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1.
AIDS Care ; 35(6): 923-933, 2023 06.
Article in English | MEDLINE | ID: mdl-35579404

ABSTRACT

Evidences on the absence of risk of sexual transmission of HIV by persons living with HIV/AIDS (PLWHA) with undetectable plasma HIV-RNA (HIV-RNA <200 copies/ml) led to the worldwide campaign "U = U" (undetectable = untransmittable). The purpose of this study was to evaluate the perceived accuracy of this message among PLWHA, HIV-negative people having unprotected sex (PHUS) and infectious diseases' (ID) physicians in Italy. A nationwide survey has been conducted using three different anonymous questionnaires (for ID physicians, PLWHA and PHUS). A total of 1121 participants filled the questionnaires: 397 PLWHA; 90 physicians; 634 PHUS. Awareness of U = U message has been reported in 74%, 92% and 47% of PLWHA, ID physicians and PHUS, respectively. The perception of accuracy of the U = U message among those aware was reported as high in 80.4%, 79.5% and 67.3% of PLWHA, ID physicians and PHUS, respectively. Physicians perceived that 11% of PLWHA have a high rate of perception of U = U, whereas among PLWHA, only 34% reported definitive positive messages from physicians. Discrepancies between awareness and perception of accuracy of the message U = U in PLWHA and physicians have been found, suggesting still low confidence in the community regarding the message itself.


Subject(s)
HIV Infections , Physicians , Humans , Unsafe Sex , Cross-Sectional Studies , Surveys and Questionnaires , Italy , Perception
2.
J Antimicrob Chemother ; 75(5): 1332-1337, 2020 05 01.
Article in English | MEDLINE | ID: mdl-32129855

ABSTRACT

BACKGROUND: We explored the combination of rilpivirine plus cobicistat-boosted darunavir [a two-drug regimen (2DR)] when switching from standard triple combined ART. METHODS: In this randomized, open-label, non-inferiority trial, participants had an HIV-RNA <50 copies/mL on a stable (>6 months) three-drug regimen. The primary endpoint was proportion with HIV-RNA <50 copies/mL at Week 24 (snapshot algorithm), with a -12% non-inferiority margin. ClinicalTrials.gov: NCT04064632. RESULTS: One hundred and sixty patients were allocated (1:1) to 2DR or to continue current ART (CAR). At Week 24, 72 (90.0%) of participants with 2DR and 75 (93.8%) with CAR maintained HIV-RNA <50 copies/mL [difference -3.75% (95% CI = -11.63 to 5.63)], confirming non-inferiority. Non-inferiority was confirmed considering an HIV-RNA >50 copies/mL (0% for 2DR; 3.7% for CAR; 95% CI = -0.4 to 7.9). Four patients reported adverse events not leading to treatment discontinuation (one patient in the 2DR group and three patients in the CAR group); eight subjects discontinued therapy in the 2DR group and three in the CAR group. With 2DR, lipid serum concentrations increased, but differences were statistically significant only for tenofovir disoproxil fumarate-containing CAR and in 2DR patients receiving a pre-switch regimen including tenofovir disoproxil fumarate. Median bone stiffness decreased in the CAR group from 86.1 g/cm2 (IQR = 74-98) to 83.2 g/cm2 (IQR = 74-97) and increased in the 2DR group from 84.9 g/cm2 (IQR = 74-103) to 85.5 g/cm2 (IQR = 74-101). The reduction within the CAR group was significant (P = 0.043). CONCLUSIONS: Once-daily rilpivirine plus cobicistat-boosted darunavir is an effective 2DR that combines a high virological efficacy with a potential to avoid major NRTI toxicities.


Subject(s)
Anti-HIV Agents , HIV Infections , HIV-1 , Pharmaceutical Preparations , Adenine/therapeutic use , Anti-HIV Agents/adverse effects , Cobicistat/therapeutic use , Darunavir/adverse effects , Emtricitabine/therapeutic use , HIV Infections/drug therapy , Humans , Rilpivirine/therapeutic use , Treatment Outcome , Viral Load
3.
HIV Med ; 20(2): 99-109, 2019 02.
Article in English | MEDLINE | ID: mdl-30461158

