Long-acting injectable antiretrovirals for HIV treatment in the ICONA cohort: physicians' and nurses' points of view.

BACKGROUND: Implementation level of long-acting injectable agents cabotegravir/rilpivirine (LAI CAB/RPV) for human immunodeficiency virus (HIV) treatment in Italy is still not known. The aim of this study is to identify the status of implementation of LAI CAB-RPV and its barriers. MATERIALS AND METHODS: A cross-sectional online survey was conducted among infectious diseases (ID) physicians and nurses belonging to the ICONA network in Italy. Three validate 4-items measures were used: Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM) and Feasibility of Intervention Measure (FIM). RESULTS: Out of 61 ICONA centres, 38 (62%) completed the survey: 57.9% were academic centres, 42.1% were hospital-based. In total, 104 respondents were ID physicians (57.4%), 77 were nurses (42.5%); 4.5% of all PWH followed at the 38 centres started LAI CAB/RPV at time of study. Centres taking care of >1000 PWH reported 95% application of procedures for LA implementation, higher than other centres (P = 0.009). Mean score of AIM was (16.0, standard deviation, SD, 3.3), of IAM (16.0, SD 3.0) and FIM (16.0, SD 2.9). A linear correlation was found between AIM and the number of people with HIV who started LAI CAB/RPV (25-50 versus <25, coefficient of correlation [b] 2.57, 95%CI 0.91-4.60, P = 0.004), academic versus hospital-based centres (b -1.59, 95%CI -2.76-0.110044, P = 0.007) and the absence of preliminary systematic assessment of staff (b -1.98, 95%CI -3.31-0.65, P = 0.004). Implementation barriers were not significantly different according to the number of PWH/centre. CONCLUSIONS: LAI CAB/RPV implementation was low, with a great variability according to centre size. Tailored and centre-specific interventions to address barriers and to optimize the LA treatment implementation should be designed.

Dyslipidaemia after switch to tenofovir alafenamide (TAF)-based cART regimens in a cohort of HIV-positive patients: what clinical relevance?

OBJECTIVES: Switching from tenofovir (TDF) to tenofovir alafenamide (TAF) affects lipid profile. The aim of this study was to evaluate whether this results in an increased frequency of patients with low-density lipoprotein (LDL) above their cardiovascular-related target. METHODS: All HIV patients switching from TDF to TAF, with no changes of the anchor drug, and with plasma lipids available within 6 months before and after the switch, were included. Demographic, HIV-related parameters, cardiovascular (CV) risk factors and lipid profile on both TDF and TAF were collected. The CV risk score and the relative target of LDL for each patient were calculated according to 2016 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for the management of dyslipidaemias. Modifications in lipid profiles and in the prevalence of patients with LDL above their CV-related target were evaluated after switch to TAF. RESULTS: Overall, 221 HIV patients were included, according to CV risk: 55% at low risk, 34% at moderate risk, and 11% at high/very high risk. By analysing lipid profiles according to CV risk, 38% of patients on TDF had LDL above their CV target; this prevalence increases to 60% after switching to TAF (P < 0.0001). The presence of cobicistat in the combination antiretroviral therapy (cART) regimen was associated with an increased risk of LDL above the CV-related target after switch to TAF [adjusted odds ratio (aOR) = 2.4, 95% confidence interval (CI): 1-5.1], P = 0.03) and with an increased prescription of lifestyle/therapeutic intervention (OR = 3.0, 95% CI: 1.7-5.3, P < 0.0001). DISCUSSION: Switching from TDF to TAF affects lipid parameters, and data from real life suggest a clinical relevance of this worsening that often leads clinicians to implement lifestyle/therapeutic interventions.

Assessment of radiological vertebral fractures in HIV-infected patients: clinical implications and predictive factors.

