Differences in Salivary Flow Level, Xerostomia, and Flavor Alteration in Mexican HIV Patients Who Did or Did Not Receive Antiretroviral Therapy

Objective and subjective alterations related to salivary flow have been reported in patients infected with human immunodeficiency virus (HIV), and these alterations are associated with the introduction of antiretroviral therapy. The aim of the current study was to discern whether these alterations are disease induced or secondary to drug therapy. Objective. The objective was to determine the relationships between low salivary flow, xerostomia, and flavor alterations in HIV patients who did or did not receive antiretroviral therapy. Materials and Methods. In this cross-sectional study, HIV patients were divided into two groups based on whether they had received antiretroviral therapy. Those patients with a previous diagnosis of any salivary gland disease were excluded. A survey was used to assess subjective variables, and colorimetry and salivary flow rates were measured using the Schirmer global test. Results. A total of 293 patients were included. The therapy group showed a significantly lower average salivary flow than did the group without therapy, and we observed that the flow rate tended to decrease after one year of therapy.The results were not conclusive, despite significant differences in xerostomia and flavor alteration between the groups. Conclusion. The study results suggest that antiretroviral therapy can cause cumulative damage that affects the amount of salivary flow

La candidiasis bucal como marcador clínico de falla a la terapia antirretroviral altamente efectiva en pacientes infectados con VIH/sida

La candidiasis bucal es una infección oportunista fácilmente detectable en la clínica, por lo que se ha utilizado para valorar tanto el estado inmunológico de los pacientes con VIH como la efectividad de la terapia antirretroviral, altamente efectiva debido a que se encuentra sujeta a diversos factores para lograr el éxito terapéutico. Objetivo: Determinar la frecuencia de candidiasis bucal entre indicadores asociados al éxito de la terapia antirretroviral. Material y método: Estudio transversal, analítico en donde inicialmente se realizaron grupos de acuerdo al uso o no de la terapia antirretroviral para proseguir con un interrogatorio que incluía preguntas sobre otros factores relacionados con la infección por cándida, así como la medición del flujo salival y la evaluación clínica de la cavidad bucal para determinar la frecuencia de la candidiasis. Resultados: La diferencia en la frecuencia de la candidiasis bucal entre los grupos con y sin terapia antirretroviral fue significativa, además de obtener una OR = 2,6 (1,58-4,48) y la asociación con la disminución en el conteo de linfocitos de CD4. Discusión: La resistencia a la terapia antirretroviral constituye uno de los problemas fundamentales en el éxito del tratamiento, en los pacientes infectados con virus de la inmunodeficiencia humana, al igual que las toxicidades y los problemas de adherencia. Los sensores clínicos como la candidiasis bucal son parámetros de fácil acceso para la detección temprana de falla en la terapia

Synbiotic therapy decreases microbial translocation and inflammation and improves immunological status in HIV-infected patients: a double-blind randomized controlled pilot trial

BACKGROUND: HIV-infection results in damage and dysfunction of the gastrointestinal system. HIV enteropathy includes pronounced CD4+ T-cell loss, increased intestinal permeability, and microbial translocation that promotes systemic immune activation, which is implicated in disease progression. A synbiotic is the combination of probiotics and prebiotics that could improve gut barrier function. Our study goal was to determine whether the use of a synbiotic, probiotics or a prebiotic can recover immunological parameters in HIV-infected subjects through of a reduction of microbial translocation and pro-inflammatory cytokine production. METHODS: A randomized, double-blind controlled study was performed; twenty Antiretroviral treatment-naïve HIV-infected subjects were subgrouped and assigned to receive a synbiotic, probiotics, a prebiotic, or a placebo throughout 16 weeks. RESULTS: We had no reports of serious adverse-events. From baseline to week 16, the synbiotic group showed a reduction in bacterial DNA concentrations in plasma (p = 0.048). Moreover, the probiotic and synbiotic groups demonstrated a decrease in total bacterial load in feces (p = 0.05). The probiotic group exhibited a significant increment of beneficial bacteria load (such as Bifidobacterium; p = 0.05) and a decrease in harmful bacteria load (such as Clostridium; p = 0.063). In the synbiotic group, the CD4+ T-cells count increased (median: +102 cells/μL; p = 0.05) and the level of Interleukin 6 cytokine decreased significantly (p = 0.016). CONCLUSIONS: Our study showed a significant increase in CD4+ T lymphocyte levels in the synbiotic group, which could delay the initiation of antiretroviral therapy and decrease costs in countries with limited resources

