted protease inhibitors or with didanosine. However, from the analysis of published papers the incidence of tenofovir-related renal toxicity seems low, as confirmed also by our personal casuistry (SCOLTA Project). Thus, a careful selection of patients including the evaluation of existent renal disease before starting an antiretroviral regimen including tenofovir is necessary to prevent renal damage. Furthermore, frequent monitoring of renal function in patients at higher risk of renal damage is strongly recommended, as well as a tenofovir dose adjustment if an alteration of renal function is detected.
Jaids Journal of Acquired Immune Deficiency Syndromes, Jun 1, 2006
The SIMONE study (SIndrome Metabolica ONE) was a cross-sectional survey designed to assess the pr... more The SIMONE study (SIndrome Metabolica ONE) was a cross-sectional survey designed to assess the prevalence and characteristics of MS in a population of Italian HIV-infected patients, employing the National Education Cholesterol Program criteria. 6 The study started in February and ...
Il presente elaborato ha la fi nalità di porre il lettore di fronte alla problematica della valut... more Il presente elaborato ha la fi nalità di porre il lettore di fronte alla problematica della valutazione dei costi nel contesto sanitario e dei possibili approcci percorribili, in tema di strumenti per la raccolta di dati inerenti il percorso diagnostico e clinico del paziente. Nello specifi co si prenderà in considerazione la metodica patient-based come sistema di assoluto interesse, sia per l'applicazione all'interno del contesto del fi nanziamento dell'offerta sanitaria, sia come strumento di valorizzazione della storia dell'utente-paziente. Differenti applicazioni a livello di sistemi informativi e di database da cui attingere informazioni saranno presi in considerazione. In particolar modo si cercherà di proporre una adeguata applicazione della metodica all'interno del contesto dei pazienti HIV positivi, nel quadro territoriale della Regione Lombardia.
Le infezioni in medicina : rivista periodica di eziologia, epidemiologia, diagnostica, clinica e terapia delle patologie infettive, 2006
HIV-infected patients may undergo renal damage related to the HIV infection itself, to the presen... more HIV-infected patients may undergo renal damage related to the HIV infection itself, to the presence of co-infections, arterial hypertension, diabetes or to the exposure to nephrotoxic drugs. Tenofovir has been associated with the development of acute renal failure with Fanconi syndrome and acute tubular necrosis and, albeit rarely, with chronic liver disease. Patients with low CD4 cell count, low body weight and with concomitant diseases such as arterial hypertension and diabetes or co-infections with HCV, HBV or Treponema pallidum seem at higher risk of tenofovir-related nephrotoxicity. Other risk factors include previous exposure to nephrotoxic drugs and the association of tenofovir with boosted protease inhibitors or with didanosine. However, from the analysis of published papers the incidence of tenofovir-related renal toxicity seems low, as confirmed also by our personal casuistry (SCOLTA Project). Thus, a careful selection of patients including the evaluation of existent renal...
Antiviral therapy, 2003
To describe the immunological and virological outcome, and the factors associated to discontinuat... more To describe the immunological and virological outcome, and the factors associated to discontinuation in patients switching to a regimen containing efavirenz (EFV), nevirapine (NVP) or abacavir (ABC) after long-term viral suppression under protease inhibitor-including HAART. Observational study at three outpatient clinics for HIV care in Italy. Patients with HIV RNA <80 copies/ml and CD4 >200 cells/ml for at least 6 months on a protease inhibitor-containing treatment who switched to NVP, EFV or ABC were included in the study. End-points were immunological failure, virological failure and discontinuation due to toxicity. Survival analyses were performed to find out any independent variables predictive of reaching the end-points. 177 patients were enrolled; 85 started EFV, 54 NVP and 38 ABC as part of the simplification regimen. 16/159 patients experienced immunological failure: the variables associated to CD4 count decrease were HIV RNA set point value (HR 2.32 for each log10 co...
Antiviral therapy, 2004
We studied the predictive value of self-reported adherence and plasma drug concentrations on viro... more We studied the predictive value of self-reported adherence and plasma drug concentrations on virological rebound to HAART. Among 238 participants in the AdICoNA study who had viral load < or = 500 copies/ml, 42 (17.6%) experienced virological rebound by 96 weeks. Both self-reported non-adherence and sub-optimal concentration were independently associated with a higher risk of virological rebound.
Cholesterol, 2010
Many infections favor or are directly implicated with lipid metabolism perturbations and/or incre... more Many infections favor or are directly implicated with lipid metabolism perturbations and/or increased risk of coronary heart disease (CHD). HIV itself has been shown to increase lipogenesis in the liver and to alter the lipid profile, while the presence of unsafe habits, addiction, comorbidities, and AIDS-related diseases increases substantially the risk of cardiovascular disease (CVD) in the HIV-infected population. Antiretroviral therapy reduces such stimuli but many drugs have intrinsic toxicity profiles impacting on metabolism or potential direct cardiotoxicity. In a moment when the main guidelines of HIV therapy are predating the point when to start treating, we mean to highlight the contribution of HIV-1 to lipid alteration and inflammation, the impact of antiretroviral therapy, the decisions on what drugs to use to reduce the probability of having a cardiovascular event, the increasing use of statins and fibrates in HIV-1 infected subjects, and finally the switch strategies, that balance effectiveness and toxicity to move the decision to change HIV drugs. Early treatment might reduce the negative effect of HIV on overall cardiovascular risk but may also evidence the impact of drugs, and the final balance (reduction or increase in CHD and lipid abnormalities) is not known up to date.