ABSTRACT

OBJECTIVES: The management of HIV disease is complicated by the incidence of a new spectrum of comorbid noncommunicable diseases (NCDs). It is important to document changes in the prevalence of NCDs over time. The aim of the study was to describe the impact of ageing on HIV markers and on the prevalence of NCDs in people living with HIV (PLWHIV) in the Italian Cohort of Individuals, Naïve for Antiretrovirals (ICONA) seen for care in 2004-2014. METHODS: Analyses were conducted separately for a closed cohort (same people seen at both times) and an open cohort (all people under follow-up). We used the χ2 test for categorical factors and the Wilcoxon test for quantitative factors to compare profiles over time. RESULTS: The closed cohort included 1517 participants and the open cohort 3668 under follow-up in 2004 and 6679 in 2014. The median age of the open cohort was 41 [interquartile range (IQR) 37-46] years in 2004 and 44 (IQR 36-52) years in 2014. Analysis of the closed cohort showed an increase in the prevalence of some NCDs [the prevalence of dyslipidaemia increased from 75% in 2004 to 91% in 2014, that of hypertension from 67 to 84%, and that of cardiovascular disease (CVD) from 18 to 32%] and a decrease in renal function (5% with eGFR < 60 mL/min per 1.73 m2 in 2004 versus 30% in 2014); the percentage of people in the high-risk group for the Framingham CHD score more than tripled (from 13 to 45%). Results in the open cohort were similar. CONCLUSIONS: The burden of NCDs in our PLWHIV population markedly worsened over a 10-year time-span, which is likely to be a result of the effects of both ageing and HIV infection as well as their interaction. Special attention must be given to the management and prevention of NCDs.


Subject(s)
Cardiovascular Diseases/epidemiology , Dyslipidemias/epidemiology , HIV Infections/complications , Hypertension/epidemiology , Adult , Comorbidity , Female , Humans , Italy/epidemiology , Male , Middle Aged , Prevalence
4.
HIV Med ; 2018 May 30.
Article in English | MEDLINE | ID: mdl-29846042

ABSTRACT

OBJECTIVES: The aim of this study was to compare the durabilities of efavirenz (EFV) and rilpivirine (RPV) in combination with tenofovir/emtricitabine (TDF/FTC) in first-line regimens. METHODS: A multicentre prospective and observational study was carried out. We included all patients participating in the Italian Cohort Naive Antiretrovirals (ICONA) Foundation Study who started first-line combination antiretroviral therapy (cART) with TDF/FTC in combination with RPV or EFV, with a baseline viral load < 100 000 HIV-1 RNA copies/mL. Survival analyses using Kaplan-Meier (KM) curves and Cox regression with time-fixed covariates at baseline were employed. RESULTS: Overall, 1490 ART-naïve patients were included in the study, of whom 704 were initiating their first cART with EFV and 786 with RPV. Patients treated with EFV, compared with those on RPV, were older [median 36 (interquartile range (IQR) 30-43) years vs. 33 (IQR 27-39) years, respectively; P < 0.001], were more frequently at Centers for Disease Control and Prevention (CDC) stage C (3.1% vs. 1.4%, respectively; P = 0.024), and had a lower median baseline CD4 count [340 (IQR 257-421) cells/µL vs. 447 (IQR 347-580) cells/µL, respectively; P < 0.001] and a higher median viral load [4.38 (IQR 3.92-4.74) log10 copies/mL vs. 4.23 (IQR 3.81-4.59) log10 copies/mL, respectively], (P = 0.004). A total of 343 patients discontinued at least one drug of those included in the first cART regimen, more often EFV (26%) than RPV (13%), by 2 years (P < 0.0001). After adjustment, patients treated with EFV were more likely to discontinue at least one drug for any cause [relative hazard (RH) 4.09; 95% confidence interval (CI) 2.89-5.80], for toxicity (RH 2.23; 95% CI 1.05-4.73) for intolerance (RH 5.17; 95% CI 2.66-10.07) and for proactive switch (RH 10.96; 95% CI 3.17-37.87) than those starting RPV. CONCLUSIONS: In our nonrandomized comparison, RPV was better tolerated, less toxic and showed longer durability than EFV, without a significant difference in rates of discontinuation because of failures.

