Dynamics and phylogenetic relationships of HIV-1 transmitted drug resistance according to subtype in Italy over the years 2000-14.

Background: Transmitted drug-resistance (TDR) remains a critical aspect for the management of HIV-1-infected individuals. Thus, studying the dynamics of TDR is crucial to optimize HIV care. Methods: In total, 4323 HIV-1 protease/reverse-transcriptase sequences from drug-naive individuals diagnosed in north and central Italy between 2000 and 2014 were analysed. TDR was evaluated over time. Maximum-likelihood and Bayesian phylogenetic trees with bootstrap and Bayesian-probability supports defined transmission clusters. Results: Most individuals were males (80.2%) and Italian (72.1%), with a median (IQR) age of 37 (30-45) years. MSM accounted for 42.2% of cases, followed by heterosexuals (36.4%). Non-B subtype infections accounted for 30.8% of the overall population and increased over time (<2005-14: 19.5%-38.5%, P < 0.0001), particularly among Italians (<2005-14: 6.5%-28.8%, P < 0.0001). TDR prevalence was 8.8% and increased over time in non-B subtypes (<2005-14: 2%-7.1%, P = 0.018). Overall, 467 transmission clusters (involving 1207 individuals; 27.9%) were identified. The prevalence of individuals grouping in transmission clusters increased over time in both B (<2005-14: 12.9%-33.5%, P = 0.001) and non-B subtypes (<2005-14: 18.4%-41.9%, P = 0.006). TDR transmission clusters were 13.3% within the overall cluster observed and dramatically increased in recent years (<2005-14: 14.3%-35.5%, P = 0.005). This recent increase was mainly due to non-B subtype-infected individuals, who were also more frequently involved in large transmission clusters than those infected with a B subtype [median number of individuals in transmission clusters: 7 (IQR 6-19) versus 4 (3-4), P = 0.047]. Conclusions: The epidemiology of HIV transmission changed greatly over time; the increasing number of transmission clusters (sometimes with drug resistance) shows that detection and proper treatment of the multi-transmitters is a major target for controlling HIV spread.

Evaluation in a clinical setting of the performances of a new rapid confirmatory assay for HIV1/2 serodiagnosis.

BACKGROUND AND OBJECTIVES: The performances of the new Geenius rapid confirmatory test (Bio-Rad) were evaluated with emphasis towards identifying acute infection (AHI) and discriminating HIV-1/2 in a clinical setting STUDY DESIGN: Serum samples from individuals attending the L. Spallanzani Institute in Rome, Italy, for HIV diagnosis (one year retrospective collection), repeatedly reactive at 4th generation HIV-1/2 screening assays, confirmed with HIV-1 and HIV-2 Western blot (New LAV I and II Bio-Rad), were retested with Geenius. RESULTS: Of 6,200 samples, 406 resulted repeatedly reactive at screening, including samples from clinically confirmed AHI. New LAV I identified 378 HIV-1-positive samples. Of these, Geenius found 377 HIV-1-positive and one unclassified HIV-positive. New LAV I classified as indeterminate 18 samples, including 14 from AHI. Among these 14, Geenius results were: 12 positive, 1 indeterminate and 1 negative. Of the remaining, 2 resulted Geenius negative (false-positive screening results) and 2 HIV-2. Ten samples were New LAV I-negative (5 AHI). Geenius results were: 1 (AHI) positive and 9 negative. Geenius detected 110 additional positive samples with no p31 reactivity with respect to New LAV I, with an almost similar prevalence of low avidity samples. Geenius confirmed 3 out of 4 HIV-2 infections identified by New LAV II (one coinfected with HIV-1), while rated as HIV-1 the remaining sample, classified as coinfection by New LAV I and II. CONCLUSIONS: Geenius allows fast, sensitive and accurate confirmation of HIV serodiagnosis, including AHI and HIV-2 infections. The high sensitivity, in particular towards AHI, could avoid additional sampling and molecular tests.

Antiretroviral treatment-based cost saving interventions may offset expenses for new patients and earlier treatment start.

