BACKGROUND:we explored predictors of CD4/CD8 ratio improvement and optimal immunological recovery (OIR) after initiation of antiretroviral therapy(ART) in naïve people living with HIV (PLWH).
...METHODS:Retrospective multicenter study including naïve PLWH starting ART with 2NRTIs + one InSTI or NNRTI or PI. PLWH were followed from the time of ART initiation (baseline) to the discontinuation of first-line regimen, virological failure, death or loss to follow-up. Estimated incidence and predictors of time to CD4/CD8 ratio normalization (defined as ≥1) and OIR (defined as CD4/CD8 ratio≥1 plus CD4≥500cells/µL plus CD4%≥30%) were explored by Kaplan Meier curves and Cox regression analysis.
RESULTS:Overall, 1428 PLWH (77.8% males, median age 39 years, 55.1% with positive CMV antibodies, median HIV-RNA 4.80 log copies/mL, median CD4 323cells/µL, median CD4/CD8 ratio 0.32) were included, of which 21.5%(n=307), 44.5%(n=636) and 34%(n=485) treated with InSTI-, PI- and NNRTI-based regimens, respectively. The estimated proportion of CD4/CD8 normalization and OIR at 36 months was 38.6% and 32.9%, respectively. Multivariate analysis showed that InSTI-based regimens had a higher probability of CD4/CD8 ratio normalization and OIR both in the total population(p<0.001 versus PI) and in advanced naïve PLWH (p≤0.001 versus PI and NNRTI). Moreover, subjects with positive CMV serology showed a lower probability of CD4/CD8 ratio normalization and OIR(p<0.001).
CONCLUSIONS:InSTI-based regimens showed a better immune recovery, suggesting that the type of first-line ART can influence immune reconstitution. PLWH with positive CMV serology showed an increased risk of suboptimal immune recovery.
Functional tricuspid regurgitation (FTR) is the most frequent etiology of tricuspid valve pathology in Western countries. In the last years, many investigators have reported evidence in favor of a ...more aggressive surgical approach to FTR and interest has been growing in the physiopathology and treatment of FTR. The purpose of this editorial is to explore the anatomical basis, pathophysiology, therapeutic approaches and the perspectives of treatment.
In 2014, an estimated 1.8 million people died from Mycobacterium tuberculosis (MTB); moreover, 680,000 people developed multidrug-resistant TB (MDRTB).
Currently available anti-MDR and XDR regimens ...are long-lasting and expensive, need high adherence and are undermined by a high frequency of adverse drug events, thus leading to a low success rate; furthermore, in the last 50 years only two new molecules, bedaquiline (BDQ) and delamanid, have been approved and released for the treatment of MDR-TB.
BDQ, patent number US 7,498,343B2, is a diarylquinoline anti-mycobacterial drug, active regardless of the state of MTB; in fact, its efficacy is conserved against replicating and non-replicating bacilli, despite extracellular or intracellular location. BDQ has been approved by the Food and Drug Administration (FDA) only for combination treatment of pulmonary multidrug-resistant tuberculosis (MDR-TB), in adult patients, when an effective treatment cannot be provided otherwise due to resistance or poor tolerability; however, due to high bactericidal activity, BDQ may be used in future to treat extrapulmonary tuberculosis and Mycobacterium other than tuberculosis (MOTT) infection.
BDQ may play a major role to get closer to TB eradication and to ensure higher retention in care, even in fully susceptible MTB strains and against non-replicating mycobacteria in latent-TB, providing an alternative to standard regimen.
Heavily treated HIV-1 infected patients may have limited therapeutic alternatives. In order to ensure sustained HIV-RNA suppression in these patients and to improve current antiretroviral treatment ...regimens in the fight against multi-drug resistant strains, new drugs are needed. Recently, two new drugs among the new generation of entry inhibitors showed promises for both their characteristics and mechanism of action.
To outline ibalizumab (Patent: US20120121597A1) and fostemsavir (Patent: US8871771) future applications in people living with multi-drug resistant HIV with few remaining treatment options.
We analysed the available literature and data from ongoing clinical trials about ibalizumab and fostemsavir.
Ibalizumab is a new humanized monoclonal antibody. It acts as post-attachment inhibitor by binding CD4 2nd domain of T lymphocyte and preventing HIV connection to CCR5 or CXCR4 and has been recently approved by Food and Drug Administration in the United States of America as a new intravenous antiretroviral agent for heavily treated HIV adults with multi -drug resistant infection. Fostemsavir (formerly BMS-663068), the oral prodrug of temsavir, is another attachment inhibitor. It acts by preventing the viral connection to CD4 by binding gp120. This drug showed encouraging results in heavily treated patients as add-on agent to current antiretroviral regimens, in particular for subtype B virus. It is currently being investigated in a phase 3, two-cohort (randomized and non-randomized), trial.
The history of ibalizumab and fostemsavir will be written in next years. Continuing the research will be crucial to obtain evidence based guidelines for the management of heavily treated HIV-1 infected patients with limited therapeutic options.
Elvitegravir/cobicistat/emtricitabine/tenofovirDF (EVG/COBI/FTC/TDF) is the new single-tablet, fixed-dose formulation containing an integrase strand transfer inhibitor recently approved as ...antiretroviral treatment. In this paper we analysed its use and advantages in naïve and experienced HIV-infected patients and we focused on special populations in which EVG/COBI/FTC/TDF could be a suitable option. Furthermore the manuscript reports the recent patent of EVG which may have an influence on the management of HIV-infected patients in the next future.
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