5.
Eur J Clin Microbiol Infect Dis ; 35(9): 1511-20, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27272121

ABSTRACT

Data on the effects of sustained virologic response (SVR) to hepatitis C virus (HCV) therapy on the outcome of extrahepatic complications are scarce. We conducted this study to assess the impact of SVR on the occurrence of chronic kidney disease (CKD), diabetes mellitus (DM), and cardiovascular disease (CVD) in a cohort of human immunodeficiency virus (HIV)-infected patients. We analyzed coinfected HIV/HCV patients in the Management of Standardized Evaluation of Retroviral HIV Infection (MASTER) cohort. Only event-free patients with a serum HCV-RNA determination at baseline were included. Patients were divided into four groups: INF-exposed with SVR; INF-exposed without SVR; spontaneous HCV clearance; untreated viremic patients. We estimated the incidence of extrahepatic complications and employed Kaplan-Meier curves and Cox regression to assess the association of SVR/INF strata adjusted for a series of confounders. Data from 1676 patients were analyzed (20.29 % started an INF-based regimen). Overall, the incidence of CKD, DM, CVD, and death was 5.32 [95 % confidence interval (CI) 3.99-6.98], 10.13 (95 % CI 8.20-12.37), 6.79 (95 % CI 5.26-8.65), and 13.49 (95 % CI 11.29-16.0) per 1000 person-years of follow-up, respectively. In the Cox model for treated patients, SVR was not associated with a lower risk of CKD, DM, CVD, and death compared to non-SVR. Cirrhosis was significantly associated with a higher risk of CKD [hazard ratio (HR) 2.13; 95 % CI 1.06-4.31], DM (HR 3.48; 95 % CI 2.18-5.57), and death (HR 6.18; 95 % CI 4.1-9.31), but not of CVD (HR 1.14; 95 % CI 0.57-2.3). There are still many unknowns regarding the impact of SVR on the occurrence of extrahepatic complications in coinfected HIV/HCV patients. Further investigations are needed in order to elucidate the role of SVR as an independent prognostic factor for extrahepatic events.


Subject(s)
Cardiovascular Diseases/epidemiology , Diabetes Mellitus/epidemiology , HIV Infections/complications , Hepatitis C, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Adult , Antiviral Agents/therapeutic use , Female , HIV Infections/drug therapy , Hepatitis C, Chronic/drug therapy , Humans , Incidence , Male , Risk Factors , Survival Analysis , Sustained Virologic Response
6.
Clin Microbiol Infect ; 21(4): 386.e1-9, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25595708

ABSTRACT

Randomized trials and observational cohorts reported higher rates of virological suppression after highly active antiretroviral therapy (HAART) including efavirenz (EFV), compared with boosted protease inhibitors (PIs). Correlations with immunological and clinical outcomes are unclear. Patients of the Italian MASTER cohort who started HAART from 2000 to 2010 were selected. Outstanding outcome (composite outcome for success (COS)) was introduced. We evaluated predictors of COS (no AIDS plus CD4+ count >500/mm(3)plus HIV-RNA <500 copies/mL) and of eight single outcomes either at month 6 or at year 3. Multivariable logistic regression was conducted. There were 6259 patients selected. Patients on EFV (43%) were younger, had greater CD4+ count, presented with AIDS less frequently, and more were Italians. At year 3, 90% of patients had HIV RNA <500 copies/mL, but only 41.4% were prescribed EFV, vs. 34.1% prescribed boosted PIs achieved COS (p <0.0001). At multivariable analysis, patients on lopinavir/ritonavir had an odds ratio of 0.70 for COS at year 3 (p <0.0001). Foreign origin and positive hepatitis C virus-Ab were independently associated with worse outcome (OR 0.54, p <0.0001 and OR 0.70, p 0.01, respectively). Patients on boosted PIs developed AIDS more frequently either at month 6 (13.8% vs. 7.6%, p <0.0001) or at year 3 (17.1% vs. 13.8%, p <0.0001). At year 3, deaths of patients starting EFV were 3%, vs. 5% on boosted PIs (p 0.008). In this study, naïve patients on EFV performed better than those on boosted PIs after adjustment for imbalances at baseline. Even when virological control is achieved, COS is relatively rare. Hepatitis C virus-positive patients and those of foreign origin are at risk of not obtaining COS.


Subject(s)
Anti-Retroviral Agents/administration & dosage , Antiretroviral Therapy, Highly Active/methods , Atazanavir Sulfate/administration & dosage , Benzoxazines/administration & dosage , HIV Infections/drug therapy , Ritonavir/administration & dosage , Adult , Alkynes , CD4 Lymphocyte Count , Cohort Studies , Cyclopropanes , Female , Humans , Italy , Male , Middle Aged , RNA, Viral/blood , Treatment Outcome , Viral Load
7.
Infection ; 42(5): 859-67, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24973981