OBJECTIVES: Combination antiretroviral therapy (cART) has become the main driver of total costs of caring for persons living with HIV (PLHIV). The present study estimated the short/medium-term cost trends in response to the recent evolution of national guidelines and regional therapeutic protocols for cART in Italy. METHODS: We developed a deterministic mathematical model that was calibrated using epidemic data for Lazio, a region located in central Italy with about six million inhabitants. RESULTS: In the Base Case Scenario, the estimated number of PLHIV in the Lazio region increased over the period 2012-2016 from 14 414 to 17 179. Over the same period, the average projected annual cost for treating the HIV-infected population was €147.0 million. An earlier cART initiation resulted in a rise of 2.3% in the average estimated annual cost, whereas an increase from 27% to 50% in the proportion of naïve subjects starting cART with a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen resulted in a reduction of 0.3%. Simplification strategies based on NNRTIs co-formulated in a single tablet regimen and protease inhibitor/ritonavir-boosted monotherapy produced an overall reduction in average annual costs of 1.5%. A further average saving of 3.3% resulted from the introduction of generic antiretroviral drugs. CONCLUSIONS: In the medium term, cost saving interventions could finance the increase in costs resulting from the inertial growth in the number of patients requiring treatment and from the earlier treatment initiation recommended in recent guidelines.

Ageing with HIV: newly diagnosed older adults in Italy.

The prevalence of HIV/AIDS among people in midlife and late adulthood has been increasing in Western countries over the last decade. We analyzed data from a prospective, observational multi-centre study on individuals newly diagnosed with HIV between January 2004 and March 2007 in 10 public counselling and testing sites in Latium, Italy. At diagnosis, routine demographic, epidemiological, clinical and laboratory data are recorded, and patients are asked to complete a questionnaire investigating socio-demographic and psycho-behavioural aspects. To analyze the association of individual characteristics with age, we compared older adults (> or = 50 years) with their younger counterpart (18-49 years). To adjust for potential confounding effect of the epidemiological, clinical and behavioural characteristics, to identify factors associated with older age at HIV diagnosis, multivariate logistic regression analysis was performed. Overall, 1073 individuals were identified, 125 of whom (11.6%) were aged 50 years or above. The questionnaire was completed by 41% (440/1073). Compared with their younger counterparts, a higher proportion of older patients were males, born in Italy, reported heterosexual or unknown HIV risk exposure, were never tested for HIV before and were in a more advanced stage of HIV infection at diagnosis. In addition, older adults had a lower educational level and were more frequently living with their partners or children. With respect to psycho-behavioural characteristics, older patients were more likely to have paid money for sex and have never used recreational drugs. Interestingly, no differences were found regarding condom use, which was poor in both age groups. These findings may have important implications for the management of older adults with HIV, who should be targeted by appropriate public health actions, such as opportunistic screening and easier access to healthcare. Moreover, strategies including information on HIV and prevention of risk behaviours are needed.

HIV infection among low-risk first lifetime testers in Rome, 1990-2000.

BACKGROUND: HIV spread among low-risk populations through heterosexual intercourse is a major public health concern. This study was aimed at describing prevalence and determinants of HIV infection among Italian low-risk subjects seeking their first lifetime HIV test. PATIENTS AND METHODS: Information collected between January 1990 and December 2000 at a major counseling and testing site in Rome, Italy, was analyzed. Multiple logistic regression odds ratios (OR) and 95% confidence intervals (CI) were computed. RESULTS: Among the 14,313 study subjects, 64 (0.4%) were seropositive for HIV infection. HIV seropositivity increased with age (OR = 4.0, 95% CI: 2.1-7.6 for >/= 40 years vs 18-24), and it seemed to be more common among men (OR = 1.6, lower 95% CI:0.9). There was no evidence of temporal variations, whereas motivations for HIV testing were strongly associated with HIV prevalence. Testing for alarming symptoms (OR = 13.8) or for heterosexual intercourse (OR = 11.0) were associated with a more than 10-fold increased HIV risk. CONCLUSION: Our findings are consistent with data from other industrialized countries and they show a strong association between HIV seropositivity and reason for first-time testing. Moreover, they indicate a stable trend of HIV prevalence among low-risk persons in the last decade. Further studies on time trends in low-risk populations would be useful to evaluate current HIV prevention programs.

Determinants of health-related quality of life in HIV-infected patients.

