[show abstract][hide abstract] ABSTRACT: In the study reported here, single-tablet regimen (STR) versus (vs) multi-tablet regimen (MTR) strategies were evaluated through a cost analysis in a large cohort of patients starting their first highly active antiretroviral therapy (HAART). Adult human immunodeficiency virus (HIV) 1-naïve patients, followed at the San Raffaele Hospital, Milan, Italy, starting their first-line regimen from June 2008 to April 2012 were included in the analysis.
The most frequently used first-line HAART regimens (>10%) were grouped into two classes: 1) STR of tenofovir disoproxil fumarate (TDF) + emtricitabine (FTC) + efavirenz (EFV) and 2) MTR including TDF + FTC + EFV, TDF + FTC + atazanavir/ritonavir (ATV/r), TDF + FTC + darunavir/ritonavir (DRV/r), and TDF + FTC + lopinavir/ritoavir (LPV/r). Data were analyzed from the point of view of the Lombardy Regional Health Service. HAART, hospitalizations, visits, medical examinations, and other concomitant non-HAART drug costs were evaluated and price variations included. Descriptive statistics were calculated for baseline demographic, clinical, and laboratory characteristics; associations between categorical variables and type of antiretroviral strategy (STR vs MTR) were examined using chi-square or Fisher's exact tests. At multivariate analysis, the generalized linear model was used to identify the predictive factors of the overall costs of the first-line HAART regimens.
A total of 474 naïve patients (90% male, mean age 42.2 years, mean baseline HIV-RNA 4.50 log 10 copies/mL, and cluster of differentiation 4 [CD4+] count of 310 cells/μL, with a mean follow-up of 28 months) were included. Patients starting an STR treatment were less frequently antibody-hepatitis C virus positive (4% vs 11%, P=0.040), and had higher mean CD4+ values (351 vs 297 cells/μL, P=0.004) than MTR patients. The mean annual cost per patient in the STR group was €9,213.00 (range: €6,574.71-€33,570.00) and €14,277.00 (range: €5,908.89-€82,310.30) among MTR patients. At multivariate analysis, after adjustment for age, sex, antibody-hepatitis C virus status, HIV risk factors, baseline CD4+, and HIV-RNA, the cost analysis was significantly lower among patients starting an STR treatment than those starting an MTR (adjusted mean: €12,096.00 vs €16,106.00, P=0.0001).
STR was associated with a lower annual cost per patient than MTR, thus can be considered a cost-saving strategy in the treatment of HIV patients. This analysis is an important tool for policy makers and health care professionals to make short- and long-term cost projections and thus assess the impact of these on available budgets.
Therapeutics and Clinical Risk Management 01/2014; 10:9-15.
[show abstract][hide abstract] ABSTRACT: We performed a cross-sectional study on adult HIV-infected patients, on HAART, without calcium or vitamin D supplementation to evaluate if the cardiovascular risk or the presence of osteoporosis may be predictive factors of an optimal daily calcium intake (DCI>1000 mg/day).
Patients underwent a dual-energy X-ray absorptiometry, measured biochemical parameters and compiled a validated questionnaire for the assessment of DCI. Osteoporosis (OP) was defined according to the WHO classification at either the vertebral spine or femoral neck. Cardiovascular risk was assessed by the 10-year Framingham cardiovascular risk score.
200 HIV-infected patients evaluated: 171 (86%) males with a median age of 48.1 (42.3-53.8) years and 10.6 (4.3-13.6) years of HAART exposure. DCI was 889 (589-1308) mg/day and 79 (40%) patients had an optimal DCI. Framingham risk>20% was found in 13 (6.7%) patients and femoral OP was diagnosed in 12 (6%) pts. By multivariate analysis, optimal DCI was more likely in patients with a Framingham risk>20% [OR = 5.547, 95% CI:1.337, p = 0.025] and less likely in patients with femoral osteoporosis [OR = 0.159, 95% CI: 0.018-0.790, p = 0.047].
