two drug regimens with dolutegravir plus rilpivirine or lamivudine in hiv 1 treatment naive virologically suppressed patients latest evidences from the literature on their efficacy and safety

Abstract Objectives In HIV-positive population, a paradigm shift from three-drug regimens to dolutegravir-based two-drug regimens as both initial and switch treatment approach is beginning to take place, virologically supported by the availability of new, potent drugs with high genetic-barrier that allow to overcome, at least in certain conditions, the dogma of three-drug regimens in HIV-effective therapy. Indeed, there is increasing evidence on their excellent and sustained long-term effectiveness and safety, that this manuscripts aims to review. Methods This review includes the most recent results on dolutegravir plus rilpivirine or lamivudine two-drug regimens from randomized clinical trials, meta-analyses and real-life studies, including relevant data presented at international conferences up to August 2019. Results As initial treatment strategy, dolutegravir plus lamivudine shows high efficacy and safety over 96 weeks in 1441 patients from GEMINI 1&2 phase III non-inferiority trials. In SWORD 1&2 trials, conducted in virologically suppressed patients, switching to once-daily dolutegravir plus rilpivirine maintained efficacy over 148 weeks; similarly, in TANGO trial no confirmed virological withdrawals were observed with dolutegravir/lamivudine through week 48. Consistent results were observed in real-life cohorts. No emergent dolutegravir-resistant virus has ever been reported in a patient in whom dolutegravir was prescribed in the context of such two-drug regimens. Switching to once-daily dolutegravir plus rilpivirine or lamivudine was generally well tolerated, and associated with favorable renal and bone safety. Conclusions The results so far available support dolutegravir-based two-drug regimens as excellent treatment options for adults with HIV-1 infection, either naive or already virologically-suppressed on their current antiretroviral regimen

Selected amino acid mutations in HIV-1 B subtype gp41 are Associated with Specific gp120V3 signatures in the regulation of Co-Receptor usage

<p>Abstract</p> <p>Background</p> <p>The third variable loop (V3) of the HIV-1 gp120 surface protein is a major determinant of cellular co-receptor binding. However, HIV-1 can also modulate its tropism through other regions in gp120, such as V1, V2 and C4 regions, as well as in the gp41 protein. Moreover, specific changes in gp41 are likely to be responsible for of damage in gp120-CCR5 interactions, resulting in potential resistance to CCR5 inhibitors.</p> <p>In order to genetically characterize the two envelope viral proteins in terms of co-receptor usage, we have analyzed 526 full-length <it>env </it>sequences derived from HIV-1 subtype-B infected individuals, from our and public (Los Alamos) databases. The co-receptor usage was predicted by the analysis of V3 sequences using Geno2Pheno (G2P) algorithm. The binomial correlation phi coefficient was used to assess covariation among gp120_V3and gp41 mutations; subsequently the average linkage hierarchical agglomerative clustering was performed.</p> <p>Results</p> <p>According to G2P false positive rate (FPR) values, among 526 env-sequences analyzed, we further characterized 196 sequences: 105 with FPR <5% and 91 with FPR >70%, for X4-using and R5-using viruses, respectively.</p> <p>Beyond the classical signatures at 11/25 V3 positions (S11S and E25D, R5-tropic viruses; S11KR and E25KRQ, X4-tropic viruses), other specific V3 and gp41 mutations were found statistically associated with the co-receptor usage. Almost all of these specific gp41 positions are exposed on the surface of the glycoprotein. By the covariation analysis, we found several statistically significant associations between V3 and gp41 mutations, especially in the context of CXCR4 viruses. The topology of the dendrogram showed the existence of a cluster associated with R5-usage involving E25D_V3, S11S_V3, T22A_V3, S129DQ_gp41and A96N_gp41signatures (bootstrap = 0.88). Conversely, a large cluster was found associated with X4-usage involving T8I_V3, S11KR_V3, F20IVY_V3, G24EKR_V3, E25KR_V3, Q32KR_V3, A30T_gp41, A189S_gp41, N195K_gp41and L210P_gp41mutations (bootstrap = 0.84).</p> <p>Conclusions</p> <p>Our results show that gp120_V3and several specific amino acid changes in gp41 are associated together with CXCR4 and/or CCR5 usage. These findings implement previous observations that determinants of tropism may reside outside the V3-loop, even in the gp41. Further studies will be needed to confirm the degree to which these gp41 mutations contribute directly to co-receptor use.</p

Phylogenesis and Clinical Aspects of Pandemic 2009 Influenza A (H1N1) Virus Infection

During the spring of 2009, a new influenza A (H1N1) virus of swine origin emerged and spread worldwide causing a pandemic influenza. Here, 329 naso-pharyngeal swabs collected from patients with flu-like symptoms were analyzed by real-time PCR for the presence of H1N1 2009 pandemic virus. Twenty-five samples collected from immunocompetent and immunodepressed patients contained the H1N1 pandemic virus. Phylogenetic analysis of the hemagglutinin and neuraminidase genes showed no obvious differences in terms of similarity and/or homology between the sequences identified in immunocompetent individuals and those obtained from immunocompromised patients. Pre-existing clinical conditions may influence the outcome of H1N1 disease

Cytomegalovirus Glycoprotein B Genotype Distribution in Italian Transplant Patients.

