Suchergebnisse

The National Government HAART Program (NGP) for the provision of HAART to uninsured HIV-infected persons in Mexico began in 2001. The objective was to describe the virologic outcome of patients enrolled in the NGP in a large HIV treatment center in Mexico City. HIV-infected persons, naive or ≤6 months on HAART, who entered the NGP from 2001 to 2005 were included. Patients with virological suppression were compared to those with virologic failure (VF) during follow-up. Of 377 patients enrolled, 191 where eligible for analysis. The median age was 35.9 (18–75 years) and 85% were male. The median baseline CD4+ T cell count was 183 cells/mm3; 63.9% had <200 cells/mm3 and/or an AIDS-defining event. During follow-up (median: 17.77 months), 55 patients (28.7%) changed their first regimen: 8.3% because of VF and the remaining due to toxicity. The probability of VF at 48 months was 20%. VF was associated with age <30 years (p = 0.003, RR 4.7, IC 95% 1.5–14.4). The use of NNRTI was associated with lower risk of VF (p = 0.042, RR 0.3, IC 95% 0.12–0.99). Nadir CD4+ and AIDS-defining at baseline were not associated with VF. Implementation of NGP for HAART access in a specialized care setting in Mexico resulted in an excellent virologic response. Younger age was a significant risk factor for VF.

AbstractIntroductionImmune reconstitution following antiretroviral therapy (ART) initiation is crucial to prevent AIDS and non‐AIDS‐related comorbidities. Patients with suppressed viraemia who fail to restore cellular immunity are exposed to an increased risk of morbidity and mortality during long‐term follow‐up, although the underlying mechanisms remain poorly understood. We aim to describe clinical outcomes and factors associated with the worse immune recovery and all‐cause mortality in people living with HIV (PLWH) from Latin America following ART initiation.MethodsRetrospective cohort study using the CCASAnet database: PLWH ≥18 years of age at ART initiation using a three drug‐based combination therapy and with medical follow‐up for ≥24 months after ART initiation and undetectable viral load were included. Patients were divided into four immune recovery groups based on rounded quartiles of increase in CD4 T‐cell count at 2 years of treatment (<150, [150, 250), [250, 350] and >350 cells/mm3). Primary outcomes included all‐cause mortality, AIDS‐defining events and non‐communicable diseases that occurred >2 years after ART initiation. Factors associated with an increase in CD4 T‐cell count at 2 years of treatment were evaluated using a cumulative probability model with a logit link.ResultsIn our cohort of 4496 Latin American PLWH, we found that patients with the lowest CD4 increase (<150) had the lowest survival probability at 10 years of follow‐up. Lower increase in CD4 count following therapy initiation (and remarkably not a lower baseline CD4 T‐cell count) and older age were risk factors for all‐cause mortality. We also found that older age, male sex and higher baseline CD4 T‐cell count were associated with lower CD4 count increase following therapy initiation.ConclusionsOur study shows that PLWH with lower increases in CD4 count have lower survival probabilities. CD4 increase during follow‐up might be a better predictor of mortality in undetectable PLWH than baseline CD4 count. Therefore, it should be included as a routine clinical variable to assess immune recovery and overall survival.

IntroductionT cell immunoglobulin and mucin domain (Tim) 3 and programmed death 1 (PD‐1) are co‐inhibitory receptors involved in the so‐called T cell exhaustion, and in vivo blockade of these molecules restores T cell dysfunction. High expression of Tim‐3 and PD‐1 is induced after chronic antigen‐specific stimulation of T cells during HIV infection. We have previously demonstrated that the interaction of Tim‐3 with its ligand galectin‐9 induces macrophage activation and killing of Mycobacterium tuberculosis. Our aim in this study was to analyze the Tim‐3 expression profile before and after six months of antiretroviral therapy and the impact of Tim‐3 and PD‐1 blocking on immunity against M. tuberculosis.Materials and methodsHIV+ patients naïve to anti‐retroviral therapy (ART) were followed up for six months. Peripheral immune‐cell phenotype (CD38/HLA‐DR/galectin‐9/Tim‐3 and PD‐1) was assessed by flow cytometry. Supernatants were analyzed with a multiplex cytokine detection system (human Th1/Th2 cytokine Cytometric Bead Array) by flow cytometry. Control of bacterial growth was evaluated by using an in vitro experimental model in which virulent M. tuberculosis‐infected macrophages were cultured with T cells in the presence or absence of Tim‐3 and PD‐1 blocking antibodies. Interleukin‐1 beta treatment of infected macrophages was evaluated by enumerating colony‐forming units.ResultsWe showed that HIV+ patients had an increased expression of Tim‐3 in T cells and were able to control bacterial growth before ART administration. By blocking Tim‐3 and PD‐1, macrophages and T cells recovered their functionality and had a higher ability to control bacterial growth; this result was partially dependent on the restitution of cytokine production.ConclusionsIn this study, we demonstrated that increased Tim‐3 expression can limit the ability of the immune system to control the infection of intracellular bacteria such as M. tuberculosis. The use of ART and the in vitro manipulation of the Tim‐3 and PD‐1 molecules restored the functionality of T cells and macrophages to restrict bacterial growth. Our results provide a novel immune strategy that may be implemented in the near future in order to improve the immune responses in HIV+ patients.