We found that an optimal dietary calcium intake was more likely in patients with high cardiovascular risk and no femoral osteoporosis.
[show abstract][hide abstract] ABSTRACT: Switches from lopinavir/ritonavir (LPV/r) to either atazanavir/ritonavir (ATV/r) or unboosted ATV (ATV) are increasingly common in clinical practice, but data on outcome comparison between these two simplification strategies are very limited. Methods. Multicenter, observational, retrospective study. Data were collected from five Italian clinics. The objective of the study was to investigate the utcome of LPV/r simplification with ATV/r or ATV and to identify factors predicting virological rebound. Patients who switched from LPV/r to ATV/r or ATV with an HIV-RNA value<50 copies/mL at the time of switch and with at least one follow-up visit were included. We evaluated 468 patients (74.1% males), followed for a median (Q1-Q3) of 547 (305-788) days: 380 (81%) and 88 (19%) switched to ATV/r and to ATV, respectively. Virological rebound was detected in 78/468 (16.7%, 95% CI: 13.6 -20.3) patients [16/88 (18.2%, 95% CI: 11.4 -27.6) switched to ATV and 62/380 (16.3%, 95% CI: 12.9 -20.4) to ATV/r (p=0.638)]. Virological rebound was more frequent in patients who started LPV/r with HIV-RNA >30000 copies/mL (28% vs 6%, p=0.014). Replacing lopinavir/r with ATV or ATV/r yielded similar rates of virological rebound. Viral load at the initiation of lopinavir/r may be useful in driving the choice between ATV/r and ATV.
Lopinavir, Atazanavir, Ritonavir, Unboosted, Simplification.
The New Microbiologica: official journal of the Italian Society for Medical Virology (SIVIM) 07/2013; 36(3):239-49. · 1.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: Human immunodeficiency virus (HIV) -infected patients with HIV RNA loads of < 50 copies/mL were followed-up for a median (interquartile range) of 30.8 (11.7-32.9) months to study the effect of residual viraemia (RV) on virological rebound (VR). At baseline, 446 (60.3%) patients had undetectable HIV RNA (group A) and 293 (39.7%) had RV (1-49 HIV RNA copies/mL, group B) by kinetic PCR. VR occurred in 4 (0.9%) patients in group A and in 12 (4.1%) patients in group B (p 0.007). Time to VR was shorter among patients of group B (Log-rank test: p 0.003). However, the proportion of VR was extremely low also among patients with RV.
Clinical Microbiology and Infection 05/2013; · 4.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND & AIMS: HIV-monoinfected patients are susceptible to liver injury by different factors and may develop liver fibrosis, which requires adequate clinical management in terms of therapy and disease monitoring. We aimed to evaluate the presence of liver fibrosis identified by transient elastography (TE), its relationships with indirect biochemical markers [the aspartate aminotransferase/platelet ratio index (APRI), the Forns index and FIB-4] and its predictive factors in HIV-monoinfected patients receiving antiretroviral therapy (ART). METHODS: Seventy-two HIV-monoinfected patients underwent TE and were evaluated using APRI, Forns and FIB-4. The clinical, immunological, virological and other biochemical characteristics were evaluated at the time of TE, together with their history of ART. RESULTS: Seven patients (10%) had liver stiffness (LS) values predicting cirrhosis, and 12 (17%) had values predicting significant or advanced fibrosis. Higher indirect biochemical scores of liver fibrosis were significantly associated with higher LS values [APRI rs = 0.4296 (P < 0.001); Forns rs = 0.4754 (P < 0.001); FIB-4 rs = 0.285 (P = 0.015)]. At multivariable analysis, APRI (β = 2.7405; P = 0.036), Forns (β = 1.4174; P = 0.029) and triglyceride levels (β = 1.3028; P = 0.007) were independently associated with LS. CONCLUSIONS: Indirect fibrosis biomarkers may increase the probability to detect liver injury enhancing a specific diagnostic workup and so contribute to improving the clinical management of HIV-monoinfected patients with clinically suspected liver disease.
