Purpose of the studyConsidering costs of antiretrovirals (ARVs) for HIV patients is increasingly needed. A simple and comprehensive tool weighing comorbidities and ARV‐related toxicities could be useful to judge the appropriateness of use of more expensive drugs. We conceived a MultiFactorial Risk Score (MFRS) to evaluate the appropriateness of ARVs prescription relative to their costs.MethodsHIV patients were consecutively enrolled in 2010‐2011. We considered socio‐demographic characteristics, HIV history, cardiovascular risk factors, low energy fractures, bone density. Psychological factors were assessed by BDI, DS14 and TAS‐20. The MFRS was calculated as the sum of the following: age (<30y 1 point; 1 point increase every 5y, 10 for≥70); AIDS diagnosis (5); CD4 nadir (5 if <100; 1 point less every 100 CD4 increase); ART line (0 first, up to 5 for≥6 lines); lipodistrophy (5); HCV coinfection (7); education (1 degree, 2 secondary, 3 primary); alcohol (3) and drug abuse (5); working activity (3 if unemployed); hypertension (3); cholesterol≥200 mg/dl (3); diabetes (3); Framingham score (7 if>7%); creatinine (0 if <1 mg/dl, 1 if<1.2; 2 if<1.5>1.2, 5 if<2> 1.5, 7 if≥2); bone fractures (7); bone status at DEXA (0 normal, 3 osteopenic, 5 osteoporotic); cancer (5); depression (3 if BDI>17); other psychiatric illness (5). Annual costs of individual ART regimens were calculated. MFRS was correlated in univariate and multivariate models with all variables. All statistical analyses were carried out using Stata 10.1.Summary of resultsWe enrolled 241 HIV patients, 74.3% males, aged 44.5±9.9y; 19 patients (7.8%) were untreated, 74.8% of treated had undetectable HIV RNA. Mean Nadir CD4 counts were 218±168, 38.5% of patients had an AIDS diagnosis. Mean individual ARV annual cost was 10,976±5,360. Mean MFRS was 28.5±13.9 (4–64). MFRS was significantly higher (p<0.001) in patients with older age, longer duration of HIV infection, lower CD4 nadirs, AIDS diagnosis, lipodistrophy, HCV, smoking, lower education, alcohol/drug abuse, hypertension, carotid plaques, higher Framingham score, diabetes, bone fractures or disorders, depression, alexithymia, and higher ARV costs. In multivariate models, ARV costs were significantly higher in patients with older age, previous AIDS diagnosis, lower CD4 nadir and higher MFRS.ConclusionsMFRS may be a simple and reliable tool to match patients' complexity and ARV costs, deserving further validation on larger samples.
Atripla is a fixed‐dose drug combining FTC/TDF/EFV into a single pill and may increase adherence. To our knowledge, there is little data comparing the durability of Atripla vs. other regimens. Our first aim was to compare the durability of Truvada (TVD)/EFV or TVD/PIr or Atripla started when ART‐naïve, in terms of time to virological failure (VF first of 2 consecutive values>50 and>200 copies/mL), time to discontinuation of any drug in the regimens, or both. Then, we aimed to compare the incidence of virological rebound (VR)>200 copies/mL in patients (pts) currently receiving these same regimens after achieving a viral load (VL)≤80 copies/mL. Pts in the Icona Foundation Study who started for the first time a cART regimen with TVD/EFV or TVD/PIr or Atripla, either while ART‐naïve (analysis 1) or while with a VL≤80 (analysis 2) were included. In analysis 1, pts' follow‐up accrued from cART initiation to the date of the event (VF or discontinuation of any drug in the regimen) or to the date of last available visit/VL. In the TVD/EFV group a switch to Atripla was not counted as an event. Survival analysis employing KM curves and Cox regression model was used. In analysis 2, follow‐up accrued from the date of first VL≤80 (which could be achieved with any cART) to VR or last VL and only person years (PY) on the regimens of interest were considered. Rates were calculated as number of VR per 1000 PY and relative rates (RR) compared using a Poisson regression model. In analysis 1, 515 pts starting TVD/EFV, 1001 TVD/PIr and 160 Atripla when ART‐naïve on average in 2010 (IQR: 2008–2011) were included. PI/r were LPV (33%), ATV (38%) fos‐APV (4%) and DRV (24%). Median age was 38 years, 19% females, 40% heterosexuals. Pts starting Atripla were younger, less likely to be female, IDU, HCV co‐infected, to have AIDS and they had higher CD4 count (334 vs. 280). By 2 years, 48% (95% CI: 43–53) of those initiating TVD/PIr experienced the composite endpoint of VF or drug discontinuation vs. 20% in the other groups (p=0.0001). Median time to switch from TVD to Atripla in the EFV group was 17 months (95% CI: 12–23). The table shows the results of the Cox regression analysis. In analysis 2 (n=1,425), the rates of VR were 16.8 per 1000 PY for TVD/PIr, 11.17 for TVD/EFV and 5.3 for Atripla (adjusted RR vs. TVD/PIr=0.51, 95% CI: 0.19–1.34). Durability of Atripla was comparable to that of TVD/EFV and potentially longer than that of TVD/PIr. Unmeasured confounding cannot be ruled out.
