"Values" in medical practice

n/

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

Minor mutations in HIV protease at baseline and appearance of primary mutation 90M in patients for whom their first protease-inhibitor ntiretroviral regimens failed

The association between minor mutations in human immunodeficiency virus (HIV) protease at baseline and development of common primary mutation 90M at virological failure (conferring some resistance to all protease inhibitors [PIs]) was evaluated in 93 previously drug-naive patients experiencing failure of their first PI-based antiretroviral regimens. In logistic regression analysis, the probability of accumulating a new 90M mutation at virological failure was associated with the presence at baseline of minor mutation 36I (naturally occurring in ∼25% of HIV clade B and in &gt;80% of HIV non-clade-B viruses) (adjusted odds ratio, 13.5 [95% confidence interval, 1.89–95.6]; P=.009) and, possibly, of 10I/V. This suggests a potential role for the presence of 36I at baseline in predicting the appearance of 90M at virological failure

Managing low-level HIV viraemia in antiretroviral therapy: a systematic review and meta-analysis

objective: HIV-1 management has advanced significantly with antiretroviral therapy (ART), yet challenges persist, including low-level HIV-1 viraemia (LLV). LLV presents a complex scenario, with varied definitions in the literature, reflecting uncertainties in its clinical interpretation. questions arise regarding the underlying mechanisms of LLV, whether it signifies ongoing viral replication or stems from other factors. this study aimed to systematically review strategies for LLV management, providing insights into optimal clinical approaches. methods: MEDLINE, EMBASE, cochrane library, web of science and canadian agency for drugs and technologies in health were searched for relevant literature on LLV management. We included studies published between 2004 and 2024, assessing interventions such as ART modification, genotypic resistance testing, adherence assessment, performing therapeutic drug monitoring, testing for chronic coinfections and assessing the viral reservoir via HIV DNA quantification. meta-analyses were conducted where feasible. results: the systematic review identified 48 eligible records. findings indicated limited evidence supporting the effectiveness of ART regimen modification in achieving virological suppression among individuals with LLV. however, studies assessing genotypic resistance testing revealed a significant association between resistance-associated mutations and virological suppression during LLV. adherence to ART emerged as a critical determinant of treatment efficacy, with interventions showing promise in achieving viral suppression. the clinical utility of therapeutic drug monitoring in managing LLV remained inconclusive. gaps in the literature were identified regarding follow-up scheduling, managing concurrent chronic infections and assessing inflammatory markers in LLV management. conclusions: While ART modification may not consistently achieve virological suppression, genotypic resistance testing may offer insights into treatment outcomes. adherence to ART emerged as a crucial factor, necessitating tailored interventions. however, further research is needed to elucidate the clinical utility of therapeutic drug monitoring and other management strategies. the study highlights the importance of ongoing research to refine therapeutic approaches and improve patient outcomes in LLV management. prospero registration number: CRD42024511492