Liver international: official journal of the International Association for the Study of the Liver 03/2013; · 3.87 Impact Factor
[show abstract][hide abstract] ABSTRACT: OBJECTIVES: The aim of the study was to assess whether pill burden is associated with self-reported adherence to current combination antiretroviral regimens and health status in a large sample of unselected and chronically treated HIV-infected patients. METHODS: An adherence and health status questionnaire was offered to all patients collecting their drugs between March and May 2010 at our clinic; both parameters were primarily evaluated using a visual analogue scale. Linear correlations were evaluated using Spearman's correlation coefficient. Wilcoxon's rank-sum test and the χ(2) test were used to compare quantitative and qualitative variables. The generalized linear model was used in multivariable analyses. RESULTS: Among 2763 subjects on treatment during the study period, 2114 (78.8% male; mean age 46.9 ± 8.84 years) were tested for adherence; 1803 (85.3%) had viral loads < 50 HIV-1 RNA copies/mL. After adjusting for age, gender, HIV risk factor, current CD4 count, pill burden and dosing interval, adherence was higher in patients with undetectable HIV RNA (P < 0.0001) and directly associated with current CD4 count (P = 0.029). After adjusting for the same variables, health status was better in patients with undetectable viraemia (P = 0.004) and in men who have sex with men (MSM) and heterosexuals compared with injecting drug users and those with other risk factors (P < 0.0001 for MSM and P = 0.008 for heterosexuals); it was also directly associated with current CD4 count (P < 0.0001) and inversely associated with age (P < 0.0001) and pill burden (P = 0.019). CONCLUSIONS: In this highly adherent population, the number of daily pills was related to self-reported health status but not to self-reported adherence, whereas the dosing interval did not influence self-reported adherence or health status.
[show abstract][hide abstract] ABSTRACT: Thirty-nine HIV-1-infected patients treated for 156 weeks with a new nucleoside analogue-sparing regimen [raltegravir, etravirine and maraviroc (REM) or raltegravir, etravirine and darunavir/ritonavir (RED)] showed a uniform increase in fasting glucose levels and a uniform decrease in insulin secretory capacity. Diabetes mellitus occurred in one RED-treated and four REM-treated patients. A worsening glucose tolerance was observed in highly treatment-experienced HIV-infected patients receiving effective antiretroviral therapy after virological failure.
AIDS (London, England) 06/2012; 26(14):1837-40. · 4.91 Impact Factor
[show abstract][hide abstract] ABSTRACT: Type 2 diabetes mellitus is a growing problem in HIV population and a comparison with the general population may help screening and prevention. In this cross-sectional study the authors determined the prevalence of type 2 diabetes mellitus in 4,249 HIV-infected subjects attending the San Raffaele Infectious Diseases Department compared with 9,148 healthy controls recruited in 15 Italian regions, and identified risk factors associated with of type 2 diabetes mellitus. Type 2 diabetes mellitus was defined as reported diabetes, a fasting plasma glucose concentration ≥7.0 mmol/l, or current use of anti-diabetic medication. Prevalence of type 2 diabetes mellitus was higher in HIV-infected than healthy subjects (4.1 vs. 2.5 %; P < 0.0001). At multivariable analysis, HIV-infected subjects (odds ratio 1.70, 95 % CI, 1.12-2.51; P = 0.009), older age (P < 0.0001), higher BMI (P < 0.0001) and hypertension (P = 0.039) were associated with a higher risk of diabetes. Among HIV-infected patients, the risk of type 2 diabetes mellitus increased with older age (P < 0.0001), higher BMI (P = 0.003), higher triglycerides (P = 0.015) lower total cholesterol (P = 0.008), longer duration of HIV infection (P = 0.036) lower nadir CD4 (P = 0.027). Prevalence of type 2 diabetes mellitus in HIV-infected subjects was almost two-fold increased than healthy subjects and it was associated with the typical risk factors of the general population and also to longer duration of HIV infection and lower nadir CD4.