ABSTRACT

PURPOSE: Migrants account for approximately 8.7% of the resident population in Italy. The immigration status deeply influences access to prevention and care, thus contributing to increase the burden of HIV/AIDS among such a fragile category. The aim of this study was to investigate socio-demographic and baseline clinical and immunological features of HIV-infected migrants, as compared to Italians. METHODS: We retrospectively analysed data for all the 1,611 HIV-infected migrant patients and a random sample of 4,230 HIV-infected Italian patients aged 18 or older who first accessed nine Italian clinical centres in 2000-2010 and were followed up at least 1 year. Differences in baseline characteristics between migrants and Italians were evaluated in univariate analysis, while factors associated with late presentation were evaluated in multivariate analysis using logistic regression models. RESULTS: The baseline profile differs between the HIV-infected migrant and Italian patients, substantially reflecting what reported by current statistics in terms of gender, age, risk category as well as clinical features. Late presenters were more frequent among migrants as compared to Italians (53.0 vs 45.8%; adjusted odds ratio [(AOR) = 1.55, 95% confidence interval (CI) 1.34-1.78]. Other factors associated with late presentation included increasing age, as well as undocumented legal status among foreign-born subjects (AOR = 1.41, 95% CI 0.97-2.04), though of borderline significance. CONCLUSIONS: Late presentation still represents a relevant problem despite the advances in the management of HIV infection. More efforts are needed to allow early diagnosis and access to care among the most vulnerable, such as undocumented foreign-born subjects in a country where migration flows are on the rise.


Subject(s)
Acquired Immunodeficiency Syndrome/epidemiology , HIV Infections/epidemiology , Transients and Migrants , Acquired Immunodeficiency Syndrome/virology , Adolescent , Adult , Female , HIV Infections/virology , Humans , Italy/epidemiology , Logistic Models , Male , Odds Ratio , Prevalence , Retrospective Studies , Young Adult
8.
Infection ; 42(1): 61-71, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24146352

ABSTRACT

PURPOSE: We have developed a sequencing assay for determining the usage of the genotypic HIV-1 co-receptor using peripheral blood mononuclear cell (PBMC) DNA in virologically suppressed HIV-1 infected patients. Our specific aims were to (1) evaluate the efficiency of V3 sequences in B versus non-B subtypes, (2) compare the efficiency of V3 sequences and tropism prediction using whole blood and PBMCs for DNA extraction, (3) compare the efficiency of V3 sequences and tropism prediction using a single versus a triplicate round of amplification. RESULTS: The overall rate of successful V3 sequences ranged from 100 % in samples with >3,000 copies HIV-1 DNA/10(6) PBMCs to 60 % in samples with <100 copies total HIV-1 DNA /10(6) PBMCs. Analysis of 143 paired PBMCs and whole-blood samples showed successful V3 sequences rates of 77.6 % for PBMCs and 83.9 % for whole blood. These rates are in agreement with the tropism prediction obtained using the geno2pheno co-receptor algorithm, namely, 92.1 % with a false-positive rate (FPR) of 10 or 20 % and of 96.5 % with an FPR of 5.75 %. The agreement between tropism prediction values using single versus triplicate amplification was 98.2 % (56/57) of patients using an FPR of 20 % and 92.9 % (53/57) using an FPR of 10 or 5.75 %. For 63.0 % (36/57) of patients, the FPR obtained via the single amplification procedure was superimposable to all three FPRs obtained by triplicate amplification. CONCLUSIONS: Our results show the feasibility and consistency of genotypic testing on HIV-1 DNA tropism, supporting its possible use for selecting patients with suppressed plasma HIV-1 RNA as candidates for CCR5-antagonist treatment. The high agreement between tropism prediction by single and triple amplification does not support the use of triplicate amplification in clinical practice.


Subject(s)
Genotyping Techniques/methods , HIV Infections/virology , HIV-1/genetics , HIV-1/physiology , Molecular Diagnostic Techniques/methods , Receptors, HIV/metabolism , Viral Tropism , Adult , DNA, Viral/chemistry , DNA, Viral/genetics , DNA, Viral/isolation & purification , Female , HIV Infections/diagnosis , HIV-1/classification , HIV-1/isolation & purification , Humans , Male , Middle Aged , Proviruses/classification , Proviruses/genetics , Proviruses/isolation & purification , Sequence Analysis, DNA , Virus Internalization
10.
HIV Med ; 14(9): 571-7, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23668660