OBJECTIVES: The aim of this study was to evaluate the clinical impact of including lateral spine X-ray in the screening of bone diseases in HIV-positive patients. METHODS: A total of 194 HIV-positive patients underwent dual-energy X-ray absorptiometry (DEXA), lateral spine X-ray and bone biochemical analysis. Vertebral fractures were identified using a morphometric analysis of X-rays and classified using the semiquantitative scoring system of Genant et al. For each patient, a spine deformity index (SDI) score was calculated by summing the grades of vertebral deformities. Reductions in vertebral body height of > 25% were considered vertebral fractures, and those < 25% were considered vertebral deformities. Risk factors associated with vertebral fractures were evaluated by univariate and multivariate analysis. RESULTS: Vertebral fractures were detected in 24 patients (12.4%) and vertebral deformities in 17 patients (8.7%); 153 patients (78.9%) did not show any vertebral deformity. Among patients with fractures, only two with SDI > 10 reported lumbar pain; the remaining were asymptomatic. Patients over 50 years old showed a higher prevalence of vertebral fracture [24.4% versus 11.8% in patients 41-50 years old (P = 0.05) and 1.9% in patients ≤ 40 years old (P = 0.04)]. No significant increase in the prevalence according to bone mineral density (BMD) reduction was observed, and 70% of fractures were diagnosed in nonosteoporotic patients. Older age [adjusted odds ratio 1.09; 95% confidence interval (CI) 1.03-1.13; P = 0.001] and steroid use (adjusted odds ratio 3.64; 95% CI 1.29-10.3; P = 0.01) were independently associated with vertebral fracture; no association was found with HIV- or highly active antiretroviral therapy (HAART)-related variables. CONCLUSIONS: A prevalence of vertebral fractures of 12.4% was observed in our HIV-positive cohort. Given that two-thirds of fractures occurred in nonosteoporotic patients, spine X-ray may be considered in patients at increased risk, irrespective of BMD; that is, in elderly patients and/or patients using steroids.

Induced first abortion rates before and after HIV diagnosis: results of an Italian self-administered questionnaire survey carried out in 585 women living with HIV.

OBJECTIVES: The aim of the study was to investigate whether HIV diagnosis affected reproductive planning over time and to assess independent predictors of abortion overall and following HIV diagnosis. METHODS: Donne con Infezione da HIV (DIDI) is an Italian multicentre study based on a questionnaire survey carried out in 585 HIV-positive women between November 2010 and February 2011. The incidence and predictors of abortion were measured by person-years analysis and Poisson regression. RESULTS: The crude incidence rate of abortion was 18.8 [95% confidence interval (CI) 16.5-21.4] per 1000 person-years of follow-up (PYFU). Compared with women who terminated their pregnancy before HIV diagnosis, women who terminated their pregnancy after HIV diagnosis but before 1990 showed a 2.56-fold (95% CI 1.41-4.65) higher risk. During 1990-1999 and 2000-2010, HIV diagnosis was not significantly associated with outcome [adjusted rate ratio (ARR) 0.93 (95% CI 0.55-1.59) and ARR 0.69 (95% CI 0.32-1.48), respectively]. Age [ARR 0.96 (95% CI 0.94-0.99) per 1 year older] and injecting drug use [ARR 1.38 (95% CI 0.98-1.94)] were found to be predictors of abortion overall. After HIV diagnosis, being on combination antiretroviral therapy [ARR 0.54 (95% CI 0.28-1.02)], monthly income < €800 [ARR 1.76 (95% CI 0.99-3.12)], younger age [ARR 0.95 (95% CI 0.91-1.00) per 1 year older] and fear of vertical transmission [ARR 1.95 (95% CI 1.04-3.67)] were found to be independently associated with abortion. CONCLUSIONS: We observed a higher incidence of abortion compared with data available for the general Italian population. Awareness of HIV diagnosis was predictive of abortion only in the 1980s. Women with HIV infection are still worried about vertical HIV transmission. Interventions promoting HIV screening among women who plan to have an abortion and informative counselling on motherhood planning in the setting of HIV care are needed.

