Antiretroviral treatment strategies and immune reconstitution in treatment-naïve HIV-infected patients with advanced disease.

Treatment-naïve advanced HIV-infected patients have a lower life expectancy than those treated early with highly active antiretroviral therapy (HAART). Early treatment allows greater immunological recovery, a reduction of AIDS progression, a reduced risk of related illnesses, and lower mortality compared with HAART initiation in advanced disease. Given the numbers with advanced disease worldwide and the high cost of care, strategies encouraging early detection may be life saving and cost effective. Factors associated with increased clinical progression include higher baseline HIV viral load and older age, emphasizing the need for early viral load suppression. HAART initiation faces many challenges; interactions between antiretroviral agents and drugs used to treat life-threatening opportunistic infections may cause subtherapeutic antiretroviral exposure and the development of resistance or supratherapeutic levels resulting in adverse effects. Immune reconstitution inflammatory syndrome can be another cause of suboptimal outcomes. The management of patients with advanced HIV infection should include rapid short-term immune reconstitution to limit the risk of disease progression plus aggressive antiviral treatment to achieve rapid virological suppression. Clear evidence on the optimal regimen and agents to use to target advanced HIV disease is lacking. Therefore, antiretroviral treatment for these patients has to be carefully tailored to the individual according to many variables

60PV Related Lesions in HIV Positive Subjects on HAART: Study of Viral Markers of Cervical Neoplasia Progression

Methods HIV pos women (N = 410) were followed since 1995 in a longitudinal study. Each one undergo periodic (6–12 months) colposcopy, PAP smear, biopsy if needed, and cervical sampling for HPV testing. HIV related parameters (CD4, HIV-RNA, ART) are recorded and related to cervical disease. HPV typing is performed by reverse hybridisation assays, viral load by in-house real time PCR and viral expression by E6/E7 mRNA detection. The Mann-Whitney rank sum test for non-parametric data and the association between discrete variables by Chi-square test of Fisher exact test were applied

HIV-1 Tropism Test Evaluation: Assessment and Clinical Implications

CCR5 and CXCR4 chemokines receptors are critical coreceptors for the binding of HIV to specific host cells. Guidelines recommend its assessment in case of virological failure or before prescription of CCR5 inhibitors. Strategies to assess viral tropism may be divided into phenotypic and genotypic assays; registrative trials of CCR5 inhibitors used phenotypic assay, but recently genotypic ones have been used in clinical practice. The presence of CXCR4 is increasing in naïve patients, with both acute and chronic HIV-1 infections; this coreceptor usage is associated with CD4 depletion. The assessment of viral tropism should be considered in every stage of HIV-1 infection

Budget impact analysis of the use of daclatasvir in Italy for the treatment of Hepatitis C Virus (HCV) genotype 3 patients

BACKGROUND: Hepatitis C Virus (HCV) infection represents a global health problem, leading to chronic cirrhosis, hepatocellular carcinoma (HCC), hepatic decompensation and liver transplant. The aim of the study was the evaluation of the impact on the budget of the Italian National Health Service (INHS) of the use of Daclatasvir (DCV) for the treatment of HCV genotype 3 in patients with advanced fibrosis.METHODS: An analytical decision model with a five year time horizon was implemented. Two scenarios were considered: a. 100% of market share for Interferon (INF-α)+Ribavirin (RBV)+Sofosbuvir (SOF) for 12 weeks; b. SOF+DCV+RBV for 24 weeks with annual market shares of 50% in 2015 and 2016, 55% in 2017 and 2018, 60% in 2019, and INF-α+RBV+SOF for 12 weeks with the remaining market shares. Every annual cycle a percentage of patients equal to the effectiveness of the antiviral treatment reach a sustained virologic response and during the first year of treatment patients may experience treatment related adverse events. The costs considered (2015) are those of the antiviral therapy, and direct medical costs for health state and adverse events management. Univariate and multivariate sensitivity analyses were performed.RESULTS: DCV would lead to an increase of the costs for the INHS (year 1 +21.31 millions, year 2 +21.35 millions, year 3 + 23.37 millions, year 4 + 23.26 millions and year 5 +16.37 millions). The sensitivity analysis confirmed the robustness of the results.CONCLUSIONS: The use of DCV is likely to have a short term impact on the INHS budget increasing resources use compared to the sole use of INF-α+RBV+SOF. However, a trend of reduction of the costs increase is observed due to the management of health states and adverse events which may lead to the possibility to reduce costs in the long term

Coronaviridae and SARS-associated Coronavirus Strain HSR1

During the recent severe acute respiratory (SARS) outbreak, the etiologic agent was identified as a new coronavirus (CoV). We have isolated a SARS-associated CoV (SARS-CoV) strain by injecting Vero cells with a sputum specimen from an Italian patient affected by a severe pneumonia; the patient traveled from Vietnam to Italy in March 2003. Ultrastructural analysis of infected Vero cells showed the virions within cell vesicles and around the cell membrane. The full-length viral genome sequence was similar to those derived from the Hong-Kong Hotel M isolate. By using both real-time reverse transcription–polymerase chain reaction TaqMan assay and an infectivity plaque assay, we determined that approximately 360 viral genomes were required to generate a PFU. In addition, heparin (100 μg/mL) inhibited infection of Vero cells by 50%. Overall, the molecular and biologic characteristics of the strain HSR1 provide evidence that SARS-CoV forms a fourth genetic coronavirus group with distinct genomic and biologic features