ABSTRACT

OBJECTIVES: We evaluated the emergence of drug resistance in patients failing first-line regimens containing one nonnucleoside reverse transcriptase inhibitor (NNRTI) administered with zidovudine (ZDV) + lamivudine (the ZDV group) or non-thymidine analogues (non-TAs) (tenofovir or abacavir, + lamivudine or emtricitabine; the non-TA group). METHODS: Three hundred HIV-1-infected patients failing a first-line NNRTI-containing regimen (nevirapine, n = 148; efavirenz, n = 152) were included in the analysis. Virological failure was defined as viraemia ≥ 400 HIV-1 RNA copies/mL for the first time at least 6 months after starting the NNRTI-based regimen. For each patient, a genotypic resistance test at failure was available. The presence of drug-resistance mutations in HIV-1 reverse transcriptase was evaluated by comparing patients treated with NNRTI + zidovudine + lamivudine vs. those treated with NNRTI + non-TA. RESULTS: A total of 208 patients were failing with NNRTI + zidovudine + lamivudine and 92 with NNRTI + non-TA. No significant differences were observed between the non-TA group and the ZDV group regarding the time of virological failure [median (interquartile range): 12 (8-25) vs. 13 (9-32) months, respectively; P = 0.119] and viraemia [median (interquartile range): 4.0 (3.2-4.9) vs. 4.0 (3.3-4.7) log10 copies/mL, respectively; P = 0.894]. Resistance to reverse transcriptase inhibitors (RTIs) occurred at a significant lower frequency in the non-TA group than in the ZDV group (54.3 vs. 75.5%, respectively; P = 0.001). This difference was mainly attributable to a significantly lower prevalence of NNRTI resistance (54.3 vs. 74.0%, respectively; P = 0.002) and of the nucleoside reverse transcriptase inhibitor (NRTI) mutation M184V (23.9 vs. 63.5%, respectively; P < 0.001) in the non-TA group compared with the ZDV group. As expected, the mutation K65R was found only in the non-TA group (18.5%; P < 0.001). CONCLUSIONS: At first-line regimen failure, a lower prevalence of RTI resistance was found in patients treated with NNRTI + non-TA compared with those treated with NNRTI + zidovudine + lamivudine. These results confirm that the choice of backbone may influence the prevalence of drug resistance at virological failure.


Subject(s)
Anti-HIV Agents/therapeutic use , Drug Resistance, Viral/drug effects , HIV Infections/drug therapy , HIV Reverse Transcriptase/adverse effects , HIV-1/drug effects , Thymidine/pharmacology , Adenine/analogs & derivatives , Adenine/pharmacology , Adenine/therapeutic use , Adult , Anti-HIV Agents/pharmacology , Antiretroviral Therapy, Highly Active/adverse effects , CD4 Lymphocyte Count , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Deoxycytidine/therapeutic use , Dideoxynucleosides/pharmacology , Dideoxynucleosides/therapeutic use , Drug Combinations , Drug Resistance, Viral/genetics , Emtricitabine , Female , HIV Infections/virology , HIV Reverse Transcriptase/therapeutic use , HIV-1/genetics , Humans , Lamivudine/pharmacology , Lamivudine/therapeutic use , Male , Middle Aged , Organophosphonates/pharmacology , Organophosphonates/therapeutic use , Tenofovir , Thymidine/analogs & derivatives , Thymidine/therapeutic use , Treatment Failure , Viral Load , Zidovudine/pharmacology , Zidovudine/therapeutic use
11.
Infection ; 40(3): 311-8, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22237471

ABSTRACT

INTRODUCTION: This study aimed at defining protease (PR) resistance mutations associated with darunavir (DRV) failure and PR resistance evolution at DRV failure in a large database of treatment-experienced human immunodeficiency virus (HIV) patients. RESULTS: Overall, 1,104 patients were included: 118 (10.7%) failed at a median observation time of 16 months. The mean number of PR mutations at baseline was 2.7, but it was higher in patients who subsequently failed DRV. In addition, the number of PR mutations increased at failure. The increase in the mean number of mutations was completely related to mutations considered to be associated with DRV resistance following the indications of the main DRV clinical trials. DISCUSSION: The higher statistical difference at baseline between failing versus non-failing patients was observed for the V32I and I84V mutations. At DRV failure, the major increase was still observed for V32I; I54L, V11I, T74P and I50V also increased. Despite the increment in the mean number of mutations per patient between baseline and failure, in 21 patients (17.8%) at baseline and 36 (30.5%) at failure, no PR mutation was detected. CONCLUSION: The HIV-DB interpretation algorithm identified few patients with full DRV resistance at baseline and few patients developed full resistance at DRV failure, indicating that complete resistance to DRV is uncommon.