Crude and adjusted relative hazards from fitting a Cox regression
*adjusted for age, gender, nation of birth, mode of HIV tranmission, hepatitis co‐infection status, AIDS diagnosis, baseline CD4 count and viral load an year of starting cART and stratified by clinical centre
Almost 1/3 of HIV‐infected individuals enter health care late in the course of infection, worsening their prognosis and costs of care. According to the recent European consensus definitions, late presenters are persons presenting with CD4 counts <350/μL, and presenters with advanced HIV disease have CD4 < 200/μL or an AIDS‐event. These latter, in particular, are at high risk of further opportunistic infections or death despite of HAART. We included all patients newly diagnosed with HIV infection at the Infectious Diseases Unit of Pescara from 2006 to present, registered for at least one day of observation. The duration of follow up was plotted for all enrolled patients up to 31/12/2011. Demographic, clinical, virological and immunological data, lines of therapy and outcome of HAART were collected for each patient. We included 140 consecutive patients, 18.6% in 2006, 17.9% in 2011; 76.4% were male, while the average age was 39.3±10.2y. AIDS diagnosis at presentation was for 39.7% (50% in 2006, 41.7% in 2011); 52.7% had advanced HIV disease (CD4 <200/μL, 53.8% in 2006, 70.8% in 2011), 67.2 % were late presenters (CD4 <350/μL, 73.1% in 2006, 79.2% in 2011). The average CD4 counts at enrollment were 313.8±294.1 in 2006, 361.3±263.1 in 2007, 281.8±295.5 in 2008, 238.4±201.6 in 2009, 394.1±183.9 in 2010, 225.7±245.2 in 2011. Eight per cent of patients were HCV coinfected. Heterosexual exposure occurred in 54% of patients, homosexual in 36%; drug addiction in 7.5%. Among enrollees, 71.4% were Italian, 18.6% from sub‐Saharan Africa, 5.7% from South America and 4.2% from Eastern Europe. With a median follow up of 2.5 years, 105 patients (75%) were still being treated as of November 30th, 2011; among these 104 (99.1%) were in virological suppression. Among the 35 patients no longer followed, 15 (11.4%) died during the first 6 months of treatment, 20 (14.3%) were lost in the first 6 months of follow‐up. All 15 deaths occurred in patients enrolled with CD4 <200/μL. After initiation of HAART only 1 patient (0.7%) switched for virological failure, 19 (13.6%) for toxicity or simplification. The proportion of late presenters at our center is high (67.2%) in the absence of appropriate local screening measures. Early mortality after diagnosis is similarly high, concentrated in patients with late presentation. Retention in care after 6 months and virological success of treated patients appear very promising, much more than recently reported in North America.
IntroductionHIV‐infected patients have a higher risk of developing cancer than the general population. Kaposi's sarcoma (KS), non‐Hodgkin's lymphoma (NHL), primary CNS lymphoma (PCL) and invasive cervical cancers are considered AIDS‐defining. An increased incidence in recent years, however, has been reported also for other malignancies after the introduction of HAART.MethodsWe performed a case‐control study to characterize all HIV‐infected patients with both AIDS and non‐AIDS‐defining neoplasms observed among all consecutive patients followed at the Infectious Diseases Unit of Pescara General Hospital, since 1991 through 2012. All cases were matched with equinumerous controls without neoplasia homogeneous for age, sex and AIDS diagnosis.ResultsOut of 626 patients consecutively assisted since 1991, 57 cases of malignancy (9.1%) were observed. Of these, 45 (79.0%) occurred in males; mean age was 43.6±9.3 years; 49 (86.0%) patients were diagnosed with AIDS. Tumors observed were: NHL, 17 (29.8%); SK, 13 (22.8%); HCC, 5 (8.8%); CPL, 6 (10.5%); Hodgkin's lymphoma, 4 (7.0%); solid tumors, 12 (21.1%), including 1 AIDS‐defining tumor (anal cancer). Among these, 37 (66.1%) patients died; of them 14 (37.8%) had non‐AIDS cancers. Cases were well matched with the 55 controls for sex (p=0.9), age (p=0.6) and AIDS diagnosis (p=0.6). In comparison with controls, CD4 nadirs were not different (153±151 in controls vs 136±154 cells/mmc), while CD4 at tumor diagnosis were very different between controls (463±283 cells/mmc) and cases (226±209 cells/mmc, p<0.0001). Among patients with malignancies, those who died had a non‐significant reduction in CD4 counts (p=0.14); seemingly irrelevant were smoking status (p=0.9), working ability (p=0.4), HCV coinfection (p=0.4). Surprisingly, in patients co‐infected with HBV, including HBsAg negative, antibody‐positive subjects, tumors were significantly more frequent (60.7% vs. 38.8%, p=0.009).ConclusionFactors potentially relevant for carcinogenesis in the prolonged survival patients of the HAART era may include HBV coinfection in spite of the lack of active biochemical activity (HbsAg negative) in the majority of coinfected patients. The potential relevance of this finding deserves prompt assessment in a larger multicentric cohort.