Browsing by Author "Arribas, Jose"
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Item Changes in lipid levels after 48 weeks of dual versus triple therapy observed in the GARDEL study(2014) Cahn, Pedro; Andrade-Villanueva, Jaime; Arribas, Jose; Gatell, Jose; Lama, Javier; Norton, Michel; Patterson, Patricia; Sierra Madero, Juan; Sued, Omar; Figueroa, Maria Ines; Rolón, María JoséIntroduction Treatment with ritonavir-boosted protease inhibitors and nucleoside analogues frequently leads to rises in lipids, which might increase the cardiovascular risk. The aim of this study was to describe changes in lipid levels among HIV positive patients participating in the GARDEL study. Materials and Methods The GARDEL study compared the efficacy and safety of a dual therapy (DT) combination of LPV/r 400/100 mg BID+3TC 150 mg BID to a triple therapy (TT) with LPV/r 400/100 mg BID+3TC or FTC and a third investigator-selected NRTI in fixed-dose combination among HIV+ treatment naïve patients. We compared changes in lipid levels from baseline to week 48 in both arms. Results Patient's characteristics were well balanced regarding mean baseline total cholesterol (157 mg/dL DT, 154 mg/dL TT), triglycerides (142 mg/dL DT, 139 mg/Dl TT), LDL-C (94 mg/dL DT, 91 mg/dL TT) and HDL-C (36 mg/dL DT, 35 mg/dL TT). Changes in total cholesterol, LDL-C and HDL-C were higher in DT arm, compared to TT (32% DT vs 26% TT for cholesterol; 25% DT vs 16% TT for LDL and 33% DT vs 28% TT for HDL). Increase in triglycerides was higher in TT compared to DT (55% DT vs 92% TT) (Table 1). In TT arm LDL-C and total cholesterol elevations were lower among patients receiving TDF compared to those treated with ZDV or ABC.Item Effectiveness of Protease Inhibitor Monotherapy versus Combination Antiretroviral Maintenance Therapy: A Meta-Analysis(2011) Mathis, Steven; Khanlari, Babak; Pulido, Francisco; Schechter, Mauro; Negredo, Eugenia; Nelson, Mark; Vernazza, Pietro; Cahn, Pedro; Meynard, Jean-Luc; Arribas, Jose; Bucher, Heiner C.Background: The unparalleled success of combination antiretroviral therapy (cART) is based on the combination of three drugs from two classes. There is insufficient evidence whether simplification to ritonavir boosted protease inhibitor (PI/r) monotherapy in virologically suppressed HIV-infected patients is effective and safe to reduce cART side effects and costs. Methods: We systematically searched Medline, Embase, the Cochrane Library, conference proceedings and trial registries to identify all randomised controlled trials comparing PI/r monotherapy to cART in suppressed patients. We calculated in an intention to treat (loss-of follow-up, discontinuation of assigned drugs equals failure) and per-protocol analysis (exclusion of protocol violators following randomisation) and based on three different definitions for virological failure pooled risk ratios for remaining virologically suppressed. Findings: We identified 10 trials comparing 3 different PIs with cART based on a PI/r plus 2 reverse transcriptase inhibitors in 1189 patients. With the most conservative approach (viral load <50 copies/ml on two consecutive measurements), the risk ratios for viral suppression at 48 weeks of PI/r monotherapy compared to cART were in the ITT analysis 0.94 8 (95% CI 0.89 to 1.00) p = 0.06; risk difference -0.06 (95%CI -0.11 to 0) p = 0.05, p for heterogeneity = 0.08, I(2) = 43.1%) and in the PP analysis 0.93 ((95%CI 0.90 to 0.97) p<0.001; risk difference -0.07 (95%CI -0.10 to -0.03) p<0.001, p for heterogeneity = 0.44, I(2) = 0%). Reintroduction of cART in 44 patients with virological failure led in 93% to de-novo viral suppression. Interpretation: Virologically well suppressed HIV-infected patients have a lower chance to maintain viral suppression when switching from cART to PI/r monotherapy. Failing patients achieve high rates of de-novo viral suppression following reintroduction of reverse transcriptase inhibitors.Item HIV and aging, biological mechanisms, and therapies: What do we know?