Subject(s)
Drug Resistance, Viral , HIV Infections/drug therapy , HIV Protease Inhibitors/therapeutic use , HIV-1/genetics , Sulfonamides/therapeutic use , Adult , Antiretroviral Therapy, Highly Active , Cohort Studies , Cross-Sectional Studies , Darunavir , Female , Genotype , HIV Infections/virology , Humans , Logistic Models , Male , Middle Aged , Mutation , Time Factors , Treatment Failure
12.
Clin Microbiol Infect ; 18(5): 449-58, 2012 May.
Article in English | MEDLINE | ID: mdl-21919996

ABSTRACT

We evaluated factors associated with normalization of the absolute CD4+ T-cell counts, per cent CD4+ T cells and CD4+/CD8+ T-cell ratio. A multicentre observational study was carried out in patients with sustained HIV-RNA <50 copies/mL. Outcomes were: CD4-count >500/mm(3) and multiple T-cell marker recovery (MTMR), defined as CD4+ T cells >500/mm(3) plus%CD4 T cells >29%plus CD4+/CD8+ T-cell ratio >1. Kaplan-Meier survival analysis and Cox regression analyses to predict odds for achieving outcomes were performed. Three hundred and fifty-two patients were included and followed-up for a median of 4.1 (IQR 2.1-5.9) years, 270 (76.7%) achieving a CD4+ T-cell count >500 cells/mm(3) and 197 (56%) achieving MTMR. Using three separate Cox models for both outcomes we demonstrated that independent predictors were: both absolute CD4+ and CD8+ T-cell counts, %CD4+ T cells, a higher CD4+/CD8+ T-cell ratio, and age. A likelihood-ratio test showed significant improvements in fitness for the prediction of either CD4+ >500/mm(3) or MTMR by multivariable analysis when the other immune markers at baseline, besides the absolute CD4+ count alone, were considered. In addition to baseline absolute CD4+ T-cell counts, pretreatment %CD4+ T cells and the CD4+/CD8+ T-cell ratio influence recovery of T-cell markers, and their consideration should influence the decision to start antiretroviral therapy. However, owing to the small sample size, further studies are needed to confirm these results in relation to clinical endpoints.


Subject(s)
Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active , CD4-CD8 Ratio , CD4-Positive T-Lymphocytes/immunology , HIV Infections/drug therapy , HIV Infections/immunology , Adult , Anti-HIV Agents/pharmacology , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/virology , Female , HIV Infections/mortality , HIV Infections/virology , HIV-1/drug effects , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , RNA, Viral/blood , Treatment Outcome , Viral Load
13.
Clin Microbiol Infect ; 18(3): E66-70, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22192680

ABSTRACT

We analysed the 12-week virological response to protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) therapy in 1108 patients carrying B or non-B human immunodeficiency virus (HIV)-1 subtypes with matched resistance mutation patterns. Response rates were not significantly different for non-B and B subtypes stratified for treatment status (51.5% vs. 41.5% in naïve patients; 46.7% vs. 38.7% in experienced patients) or regimens (46.9% vs. 39.7% with PI; 56.7% vs. 40% with NNRTI). No difference in response was detected in patients harbouring B and non-B subtypes with any resistance profile. Further studies are advisable to fully test this approach on larger datasets.


Subject(s)
Anti-HIV Agents/administration & dosage , Antiretroviral Therapy, Highly Active , Drug Resistance, Viral , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/drug effects , HIV-1/genetics , Adult , Female , Genotype , HIV-1/classification , HIV-1/isolation & purification , Humans , Male , Middle Aged , Treatment Outcome , Viral Load
14.
Infection ; 39(1): 13-20, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21246246

ABSTRACT

OBJECTIVE: We aimed to examine the clinical outcome in HIV-1-infected patients after more than 10 years of highly active antiretroviral therapy (HAART). METHODS: We analyzed data from 1,236 treatment-naïve adults who had started HAART. The primary endpoint was the yearly prevalence of death for AIDS-related causes (ARC) or for non-AIDS related causes (non-ARC). The data from our cohort were compared with that of the general population (GP) of our region. RESULTS: We observed that 116 patients died, and 58.6% of deaths were non-ARC. The death incidence decreased from 18.8% in 1998-1999 to 1.2% in 2008-2009. The leading causes of death were malignancies (35.3%), infections (21.6%), end-stage liver diseases (18.1%), and cardiovascular diseases (CVD) (6.9%). Yearly death rates were similar in the HIV-infected cohort and in the crude GP (odds ratio [OR] 1.1, 95% confidence interval [CI] 0.5-2.5), but when adjusted for age, HIV-infected patients showed a greater risk (OR 7.4, 95% CI 4.1-13.4). The difference was still highly significant when the analysis was restricted to non-ARCs (OR 4.3, 95% CI 2.07-9.2). Overall, malignancies (OR 5.7, 95% CI 2.6-12.8) and end-stage liver diseases (OR 35.0, 95% CI 15.5-78.8) were significantly more frequent than in the age-adjusted GP. CONCLUSIONS: Despite HAART, HIV-infected patients are at greater risk of death compared to a reference uninfected population.