In the era of new antiretroviral treatments that have dramatically reduced both morbidity and mortality, a primary goal is to maximize function and wellbeing in the everyday life of HIV-infected patients. To be able to do so, it would be important for clinicians and policy makers to identify factors that influence health-related quality of life (HRQoL). The objective of this multicentre prospective cohort study was to identify determinants of HRQoL in a cohort of Italian HIV-infected patients, the majority of whom were taking highly active antiretroviral therapy (HAART). A total of 809 patients were enrolled. The MOS-HIV Health Survey (summarized using two scores, physical health (PHS) and mental health (MHS)), and an HIV-related symptom scale were administered at enrolment and six months later. At baseline, low CD4+ cell count, hospitalization during the three months before the enrollment and symptoms were independently related to poor PHS; hospitalization during the three months before the enrollment, symptoms and poor satisfaction with information from providers were independently related to MHS. Predictors of PHS at six months included the stage of HIV infection, baseline CD4+ cells count, PHS and symptom score; while age, baseline MHS, symptom score and education predicted six-month MHS. Among these factors, symptoms, recent hospitalization and satisfaction with information are most amenable to clinical intervention.

Short-term adverse effects from and discontinuation of antiretroviral post-exposure prophylaxis.

OBJECTIVE: To evaluate short-term toxicity from and discontinuation of antiretroviral combination prophylaxis in HIV-exposed individuals in Italy. DESIGN: Longitudinal, open study conducted by prospective collection of data in the National Registry of PEP. SETTING: All the Italian centres dedicated to HIV related care and licensed by the Ministry of Health to dispense antiretroviral drugs. STUDY POPULATION: Health care workers and other persons consenting to be treated with post exposure prophylaxis (PEP) after exposures to HIV. RESULTS: Until October, 2000, 207 individuals receiving two nucleoside reverse transcriptase inhibitors (NRTIs), and 354 receiving two NRTIs plus a protease inhibitor (PI) were enrolled. More individuals experienced side-effects in the 3-drug group (53% and 62%, respectively; OR 0.68, (95% CI 0.48-0.98), p < 0.03). However, the proportion of individuals discontinuing prophylaxis because of side-effects did not differ significantly between the 2 groups (21% and 25% respectively; OR 0.82 (95% CI 0.53-1.26); p=0.4). The 43 individuals in the 2 NRTI group discontinued PEP after a mean of 10.4 days of treatment (median 8, range 1-27), similarly to the 88 discontinuations observed in the 3-drug group (mean duration 10.5 days, median 7.5, range 1-26). Type and incidence of specific adverse effects were similar to those reported in the literature. CONCLUSION: Our study indicates that the difference in the proportion of individuals developing side effects and discontinuing PEP is not significant. The rate of discontinuation because of protease inhibitor side-effects does not justify per se the initial use of a less potent PEP regimen. We suggest initiating PEP with a three-drug regimen and discontinuing the protease inhibitor in the case of adverse effects.

Home care for persons with AIds: a case-control study to identify determinants of referral to a hospital-based scheme.

We conducted a multicenter, hospital-based case-control study to identify specific characteristics of AIDS patients which determine referral to hospital care at home. The cases were patients referred to a hospital-based home care scheme, in the metropolitan area of Rome, during 1997. Each case was matched with two controls. Social, demographic and clinical characteristics were collected at referral. Univariate and multivariate analysis were performed. In the study period, 119 cases and 238 controls were recruited. In logistic regression analysis, social characteristics were not found to affect referral to the hospital-at-home scheme. A severely impaired functional status--assessed by the Functional Independent Measure--identified by a score below 100 (Odds Ratio [OR]=15.2, 95% confidence interval [CI] 2.8-82.7), and the need for prolonged intravenous therapy (OR=12.4, 95% CI=3.3-46.3) were the only two independent predictors of home-care referral. We conclude that home care, even in a period when new potent combination antiretroviral therapies are widely available, is an important integrated service component for persons with AIDS with severe functional impairment or requiring intravenous therapy.

Changing patterns of "hospital-at-home" care use by persons with AIDS in the era of combination antiretroviral therapy.