Two different patterns of mutations are involved in the genotypic resistance score for atazanavir boosted versus unboosted by ritonavir in multiple failing patients.

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 >or= 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 (>or= 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 chi(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 x 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 >or= 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 x 10(-8)) were most strongly associated with VR (VR: 83.3%, 66.7%, 5.9%, 0% of patients with 0, 1/2, 3, and >or= 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.

Women facing HIV. Key question on women with HIV infection: Italian consensus workshop.

A panel of leading Italian specialists in infectious diseases, obstetrics and gynaecology met in a national consensus workshop on women facing HIV to review critical aspects and discuss recommendations for selected key questions on four issues: (1) women and highly active antiretroviral therapy (HAART): access to care and adherence to therapy, side effects and drug-drug interaction; (2) HIV-infected pregnant women: prevention of mother to child transmission; (3) desire for children among women living with HIV: assisted reproduction; (4) sexually transmitted diseases and genital disturbances. The method of a nominal group meeting was used, and recommendations were graded for their strength and quality of evidence using a system based on the one adopted by the Infectious Diseases Society of America. Main conclusions are summarized and critically discussed, and some of the most recent data supporting recommendations are provided.

Cardiovascular adverse events during treatment with darunavir-based regimens in an Italian observational study.

Background: The protease inhibitor (PI) darunavir (DRV) has proven to be highly effective and well tolerated for HIV treatment. The DAD (Data collection on Adverse Effects of Anti-HIV Drugs) cohort showed an increased 5-year cumulative cardiovascular (CV) risk in patients given various PIs, including DRV, whereas two other recent studies found no association between DRV and CV diseases. Methods: We performed a post-hoc analysis of CV adverse events (CVAEs) in an Italian cohort, the TMC114-HIV4042 observational study, where 875 patients treated with ritonavir-boosted DRV-based regimens were followed for a total of 1,566 patient-years. Results: We observed 23 CVAEs of any type, including 17 [12 (95%CI, 7-19) per 1,000 patient-years] primary; 14 [10 (95%CI, 5-17) per 1,000 patient-years] were primary Framingham-type general CVAEs, close to what expected according to the Framingham algorithm based on traditional risk factors. Age and systolic blood pressure (SBP) at the time of study enrolment were the only relevant (p<0.01) independent predictors of CVAEs in all models; patients with any CVAE were on average 10 years older and had an SBP 14 mmHg higher than patients without CVAEs. When controlling for age and SBP, the association with other traditional factors, including serum lipids, and with HIV-specific factors was not statistically significant (p>0.05). Models that also adjusted for previous ARV exposure showed no statistically significant association between any-type CVAEs and either DRV doses, 1,200 or 800 mg/daily (as also suggested by propensity score stratification), or previous DRV exposure duration. Conclusion : We found no evidence of a relationship between DRV use and increased CV risk.

Predictive factors of vascular intima media thickness in HIV-positive subjects.

BACKGROUND: The predictive factors of intima media thickness (IMT) in the HIV-infected population are still poorly understood. PATIENTS AND METHODS: We studied three groups of subjects, aged 30-50 years, to find potential predictive factors of carotid and/or femoral thickening (IMT > 1 mm in at least one area): healthy controls (G1, n = 54), HIV-infected naive (G2, n = 53) and highly active antiretroviral treatment (HAART)-treated subjects (G3, n = 133). All the subjects underwent ultrasonography of the carotid and femoral vessels to evaluate IMT. RESULTS: Demographic characteristics of the three groups were comparable, except for gender (G1 had a higher percentage of females) and lipid levels (higher in G3). A total of 115 subjects (47.9%) had carotid and/or femoral IMT: 26 in G1 (48.1%), 21 in G2 (39.6%) and 68 in G3 (51.1%). Independent predictive factors of carotid and/or femoral IMT were older age (OR: 2.81, 95% CI: 1.95-4.04, P < 0.01, for each additional 5 years), triglycerides >or=150 mg/dL (OR: 2.66, 95% CI: 1.27-5.57, P < 0.001), serum glucose >or=110 mg/dL (OR: 5.24, 95% CI: 1.02-27.05, P = 0.04), high homocysteinaemia (OR: 2.75, 95% CI: 1.17-6.46, P = 0.02) and high body mass index (OR: 1.10, 95% CI: 1-1.22, P = 0.05 for each additional unit); females had a lower risk (OR: 0.38, 95% CI: 0.18-0.79, P < 0.01 versus males). HAART use was not associated with IMT (OR: 0.64, 95% CI: 0.27-1.53, P = 0.32 and OR: 0.80, 95% CI: 0.30-2.13, P = 0.20 for G3 and G2 versus G1, respectively). CONCLUSIONS: This study demonstrates that traditional risk factors for cardiovascular diseases overshadow the role of HAART in determining premature vascular lesions.