Subject(s)
Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active/methods , HIV Infections/drug therapy , HIV Infections/mortality , Adolescent , Adult , Aged , Cause of Death , Female , Humans , Male , Middle Aged , Risk Factors , Survival Analysis , Treatment Outcome , Young Adult
15.
HIV Med ; 11(8): 530-4, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20236364

ABSTRACT

OBJECTIVES: To evaluate whether etravirine (TMC125) might be effective in patients failing therapy with current nonnucleoside reverse transcriptase inhibitors (NNRTIs), we analysed the prevalence of TMC125 mutations and the possible determinants of genotypic resistance to this drug among sequences reported to a large database in Italy [Antiretroviral Resistance Cohort Analysis (ARCA)]. METHODS: We analysed the prevalence of TMC125 resistance-associated mutations (RAMs) and the TMC125 weighted genotypic score (WGS) together with the determinants of genotypic resistance. A total of 5011 sequences from 2955 patients failing NNRTI therapy were evaluated. RESULTS: Among the sequences in ARCA, 68% had at least one and 9.8% at least three TMC125 RAMs, whereas 31% had a WGS>2. Frequent RAMs were Y181C, G190A, K101E and A98G, whereas V179F, Y181V and G190S appeared in <5% of sequences. Multivariate analysis revealed a higher risk of developing at least three TMC125 RAMs associated with both nevirapine and efavirenz exposure, whereas CD4 counts > or = 200 cells/microL retained their protective effect. An increased risk of WGS>2 was linked to higher HIV RNA values (maximum risk at >5 log(10) copies/mL) and nevirapine exposure; CD4 counts > or = 200 cells/microL were protective. CONCLUSIONS: The prevalence of TMC125 resistance mutations in the ARCA cohort was 68%. The DUET studies showed that at least three TMC125-associated mutations were required to impair the efficacy of the drug and Y181C/V, V179F and G190S had the greatest effect on response. The prevalence of these mutations among the patients examined in our study was low. However, WGS>2 was found for one-third of our sequences. Previous nevirapine exposure was associated with an increased risk of having WGS>2 (adjusted odds ratio 1.76).


Subject(s)
Anti-Retroviral Agents/pharmacology , Drug Resistance, Viral/genetics , HIV Infections/virology , HIV-1/genetics , Mutation , Pyridazines/pharmacology , Adult , Anti-Retroviral Agents/therapeutic use , Female , Genotype , HIV Infections/drug therapy , HIV Reverse Transcriptase/genetics , HIV-1/drug effects , Humans , Italy/epidemiology , Male , Multivariate Analysis , Nitriles , Prevalence , Pyridazines/therapeutic use , Pyrimidines , Retrospective Studies , Treatment Failure
16.
Infection ; 37(3): 244-9, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19471856

ABSTRACT

BACKGROUND: Although the mechanism of atazanavir (ATV)-related hyperbilirubinemia is well identified, its prevalence, risk factors, and association with transaminase flares have rarely been assessed in a large population from the "real life" setting. METHODS: Prospectively collected data on 2,404 patients from the Italian MASTER Cohort and the Italian ATV expanded access program database were examined. Uni- and multivariable Cox proportional hazards regression models were conducted to identify risk factors for grade >or= III hyperbilirubinemia during the administration of ATV. The risk of increased levels of serum alanine aminotransferase (ALT) was compared between patients with or without grade >or= III hyperbilirubinemia in a Cox regression analysis stratified by hepatitis C virus (HCV) serostatus. RESULTS: Grade III and IV hyperbilirubinemia were observed in 1,072 (44.6%) and 174 (7.2%) of the patients, respectively. Higher CD4+ T-cell counts, abnormal bilirubinemia at baseline, and ritonavir co-administration were associated with a higher risk of developing grade >or= III hyperbilirubinemia. In contrast, female gender, clinical class C, and non-nucleoside reverse transcriptase co-administration appeared to be protective. Higher bilirubinemia at baseline and the use of ritonavir were associated with a higher risk of grade IV hyperbilirubinemia. The occurrence of grade >or= III hyperbilirubinemia was not associated with severe hepatotoxicity (hazard ratio 1.00, 95% confidence interval 0.64-1.57; p = 0.997). CONCLUSIONS: Hyperbilirubinemia is a common side effect of an ATV pharmacotherapeutic regimen. However, grade IV increase in bilirubin was rarely found. In most cases, ATV hyperbilirubinemia appeared to be an innocent phenomenon as far as the risk of a subsequent increase in liver enzyme level is concerned.