(Permanyer Publications, 2022) Grosso, Tomás M.; Alcamí, José; Arribas, Jose; Martín, Marta; Sereti, Irini; Tarr, Philip; Cahn, Pedro; Clotet, Bonaventura; Sued, Omar; Negredo, EugeniaAging, a time-dependent loss of physiological function, and its drivers are turning into a significant topic of research as the population's mean age increases. Epigenetic alterations, telomere shortening or dysfunction, mitogenic stress, oxidative stress, or accumulation of DNA damage can drive the cell to senescence: a permanent cell cycle arrest sometimes associated with a secretory phenotype and inflammatory consequences in the surrounding tissue. The amount of senescent cells grows over time in older organisms and may induce tissue inflammation and threaten overall tissue homeostasis, favoring aging. Senolytic and senomorphic therapeutics are an emerging approach to eliminate senescent cells or to block their secretory phenotypes respectively. Given that people living with HIV suffer non-AIDS comorbidities in a higher prevalence than the general population, aging is accentuated among them. Inflammation biomarkers may be helpful to assess prognosis or act as surrogate endpoints for studies of strategies focused on reversal of HIV-associated accelerated aging. This review summarizes the latest findings in aging and its major drivers, under the light of HIV infection. Since the number of older PLWH is currently rising, it will be of great importance to address and treat their age-related conditions, as well as to better decipher their biological mechanisms.Item Need for clear inclusion criteria in reviews of antiretroviral treatments(2023-02) Gibas, Kevin M.; Arribas, Jose; Cahn, Pedro; Daar, Eric S.; Taiwo, Babafemi O.On behalf of the writing group, we appreciate the correspondence from Alexandra Calmy and colleagues regarding our Review. Our main goal was to provide clinicians with an overview of two-drug antiretroviral therapy, by means of relevant data from the literature that would inform clinical practice. On the basis of these criteria, dolutegravir plus emtricitabine did not meet our selection standard. First, this combination for HIV treatment had previously been examined only in a small retrospective study. Furthermore, the SIMPL’HIV trial, an open-label study that randomly assigned 93 participants to dolutegravir plus emtricitabine, showed non-inferiority with a primary endpoint that used a 12% margin for the proportion of participants with HIV RNA less than 100 copies per mL up to 48 weeks. This study is very small and had a primary endpoint that deviates from the US Food and Drug Administration recommendation of a 4% non-inferiority margin for the proportion with HIV RNA greater than 50 copies per mL for switch trials. The clinical relevance of SIMPL’HIV to our comprehensive review was further lowered by the absence of any scenario, to our knowledge, in which the two-pill dolutegravir plus emtricitabine regimen would be preferred over single-pill dolutegravir plus lamivudine. In addition to not being available as a fixed-dose combination, in many low-income and middle-income countries, lamivudine, a generic drug, is substantially cheaper than emtricitabine. We believe that inclusion of SIMPL’HIV would have neither advanced the understanding of clinicians seeking relevant information on two-drug therapy nor benefitted researchers seeking to advance HIV therapeutics.Item Pneumocystis jirovecii pneumonia in Spanish HIV-infected patients in the combined antiretroviral therapy era: prevalence of dihydropteroate synthase mutations and prognostic factors of mortality(2008) Alvarez-Martínez, Miriam J.; Moreno, Asunción; Miro, Jose M.; Valls, Maria Eugenia; Rivas, Paula V.; Lazzari, Elisa