Background: The cytomegalovirus (CMV) UL55 gene encodes for a glycoprotein implicated in virus pathogenesis. Based on UL55 polymorphism, CMV has been divided into 4 genotypes. Previous studies investigated the possible role of genotypes in the clinical outcome of infection in different categories of patients; however, few data are available, particularly in the transplant setting and Italian case records. Methods: Phylogenetic analysis through a maximum likelihood tree was used to evaluate the prevalence and distribution of CMV genotypes in whole blood specimens from 47 transplant patients and investigate the relation with demographic and clinical features. Results: Overall, 40.4% of patients were classified as single genotype (12.8% gB1, 23.4% gB2, 4.2% gB3); mixed genotypes were detected in 59.6%. Genotype 4 was detected only in mixed cases. In comparison to single genotypes, mixed genotypes were more frequently associated with a higher duration of DNA viremia and higher peak viral load. Conclusions: Mixed infections seem to be prevalent in Italian transplant patients; it is likely that mixed infections are more difficult to control by immunological response in comparison to single genotype infections. In this context, the genetic profile of infecting viruses and relation to clinical outcome should be investigated, also taking into account the CMV-specific cellular immune response

po 8580 treatment response among cameroonian adolescents receiving antiretroviral therapy in urban and rural settings preliminary findings from the ready study

BackgroundTransitioning from paediatric to adult healthcare requires successful antiretroviral treatment (ART) for adolescents living with HIV (ADLHIV). Implementing such a policy implies monitoring ART response and selecting for therapeutic options for ADLHIV in resource-limited settings (RLS) like Cameroon.MethodsThe Ready study (EDCTP-CDF-1027) is conducted amongst ART-experienced ADLHIV (10–19 years old) in the Centre region, Cameroon. WHO-clinical staging, CD4-counts and viraemia were determined; in case of virological failure [VF] (viraemia ≥1000 copies/ml), HIV drug resistance (HIVDR) and subtyping were performed, and p<0.05 considered significant.ResultsOut of 279 ADLHIV (212 urban vs 67 rural), the gender distribution was similar (54.5% female); median age was higher in urban (15 [IQR: 13–17] years) compared to rural (13 [IQR: 11–17] years), as well as the median duration on ART (7 [IQR: 3–10] years compared to 4 [IQR: 2–7] years, respectively); and the majority was on first-line ART (79.4% [162/204] urban vs 98.5% [66/67] rural, p<0.0004). Following treatment response, clinical failure (WHO-stage 3/4) was similarly low in both urban (5.7% [12/210]) and rural (4.5% [3/67]), p=0.938; CD4 increased similarly (p=0.298) from ART-initiation (370 cells/mm3[urban] vs 332 cells/mm3[rural]) to 6 years after initiation (938 cells/mm3[urban] vs 548 cells/mm3[rural]) and rate of immunodeficiency (<500 CD4 cells/mm3) was 41.0% (87/208) in urban vs 47.5% (29/61) in rural, p=0.428. VF was 43.2% (41/95) in urban vs 60.9% (14/23) in rural, p=0.126. Among nine (9) sequences available from those experiencing VF, overall HIVDR was found in 88.8%, with 77.7% NNRTI, 55.6% NRTI and 22.2% PI/r. All were HIV-1 group M, with 55.6% CRF02_AG, 22.0% F1 and 22.4% others.ConclusionADLHIV appear clinically asymptomatic, with considerable immune recovery overtime. Despite differences in ART duration between urban and rural settings, VF was similarly high, associated with HIVDR mainly to NNRTI-based regimens. Thus, NNRTI-sparing regimens might be highly convenient when transitioning ADLHIV to adult ART-regimens in RLS like Cameroon

Peroxynitrite decomposition catalyst prevents apoptotic cell death in a human astrocytoma cell line incubated with supernatants of HIV-infected macrophages

BACKGROUND: Oxidative stress has shown to contribute in the mechanisms underlying apoptotic cell death occuring in AIDS-dementia complex. Here we investigated the role of peroxynitrite in apoptosis occurring in astroglial cells incubated with supernatants of HIV-infected human primary macrophages (M/M). RESULTS: Flow cytometric analysis (FACS) of human cultured astrocytes shortly incubated with HIV-1-infected M/M supernatants showed apoptotic cell death, an effect accompanied by pronounced staining for nitrotyrosine (footprint of peroxynitrite) and by abnormal formation of malondialdehyde (MDA). Pretreatment of astrocytes with the peroxynitrite decomposition catalyst FeTMPS antagonized HIV-related astrocytic apoptosis, MDA formation and nitrotyrosine staining. CONCLUSIONS: Taken together, our results suggest that inibition of peroxynitrite leads to protection against peroxidative stress accompanying HIV-related apoptosis of astrocytes. Overall results support the role of peroxynitrite in HIV-related programmed death of astrocytes and suggest the use of peroxynitrite decomposition catalyst to counteract HIV-1-related neurological disorders

School in Italy: a safe place for children and adolescents

Background: During the first SARS-CoV-2 pandemic phase, the sudden closure of schools was one of the main measures to minimize the spread of the virus. In the second phase, several safety procedures were implemented to avoid school closure. To evaluate if the school is a safe place, students and staff of two school complexes of Rome were monitored to evaluate the efficacy of prevention measures inside the school buildings. Methods: Oral secretions specimens were collected from 1262 subjects for a total of 3431 samples, collected over a 3 months period. Detection of Coronavirus SARS-CoV-2 was performed by real-time PCR. Target genes were represented by E gene, RdRP/S gene and N gene. Results: Among the 3431 samples analyzed, just 16 sample resulted as positive or low positive: 1 sample in the first month, 12 samples in the second month and 3 in the third month. In each period of evaluation, all positive children attended different classes. Conclusions: Even if the school has the potential for spreading viruses, our preliminary results show the efficacy of the implementations undertaken in this setting to minimize virus diffusion. Our evidence suggests that school does not act as an amplifier for transmission of SARS-CoV-2 and can be really considered a safe place for students