Subject(s)
Alanine Transaminase/blood , Anti-HIV Agents/adverse effects , HIV Infections/drug therapy , Hyperbilirubinemia/chemically induced , Liver/drug effects , Oligopeptides/adverse effects , Pyridines/adverse effects , Adult , Alanine Transaminase/metabolism , Analysis of Variance , Antiretroviral Therapy, Highly Active , Atazanavir Sulfate , CD4 Lymphocyte Count , Cohort Studies , Female , HIV Infections/complications , HIV Infections/pathology , Hepatitis C/complications , Hepatitis C/drug therapy , Humans , Hyperbilirubinemia/epidemiology , Hyperbilirubinemia/pathology , Liver/enzymology , Male , Multivariate Analysis , Prevalence , Proportional Hazards Models , Risk Factors , Ritonavir/therapeutic use , Severity of Illness Index
18.
Infection ; 36(3): 244-9, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18454340

ABSTRACT

BACKGROUND: There is very less information on the use of antiretroviral (ARV) drugs and viro-immunological outcome over calendar years in Italy. PATIENTS AND METHODS: We performed an analysis of a prospective observational cohort (MASTER) to assess antiretroviral drug use in first line HAART and explore whether initial treatment response changed over the years. RESULTS: 3,648 ARV-naive patients with available HIV-RNA and CD4+ T cell count at baseline who started their first HAART between 1997 and 2004 were studied. Mean age was 37.7 years; they were mostly males (72.3%) and Italians (81.4%). Prescription of non-nucleoside reverse transcriptase inhibitors and protease inhibitors boosted with ritonavir rose from 0.3% in 1997 to 58% in 2004 and from 0.3%in 1997 to 33.4% in 2004, respectively. Virological failures decreased over calendar years: from 42.9% in 1997 to 8.1%in 2004 after 6 months of HAART (p<0.001); from 42.1%(1997) to 10.7% (2004) after 12 months (p<0.001) and; from 39.5% (1997) to 8.2% (2004) after 18 months (p<0.001). The same trend, but less striking, was found for immunological failure rates. CONCLUSIONS: In the general Italian population of HIV-positive patients, evolution of treatment prescription correlated with improved viro-immunological outcome.


Subject(s)
Anti-HIV Agents/therapeutic use , Drug Administration Schedule , HIV Infections/drug therapy , Reverse Transcriptase Inhibitors/therapeutic use , Adult , Anti-HIV Agents/administration & dosage , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , Cohort Studies , Drug Therapy, Combination , Female , HIV Infections/immunology , HIV Infections/virology , Humans , Italy , Longitudinal Studies , Male , RNA, Viral/blood , Reverse Transcriptase Inhibitors/administration & dosage , Treatment Failure , Treatment Outcome
19.
J Antimicrob Chemother ; 57(6): 1055-64, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16606637

ABSTRACT

A panel of leading Italian specialists in infectious diseases, virologists and immunologists met in Rome in 2005 to review critical data and discuss recommendations for each of the key questions in antiretroviral therapy today: When to start treatment? How to start? When to switch? What to switch to? Whether to stop or not to stop treatment, and how? The method of a nominal group meeting was used and recommendations were graded for their strength and quality using a system based on the one adopted by the Infectious Diseases Society of America. Main conclusions are summarized and critically discussed in this consensus statement, as well as some of the most recent data supporting these recommendations are provided.


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , Humans
20.
Scand J Infect Dis ; 35(5): 348-51, 2003.
Article in English | MEDLINE | ID: mdl-12875528

ABSTRACT

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.


Subject(s)
Antiretroviral Therapy, Highly Active/methods , HIV Infections/drug therapy , Lung Diseases, Interstitial/diagnosis , Adult , Anti-HIV Agents/administration & dosage , Female , HIV Infections/complications , HIV Infections/diagnosis , Humans , Lung Diseases, Interstitial/complications , Prognosis , Radiography, Thoracic , Risk Assessment , Severity of Illness Index , Tomography, X-Ray Computed , Treatment Outcome
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