European Journal of Epidemiology 06/2012; 27(8):657-65. · 5.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: Patients treated with maraviroc frequently show high CD4+ T cell increases. The aim of this study was to detail the characteristics of maraviroc-induced immune recovery.
We studied T cell subsets from frozen peripheral blood mononuclear cells of patients treated with raltegravir, etravirine and either maraviroc (REM, n = 24) or darunavir/ritonavir (RED, n = 17).
The two groups showed a similar decrease in activated CD4+ and CD8+ T cells. A greater loss of naive CD4+ T cells and a reduction in cells expressing CXCR4 were observed in REM patients, while RED patients showed a greater loss of cells expressing CCR5.
Our findings do not support a role for reduction in activated T cell subsets to explain the greater maraviroc-induced immune recovery. Reduction in CXCR4+CD4+ and higher expression of CCR5+CD4+ T cells might represent a potential protection from non-R5 tropic viral strain overgrowth.
Journal of Antimicrobial Chemotherapy 06/2012; 67(10):2474-8. · 5.34 Impact Factor
[show abstract][hide abstract] ABSTRACT: We evaluated the single-tablet regimen (STR) versus multiple-tablet regimen (MTR) strategies through an incremental cost-effectiveness analysis in a large cohort of patients starting their first HAART. Adult HIV-1-naïve patients, followed at the San Raffaele Hospital, starting their first-line regimen from June 2008 to April 2012, were included in the analysis. First-line HAART regimens more frequently used (>10%) were grouped into two classes as follows: a) single-tablet regimen (STR) of TDF + FTC + EFV; b) multiple-tablet regimen (MTR) including TDF + FTC + EFV, TDF + FTC + ATV/r, TDF + FTC + DRV/r TDF + FTC + LPV/r. The incremental cost-effectiveness analysis was carried out by means of a Markov model calculating quality of life and costs for each patient, according to the given regimen (including any subsequent switch if occurred), through 1-year cycles. The outcome measure was quality-adjusted life-years (QALYs). Data were analysed from the point of view of the Lombardy Regional Health Service (RHS): HAART, hospitalisations, visits, examinations and other concomitant non-HAART drugs costs were evaluated, price variations included. 474 naïve patients: 90% males, mean age 42.2 years, mean baseline HIV-RNA 4.50 log10copies/ml and CD4+ count of 310 cells/µL with a mean follow-up of 28 months. Patients starting with an STR treatment were less frequently HCVAb positive (4% vs 11%, P=0.040), had higher mean CD4+ values [351 vs 297, P=0.004] as compared to MTR patients. The mean year cost/patient was €9,213 (range: €6,574.71-€33,570.00) with a mean per patient QALYs of 0.986 (range: 0.878-0.999) among STR patients; the mean year cost/patient was €14,277 (range: €5,908.89-€82,310.30) with a mean QALY of 0.933 (0.830-0.976) among MTR patients. STR dominates (i.e. is more effective and less costly) compared to MTR. (Fig. 1) At multivariable analysis, after adjustment for age, gender, HCVAb status, HIV risk factor, baseline CD4+ and HIV-RNA, the cost-effectiveness ratio was significantly lower among patients starting an STR treatment as compared to a MTR regimen (adjusted mean: €12,096 vs. €16,106; P=0.0001). The incremental cost-effectiveness ratio (ICER) values comparing the two treatment strategies reported in the table. Starting with a first-line STR regimen compared to multiple-tablet regimens resulted cost-effective showing lower costs and better efficacy as measured by QALYs.
Journal of the International AIDS Society 01/2012; 15(6):18386. · 3.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: It is currently debated whether patients with residual viraemia are at higher risk of virological failure than those attaining <1 HIV RNA copy/mL. We therefore investigated the effect of residual viraemia on virological rebound.
We used a prospective, non-interventional, single-centre, study. This analysis was based on HIV-infected patients with two consecutive HIV RNA viral loads (VLs) of <50 copies/mL as tested by Versant bDNA, followed by two HIV RNA VLs of <50 copies/mL as tested using the Versant kinetic PCR molecular system (kPCR; limit of quantification = 1 copy/mL). Virological rebound was defined as two consecutive HIV RNA values of >50 copies/mL after baseline, and the time to virological rebound was calculated using the Kaplan-Meier method.