Effect of radio-opaque filler on biodegradable stent properties.

The effect of the addition of a radio-opaque filler, barium sulfate (BaSO(4)), on the mechanical properties of a biodegradable amorphous polymer film (poly-lactic-co-glycolic acid, PLGA) was studied, as a function of degradation. With up to about 18% loading (v/v), the modulus of the filled polymer increases; beyond this concentration, agglomerates are formed. The filled systems are also radio-opaque, over a thickness range of 0.07-0.19 mm in stent form (helicoidal). These stents were then immersed in phosphate buffer pH 7.4 at 37(o)C for 2 weeks. The radial strength of stent was measured by using a compression test. It was found that filler-loaded stent (FS) increased in radial strength by about 4 times (14.95 +/- 1.20 N/mm) compared to the unfilled stent (UFS). However, both samples lost radial strength as the polymer degraded in buffer, but FS retained 60% (9.05 +/- 0.07 N/mm) of its strength after 2 weeks whereas only 36% (1.39 +/- 1.04 N/mm) was retained for UFS. Moreover, UFS lost its helical shape after 3 weeks. The findings have implications for optimization of degradable stent formulations.

AIDS-defining diseases in 250 HIV-infected patients; a comparative study of clinical and autopsy diagnoses.

OBJECTIVE: To evaluate the correlation between clinical and autopsy findings in 250 AIDS patients. METHODS: Clinical and autopsy diagnoses of AIDS-defining diseases in 250 AIDS patients who died in Milan between May 1984 and February 1991 were compared. RESULTS: Pneumocystis carinii (PCP) and oesophageal candidiasis were the most frequent clinical diagnoses, while cytomegalovirus (CMV) infection was observed in almost half of the autopsies. Forty-seven per cent of the diseases found at autopsy had not been diagnosed during life; CMV infection, mycoses, HIV-specific brain lesions, cerebral lymphomas and progressive multifocal leukoencephalopathy (PML) had a higher rate of non-diagnosis in life. CMV visceral infection accounted for the majority of the diseases not recognized in life. In contrast, clinically diagnosed PCP, oesophageal candidiasis and, to a lesser degree, brain toxoplasmosis were often not found at autopsy, possibly indicating a significant rate of recovery and prevention of relapse. Finally, bacterial pneumonia and sepsis, although not AIDS indicator diseases, were observed in approximately one-third of the autopsies. CONCLUSION: Considerable differences in the frequency and type of the AIDS-defining diseases diagnosed during life and at post mortem were found.

Rheumatoid factors and circulating immune complexes in HIV-infected individuals.