de; Sued, Omar; Benito, Natividad; Domingo, Pere; Ribera, Esteban; Santín, Miguel; Sirera, Guillermo; Segura, Ferràn; Vidal, Francesc; Rodríguez, Francisco; Riera, Melchor; Cordero, Maria Elisa; Arribas, Jose; Anta, Maria Teresa Jiménez de; Gatell, Jose; Wilson, Paul E.; Meshnick, Steven R.; Spanish PCP Working GroupThe incidence of Pneumocystis jirovecii pneumonia (PCP) in HIV-infected patients has decreased thanks to sulfa prophylaxis and combined antiretroviral therapy. The influence of P. jirovecii dihydropteroate synthase (DHPS) gene mutations on survival is controversial and has not been reported in Spain. This prospective multicenter study enrolled 207 HIV-infected patients with PCP from 2000 to 2004. Molecular genotyping was performed on stored specimens. Risk factors for intensive care unit (ICU) admission and mortality were identified using a logistic regression model. Seven patients (3.7%; 95% confidence interval [CI], 1.5-7.5%) had DHPS mutations. Overall mortality was 15% (95% CI, 10-21%), rising to 80% (95% CI, 61-92%) in patients requiring mechanical ventilation. None of the patients with DHPS mutants died, nor did they need ICU admission or mechanical ventilation. PaO(2) <60 mm Hg at admission was a predictor of ICU admission (P = 0.01), and previous antiretroviral therapy predicted non-ICU admission (P = 0.009). PaO(2) <60 mm Hg at admission and ICU admission during the 1st week were predictors of mortality (P = 0.03 and P < 0.001, respectively). The prevalence of DHPS mutants in Spain is low and is not associated with a worse outcome. Severe respiratory failure at admission is the strongest predictor of PCP outcome.Item Three-year durable efficacy of dolutegravir plus lamivudine in antiretroviral therapy - naive adults with HIV-1 infection(2022-01-01) Cahn, Pedro; Sierra Madero, Juan; Arribas, Jose; Antinori, Andrea; Ortiz, Roberto; Clarke, Amanda E; Hung, Chien-Ching; Rockstroh, Jürgen K; Girard, Pierre-Marie; Sievers, Jörg; Man, Choy Y; Urbaityte, Rimgaile; Brandon, Daisy J; Underwood, Mark; Pappa, Keith A; Curtis, Lloyd; Smith, Kimberly Y; Gartland, Martin; Aboud, Michael; van Wyk, Jean; Wynne, Brian[ABSTRACTS]. OBJECTIVE: To assess efficacy and safety of dolutegravir (DTG) + lamivudine (3TC) vs. DTG + tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in treatment-naive adults with HIV-1 in the prespecified 144-week secondary analyses of GEMINI-1 and GEMINI-2. DESIGN: Identical, multicenter, phase III, randomized, non-inferiority studies (double-blind through 96 weeks). METHODS: Participants with HIV-1 RNA ≤500 000 copies/ml and no major viral resistance mutations to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, or protease inhibitors were randomized 1:1 to once-daily DTG + 3TC or DTG + TDF/FTC. RESULTS: At week 144, DTG + 3TC (N = 716) was noninferior to DTG + TDF/FTC (N = 717) in proportion of participants achieving HIV-1 RNA <50 copies/ml (Snapshot algorithm) in the pooled analysis (82% vs. 84%, respectively; adjusted treatment difference [95% confidence interval (CI)], -1.8% [-5.8, 2.1]), GEMINI-1 (-3.6% [-9.4, 2.1]), and GEMINI-2 (0.0% [-5.3, 5.3]). Twelve DTG + 3TC participants and nine DTG + TDF/FTC participants met protocol-defined confirmed virologic withdrawal (CVW) criteria; none developed treatment-emergent resistance. One DTG + 3TC participant who did not meet CVW criteria developed M184V at week 132 and R263R/K at week 144, conferring a 1.8-fold change in susceptibility to DTG; non-adherence to therapy was reported. Significantly fewer drug-related adverse events occurred with DTG + 3TC vs. DTG + TDF/FTC (20% vs. 27%; relative risk [95% CI], 0.76 [0.63-0.92]). Renal and bone biomarker changes favored DTG + 3TC. CONCLUSIONS: Three-year durable efficacy, long-term tolerability, and high barrier to resistance support first-line use of DTG + 3TC for HIV-1 treatment (see Supplemental Digital Content 1, http://links.lww.com/QAD/C297; video abstract).