There were 739 eligible patients; 446 (60.4%) had HIV RNA <1 copy/mL (group A) and 293 (39.6%) had residual viraemia (1-49 HIV RNA copies/mL; group B). After a follow-up (median 48.9 weeks), virological rebound occurred in four patients in group A (0.9%) and six patients in group B (2%); the time to virological rebound was similar in the two groups (log-rank test P = 0.231). CD4+ cell recovery (slope) was significantly less in the patients with residual viraemia; +14.3 (-7.7, 43.9) cells/mm(3) per year versus +21.2 (-2.5, 53.2) cells/mm(3) per year; P = 0.036.
Residual viraemia assessed by kPCR was not associated with virological rebound during 1 year of follow-up. However, the patients attaining <1 HIV RNA copy/mL showed a small but statistically significant improvement in CD4+ cell recovery.
Journal of Antimicrobial Chemotherapy 01/2012; 67(1):213-7. · 5.34 Impact Factor
[show abstract][hide abstract] ABSTRACT: HAART has reduced mortality in HIV-infected patients; however, the risk of non-AIDS-related events has increased, including cancer. We compared mortality in HIV-infected patients with or without cancer with the general population in Italy.
Eligible patients were recorded in the San Raffaele Infectious Diseases Department database. The ratio of observed deaths to expected all-cause deaths (standardized mortality ratio [SMR]) was standardized for age and gender, and stratified by cancer occurrence or year of HIV infection (≤1998 or >1998). Expected all-cause deaths were obtained from the Istituto Superiore di Sanità (Rome, Italy; 2002 data).
Among 6,495 HIV-infected patients, contributing 75,171 person-years, the SMR was 6.0 (95% CI 5.7, 6.4); SMRs decreased as age increased. Mortality rates were significantly higher than the general population for patients with or without cancer (SMR=15.1 [95% CI 13.6, 16.7] and 4.8 [95% CI 4.5, 5.1], respectively). For patients with or without cancer, SMRs were higher in those aged <45 years than older patients. SMRs for patients with cancer were almost stable in those infected with HIV ≤1998 (15.3; 95% CI 13.7, 17.0) or >1998 (13.5; 95% CI 9.2, 19.1). Among patients with cancer diagnosed with HIV >1998, age-adjusted SMRs ranged from 216.0 (95% CI 43.4, 631.3) to 6.8 (95% CI 4.7, 9.7) in patients <30 years or ≥70 years, respectively.
Mortality in HIV-infected patients remains higher than the general population in Italy, with marked differences according to age, and cancer contributing to an increased excess of mortality.
[show abstract][hide abstract] ABSTRACT: Few data are available regarding the 10-year survival among subjects with HIV and cancer. The aim of this study was to evaluate the 10-year survival of HIV-infected subjects with AIDS-defining malignancies (ADM) or non-AIDS-defining malignancies (NADM). This was a single center, retrospective, observational study of subjects with HIV infection and a subsequent cancer diagnosis; the data were collected from January 1991 to April 2010. Malignancies were divided into ADM or NADM on the basis of the Centre of Diseases Control-1993 classification. Survival curves were estimated using Kaplan-Meyer method and compared by the log-rank test. Six hundred and fifteen (9.5%) of the 6,495 subjects recorded in the San Raffaele Infectious Diseases Database developed a malignancy: 431 (70%) an ADM and 184 (30%) a NADM. In the case of ADM, survival was more favorable when cancer was diagnosed during post-highly active antiretroviral therapy (HAART) era (10-year survival: 43.2% ± 4.4%) than when diagnosed during the pre-HAART era (10-year survival: 16.4% ± 2.7%; log-rank test: p < 0.001). The same was true in the case of NADM (10-year survival: 44.7% ± 5.5% vs. 33.3 ± 9.6%; log-rank test: p = 0.03). An evaluation of survival probability by cancer type showed higher survival rates during the post-HAART era in the case of non-Hodgkin lymphoma (10-year survival: 42.1% ± 5.3% vs. 11.4% ± 3.3%; log-rank test: p = <0.001), Kaposi's sarcoma (10-year survival: 44.0% ± 8.4% vs. 23.5% ± 3.9%; log-rank test: p < 0.001) and Hodgkin's disease (10-year survival: 49.5% ± 14.5% vs. 40.0% ± 12.7%; log-rank test: p = 0.005). Despite the better cancer prognosis during the post-HAART era, the 10-year survival of HIV-infected subjects with an ADM or NADM is poor.