We studied serological aspects of autoimmunity in patients with AIDS, AIDS-related complex (ARC) and in individuals at risk for AIDS. Immunoglobulin (Ig) M, IgG and IgA rheumatoid factors (RF) were quantified by enzyme-linked immunosorbent assay (ELISA), Ig by radial immunodiffusion, and circulating immune complexes (CIC) by the CIC-conglutinin and CIC-complement 1q (C1q) assays. Mean IgM RF levels were normal in AIDS patients, but those of ARC patients were higher and more frequent than the levels defined by agglutination methods. Similar observations were made for intravenous drug users (IVDU) and for both HIV-seropositive and HIV-seronegative homosexual men. Mean IgG RF levels were normal in AIDS and ARC patients but high in homosexual men and, to a lesser degree, in IVDU. IgA RF levels were high in many AIDS and ARC patients, in homosexual men, and in haemophiliac and control groups. The selective increase of the IgA isotype in AIDS was confirmed by the Ig results, which also showed an IgG increase in all groups. IgM were mainly high in people with ARC. CIC were detected in 68% of ARC patients by both methods, and in 55% of AIDS patients by CIC-Clq. A high incidence of positive samples in all at-risk populations, but particularly in seronegative individuals, was observed using CIC-conglutinin. CIC-C1q also revealed larger amounts of CIC in HIV-seronegative individuals, mainly in homosexual men. The study of these humoral aspects of autoimmunity provides useful information on the impairment of B-cells in patients with AIDS and ARC.(ABSTRACT TRUNCATED AT 250 WORDS)

Predictors of cytomegalovirus disease, natural history and autopsy findings in a cohort of patients with AIDS.

OBJECTIVE: To identify the predictors of acquiring cytomegalovirus (CMV) disease, and to describe natural history, therapeutic management and autopsy findings in affected patients. DESIGN: Observational study of a consecutive cohort of AIDS patient diagnosed and followed in the same institution. METHODS: All of the patients with CMV were included. Statistical analyses were performed to establish the risk of acquiring the disease at or after AIDS presentation, survival, and the occurrence and time of relapses in relation to maintenance therapy. The presence of CMV infection at autopsy was also investigated. RESULTS: CMV disease was diagnosed in 304 (24.8%) out of 1,227 patients, its incidence increasing according to the year of AIDS diagnosis. Women, homosexual men, patients given zidovudine and Pneumocystis carinii pneumonia (PCP) prophylaxis before AIDS, and severely immunodepressed patients were at higher risk for the disease. CMV disease was an independent factor of worse survival (hazard ratio, 1.7 versus PCP; 95% confidence intervals, 1.28-2.13). Patients untreated during the acute phase had a 4.3 higher risk of dying than those treated. Relapses occurred less frequently and later in patients given continuous maintenance treatment (23 out of 113; 17 months) than in untreated patients (13 out of 16; 3 months) or those given discontinuous therapy (22 out of 40; 7 months), whereas survival was independent from treatment. CMV infection was found in 97 out of 134 patients at autopsy, but was unassociated with relapse. CONCLUSIONS: CMV is a severe disease whose frequency is higher in severely immunodepressed patients. Continuous treatment leads to a lower relapse rate even if it does not change survival or eradicate the infection.

Clinical outcome and predictive factors of failure of highly active antiretroviral therapy in antiretroviral-experienced patients in advanced stages of HIV-1 infection.

OBJECTIVE: To verify the effectiveness of highly active antiretroviral therapy (HAART) and to identify any factors predictive of clinical outcome in a clinical setting. DESIGN: Observational study. METHODS: Treatment failure (i.e., the occurrence of new or recurrent AIDS-defining events, death or any definitive discontinuation) and the course of CD4+ cell counts and HIV RNA copies were evaluated in 250 heavily pretreated HIV-infected patients starting HAART [153 with indinavir (IDV), 55 with ritonavir (RTV), 43 with saquinavir (SQV)]. Univariate and multivariate analyses were performed to identify predictors of worse outcome. RESULTS: During a median follow-up of 8 months, 75 patients (30%) had treatment failure because of the occurrence of an AIDS-defining event or death (n = 24), inefficacy (n = 24), or severe intolerance (n = 27). Twenty new and six recurrent AIDS-defining events, and nine deaths occurred (six out of 20 AIDS-defining events and two out of nine deaths within 1 month of treatment). CD4+ counts were above 200 x 10(6)/l at AIDS diagnosis in only two patients. None of the SQV patients, 12 (7.8%) of the IDV patients, and 15 (27.3%) of the RTV-treated patients were considered non-compliant. The SQV-containing regimens independently correlated with treatment failure (relative risk, 2.46; 95% confidence interval, 1.20-5.03; versus IDV). Low compliance partially determined outcome in RTV-treated patients; both severe immunodepression and AIDS at baseline were predictive of treatment failure. There was a 10-fold increase in CD4+ cell counts in the patients treated with IDV and RTV; the best virological outcome occurred in IDV-treated patients, with 68.4% of patients showing undetectable HIV RNA copies after 6 months. CONCLUSIONS: HAART was effective in 70% of patients; low compliance and previous AIDS diagnosis represented predictive factors of therapy failure.