PLoS ONE, 2012
Background: Long term efficacy of raltegravir (RAL)-including regimens in highly pre-treated HIV-... more Background: Long term efficacy of raltegravir (RAL)-including regimens in highly pre-treated HIV-1-infected patients has been demonstrated in registration trials. However, few studies have assessed durability in routine clinical settings.
Journal of Antimicrobial Chemotherapy, 2003
The immunovirological outcome of lopinavir/ritonavir was evaluated in 70 antiretroviralexperience... more The immunovirological outcome of lopinavir/ritonavir was evaluated in 70 antiretroviralexperienced HIV patients; at baseline, median CD4+ cell count was 218 cells/mm 3 and median plasma viraemia 4.58 log 10 copies/mL. After 12 months, we observed an increase in CD4+ cell count to 322 cells/mm 3 (P = 0.0001) and a decrease in plasma viraemia to 2.35 log 10 copies/mL (P = 0.0001). Four patients discontinued lopinavir/ritonavir during observation. Among metabolic parameters, only triglyceride concentrations increased during treatment (P = 0.02). Twenty-six patients had a genotypic resistance test at baseline; four had ≥6 mutations known to reduce susceptibility to lopinavir/ritonavir. Undetectable plasma viraemia was obtained only in patients with ≤5 mutations (61.9%).
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2002
Adherence to highly active antiretroviral therapy (HAART) plays a critical role in the effectiven... more Adherence to highly active antiretroviral therapy (HAART) plays a critical role in the effectiveness of HIV treatment. Nevertheless, the complexity of regimens and frequent side effects make HAART extraordinarily difficult to take, and many HIV-infected persons fail to adhere. The current study offers an overview of the relationship between adherence and antiretroviral treatment-related variables. As for other chronic diseases, medication regimen complexity also has an impact on adherence in the management of HIV infection. In particular, the authors discuss the effect of pill burden, dosing frequency, dietary instructions, number and type of different medications prescribed, short- and long-term side effects, convenience, and ability to incorporate the treatment regimen into a daily routine. Medication side effects are common in HAART-treated persons and are associated with concurrent and future nonadherence. Simplification of regimens, adjustment of the drug schedule to the patient&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;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;s specific lifestyle, and anticipation and self-management of side effects are treatment-based strategies to optimize HAART adherence and ensure the most effective, convenient, safe, and well-tolerated antiretroviral treatment.
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2005
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2006
The SIMONE study (SIndrome Metabolica ONE) was a cross-sectional survey designed to assess the pr... more The SIMONE study (SIndrome Metabolica ONE) was a cross-sectional survey designed to assess the prevalence and characteristics of MS in a population of Italian HIV-infected patients, employing the National Education Cholesterol Program criteria. 6 The study started in February and ...
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2000
The outcome of second-line protease inhibitor (PI)-containing highly active antiretroviral therap... more The outcome of second-line protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) was investigated in 263 patients who were failed by (n = 148) or intolerant of (n = 115) a first HAART regimen. The endpoints were virologic failure (decline in HIV RNA &amp;amp;amp;amp;amp;lt; 1 log10 copies/ml after &amp;amp;amp;amp;amp;gt; or = 2 months) and discontinuation due to intolerance/toxicity. During a median follow-up of 483 days (33-1087 days), 154 patients (59%) discontinued the second regimen, 86 (33%) because of intolerance/toxicity; another 135 patients (51.3%) showed virologic failure. Independent factors associated with virologic failure (Cox&amp;amp;amp;amp;amp;#39;s model) were 7 to 12 months of first HAART (hazard ratio [HR] 1.70 versus &amp;amp;amp;amp;amp;lt; or = 6 months: 95% confidence interval [CI], 1.08-2.70) and gender (HR 1.58 males versus females: 95% CI, 1.04-2.30); the negatively associated factors were advanced age (HR 0.61 &amp;amp;amp;amp;amp;gt; 34 years versus &amp;amp;amp;amp;amp;lt; or = 34 years: 95% CI, 0.42-0.88), a saquinavir-containing first HAART (HR 0.57 versus indinavir: 95% CI, 0.34-0.93) and change due to intolerance/toxicity (HR 0.58 versus failure: 95% CI, 0.35-0.98). The independent variables predictive of discontinuation due to intolerance/toxicity were the reason for switching (HR 1.79 intolerance versus failure: 95% CI, 1.02-3.16) and the first protease inhibitor (PI) regimen (HR 0.42 ritonavir versus indinavir: 95% CI, 0.22-0.80). Given that patients who are failed by a first regimen are at high risk of having rescue therapy fail as well, second-line regimens including therapies directed by testing of drug resistance patterns of clinical viral isolates are warranted. Patients experiencing toxicity due to a first PI-containing regimen are at risk of toxicity to other PIs and should be addressed to PI-sparing HAART.