International Journal of Cancer 07/2011; 130(12):2990-6. · 6.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: The hepatic safety profile of ART including DRV/r was retrospectively evaluated in antiretroviral-experienced HIV-infected patients (18 HIV/HCV coinfected, group A and 29 infected with HIV alone, group B) during a 72 week study. During the study, liver enzyme values were higher in group A, but in the case of abnormal transaminase levels, the median values did not exceed 1.6xULN. This study showed evidence of long-lasting hepatic safety of ART including PI DRV/r in HIV/HCV coinfected and in HIV monoinfected persons.
The New Microbiologica: official journal of the Italian Society for Medical Virology (SIVIM) 07/2011; 34(3):317-21. · 1.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: As a proactive diagnosis of diabetes mellitus (DM) may prevent the onset of severe complications, we used an oral glucose tolerance test (OGTT) to check for impaired glucose tolerance (IGT) and DM in patients with long-standing HIV infection and long durations of exposure to antiretroviral drugs with normal fasting plasma glucose (FPG) levels.
This was a cross-sectional, single-centre study. The homeostatic model assessment for insulin resistance (HOMA-IR) and 2-h post-load glucose levels were used to evaluate patients with known HIV-1 infection since before 1988 and no previous diagnosis of DM for whom data on hepatitis C virus (HCV) and hepatitis B virus (HBV) infection were available.
Eighty-four Caucasian patients [67 (80%) male; median age 45.7 years; range 43.8-49.1 years] were able to be evaluated; 65 (77%) were coinfected with HCV, and seven (8%) were coinfected with HBV. Median (interquartile range [IQR]) exposure to antiretrovirals was 12.8 (10.4-16.5) years. Fifteen patients (18%) had a previous AIDS-defining event, 64 (76%) had HIV RNA<50 copies/mL, and the median (IQR) CD4 count was 502 (327-628) cells/μL. The median [IQR] FPG was 81 mg/dL (4.5 mmol/L) [75-87 mg/dL (4.2-4.8 mmol/L)], and the median (IQR) HOMA-IR was 2.82 (1.89-4.02). After OGTT, nine patients (11%) were diagnosed as having IGT (6) or DM (3). A first multivariable analysis showed that CD4 cell count (P=0.038) and HOMA-IR (P=0.035) were associated with IGT or DM, but a second model including only the variables with a P-value of <0.2 in the univariable analysis (CD4 cell count, HBV coinfection, and HOMA-IR) found that only HOMA-IR independently predicted IGT or DM.
In patients with long-standing HIV infection and normal FPG levels, an OGTT can reveal IGT or DM.
HIV Medicine 02/2011; 12(2):109-17. · 3.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: We prospectively evaluated 28 triple-class experienced HIV-1-infected patients harbouring R5 virus, who received maraviroc, raltegravir and etravirine. By on-treatment analysis, 26 (92%) had less than 50 copies HIV-RNA/ml at week 48. The median (interquartile range) 48-week increase in CD4 cell counts was 267 (136-355) cells/microl. Three serious adverse events occurred: one recurrence of mycobacterial spondylodiscitis, one anal cancer, one Hodgkin lymphoma. Although long-term safety needs further study, this protease inhibitor and nucleoside analogue-sparing regimen showed sustained efficacy.
AIDS (London, England) 02/2010; 24(6):924-8. · 4.91 Impact Factor