CD4 cell counts at the third month of HAART may predict clinical failure.

OBJECTIVE: To evaluate the influence of immunological and virological markers on clinical outcome in patients receiving their first highly active antiretroviral therapy (HAART) regimen. DESIGN AND METHODS: Observational study of 585 patients initiating HAART in a clinical setting. Clinical failure was defined as the occurrence of new or recurrent AIDS-defining events or death, and was analysed by means of intention-to-treat, univariate and multivariate analyses. An adjusted Cox regression model was used to evaluate the effect of 3-month CD4 cell counts on clinical outcome. RESULTS: Clinical failure occurred in 55 patients (9.4%) during a median follow-up of 483 days (range 33-1334 days): 45 new AIDS-defining events (ADEs) in 38, ADE recurrence in six, and death in 11. Twenty-four of the 45 new ADEs (53.4%) occurred during the first 3 months of HAART, and 11 of 45 (24.4%) in the presence of CD4 cell counts > 200 x 10(6) cells/l. The mean (median, range) CD4 counts were 144 x 10(6) cells/l (128, 4-529) in patients with and 322 x 10(6) cells/l (288, 14-1162) in patients without clinical failure (P < 0.0001). Moreover, the proportion of patients with mean CD4 cell counts < 200 x 10(6) cells/l was higher in those experiencing subsequent clinical failure (X2 test: 26.75; P < 0.00001). Multivariate analysis showed that baseline CD4 cell counts < 50 x 10(6) cells/l and AIDS at enrolment predicted failure; after adjusting for 3-month CD4 cell counts, this marker was the only one independently associated with clinical failure (hazard risk, 4.79; 95% confidence interval, 1.40-16.47). CONCLUSIONS: The 3-month immunological response is a reliable predictor of long-term clinical outcome.

Nephrolithiasis and hydronephrosis in an HIV-infected man receiving tenofovir.

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.

Peripheral nerve regeneration by microbraided poly(L-lactide-co-glycolide) biodegradable polymer fibers.

Tiny tubes with fiber architecture were developed by a novel method of fabrication upon introducing some modification to the microbraiding technique, to function as nerve guide conduit and the feasibility of in vivo nerve regeneration was investigated through several of these conduits. Poly(L-lactide-co-glycolide) (10:90) polymer fibers being biocompatible and biodegradable were used for the fabrication of the conduits. The microbraided nerve guide conduits (MNGCs) were characterized using scanning electron microscopy to study the surface morphology and fiber arrangement. Degradation tests were performed and the micrographs of the conduit showed that the degradation of the conduit is by fiber breakage indicating bulk hydrolysis of the polymer. Biological performances of the conduits were examined in the rat sciatic nerve model with a 12-mm gap. After implantation of the MNGC to the right sciatic nerve of the rat, there was no inflammatory response. One week after implantation, a thin tissue capsule was formed on the outer surface of the conduit, indicating good biological response of the conduit. Fibrin matrix cable formation was seen inside the MNGC after 1 week implantation. One month after implantation, 9 of 10 rats showed successful nerve regeneration. None of the implanted tubes showed tube breakage. The MNGCs were flexible, permeable, and showed no swelling apart from its other advantages. Thus, these new poly(L-lactide-co-glycolide) microbraided conduits can be effective aids for nerve regeneration and repair and may lead to clinical applications.