Cobicistat Versus Ritonavir as a Pharmacoenhancer of Atazanavir Plus Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-Naive HIV Type 1-Infected Patients: Week 48 Results

Background. Cobicistat (COBI) is a pharmacoenhancer with no antiretroviral activity in vitro. Methods. An international, randomized, double-blind, double-dummy, active-controlled trial was conducted to evaluate the efficacy and safety of COBI versus ritonavir (RTV) as a pharmacoenhancer of atazanavir (ATV) in combination with emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) in treatment-naive patients. The primary end point was a human immunodeficiency virus type 1 (HIV-1) RNA load of 100 000 copies/mL, rates were similar (86% vs 86%). Similar percentages of patients in both groups had serious adverse events (10% of COBI recipients vs 7% of RTV recipients) and adverse events leading to discontinuation of treatment with the study drug (7% vs 7%). Median increases in the serum creatinine level were 0.13 and 0.09 mg/dL, respectively, for COBI and RTV recipients. Conclusions. COBI was noninferior to RTV in combination with ATV plus FTC/TDF at week 48. Both regimens achieved high rates of virologic success. Safety and tolerability profiles of the 2 regimens were comparable. Once-daily COBI is a safe and effective pharmacoenhancer of the protease inhibitor ATV. Clinical Trials Registration. NCT0110851

Brief report: cobicistat compared with ritonavir as a pharmacoenhancer for atazanavir in combination with emtricitabine/tenofovir disoproxil fumarate: week 144 results

BACKGROUND: Cobicistat (COBI) is a pharmacoenhancer with no antiretroviral activity. METHODS: International, randomized double-blind active-controlled trial to evaluate the efficacy and safety of COBI vs ritonavir (RTV) as a pharmacoenhancer of atazanavir in combination with emtricitabine/tenofovir disoproxil fumarate in HIV treatment-naive patients followed through week 144. RESULTS: At Week 144, virologic suppression was achieved in 72% (COBI) and 74% (RTV) of patients. Adverse events leading to study drug discontinuation occurred in 11% of patients in each group. Median changes in serum creatinine (mg/dL) were +0.13 (COBI) and +0.07 (RTV) and were unchanged from week 48. CONCLUSIONS: Once-daily COBI is a safe and effective pharmacoenhancer of the protease inhibitor atazanavir

Differences in response to antiretroviral therapy in HIV-positive patients being treated for tuberculosis in Eastern Europe, Western Europe and Latin America.

BACKGROUND: Efavirenz-based antiretroviral therapy (ART) regimens are preferred for treatment of adult HIV-positive patients co-infected with tuberculosis (HIV/TB). Few studies have compared outcomes among HIV/TB patients treated with efavirenz or non-efavirenz containing regimens. METHODS: HIV-positive patients aged ≥16 years with a diagnosis of tuberculosis recruited to the TB:HIV study between Jan 1, 2011, and Dec 31, 2013 in 19 countries in Eastern Europe (EE), Western Europe (WE), and Latin America (LA) who received ART concomitantly with TB treatment were included. Patients either received efavirenz-containing ART starting between 15 days prior to, during, or within 90 days after starting tuberculosis treatment, (efavirenz group), or other ART regimens (non-efavirenz group). Patients who started ART more than 90 days after initiation of TB treatment, or who experienced ART interruption of more than 15 days during TB treatment were excluded. We describe rates and factors associated with death, virological suppression, and loss to follow up at 12 months using univariate, multivariate Cox, and marginal structural models to compare the two groups of patients. RESULTS: Of 965 patients (647 receiving efavirenz-containing ART, and 318 a non-efavirenz regimen) 50% were from EE, 28% from WE, and 22% from LA. Among those not receiving efavirenz-containing ART, regimens mainly contained a ritonavir-boosted protease inhibitor (57%), or raltegravir (22%). At 12 months 1.4% of patients in WE had died, compared to 20% in EE: rates of virological suppression ranged from 21% in EE to 61% in WE. After adjusting for potential confounders, rates of death (adjusted Hazard Ratio; aHR, 95%CI: 1.13, 0.72-1.78), virological suppression (aHR, 95%CI: 0.97, 0.76-1.22), and loss to follow up (aHR, 95%CI: 1.17, 0.81-1.67), were similar in patients treated with efavirenz and non-efavirenz containing ART regimens. CONCLUSION: In this large, prospective cohort, the response to ART varied significantly across geographical regions, whereas the ART regimen (efavirenz or non-efavirenz containing) did not impact on the proportion of patients who were virologically-suppressed, lost to follow up or dead at 12 months

Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: Two randomised, double-blind, phase 3, non-inferiority trials

none27siBackground Tenofovir disoproxil fumarate can cause renal and bone toxic effects related to high plasma tenofovir concentrations. Tenofovir alafenamide is a novel tenofovir prodrug with a 90% reduction in plasma tenofovir concentrations. Tenofovir alafenamide-containing regimens can have improved renal and bone safety compared with tenofovir disoproxil fumarate-containing regimens. Methods In these two controlled, double-blind phase 3 studies, we recruited treatment-naive HIV-infected patients with an estimated creatinine clearance of 50 mL per min or higher from 178 outpatient centres in 16 countries. Patients were randomly assigned (1:1) to receive once-daily oral tablets containing 150 mg elvitegravir, 150 mg cobicistat, 200 mg emtricitabine, and 10 mg tenofovir alafenamide (E/C/F/tenofovir alafenamide) or 300 mg tenofovir disoproxil fumarate (E/C/F/tenofovir disoproxil fumarate) with matching placebo. Randomisation was done by a computer-generated allocation sequence (block size 4) and was stratified by HIV-1 RNA, CD4 count, and region (USA or ex-USA). Investigators, patients, study staff, and those assessing outcomes were masked to treatment group. All participants who received one dose of study drug were included in the primary intention-to-treat efficacy and safety analyses. The main outcomes were the proportion of patients with plasma HIV-1 RNA less than 50 copies per mL at week 48 as defined by the the US Food and Drug Adminstration (FDA) snapshot algorithm (pre-specified non-inferiority margin of 12%) and pre-specified renal and bone endpoints at 48 weeks. These studies are registered with ClinicalTrials.gov, numbers NCT01780506 and NCT01797445. Findings We recruited patients from Jan 22, 2013, to Nov 4, 2013 (2175 screened and 1744 randomly assigned), and gave treatment to 1733 patients (866 given E/C/F/tenofovir alafenamide and 867 given E/C/F/tenofovir disoproxil fumarate). E/C/F/tenofovir alafenamide was non-inferior to E/C/F/tenofovir disoproxil fumarate, with 800 (92%) of 866 patients in the tenofovir alafenamide group and 784 (90%) of 867 patients in the tenofovir disoproxil fumarate group having plasma HIV-1 RNA less than 50 copies per mL (adjusted difference 2·0%, 95% CI -0·7 to 4·7). Patients given E/C/F/tenofovir alafenamide had significantly smaller mean serum creatinine increases than those given E/C/F/tenofovir disoproxil fumarate (0·08 vs 0·12 mg/dL; p<0·0001), significantly less proteinuria (median % change -3 vs 20; p<0·0001), and a significantly smaller decrease in bone mineral density at spine (mean % change -1·30 vs -2·86; p<0·0001) and hip (-0·66 vs -2·95; p<0·0001) at 48 weeks. Interpretation Through 48 weeks, more than 90% of patients given E/C/F/tenofovir alafenamide or E/C/F/tenofovir disoproxil fumarate had virological success. Renal and bone effects were significantly reduced in patients given E/C/F/tenofovir alafenamide. Although these studies do not have the power to assess clinical safety events such as renal failure and fractures, our data suggest that E/C/F/tenofovir alafenamide will have a favourable long-term renal and bone safety profile. Funding Gilead Sciences.openSax, Paul E; Wohl, David; Yin, Michael T.; Post, Frank; Dejesus, Edwin; Saag, Michael; Pozniak, Anton; Thompson, Melanie; Podzamczer, Daniel; Molina, Jean Michel; Oka, Shinichi; Koenig, Ellen; Trottier, Benoit; Andrade-Villanueva, Jaime; Crofoot, Gordon; Custodio, Joseph M.; Plummer, Andrew; Zhong, Lijie; Cao, Huyen; Martin, Hal; Callebaut, Christian; Cheng, Andrew K.; Fordyce, Marshall W.; Mccallister, Scott; for the GS-US-292-0104/0111 Study Team [...; Pierluigi Viale; ...]Sax, Paul E; Wohl, David; Yin, Michael T.; Post, Frank; Dejesus, Edwin; Saag, Michael; Pozniak, Anton; Thompson, Melanie; Podzamczer, Daniel; Molina, Jean Michel; Oka, Shinichi; Koenig, Ellen; Trottier, Benoit; Andrade-Villanueva, Jaime; Crofoot, Gordon; Custodio, Joseph M.; Plummer, Andrew; Zhong, Lijie; Cao, Huyen; Martin, Hal; Callebaut, Christian; Cheng, Andrew K.; Fordyce, Marshall W.; Mccallister, Scott; for the GS-US-292-0104/0111 Study Team [..; Pierluigi Viale; ..