Sustained virological response after ten days of triple anti-hepatitis C virus (HCV) therapy with telaprevir plus pegylated interferon and ribavirin in an HIV/HCV co-infected cirrhotic woman

The introduction of first-generation protease inhibitors for the treatment of chronic hepatitis C in subjects infected with hepatitis C virus (HCV) genotype 1 has significantly improved the sustained virological response (SVR) rate. As liver cirrhosis reduces the probability of achieving SVR, current guidelines discourage response-guided therapy in cirrhotic patients. We report the first case of a cirrhotic woman with chronic HCV and HIV co-infection achieving virological response after an ultra-short course of therapy. A 40-year-old HIV/HCV co-infected woman with compensated liver cirrhosis was treated with anti-HCV triple therapy containing telaprevir plus pegylated interferon and ribavirin. Baseline plasma HCV RNA was 3.6 log IU/ml and transaminases were within the normal range. She harboured IL28B rs12979860 C/C alleles. Ten days after starting therapy, the patient stopped treatment because of mild anorexia and nausea. Virological response was detected at treatment discontinuation and was maintained up to 24 weeks. This case describes an unexpected SVR after a 10-day course of antiviral therapy in a cirrhotic HIV/HCV co-infected woman presenting positive predictive factors for a response (low viral load, IL28B genotype). Nonetheless, there is no evidence to suggest a shorter duration of treatment in this subset of patients

Lopinavir/ritonavir + tenofovir Dual Therapy versus Lopinavir/ritonavir-Based Triple Therapy in HIV-Infected Antiretroviral Naïve Subjects: The Kalead Study

Purpose: With reference to the clinical need for simple, potent and safe antiretroviral regimens, Lopinavir/ ritonavir + tenofovir (LPV/r+TDF) two-drug initial regimen was studied for efficacy and safety in HIV-infected patients. Methods: Kalead was a prospective, randomized, open-label, 72-week trial comparing LPV/r+TDF versus LPV/r+ two (non-TDF) NRTIs in HIV-infected adults with HIV-RNA >400 copies/mL and any CD4 count. Primary endpoint was the proportion of subjects with HIV-RNA <50 copies/mL at week 72. Results: 152 subjects were randomized. Eleven (15.3%) subjects in the dual therapy arm and seven (8.8%) in the triple therapy arm who did not achieve HIV-RNA <50 copies/mL at least twice prior to and including week 24 were discontinued per protocol (p=0.21). Overall discontinuations were 41.7% and 43.8% in the dual therapy and triple therapyarms. At week 72, 51.4% and 52.5% of subjects in the dual therapy and triple therapy arms had HIV-RNA <50 copies/mL (p=0.89, ITT, NC=F). In an on-treatment analysis, 87.2% and 93.0% of subjects in the dual therapy and triple therapy arms had a HIV-RNA <50 copies/mL (p=0.47). Over 72 weeks of therapy, mean CD4 count increases were greater in the dual therapy arm (+332 cells/mm3 vs +234 cells/mm3, p=0.01). Adherence, overall incidence of adverse events, drugrelated adverse events, and Grade I-IV laboratory abnormalities were comparable between the two arms. Conclusions: A two-drug regimen of LPV/r+TDF suggests sufficient safety and efficacy warranting further investigation. However, high discontinuation rate and study design limitations restrict overall interpretation

Factors Associated with the Development of Opportunistic Infections in HIV-1-Infected Adults with High CD4+ Cell Counts: A EuroSIDA Study

BackgroundLimited data exist on factors predicting the development of opportunistic infections (OIs) at higher-than-expected CD4+ cell counts in human immunodeficiency virus (HIV) type 1-infected adults MethodsMultivariate Poisson regression models were used to determine factors related to the development of groups of OIs above their respective traditional upper CD4+ cell count thresholds: group 1 (⩾100 cells/μL), OIs caused by cytomegalovirus, Mycobacterium avium complex, and Toxoplasma gondii; group 2 (⩾200 cells/μL), Pneumocystis pneumonia and esophageal candidiasis; and group 3 (⩾300 cells/μL), pulmonary and extrapulmonary tuberculosis ResultsIn groups 1, 2, and 3, 71 of 9219, 125 of 7934, and 36 of 7838 patients, respectively, developed ⩾1 intragroup OI. The strongest predictor of an OI in groups 1 and 2 was current CD4+ cell count (for group 1, incidence rate ratio [IRR] per 50% lower CD4+ cell count, 5.37 [95% confidence interval {CI}, 3.71-7.77]; for group 2, 4.28 [95% CI, 2.98-6.14]). Injection drug use but not current CD4+ cell count predicted risk in group 3. Use of antiretroviral treatment was associated with a lower incidence of OIs in all groups, likely by reducing HIV-1 RNA levels (IRR per 1-log10 copies/mL higher HIV-1 RNA levels for group 1, 1.50 [95% CI, 1.15-1.95]; for group 2, 1.68 [95% CI, 1.40-2.02]; and for group 3, 1.89 [95% CI, 1.40-2.54]) ConclusionAlthough the absolute incidence is low, the current CD4+ cell count and HIV-1 RNA level are strong predictors of most OIs in patients with high CD4+ cell count

O415 Efficacy and safety of 48-week maintenance with QD ATV vs ATV/r (both + 2NRTIs) in patients with VL <50 c/mL after induction with ATV/r + 2NRTIs: study AI424136

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