Predictive role of the three-month CD4 cell count in the long-term clinical outcome of the first HAART regimen.

The aim was to evaluate whether the three-month CD4 cell counts are a reliable predictor of the long-term clinical outcome of HAART-treated patients, by an observational study of 585 patients initiating HAART in a clinical setting. Clinical failure was defined as the occurrence of new or recurrent AIDS-defining events or death, and was analysed by means of intention-to-treat, univariate and multivariate analyses. An adjusted Cox regression model was used to evaluate the effect of three-month CD4+ counts on clinical outcome. Clinical failure occurred in 65 patients (11.1%) during a median follow-up of 31 months (1-65) as a result of new AIDS-defining events (ADEs) in 48 patients, ADE recurrence in six, and death in 11. The mean (median; range) CD4+ counts were 156/microL (155; 4--529) in patients with and 362/microL (326; 18--1162) in patients without clinical failure (P < .0001). Moreover, the proportion of patients with mean CD4+ counts < 200 microL was higher in those experiencing subsequent clinical failure (chi2: 41.11; P< .00001). Multivariate analysis showed that baseline CD4+ counts < 50 microL, HIV-RNA > 100,000 copies/mL and AIDS at baseline predicted failure; after adjusting for three-month CD4+ counts, this marker was the only one independently associated with clinical failure (HR 2.93; 95% Cl: 1.16--7.38). The three-month immunologic response is a reliable predictor of long-term clinical outcome.

Body habitus alterations in HIV-infected women treated with combined antiretroviral therapy.

Fat distribution alterations are among the most frequent and unexpected side effects of combined antiretroviral therapy. They may occur in patients receiving protease inhibitor-containing regimens and those treated with combinations of only nucleoside reverse transcriptase inhibitors. The broad spectrum of body fat alterations, which are variably associated with metabolic abnormalities, raises the question as to whether they represent different components of the same syndrome or are manifestations of different pathogenetic mechanisms. Recent clinical evidence is consistent with a higher risk of developing body fat alterations in females. We here report three different aspects of body habitus changes in women treated with various antiretroviral regimens and describe their short-term follow-up. We also discuss the possible pathogenetic implications and the role of different drug classes according to present knowledge.

[Not Available]. / Toxoplasmosi cerebrale nella sindrome da immunodeficienza acquisita.

UNLABELLED: Toxoplasmic encephalitis (TC) is the most common opportunistic infection of the Central Nervous System (CNS) in patients with the acquired immunodeficiency syndrome (AIDS). In order to investigate its clinical course, we reviewed the records of 133 patients with AIDS and central nervous system (CNS) toxoplasmosis treated at the Clinic of Infectious Diseases, University of Milan, between 1987 and 1992. The most common presenting symptoms were headache, confusion, disorientation and fever. Focal neurologic deficits were present in more than half of cases. Median CD4+ cell count at presentation was 65 per cubic millimeter. 25 (19%) out of 133 patients diagnosed with TC had undetectable anti-T. gondii IgG antibodies using an Elisa technique. Enhancing lesions on Computered Tomography (CT) were demonstrated in 119 (90%) patients. Solitary lesions were present in 26 cases; edema was evident in 19 patients. A complete clinica! and neuroradiological improvement after the acute episode was obtained in 126 (95%) of the cases. Adverse drug reactions occurred in 40 (30%) cases. Relapses occurred in 18/92 patients after a median time of 6 months. IN CONCLUSION: TC occurs in advanced stages of human immunodeficiency syndrome, and the absence of anti-T.gondii antibodies does not exclude the diagnosis. The clinical and radiographic response to therapy is usually rapid, but long-term treatment is frequently limited by adverse drug effects.