International Journal of Antimicrobial Agents, 2014
Apart from the BENCHMRK study, there are no large observational experiences describing the longte... more Apart from the BENCHMRK study, there are no large observational experiences describing the longterm efficacy and safety of rescue regimens for human immunodeficiency virus type 1 (HIV-1) infection. Antiretroviral-experienced patients with detectable viraemia starting a raltegravir (RAL)-based regimen between March 2007 and June 2009 were consecutively enrolled and followed for ≥4 years. Data were censored at Week 206 for homogeneity. Of 333 patients, 258 (77.5%) were still on RAL-based therapy at Week 206, and 241 had undetectable HIV-1 RNA (73% in intention-to-treat analysis). Of the 75 subjects who discontinued RAL therapy, 36 were lost to follow-up, 15 changed their regimen due to virological failure, 2 simplified their regimen stopping RAL, 9 stopped all antiretrovirals and 13 died. Overall, 100 subjects (30.0%) had at least one detectable viraemia, but only 32 (9.6%) had true viral failure. Seventeen patients continued their failing regimen. 'Blips' were experienced by 53 patients (15.9%), whilst 15 (4.5%) had confirmed viral rebound due to adherence issues and were re-suppressed upon treatment re-introduction. In a multivariate analysis of predictors of interruption or failure, each baseline HIV-1 RNA log 10 increase was associated with an adjusted hazard ratio for failure of 1.6; having more than 13 previous treatment courses also emerged as a predictor. Overall, adverse events were rare (n = 64), with 13 deaths. Tumours were mainly early events, often fatal (7/15), mainly non-Hodgkin's lymphomas (8), followed by hepatocarcinoma (2). RAL proved effective and well tolerated in this cohort, and few patients experienced viral failure after 4 years.
International Journal of Antimicrobial Agents, 2004
The use of tenofovir as part of a HAART regimen has been widely used in HIV-multi-experienced-pat... more The use of tenofovir as part of a HAART regimen has been widely used in HIV-multi-experienced-patients because of its favourable resistance profile. Tenofovir is mainly eliminated by the kidneys and renal toxicity should be carefully monitored. We describe here the case of an HIV-infected patient, without a prior history of renal failure who developed nephrolithiasis and hydronephrosis after starting a tenofovir-containing HAART regimen.
Infection, 2009
Objectives: The protease inhibitor atazanavir (ATV) can be used either boosted by ritonavir (ATV3... more Objectives: The protease inhibitor atazanavir (ATV) can be used either boosted by ritonavir (ATV300/r) or unboosted (ATV400). To date, however, genotypic resistance scores (GRSs) have been developed only for boosted-ATV. We have determined GRS associated with virologic response (VR) for both ATV300/r and ATV400 in highly pre-treated HIV-1 infected patients. Patients and Methods: We analyzed the results of genotypic tests available 0-3 months before the initiation of an ATV-containing regimen in 159 patients with HIV-RNA ‡ 500 copies/ml (ATV300/r group: 74; ATV400 group: 85) who were enrolled in the CARe study through an Early Access Program. The impact of baseline protease mutations on VR ( ‡ 1 log 10 copies/ml HIV-RNA decrease at 12-24 weeks) was analyzed using Fisher's exact test. Mutated protease amino acid positions (MPP) with p < 0.20 were retained for further analysis. The GRSs were determined by a step-by-step analysis using the v 2 test for trend. Results: The GRSs for ATV300/r and ATV400 revealed differing sets of mutations. For ATV300/r, 12 MPPs (10C/ I/V + 32I + 34Q + 46I/L + 53L + 54A/M/V + 82A/F/I/ T + 84V + 90M -15E/G/L/V -69K/M/N/Q/R/T/Y -72M/ T/V; p = 1.38 · 10 -9 ) were the most strongly associated with VR (VR: 100%, 78.3%, 83.3%, 75% and 0% of patients with a score of -2/-1, 0, 1, 2, and ‡ 3, respectively); the last three MPPs (I15/H69/I72) were associated with a better VR. For ATV400, nine MPPs (16E + 20I/M/R/T/V + 32I + 33F/I/V + 53L/Y + 64L/M/ V + 71I/T/V + 85V + 93L/M; p = 9.42 · 10 -8 ) were most strongly associated with VR (VR: 83.3%, 66.7%, 5.9%, 0% of patients with 0, 1/2, 3, and ‡ 4 MPP, respectively). Differences between GRSs for ATV300/r and ATV400 may be due to different ATV drug levels (boosted vs unboosted), favoring different pathways of escape from antiviral pressure. Conclusions: Both GRSs were independent predictors of response in a multivariable logistic regression model. Nevertheless, cross-validation of these GRSs on different patient databases is required before their implementation in clinical practice.
Journal of general internal medicine, 2004
To evaluate the rate of discordance between patients and physicians on adherence to highly active... more To evaluate the rate of discordance between patients and physicians on adherence to highly active antiretroviral therapy (HAART) and identify factors related to discordance in these two assessments.