IntroductionHIV‐1 plasma viral load during treatment can be highly variable. Thus, there is the need to find a measure of cumulative viremia that can be used to assess both the short‐ and long‐term efficacy of highly active antiretroviral therapy (HAART). Here, we validate a measure of cumulative viremia to evaluate HAART efficacy.MethodsWe accessed HAART efficacy using data from a randomized clinical trial conducted in Mexico. We compared the proportion of individuals achieving a viral load <50 and <400 copies/mL at week 48, against the cumulative plasma viral load, estimated as the area under the plasma viral load curve (AUVLC). High AUVLC indicates high cumulative viremia.Results and discussionThere was a strong and significant association between the proportion of individuals achieving a viral load <50 and <400 copies/mL at week 48, with individuals suppressed having significant lower cumulative viremia. The median area was 7513 (25th–75th percentile [Q1–Q3] 6634−8180) if viral load <50 copies/mL and 7679 (Q1–Q3 6899−9373) if viral load ≥50 copies/mL (p‐value 0.0284). When the analysis was stratified by study arm, individuals on efavirenz had lower cumulative viremia than those on boosted lopinavir.ConclusionsOur findings suggest that cumulative viremia should be explored further as a tool to simultaneously evaluate the individual and public health efficacy of HAART. This is particularly relevant to the implementation and evaluation of the Treatment 2.0 strategy recently proposed by UNAIDS and the WHO, as a means to maximize the individual and public health benefit of HAART.

IntroductionTreatment 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 MethodsThe 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.ResultsPatient'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.ConclusionChanges in lipid parameters were observed in both arms. Albeit the increase was numerically higher for cholesterol (total and LDL‐C) in DT arm while TT arm had higher increases in TG; no difference was observed when week 48 values were compared with the NCEP ATP III goals for cardiovascular risk reduction [1]. So, the DT strategy, even missing the lipid‐lowering effect observed with tenofovir, does not seem to add significant risk to patients treated with this novel strategy.

AbstractIntroductionThe "greying" of the HIV epidemic necessitates a better understanding of the healthcare needs of older HIV‐positive adults. As these individuals age, it is unclear whether comorbidities and their associated therapies or the ageing process itself alter the response to antiretroviral therapy (ART). In this study, HIV treatment outcomes and corresponding risk factors were compared between older ART initiators and those who were younger using data from the Caribbean, Central and South America Network for HIV Epidemiology (CCASAnet).MethodsHIV‐positive adults (≥18 years) initiating ART at nine sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru were included. Patients were classified as older (≥50 years) or younger (<50 years) based on age at ART initiation. ART effectiveness was measured using three outcomes: death, virologic failure and ART treatment modification. Cox regression models for each outcome compared risk between older and younger patients, adjusting for other covariates.ResultsAmong 26,311 patients initiating ART between 1996 and 2016, 3389 (13%) were ≥50 years. The majority of patients in both ≥50 and <50 age groups received a non‐nucleoside reverse transcriptase inhibitor‐based regimen (89% vs. 87%), did not have AIDS at baseline (63% vs. 62%), and were male (59% vs. 58%). Older patients had a higher risk of death (adjusted hazard ratio (aHR) 1.64; 95% confidence intervals (CI): 1.48 to 1.83) and a lower risk of virologic failure (aHR: 0.73; 95% CI: 0.63 to 0.84). There was no difference in risk of ART modification (aHR: 1.00; 95% CI: 0.94 to 1.06). Risk factors for death, virologic failure and treatment modification were similar for each group.ConclusionsOlder age at ART initiation was associated with increased mortality and decreased risk of virologic failure in our cohort of more than 26,000 ART initiators in Latin America and the Caribbean. To the best of our knowledge this is the first study from the region to evaluate ART outcomes in this growing and important population. Given the complexity of issues related to ageing with HIV, a greater understanding is needed in order to properly respond to this shifting epidemic.