This study describes how hospital-at-home care (HHC) use by persons with acquired immune deficiency syndrome (PWA) has changed since the introduction of combination antiretroviral therapy (ART). For this study, all adult PWA (877) admitted for the first time to the HHC program, established for PWAs in the metropolitan area of Rome, between January 1994 and December 1998, were enrolled. Temporal changes in sociodemographic and clinical characteristics were evaluated. For subjects who concluded their first HHC cycle (851/877), the reasons for ending the service were assessed over time. From 1994 to 1998, the proportion of patients admitted to HHC of those living with AIDS in the Rome area decreased significantly (from 15.1% to 7.5%), while the median CD4+ cell count at HHC entry increased significantly. The proportion of patients referred to outpatient services at the end of their cycle of HHC increased sevenfold from 1994 to 1998, with a steep increase between 1996 and 1997. In multivariate analysis, only the use of triple-combination ART was significantly associated with referral to outpatient care (odds ratio [OR] = 4.26; 95%, confidence interval [CI] = 1.94-9.34). The results suggest that HHC use by PWAs in the ART era has diminished, while the HHC use pattern has also changed: there is a growing tendency to provide care to patients with less advanced human immunodeficiency virus (HIV) disease, prior to the beneficial effects of drugs, and the consequent referral to outpatient care.

Metabolic and morphologic disorders in patients treated with highly active antiretroviral therapy since primary HIV infection.

UNLABELLED: Our objective was to describe morphologic and metabolic disorders in patients treated with highly active antiretroviral therapy (HAART) since primary HIV infection (PHI). Our method was prospective evaluation of patients with PHI initiating HAART at the time of diagnosis. Outcome measures were: development of hyperglycemia, hypercholesterolemia, hypertriglyceridemia, and of body shape abnormalities indicative of lipodystrophy, assessed through self-reported questionnaires and physical examination. RESULTS: From May 1997 to April 2001, 41 patients (35 males) with PHI presented at the National Institute for Infectious Diseases "Lazzaro Spallanzani" in Rome, Italy. A protease inhibitor-including regimen was started in 30 patients, and a nonnucleoside reverse transcriptase-inhibitor in 11. Median interval between enrollment and treatment initiation was 30 days (mean 39, range 10-150). Median HAART duration was 19 months (mean 21.2, range 3-47). Thirty-eight patients had undetectable (less than 80 cp/mL) HIV RNA after a median of 3 months (mean 4.1, range 1-15). Mean CD4 cells count increased from 632/mmc at baseline to 936/mmc at the last follow up. No cases of hyperglycemia (glucose level greater than 110 mg/dL) were observed. After a median of 6 months on HAART, 10 patients developed beyond grade 2 (greater than 240 mg/dL) hypercholesterolemia, 5 developed beyond grade 2 (greater than 400 mg/dL) hypertrygliceridemia, and two developed both. Body mass index did not change significantly. Five patients (12.2%) developed lipodystrophy after a median of 14.5 months (mean 15.3, range 2-30), with an incidence of 7.3 per 100 patient-years. CONCLUSIONS: Dyslipidemia and lipodystrophy can occur in patients treated with HAART since PHI. This risk of should be taken into account when considering this early antiretroviral treatment of HIV infection.

Intravenous drug use, relationship with providers, and stage of HIV disease influence the prescription rates of protease inhibitors.

OBJECTIVE: To assess rates of prescriptions of protease inhibitors (PI) and determinants of not being prescribed PIs in a cohort of HIV-infected people eligible (according to published guidelines) for highly active antiretroviral therapy (HAART). DESIGN: Cross-sectional survey. METHODS: A total of 684 patients with CD4+ counts <500 cells/microl were enrolled from seven Italian HIV treatment centers from October 1997 to April 1998. A questionnaire on health-related quality of life (MOS-HIV) and patient ratings of the quality of care was administered. Sociodemographic variables, HIV disease-related factors, and prescribed antiretroviral therapy were also recorded. RESULTS: 61% of those enrolled were prescribed PI (median, 7.5 months). In addition, 75% of patients had previously received antiretroviral therapy. Fewer than 1% were prescribed nonnucleoside reverse transcriptase inhibitors (NNRTIs). Using multivariable logistic regression considering those with CD4+ counts <500 cells/microl, patients reporting the least information received (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.23-2.58), injecting drug users (IDUs; OR, 1.73; 95% CI, 1.18-2.54), people with CD4+ counts >200 cells/microl (OR, 1.76; 95% CI, 1.19-2.61), and patients with early stage disease (OR, 2.24; 95% CI, 1.73-2.90) were less likely to have be prescribed PIs. CONCLUSIONS: Of patients eligible for HAART, only 61% were prescribed PIs. People who wanted more information, IDUs, and patients in earlier disease stages are significantly less likely to be prescribed PIs. Access to HAART remains a critical issue in the management of HIV disease.