National prevalence and trends of HIV transmitted drug resistance

Abstract Background: Transmitted drug resistance (TDR) remains an important concern for the management of HIV infection, especially in countries that have recently scaled-up antiretroviral treatment (ART) access

Randomized elimination and prolongation of ACE inhibitors and ARBs in coronavirus 2019 (REPLACE COVID) Trial Protocol

Severe acute respiratory syndrome coronavirus 2 (SARS- CoV- 2), the virus responsible for coronavirus disease 2019 (COVID- 19), is associated with high incidence of multiorgan dysfunction and death. Angiotensin- converting enzyme 2 (ACE2), which facilitates SARS- CoV- 2 host cell entry, may be impacted by angiotensin- converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), two commonly used antihypertensive classes. In a multicenter, international randomized controlled trial that began enrollment on March 31, 2020, participants are randomized to continuation vs withdrawal of their long- term outpatient ACEI or ARB upon hospitalization with COVID- 19. The primary outcome is a hierarchical global rank score incorporating time to death, duration of mechanical ventilation, duration of renal replacement or vasopressor therapy, and multiorgan dysfunction severity. Approval for the study has been obtained from the Institutional Review Board of each participating institution, and all participants will provide informed consent. A data safety monitoring board has been assembled to provide independent oversight of the project.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163400/2/jch14011_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163400/1/jch14011.pd

Long-acting injectable Cabotegravir + Rilpivirine for HIV maintenance therapy: Week 48 pooled analysis of phase 3 ATLAS and FLAIR trials

BACKGROUND: Long-acting (LA) injectable regimens are a potential therapeutic option in people living with HIV-1. SETTING: ATLAS (NCT02951052) and FLAIR (NCT02938520) were 2 randomized, open-label, multicenter, multinational phase 3 studies. METHODS: Adult participants with virologic suppression (plasma HIV-1 RNA &lt;50 copies/mL) were randomized (1:1) to continue with their current antiretroviral regimen (CAR) or switch to the long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In the LA arm, participants initially received oral CAB + RPV once-daily for 4 weeks to assess individual safety and tolerability, before starting monthly injectable therapy. The primary endpoint of this combined analysis was antiviral efficacy at week 48 (FDA Snapshot algorithm: noninferiority margin of 4% for HIV-1 RNA ≥50 copies/mL). Safety, tolerability, and confirmed virologic failure (2 consecutive plasma HIV-1 RNA ≥200 copies/mL) were secondary endpoints. RESULTS: The pooled intention-to-treat exposed population included 591 participants in each arm [28% women (sex at birth), 19% aged ≥50 years]. Noninferiority criteria at week 48 were met for the primary (HIV-1 RNA ≥50 copies/mL) and key secondary (HIV-1 RNA &lt;50 copies/mL) efficacy endpoints. Seven individuals in each arm (1.2%) developed confirmed virologic failure; 6/7 (LA) and 3/7 (CAR) had resistance-associated mutations. Most LA recipients (83%) experienced injection site reactions, which decreased in incidence over time. Injection site reactions led to the withdrawal of 6 (1%) participants. The serious adverse event rate was 4% in each arm. CONCLUSION: This combined analysis demonstrates monthly injections of CAB + RPV LA were noninferior to daily oral CAR for maintaining HIV-1 suppression